The ,Health Benefits
      of
SMOKING CESSATION

a report of the
Surgeon General

1990

U.S. DEPARTMENT OF HEALTH AND HCIMAN SERVICES
Public Health Service
Centen for Disease Control

Center for Chrome Disease Prevention and Health Promorwn CDC
                                      CENTERS FOR DGEASE CONTROL

Office on Smoking and Health
Rockvllle. Maryland 20857


U.S. Department of Health and Human Ser\ ice\.  7%1> filwlllr Rlvrcytr\ /!f .S/?i,JX-
/~,q L`c~c.wfio/~. U.S. Department of Health and Human St'r\~ices. Public Health
Service. Center3 for Diwaw Control. Center for Chronic Die;Le Pre\ ention and
Health Promotion. Ofke on Smohing and Health.  DHHS Publication No.
(CDC) YO-K-116. 1990.


The Honorable Thomas S. Foley
Speaker of the House of
-RSpreSSlltSti"eS
Washingcon, D.C.  20515

Dear nr. Speaker:

It is my pleasure to transmit to the Congress the 1990 Surgeon General's
Report on the health consequences of smoking as mandated by Section E(a) of
the Public Health Cigarette Smoking Act of 1969 (Pub. L. 91-222). The report
YSS prepared by the Centers for Disease Control's Office on Smoking and Health.

This report, entitled The Health Benefits of Smoking Cessation, examines hov
an individual's risk of smoking-related diseases declines after quittins
smoking.  The evidence is overvhelming that smoking cessation has major and
inmediate health benefits for me" and women of all ages. Smoking cessation
increases overall life expectancy and reduces the risk of lung ca"cer, other
cancers. heart attack. stroke. and chronic 1"~ disease such as emphysema.
The health benefits of smoking cessation far e;ceed any risks from the average
S-pound weight gain or any adverse psychological effects that may follov
quitting.

Cigsrette smoking is the most important preventable cause of death in our
sWC.i.Sty.  It is responsible for approximately 390,000 deaths each year in the
United States, or more than one of every six deaths.  We must dl, Sll YP can to
prevent young people from taking up this deadly addiction, and ve m"st help
smckers quit.  Give" the enormous benefits of smoking cessation, and the fact
that good smoking cessation programs can achieve abstinence rates of 20 to 40
percent at one-year follovup, these programs are likely to be extremely
cost-effective compared with other preventive or curative services.
Therefore. I would encourage health insurers to provide psyment for smoking
cessation treatments that arc show" to be effective.  At a minimum, the
treatment of nicotine addiction should be considered as favorably by
third-party payers as treatment of alcoholism and ill!clt drug addiction

This report should help convince all smokers of the compelling need to quit
smoking.

Sincerely,

Louis W. Sullivan, U.D.
SWXetFlLY

Enclosure


The Honorable Dan Quayle
President of the Senate
Washington, D.C.  20515

Dear Mr. President:

It is my pleasure to transmit co the Congress the 1990 Surgeon General's
Report on the health consequences of smoking as mandated by Section g(a) of
the Public Health Cigarette Smoking Act of 1969 (Pub. L. 91-222). The report
was prepared by the Centers for Disease Control's Office 0" Smoking and Health.

This report, entitled The Health Benefits of Smokinn Cessation, examines how
a" individual's risk of smoking-related diseases declines after quitting
smoking. The evidence is overwhelming that smoking cessation has major and
immediate health benefits for me" and wme" of all ages. Smoking cessation
increases overall life expectancy and reduces the risk of lung cancer, other
cancers, heart attack, stroke, and chronic lung disease such as emphysema.
The health benefits of smoking cessation far exceed any risks from the average
S-pound weight gain or any adverse psychological effects that may follow
quitting.

Cigarette smoking is the most important preventable cause of death in our
SOCiStY.  It is responsible for approximately 390,000 deaths each year in the
United Stares, or more than one of every six deaths. We must do all ue can to
prevent young people from taking up this deadly addiction, and "e must help
smokers quit.  Given the enormous benefits of smoking cessation, and the fact
that good smoking cessation programs can achieve abstinence rates of 20 to 40
percent at one-year followup. these programs are likely to be extremely
&at-effective eonpared withother preventive or curative services.
Therefore, I would encourage health insurers to provide payment for smoking
cessation treatments that are show" to be effective.  At a minimum, the
treatment of nicotine addiction should be considered as favorably by
third-party psyors as treatment of slcoholism and illicit drug addiction.

This report should help convince all smokers of the compelling need to quit
smoking.

Sincerely,

~&&j,&&&
LOUiS w. Sullivan, M.D.
secretary

Enclosure


FOREWORD

More than 38 million Americans have quit smoking cigarette\. and nearI> half of all
living adults who ever smoked have quit. Unfortunately. \ome SO million American\
continue to smoke cigarettes. despite the many health education programs and anti-
smoking campaigns that have been conducted during the past quarter century. despite
the declining social acceptability of smoking, and despite the consequences of \mohing
to their health.

Twenty previous report\ of the Surgeon General have reviewed the health effect\ of
smoking. Scientific data are now available on the consequences of smohing ce\\ation
for most smoking-related disease\. Previous reports have considered \ome of thece
data. but this Report is the first to provide a comprehensive and unified re\,ieu of [hi\
topic.

The major conclusions of this volume are:

I. Smoking cessation has major and immediate health benefits for men and w-omen
of all ages. Benefits apply to persons with and without smoking-related disease.
2. Former smokers live longer than continuing smokers. For example, persons
who quit smoking before age 50 have one-half the risk of dying in the next 15
years compared with continuing smokers.
3. Smoking cessation decreases the risk of lung cancer, other cancers, heart attack,
stroke, and chronic lung disease.

1. Women who stop smoking before pregnancy or during the first 3 to 4 months
of pregnancy reduce their risk of having a low hirthweight baby to that of
  women who never smoked.

5. The health benefits of smoking cessation far exceed any risks from the average
5pound (2.3-kg) weight gain or any adverse psychological effects that ma!
follow quitting.

With the long-standing evidence that smoking is extremely harmful to health and the
mounting evidence that smoking cessation confers major health benefits. we remain
faced with the task of developing effective strategies to curtail the use of tobacco. Two
broad categories of intervention are available: prevention of smoking initiation among
youth and smoking cessation.  Resources for tobacco control are limited. and
policymakers must decide how best to allocate those resource\ to smohing prevention
and cessation.

The goal of public health i\ to intervene a\ earl! a\ pos\iblc to prc`\`ent di\ea\c.
disability. and premature death. From that standpoint. prevention of~mokin~ initiation


should he a maior priorit!. More than 3.000 tecnafer\ become regular w~oker~ (`UC /I
tltr~, in the United State\. Becauw of the strength of nicotine addiction. wme have
argued that public health effort\ should focu\ on smohing prevention rather than
wioking cessation. Houevcr. thi\ need not be an "either-or" Gtuation.

Public health practitioners have categorized interwntion\ into primary. secondnr!.
and tertiary prevention. Primary prevention generally refer\ to the elimination of ri\h
factors for di\ea\e in asymptomatic persons. Secondary prevention i\ defined a\ the
early detection and treatment ofdi\ease. and is practiced using toots wch 3s Pup smear\
and blood pressure \creenin_r.  Tertiary prevention con\i\ts of measures to reduce
impairment, diaabilit),. and suffering in people I$ ith existing disease.

Smoking cessation fall> under the catepor\' of primary prevention a\ does the
prevention of smoking initiation. Smoking cessation meets the definition of primq
prevention by reducing the rich of morbidity and premature mortality in asymptomatic
people. In addition. parent\ who quit smohing reduce or eliminate the rish ofpa~ive-
smoking-related disease among their children and reduce the probability that their
children will become smoher\. Thu\. there should be no debate about the need for
smoking prevention versw cessation-both are important.

Public awareness of the health effect\ of smoking ha\ increased substantialI!, through
the years. Neverthelcah. important gaps in public hnowledge still exist. Some \moher\
may have failed to quit hecawe of a lath of appreciation of the health hazards of
smoking and the benefits of quitting. In the 1987 National Health Intervie% Survey ot
Cancer Epidemiology and Control. rehpondentz were asked whether making increases
the risk of variou\ disease:, (lung cancer. cancer of the mouth and throat. heart disease.
emphysema. and chronic bronchitis) and uhethrr mohing ceaation reduces the rish.
Thirty to forty percent of smoker\ either did not believe that \mohiry increases thew
risks or did not beliebe that cessation reduces these ri\hs. The\e proportion\ correspond
to IS to 20 million smohen in the United State\. Clearly. our efforts to educate the
public on the health haLard\ ofmohing and the benefits ofquitting are not yet complete.

As we continue and intensit) our efforts to inform the public of thehe finding\. we
must make available wwhing cc\sation programs and ser\ ices to those Q ho need them.
Although 90 percent of former \moher\ quit without using smoking ce\Mion program\.
counseling. or nicotine pm. smoher\ Mho do need this asistancc should ha\e it
available. WC endorw the vie\\ rxprewxi in the Preface to the Ic)XX Surgeon General'\
Report that treatment of nicotine addiction should be con\idrred at least ;I\ fa\orabl!
by third-part) ptiyor\ ;I\ treatment of atcoholim anti illicit drug addiction. Good
smohing cessation trcatmt'nt\ C;III xhie\e :rh\tinencc rate\ of 20 to 40 percent at I -\car
followup. Those SLICLYS\ rate\. combined with the enormou\ health benefits ofmokinf
cessation. would libel) mahc pa! IIICIII for WIIIC wlohln, (I ce4ation tre3tments cwt-
beneficial. For example. research b! the Center\ for Diwazc Control suggests that a
smoking cessation program offered to all pregnant \mohers could sa\`e $5 for e\er!,
dollar spent b> prz\entin, 0 tow hirthuttiflit-3s~oc~icltt`tl nrc~natul intt`n\i\ e cure and
long-term cure.

ii


This Report should galvanize the health community, to stres\ repeatedly at every
opportunity the value of smoking cessation to the 50 million American\ who continue
to smoke.

James 0. Mason. M.D.. Dr.P.H.    William L. Roper. M.D.
Assistant Secretaq for Health       Director
Public Health Service           Centers for Disease Control

lil


PREFACE

This Report of the Surgeon General is the 2lst Report of the U.S. Public Health
Service on the health consequences of smoking and the first issued during my tenure
as Surgeon General. Whereas previous reports have focused on the health effects ot
smoking. this Report is devoted to the benefits of smoking cessation.

The public health impact of smoking is enormous. As documented in the 1989
Surgeon General's Report. an estimated 390.000 Americans die each year from diseases
caused by smoking. This toll includes 1 IS.000 death\ from heart disease: 106.000 from
lung cancer: 31.600 from other cancers; 57,000 from chronic obstructive pulmonary
disease; 27,500 from stroke: and 52.900 from other conditions related to smoking.
More than one of every six deaths in the United States are caused by smoking. For
more than a decade the Public Health Service has identified cigarette smoking as the
most important preventable cause of death in our society.

It is clear, then, that the elimination of smoking would yield substantial benefits for
public health. What are the benefits. however, for the individual smoker who quits'? A
large body of evidence has accumulated to address that question and derives from cohort
and case-control studies, cross-sectional surveys, and clinical trials. In studies of the
health effects of smoking cessation. persons classified as former smokers may include
some current smokers; this misclassification is likely to cause an underestimation of
the health benefits of quitting. Taken together. the evidence clearly indicates that
smoking cessation has major and immediate health benefits for men and w'omen of all
ages.

Overall Benefits of Smoking Cessation

People who quit smoking live longer than those who continue to smoke. To what
extent is a smoker's risk of premature death reduced after quitting smoking'? The
answer depends on several factors, including the number of years of smoking. the
number of cigarettes smoked per day, and the presence or absence of disease at the time
of quitting. Data from the American Cancer Society's Cancer Prevention Study II
(CPS-II) were analyzed in this Report to estimate the risk of premature death in
ex-smokers versus current smokers. These data show, for example. that persons who
quit smoking before age 50 have one-half the risk of dying in the next IS years compared
with continuing smokers.

Smoking cessation increases life expectancy because it reduces the risk of dying from
specific smoking-related diseases. One such disease is lung cancer, the most common
cause of cancer death in both men and women. The risk of dying from lung cancer is


22 times hitcher among male smohers and 12 times higher among female smokers
        L
compared with people u ho have never smoked.The risk of lung cancer declines steadil)
in people who quit smoking; after IO years of abstinence, the risk of lung cancer is about
3) to 50 percent of the risk for continuing smokers,. Smoking cessation also reduces
the risk of cancers of the larynx. oral cavity. esophagus. pancreas. and urinary bladder.

Coronary heart disease (CHD) is the leading cause of death in the United States.
Smokers have about twice the risk of dying from CHD compared with lifetime
nonsmokers. This excess risk is reduced by about half among ex-smokers after only 1
year of smoking abstinence and declines gradually thereafter. After 15 years ot
abstinence the risk of CHD is similar to that of persons who have never smoked.

Compared with lifetime nonsmokers. smokers have about twice the risk ofdying from
stroke, the third leading cause of death in the United States. After quitting smoking.
the risk of stroke returns to the level of people who have never smoked: in some studies
this reduction in risk has occurred within 5 years. but in others as long as IS years of
abstinence were required.

Cigarette smoking is the ma.jor cause of chronic obstructive pulmonary disease
(COPD). the fifth leading cause of death in the United States. Smoking increases the
risk of COPD by accelerating the ape-related decline in lung function. With sustained
abstinence from smoking. the rate of decline in lung function among former smokers
returns to that of never smokers. thus reducing the risk of developing COPD.
Influenza and pneumonia represent the sixth leading cause of death in the United
States. Cigarette smohing increases the risk of respiratory infections such as intluenla.
pneumonia. and bronchitis. and smoking cessation reduces the rish.
Cigarette smohing is a major cause of peripheral artery occlusive disease. This
condition causes substantial mortality and morbidity: complications may include inter-
mittent claudication. tissue ischemiu and gangrene. and ultimately. loss of limb.
Smoking cessation substantially reduces the risk of peripheral arter) occlusive disease
compared with continued smoking.

The mortalit> rate from abdominal aortic aneurysm is two to fi\,e times higher in
current smokers than in never smohers. Former smohers ha\e half the excess rish of
dying from this condition relative to current smohcrs.
About 20 million Americans currently ha\,e. or ha\c had. an ulcer of the stomach 01
duodenum. Smohers have an increased rish of developin g gastric or duodenal ulcers.
and this increased rish is reduced h> quitting smohing.

Benefits at All Ages

According to a I YXY Gallup survq. the proportion of smohers 14 ho say they would
lihc to give up smohing is loL\er for smokers aged 50 and older (57 percent) than for
smokers aged I X-24, (6X percent) and 3019 (67 percent ). Older smokers ma)' be less
motivated to quit smohin g because the highly motivated may have quit already at
younger ages. leaving a relatively "hard-core" group of older smohers. But man>
long-term smohers may Iach motivation to quit for other reasons. Some may believe
they are no longer at risk of smohing-related diseases because they have alread)
survived smohing for man)' j'ears. Others ma> believe that an) damage that may ha\,e

vi


been caused by smoking is irreversible after decades of smohing. For similar reasons.
many physicians may be less likeI) to counsel their older patients to quit.

CPS-II data were used to estimate the effects of quittin, (7 smoking at various ases on
the cumulative risk of death during a fixed interval after cessation. The results she\+
that the benefits of cessation extend to quitting at older ages. For example. a health!
man aged 60-63 u ho smohes I pack of cigarettes or more per da\ reduces his rish of
dying during the next IS learx by IO percent if he quits smoking.

These findings support the recommendations of the Surgeon General's I'SXX
Workshop on Health Promotion and Aging for the de\~elopmrnt and dissemination of
smoking cessation messages and interventions to older persons. I am pleased that a
coalition oforganirations and agencies is now worhing toward implementation of those
recommendations. including the Centers for Disease Control; the Nut~onal Cancer
Institute: the National Heart. Lun g. and Blood Institute: the Administration on Aging:
the Department of Veterans Affairs: the Office of Disease Pre\,ention and Health
Promotion: the American Association of Retired Persons: ;md the Fox Chase Cancer
Center. The major mcssafc of this campaign bill be that it is nc\cr too late to quit
smoking.

Two facts point to the urgent need for a strong smohing cessation campaign targetin?
older Americans: ( I ) 7 million smohers are aged 60 or older: and (2) smoking is :I ma,ior
rish FActor for 6 of the I3 leading causes of death among those aged 60 and older. and
is a complicating factor for 3 others.

Benefits for Smokers with Existing Disease

Many smokers who have already developed smoking-related disease or symptoms
may be less motivated to quit because of a belief that the damage is already done. For
the same reason, physicians may be less motivated to advise these patients to quit.
However, the evidence reviewed in this Report shows that smoking cessation yields
important health benefits to thoe who already suffer from smoking-related illness.

Among persons with diagnosed CHD, smoking cessation markedly reduces the risk
of recurrent heart attack and cardiovascular death. In many studies. this reduction in
risk has been 50 percent or more. Smoking cessation is the most important intervention
in the management of peripheral artery occlusive disease: for patients with this condi-
tion, quitting smoking improves exercise tolerance, reduces the risk of amputation after
peripheral artery surgery, and increases overall survival. Patients with gastric and
duodenal ulcers who stop smoking improve their clinical course relative to smokers
who continue to smoke. Although the benefits of smoking cessation among stroke
patients have not been studied. it is reasonable to assume that quitting smoking reduces
the risk of recurrent stroke just as it reduces the risk of recurrence of othercardiovascular
events.

Even smokers who have already developed cancer may benefit from smoking
cessation. A few studies have shown that persons who stopped smoking after diagnosis
of cancer had a reduced risk of acquiring a second primary cancer compared with
persons who continued to smoke. Although relevant data are sparse. longer survival
might be expected among smokers with cancer or other serious illnesses if they stop


smoking. Smoking cessation reduces the rihk of respiratory infection\ such as
pneumonia. w,hich are often the immediate causes of death in patient5 with an under-
lying chronic disease.

The important role of health care providers in counseling patients to quit smoking is
well recognized. Health care providers should give smoking cessation advice and
assistance to all patients v. ho smohe. including those uith existing illness.

Benefits for the Fetus

Maternal smoking is associated with several complications of pregnancy including
abruptio placentae. placenta previa. bleeding during pregnancy. premature and
prolonged rupture of the membranes. and preterm delivery. Maternal smoking retards
fetal growth. causes an average reduction in birthweight of 100 g, and doublej the risk
of having a low birthueight baby. Studies have shown a 25- to S0-percent higher rate
of fetal and infant death\ among women who smoke during pregnancy compared with
those wsho do not.

Women who stop smohing before becoming pregnant have infants of the \ame
birthweight ah those born to women who have never smoked. The same benefit accrue5
to women who quit smoking in the first 3 to 4 month\ of pregnancy and who remain
abstinent throughout the remainder of pregnancy. Women who quit smoking at later
stages of pregnancy. up to the 30th weeh of gestation. have int'ants with higher
birthueight than do women who smoke throughout pregnancy.

Smoking is probably the most important modifiable cause of poor pregnanq Cutcome
among women in the United State\. Recent estimate\ suggest that the elimination of
smoking during pregnancy could prevent about 5 percent of perinatal death\. about 20
percent of low birthweight births. and about 8 percent of preterm deliveries in the United
State\. In groups with a high prevalence of smohin, 0 (e.g.. women who have not
completed high school I. the elimination of smohing during prepnanq could prevent
about IO percent of perinatal death\. about 35 percent of low birth\\eight birth\. and
about IS percent of preterm deliverie\.

The prevalence of mohing during pregnancy haj declined over time but remain\
unacceptabl!, hi2h. ApproximateI! 30 percent of U.S. women L\ ho are cigarette
smokers quit after recognition of pregnancy. and other\ quit later in preganq.
However. about 25 percent of pregnant \\omen in the United State\ \mohe throughout
preynanc\. A \hoching \tatlstic i\ that half of pregnant uomcn who ha\,e not completed
      2
high school smoke throughout prqnanc!. .Van) Momen N ho do not quit mohing
during pregnanq reduce their dail? ci garettc consumption: however. reduced con-
sumption without quitttng ma> have little or no benetit for hlrthuerfht. Of the ltomen
who quit smoking during prepnanc!. 70 percent re\umt' \mohing within t >ear of
deliver).

Initiatives ha1.e been launched In the public and pri\ate sector\ to reduce smohing
during pregxmc!. The\e pqrams should lx expanded. and le\\ educated pregnant
women should be a \peciat target of these et'fort\. Strategic\ need to be developed to
address the problem of relapse after deli\ er!


Benefits for Infants and Children

As a pediatrician. 1 am particularly concerned about the effects of parental smohing
on infants andchildren. Evidence re\ ieued in the 1986 Surgeon General's Report. 7`1~
HW/I/I Co//.\(,y~rc,/r(.f,.\ c!f'/l/l.~/lllltu~.\, SINI&III~~. indicates that the children of parents
who smoke, compared with the children of nonsmohinf parents. have an increased
frequency of respiratoq infections 4uch as pneumonia and bronchitis. Man>, studies
have found a dose-response relationship between respiratory illness in children and
their level of tobacco smoke exposure.

Several studies have shown that children exposed to IO~XILXXI smohe in the home are
more libel) to develop acute otitis media and persistent middle ear effu\ions. Middle
ear disease imposes a substantial burden on the health care system. Otitis media is the
most frequent diagnosis made by physicians who care for children. The m> ringotom>
and-tube procedure. used to treat otitis media in more than 1 million American children
each year. is the most common minor surgical operation performed under general
anesthesia.

The impact of smoking cessation during or after prepnancq on these associations has
not been studied. Hotiever. the dose-response relationship between parental smohing
and frequency of childhood respirator), infection{ suggests that smohing cessation
during pregnancy and abstinence after delivery would eliminate most ora1 I of the excess
risk by eliminating mo\t or all of the exposure.

If parents are unwilling to quit smoking for their own sake. I hould urge them to quit
for the sake of their children. Passive-smohing-induced infections in infants and )`oung
children can cause serious and even fatal illness. .Moreo\,er. children whose parents
smoke are much more likely to become smokers themselves.

Smoking Cessation and Weight Gain

The fear of postcessation weight gain may discourage man) smoher\ from trying to
quit. The fear or occurrence of height gain may precipitate relapse among many of
those who already have quit. In the I%% Adult Use ofTobacco Survey. current smokers
who had tried to quit were asked to judge the importance of several possible reasons
for their return to smoking. Twenty-seven percent reported that "actual weight pain"
was a "very important" or "somewhat important" reason why they resumed smoking:
22 percent said that "the possibility of gaining weight" was an important reason for
their relapse. Forty-seven percent of current smokers and 48 percent of former smohers
agreed with the statement that "smoking helps control weight."

Fifteen studies involving a total of 20.000 persons were reviewed in this Report to
determine the likelihood of gaining weight and the average height gain after quitting.
Although four-fifths of smokers who quit gained weight after cessation. the average
weight gain was only 5 pounds (2.3 kg). The average weight gain among subjects who
continued to smoke was I pound. Thus, smoking cessation produce< a&pound greater
weight gain than that associated with continued smoking. This weight gain poses a
minimal health risk. Moreover. evidence suggests that this small weight pain is
accompanied by favorable changes in lipid profiles and in body fat distribution.

i\


Smoking cessation programs and messages should emphasize that weight gain after
quitting is small on average.

Not onI\, is the average postcessation weight gain small. but the risk of large weight
gain after quitting is extremely low. Less than -4 percent of those who quit smoking
gain more than 20 pounds. Nevertheless. special advice and assistance should be
available to the rare person who does gain considerable weight after quitting. For these
individuals. the health benefits of cessation still occur. and weight control programs
rather than smoking relapse should be implemented.

Increases in food intake and decreases in resting energy expenditure are largely
responsible for postcessation weight gain. Thus. dietary advice and exercise should be
helpful in prevaentinp or reducing postcessation weight pain. Unfortunately. minor
weight control modifications to smoking cessation programs do not generally yield
beneficial effects in terms of reducing weight gain or increasing cessation rates. A few
studies have investigated pharmacologic approaches to postcessation weight control:
preliminary results are encouraging but more research is needed. High priority should
be given to the development and evaluation of effective weight control programs that
can be targeted in a cost-effective manner to those at greatest need of assistance.

Psychological and Behavioral Consequences of Smoking Cessation

Nicotine withdrawal symptoms include anxiety. irritability. frustration, anger. dif-
ficulty concentrating. increased appetite. and urses to smohe. With the possible
exception of urges to smohe and increased appetite. these effects soon disappear.
Nicotine withdrav~al peaks in the first I to 7 days following cessation and subsides
rapidly during the following weeks. With long-term abstinence. former smokers are
likely to en.job favorable psychological changes such as enhanced self-esteem and
increased iense of self-control.

Although most nicotine withdrawal symptoms are short-lived. thej, often exert a
strong influence on smokers ability to quit and maintain abstinence.  Yicotine
withdrawal may discourage many smohers from tr>inF to quit and may precipitate
relapse among those who have recently quit. In the I%6 Adult U\e ofTobacco Survey.
39 percent of current smokers reported that irritability was a "very important" or
"somew hat important" reason M hy the, resumed smoking after a previous quit attempt.

Smokers and ex-smohcrs should be counseled that adverse psychological effects of
smohing subside rapid]! over time.  Smohing cessation materials and programs.
nicotine replacement. exercise. \tre\s management. and dietary counseling can help
smohers cope with these symptoms until the!, abate. after LI hich favorable psyhologi-
cal changes are likeI> to occur.

Support for a Causal Association Between Smoking and Disease

Ten> of thousands of studies have documented the associations between cigarette
smoking and a Iaye number of serious disease?;. It is safe to say that smoking represents
the most extensively documented cause of disease ever investigted in the history of
biomedical research.


Previous Surgeon General's reports. in particular the landmarh 1964 Report of the
Surgeon General's Advisory Committee on Smokin, L 0 ,tnd Health and the I982 Surgeon
General's Report on smoking and cancer, examined these associations with respect to
the epidemiologic criteria forcausality. These criteria include the consistent>. strength.
specificity. coherence. and temporal relationship of the association. Based on these
criteria. previous reports have recognired a causal association betueen smohing and
cancers of the lung. larynx. esophagus. and oral cavity: heart disease: strobe: peripheral
artery occlusive disease: chronic obstructive pulmonary disease: and intrauterine
growth retardation. This Surgeon General's Report is the first to conclude that the
evidence is now sufficient to identify cigarette smohin, (7 as a cause of cancer of the
urinary bladder: the 1983 Report concluded that cigarette smohing is a contributing
factor in the development of bladder cancer.

The causal nature of most of these associations was v.ell established long before
publication of this Report. Nevertheless. it is worth notin, ~7 that the findings of thi\
Report add even more weight to the evidence that these associations are causal. The
criterion of coherence requires that deacriptibc epidemiologic findings on disease
occurrence correlate with measures of exposure to the suspected agent. Coherence
would predict that the increased risk of disease associated with an exposure Lvould
diminish or disappear after cessation of exposure. As this Report shows in great detail.
the risks of most smoking-related diseases decrease after cessation and with increasing
duration of abstinence.

Evidence on the risk of disease after smoking cessation is especially important for
the understanding of smoking-and-disease associations of unclear causality. For ex-
ample, cigarette smoking is associated with cancer of the uterine cervix. but this
association is potentially confounded by unidentified factors (in particularby a sexually
transmitted etiologic agent). The evidence reviewed in this Report indicates that former
smokers experience a lower risk of cervical cancer than current smokers. even after
adjusting for the social correlates of smoking and risk of sexually acquired infections.
This diminution of risk after smoking cessation supports the hypothesis that smoking
is a contributing cause of cervical cancer.

Conclusion

The Comprehensive Smoking Education Act of 1983 (Public Law 98473) requires
the rotation of four health warnings on cigarette packages and advertisements, One of
those warnings reads. "SURGEON GENERAL'S WARNING: Quitting Smoking
Now Greatly Reduces Serious Risks to Your Health." The evidence reviewed in this
Report confirms and expands that advice.

The health benefits of quitting smoking are immediate and substantial. They far
exceed any risks from the average S-pound weight gain or any adverse psychological
effects that may follow quitting. The benefits extend to men and women. to the young
and the old. to those who are sick and to those who are well. Smoking cessation
represents the single most important \tep that smokers can take to enhance the length
and quality of their lives.

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Public opinion poll\ tell u\ that mat smoker\ &ant to quit. This Report provides
smokers with new and more pouerf-ul motivation to give up thi\ self-destructive
beha\ ior.

Antonia C. Novello. M.D.. M.P.H
Surgeon General

xii


ACKNOWLEDGMENTS

This Report was prepared by the Department of Health and Human Serv,ices under
the general editorship of the Office on Smoking and Health. Ronald M. Davis. M.D..
Director. The Managing Editor wa\ Susan A. Hawk. Ed.M.. MS.

Jonathan M. Samet. M.D. (Senior Scientific Editor). Professor of Medicine and Chief.
Pulmonary Division. Department of Medicine and the New MexicoTumor Registry.
Cancer Center. University of New Mexico, Albuquerque. New Mexico
Ronald M. Davis, M.D., Director. Office on Smoking and Health, Center for Chronic
Disease Prevention and Health Promotion (CCDPHP), Centers for Disease Control
(CDC), Rockville, Maryland

Neil E. Grunberg, Ph.D., Professor. Department of Medical Psychology. Uniformed
Services University of the Health Sciences. Bethesda, Maryland
Judith K. Ockene. Ph.D.. Professor of Medicine, and Director, Division of Preventive
and Behavioral Medicine. Department of Medicine, University of Massachusetts
Medical School, Worcester, Massachusetts
Diana B. Petitti, M.D., M.P.H., Associate Professor, Department of Family and Com-
munity Medicine, University of California at San Francisco, School of Medicine. San
Francisco, California

Walter C. Willett, M.D.. Dr.P.H.. Professor of Epidemiology and Nutrition. Harvard
School of Public Health, and The Channing Laboratory, Department of Medicine.
Harvard Medical School and Brigham and Women's Hospital. Boston. Mas-
sachusetts

Robert Anda. M.D., Epidemiologist. Office of Surveillance and Analysis, CCDPHP.
CDC. Atlanta, Georgia

John Baron, M.D., Associate Professor of Medicine. Department of Medicine.
Dartmouth Medical School, Hanover, New Hampshire
Tim Byers. M.D.. M.P.H., Chief, Epidemiology Branch. Division of Nutrition.
CCDPHP. CDC, Atlanta. Georgia

Arden G. Christen, D.D.S., M.S.D., M.A.. Chairman. Professor, Department of Preven-
tive and Community Dentistry, Indiana University School of Dentistry. Indianapolis.
Indiana

Graham Colditz. Dr.P.H., Assistant Professor of Medicine. Harvard School of Public
Health, and the Channing Laboratory, Department of Medicine. Harvard Medical
School and Brigham and Women's Hospital. Boston. Massachusetts


Carlo C. DiCiemente. Ph.D.. Associate Professor. Department of Psychology. Univer-
sity of Houston. Houston, Texas

Douglas W. Docket-y, Sc.D.. Associate Professor. Department of Environmental
Health. Environmental Epidemiology Program. Harvard School of Public Health.
Boston, Massachusetts

Gary A. Giovino. Ph.D.. Acting Chief. Epidemiology Branch. Office on Smoking and
Health. CCDPHP. CDC. Rockville. Maryland
Deborah Grady, M.D., Assistant Professor. Departments of Epidemiology and
Medicine, University, of California at San Francisco. School of Medicine. San
Francisco. California

Neil E. Grunberg. Ph.D.. Professor, Department of Medical Psychology. Uniformed
Services University of the Health Sciences. Bethesda, Maryland
John R. Hughes. M.D., Associate Professor. Human Behavioral Pharmacology
Laboratory, Departments of Psychiatry. Psychology. and Family Practice. University,
of Vermont. Burlington. Vermont

Robert W. Jeffery. Ph.D., Professor, Division of Epidemiology. School of Public
Health. University of Minnesota, Minneapolis, Minnesota
LTC James W. Kikendall, M.D.. Assistant Chief. Gastroenterology Section. Walter
Reed Army Medical Center, Washington. D.C.
Robert Klesges. Ph.D.. Associate Professor. Department of Psychology. Memphis State
University, Memphis, Tennessee

Lynn Kozlowski. Ph.D.. Head, Behavioral Tobacco Research. Socio-behavioral Re-
search Department, Addiction Research Foundation, Toronto. Ontario. Canada
Stephen Marcus. Ph.D.. Epidemiologist. Office on Smoking and Health. CCDPHP.
CDC. Rockville, Maryland

James L. McDonald. Jr.. Ph.D.. Assistant Chairman. Professor. Department of Preven-
tive and Community Dentistry. Indiana University School of Dentistry. Indianapolis.
Indiana

Sherry L. Mills, M.D.. M.P.H.. Medical Officer. Office on Smoking and Health.
CCDPHP. CDC. Rockville. Maryland

Judith K. Ockene. Ph.D.. Profeswr of Medicine. and Director. Division of Preventive
and Behavioral Medtctne. Department of Medicine. Univjersity of Massachusetts
Medical School. Worcester. Massachusett\
Carolr Tracy Orleans. Ph.D.. Director. Smohing Cc\sation Srrv,ice\. Fox Chaw Cancer
Center. Cheltenham. Pennsylvania

Diana B. Pctitti. M.D.. M.P.H.. .Aswciatc Professor. Department of Family and Com-
munity, Medtctne. University ofCalifomiaat San Franciwo. School of Medicine, San
Franci\co. California

John P. Pierce. Ph.D.. Associate Professor. Director. Population Studies and Cancer
Prevention. Tobacco Control Pro.icct. University of California. San Diego Cancer
Center. San Diego. California

Paul R. Pomrehn. Ph.D.. M.S.. Associate Profe\wr. Department of Preventive
Medicine and Environmental Health. University of Iowa College of Medicine. Iowa
City. Iowa

James 0. Procha\ka. Ph.D.. Professor. Director. Cancer Prevention Research Unit.
Department of Psychology. Liniversity of Rhode Island. Kirqston. Rhode Island

xiv


Barbara Rimer. Dr.P.H.. Director, Beha\ ioral Research. Fox Chase Cancer Center.
Philadelphia. Pennsylvania

Mary Ann Salmon. Ph.D.. Research Specialrst. School of Social Worh. C.A.R.E.S..
University of' North Carolina. Chapel Hill. North Carolina
Jonathan M. Samet. M.D. (Senior Scientific Editor). Profehsor of Medicine and Chief.
Pulmonary Division. Department of Medicine and the Nea Mexico Tumor Registry.
Cancer Center. University of New Mexico. Albuquerque. New Mexico
David Savitz. Ph.D.. Associate Professor. Department of Epidemiolog>. School oi
Public Health. University of North Carolina. Chapel Hill. North Carolina
Charles B. Sherman, M.D.. Director. Pulmonar! Division. Miriam Hospital.
Providence. Rhode Island

Meir Stampfer. M.D.. Dr.P.H.. Associate Professor of Epidemiolog! Har\ ard School
of Public Health. and The Charming Laboratory. Department of Medicine. Harvard
Medical School and Brigham and Womm's Hospital. Boston. Massachusetts
Wayne F. Velicier. Ph.D.. Professor. Co-Director. Cancer Prclention Research Unit.
Department of Psychology. Cnivcrsity of Rhode Island. Kingston. Rhode Island
Thomas Vogt. Ph.D., Principle Investigator. Center for Health Research. Portland.
Oregon

Scott T. Weiss. M.D.. Associate Professor. Harvard School of Public Health. and The
Charming Laboratory. Department of Medicine. Harvard Medical School and
Brigham and Women's Hospital. Boston. Massachusetts
Anna H. Wu-Williams. Ph.D.. Associate Professor. Department of Preventive
Medicine. University of Southern California. Los Angeles. California

David B. Abrams, Ph.D., Director. Division of Behavioral Medicine. The Miriam
Hospital. Associate Professor, Psychiatry and Human Behavior. Brown Universit)
Program in Medicine, Providence. Rhode Island
Duane Alexander, M.D.. Director. National Institute of Child Health and Human
Development. National Institutes of Health. Bethesda. Maryland
David Bates. M.D.. FRCP, FRCPC. FACP. FRSC, Professor Emeritus of Medicine.
Department of Health Care. University of British Columbia. Vancouver. British
Columbia

James S. Benson, Acting Commissioner. Food and Drug Administration. Rockville.
Maryland

Trudy S. Berkowitz, Ph.D.. Associate Professor. Department of Obstetrics. Gynecol-
ogy. and Reproductive Science, Mount Sinai School of Medicine. New York. New
York

Ruth Bonita, M.P.H., Ph.D., Masonic Senior Research Fellow. Geriatric Unit. Univer-
sity of Auckland. Auckland 9. New Zealand


Lester Breslow, M.D.. M.P.H.. Professorof Public Health and Director. Health Services
Research. Division of Cancer Control, Jonsson Comprehensive Cancer Center.
University of California. Los Angele\. Los Angeles. California
Samuel Broder. M.D.. Director, National Cancer Institute. National Imtitutes of Health.
Bethesda, Maryland

David Bums. M.D.. Associate Professor. Pulmonary Division. Division of Pulmonary
Medicine and Critical Care, University of California at San Diego Medical Center,
San Diego, California

Benjamin Burrows. M.D.. Director, Division of Respiratory Sciences. University of
Arizona Health Sciences Center. University of Arizona School of Medicine, Tucson,
Arizona

Jane Cauley. Dr.P.H.. Assistant Professor of Epidemiology. Department of Epidemiol-
ogy. University of Pittsburgh. Pittsburgh. Pennsylvania
Gregory N. Connolly, D.M.D., M.P.H.. Director, Office on Nonsmoking and Health.
Massachusetts Department of Public Health. Boston. Massachusetts
Thomas M. Cooper, D.D.S.. Professor. University of Kentucky Medical Center. Col-
lege of Dentistry. Lexington. Kentucky

Stephen Corbin. D.D.S.. M.P.H., Policy Analyst, Disease Prevention. Center for
Preventive Services (CPS). CDC. Bethesda, Maryland
K. Michael Cummings. Ph.D.. M.P.H.. Cancer Control and Epidemiology. Roswell
Park Cancer Institute. Buffalo, New York
Joseph W. Cullen. Ph.D.. Director. AMC Cancer Research Center, Denver. Colorado
Sir Richard Doll. ICRF Cancer Studies Unit. Oxford. United Kingdom
Virginia Ernster. Ph.D.. Professor of Epidemiology. Department of Epidemiology and
International Health. University of California. San Francisco. San Francisco.
California

Jonathan E. Fielding. M.D.. M.P.H.. Vice President and Health Director. Johnson and
Johnson Health Management. Inc.. Santa Monica. California
Gary D. Friedman. M.D.. M.S.. Division of Research. Kaiser Permanente Medical Care
Program. Northern California Region. Oakland. California
William Foege. M.D., Executive Director. The Carter Center of Emory University.
Atlanta. Georgia

Lawrence J. Furman. D.D.S.. M.P.H.. Chief. Dental Disease Prevention Activity. CPS.
CDC, Atlanta. Georgia

LawrenceGarfinkel. Vice President for Epidemiolog) and Statistic>. DirectorofCanccr
Prevention, American Cancer Society. Inc.. New York. New York
Barbara A. Gilchrest. M.D.. Professor and Chairman. Department of Dermatolog .
Boston University Medical Center. Boston. Mahjachu\ett\
Frederick K. Goodwin. M.D.. Administrator. Alcohol. Drug Abuse. and Mental Health
Administration. Rochville. Maryland

Robert 0. Greer. Jr.. D.D.S.. Sc.D.. Profes5orand Chairman. Division ofOral Patholog
and Oncology. Department of Diagnostic and Biological Sciences. School of Den-
tistry. University of Colorado Health Sciences Center. Boulder. Colorado
Ellen Gritz. Ph.D.. Director. Division of Cancer Control. Jon\\on Comprehensive
Cancer Center. University of California. Lo\ Angele\. Los Angeleh. California

xvi


Nanq J. Haley. Ph.D.. Associate Chief. Division of Nutrition and Endocrinology.
American Health Foundation, Valhalla, New> York
Sharon M. Hall. Ph.D.. Professor of Medical Psychology. Department of Psychiatry.
University of California. San Francisco. San Francisco Veterans Administration
Medical Center. San Francisco. California
Robert Harmon. M.D.. Administrator. Health Resources and Services Administration,
Rockville. Maryland
Jeffrey E. Harris. M.D.. Ph.D.. Associate Professor. Department of Economics. Ma\-
sachusetts Institute of Technology. Cambridge. Massachusett\. Clinical Associate.
Medical Services. Massachusetts General Hospital. Boston. Massachusetts
Norman 0. Harris, D.D.S.. M.S.. University of Texas Health Science Center. San
Antonio. Texas
Jack Henningfield. Ph.D.. Chief. Clinical Pharmacology Branch. National Institute on
Drug Abuse Addiction Research Center, National Institutes of Health. Baltimore.
Maryland
Robert A. Hiatt. M.D.. Ph.D.. Senior Epidemiologist. Division of Research. Kaiser
Permanente Medical Care Program. Oakland California
Millicent Higgins. M.D.. Associate Director. Epidemiology and Biometry Program.
Division of Epidemiology and Clinical Applications. National Heart. Lung. and
Blood Institute. National Institutes of Health. Bethesda. Maryland
Carol Hogue. Ph.D., M.P.H.. Director, Division of Reproductive Health. CCDPHP.
CDC. Atlanta. Georgia
John Holbrook. M.D.. Professorof Internal Medicine. Department of Internal Medicine.
University of Utah School of Medicine. Salt Lake City. Utah
Richard Hunt. M.D.. Division of Gastroenterology. McMaster University Medical
Center. Hamilton, Ontario, Canada
Dwight Janerich. D.D.S.. M.P.H.. Professor of Epidemiology. Department of
Epidemiology and Public Health. Yale University School of Medicine, New Haven.
Connecticut
William Kannel. M.D., Professor of Medicine. Department of Preventive Medicine.
Boston University School of Medicine, Boston, Massachusetts
LTC James W. Kikendall. M.D., Assistant Chief, Gastroenterology Section. Walter
Reed Army Medical Center, Washington. D.C.
Dushanka V. Kleinman. D.D.S.. M.Sc.D., Section Chief. National Institute on Dental
Research. National Institutes of Health. Bethesda, Maryland
C. Everett Koop. M.D.. Sc.D., U.S. Surgeon General, I98 i-89. Bethesda. Maryland
Jeffrey P. Koplan, M.D.. M.P.H., Director, CCDPHP, CDC. Atlanta. Georgia
Lewis H. Kuller, M.D.. Dr.P.H., Professor and Chairperson. Department of Epidemiol-
ogy, University of Pittsburgh Graduate School of Public Health. Pittsburgh. Pennsyl-
vania
Charles L. LeMaistre. M.D., President, The University of Texas M.D. Anderson Cancer
Center. Houston. Texas
Claude Lenfant, M.D., Director. National Heart, Lung. and Blood Institute. National
Institutes of Health, Bethesda, Maryland
Richard J. Levine. M.D.. M.S.. M.P.H., Chief Epidemiologist. Chemical Industr!
Institute of Toxicology. Research Triangle Park. North Carolina


Edward Lichtensrein. Ph.D.. Research Scientist. Oregon Research Institute. Eugene.
Oregon

Jay H. Luhin. Ph.D.. National Cancer Institute. National Institutes of Health. Rockville.
Maryland

Alfred C. Marcus, Ph.D., Director. Community Research and Applications. AMC
Cancer Research Center. Denver. Colorado
Denis M. McCarthy. M.D.. MSc.. Chief. Division of Gastroenterology. University of
New Mexico. Department of Medicine. Veterans Administration Medical Center.
Albuquerque. New Mexico

J. Michael McGinnis. M.D.. Deputy Assistant Secretary for Health. Disease Prevention
and Health Promotion. Department of Health Human Services. Washington. D.C.
Sonja M. McKinlay. Ph.D.. M.Sc.. M.A.. B.A.. ASA. APHA. AER. SCt. Biometrics
Society. Institute of Mathematical Statistics. International Menopause Society.
American Association for the Advancement of Science. President. New England
Research Institute. Inc.. Watertown. Massachusetts
Robert E. Mecklenberg. D.D.S.. M.P.H.. Potomac. Maryland
L. Joseph Melton. III. M.D.. Head. Section of Clinical Epidemiology. Department of
Health Sciences Research. Mayo Clinic and Foundation. Rochester. Minnesota
Anthony Miller. B.A., M.B.B.. M.R.C.P.. M.F.C.M.. F.R.C.P.C.. Professor. Depart-
ment of Preventive Medicine and Biostatistics. University of Toronto. Toronto.
Ontario, Canada

Gregory Morosco. Ph.D.. M.P.H.. Chief. Health Education Branch and Coordinator.
Smoking Education Program. National Heart. Lung. and Blood Institute. National
Institutes of Health. Bethesda. Maryland
Richard L. Naeye. M.D.. Professor and Chairman. Department of Pathology. Pennsyl-
vania State University School of Medicine. Hershey. Pennsylvania
Thomas A. Pearson. M.D.. M.P.H.. Ph.D.. Director. Mary lmogene Bassett Research
Institute,Cooperstown. New York. ProfessorofPuhlic Health in Medicine. Columbia
University. New Yorh. New Yorh

Terry Pechaceh. Ph.D.. Acting Chief. Smohing. Tobacco, and Cancer Branch. Nation;tI
Cancer Institute. National Institutes of Health. Bethesda. Maryland
Michael G. Perri. Ph.D.. Professor and Deputy Chairman. Psychology Department.
Fairleigh Dichinson University. Teanech. New Jersey
Richard Peto. FRS. ICRF Cancer Studies Unit. Oxford. United Kingdom
John M. Pinney,. Executive Director. Institute for the Study, of Smohing Brhav ior and
Policy. John F. Kennedy School of Government. Harvard University. Cambridge.
Massachusetts

William F. Raub. Ph.D.. Acting Director. National Institute\ of Health. Bethesda.
Maryland

Patrick L. Remington. M.D.. Bureau of Community Health Prevention. Wisconsin
Division of Health. Madison. Wisconsin
Everett R. Rhoades. M.D.. Director. Indian Health Service. Rocbville. Maryland
Julius Richmond. M.D.. John D. MacArthur Professor of Health Policy. Emeritus.
Division of Health Policy. Research. and Education. Harvard Cniuersity. Boston.
Massachusetts


XVIII


Williatn A. Robinson, M.D.. M.P.H.. Director. Office ot'\linorit! Health. Department
of Health and Human Service\. Washington. D.C.
William L. Roper. M.D.. M.P.H.. Director. CDC. Atl;rn~~. Georgia
Richard B. Rothcnhq. M.D.. A\si\Iant Director for Science. CCDPHP. CDC. Atlanta.
Georgia

Thomas C. Schelling. Ph.D.. Director. Iwtitute t'or the Stud\ of Smoking Behavior and
Policy. Lucius Iv. Littauer Professor of' Political Econotii~, tlar\ard L'ni\,ersit>.
Cambridge. Massachusetts

Marc B. Schenker. M.D.. M.P.H.. Associate Professor ;md Di\ i\ion Chief. Occupation-
al and Environmental Medicine. University of California. Da\ i\. Da\ i\. California
Da\,id Schottenfeld. M.D.. Professor and Chairman. Department of Epidetniolog .
University of Michigan School of Public Health. Ann Arbor. hlichigan
Kathleen L. Schroeder, D.D.S., M.Sc.. Assistant Professor. Section of Oral Biology.
The Ohio State University College ot`Dentistr\,. Columbus. Ohto
Mary J. Sexton. Ph.D.. M.P.H.. Professor. Department ofEl-7idrmiolo~! and Ptwentive
Medicine. University of Maryland School of` Medtcine. Baltimore. Mar! land
Saul Shiffman. Ph.D.. Associate Professor. Department of Psychology. L'niwrsit>, ot
Pittsburgh. Pittshurgh. Pennsylvania

Donald Shopland. Smoking. Tobacco. and Cancer Branch. 2iational Cancer Institute.
National Institutes of Health. Bethesda. blur> land
Amnon Sonnenberg. M.D.. Associate Professor. Gastroentet.olof! Section. Medical
College of Wisconsin. Veterans Administration Medical Center. Milwaukee. Wis-
consin

Frank E. SpeiLer. M.D.. Professor of Medicine, Harvard Medical School. Professor of
Environmental Epidemiology. Harvard School of Public Health. Co-Director. The
Channing Laboratory. Department of Medicine. Brigham and Women's Hospital.
Boston. Massachusetts

Jesse Steinfeld. M.D., San Diego. California
Steven D. Stelltnan. Ph.D.. Assistant Commissioner. New Yorh Cit>, Department of
Health. New York. Neu York

Ira B. Tager, M.D.. M.P.H., Associate Professor of Medicine and Epidemiology and
Biostatistics, University ofcalifornia. San Francisco. Veterans Administration Medi-
cal Center, San Francisco, San Francisco. California
Kenneth Warner. Ph.D.. Senior Fellow. Institute of Gerontology. University, of
Michigan. Ann Arbor. Michigan

Jonathan S. Weiss. M.D.. Assistant Professorof Dertnatologz. Section of Dertnatology.
Emory Clinic, Atlanta. Georgia

Noel S. Weiss. M.D., Dr.P.H.. Professor and Chairman. Department of Epidemiology.
University of Washington. Seattle, Washington
Gail R. Wilensky. Ph.D., Administrator. Health Care Financing .4dministr:ttion.
Washington. DC

Deborah Winn. Ph.D.. Deputy Director. Division of Health Interview Stati\lics. Na-
tional Center for Health Statistics. CDC. Hyattsvillc. Mqland
Philip A. Wolf, M.D.. Professor of Neurology. Department of Neurology. Boston
University School of Medicine. Boston, Massachusetts
Ernst L. Wynder. M.D.. President. American ffcalth Foundation. Neu Yorh. Ur\\ Yorh

\i\


Cxnwn Aguirrr. Secretq. Officeon Smohtng and He;~l~h. C'CDPHP. (`DC`. Roc,h\ 111~`.
hlar! land
Andrea Anderwn. Student Intern. Of`t~ice on Smohln $! ~11111 tic~lltll. C`C`DPI it'. (`I)(`.
Rochville. Marylnnd
Mxgaret Anglin. Secretq. Oft'icr on Smohin, `7 and Health. CCDPHP. (`DC`. Koch-
ville. Maryland
Cathy Arney. Graphic Artist. The Circle. Inc.. MCLC;III. Virginia
John Arti>. Courier. The Circle. Inc.. McLean. Virgini;
Michele Awael. Confrrenctr Coordinator. The C'il-ck. Inc... ZlcLcan. 1'11.21111s
John L. Bqrwhy. A\wciate Director for Progr;lm C>pcl-ation\. Ol'l.ic~ on Snlohlns ;111d
Health. CCDPHP. CDC. Roch\~ille. Mql;~nd
Sonia Bslahirsky. Srcrctary. Office on Snlohin, $1 and Hcal~h. (`(`DPHP. C`D(`. Roc,h-
ville. Maryland
Barbara Barme\. Admini\tratiw A\\istant. The Circle. Inc.. \lc,l.c;~n. L'Irglnl;l
Carol A. Bean. Ph.D.. Acting 2l;ulaging Editor. ..Irtcntl\ Tcc~hnol~~gic~. IIIC...
Springfield. Virginia
Mari\sa A. Bernctrin. Editor. The Circle. Inc.. IllcLean. L'irslnia
Em' Ria Brikcoe. Cont'erencr Coordinator. The Circk. Inc.. \lcl~can. \`irglni.r
Karen Broder. Public Information Spwiali\t. Ot't`icc on Smohing a~ld ticalrh. (`CDPtt P.
CDC. Rochville. Mar> INKI
Barbara M. Broun. Editowl h\\l\t;unt. 00'~ cw Smoking ;untl Health. Rc)ch\ 111~~.
h4aryland
Catherine E. Burchhardt. Public Int'ormation Speci,llist. Ol't'iw on Srnc\hlns and ticL\l\ll.
CCDPHP. CDC. Roth\ ilk. Mar! land
Ltx Chapell. Courier. The Circle. Inc.. McLtxn. Virginia
Won Choi. Revarch A\\l\tant. Ot't`iw m Smohing and Health. CCDPI IP. C'DC`.
Roch\,ilk. Mar> Im~d
Trihh Da\.itlwn. Studtxt Intam. Ot't`icc on Smohlng and Health. C`C`DPtiP. C`tX`.
Rochville. Maryland
Susan E. Da!. Sawtar!. Office OII Snlohln, cr and Health. CCDPHP. C-LX`. Roi,h\ 111~`.
hlaryiand
Karen M. Dtxs~. .-I\soci;nc Dirt'ctot- I'oI- PoIIc,!. Ott~c~ OH Smohir); and tlcalttj.
CCDPHP. CDC'. Roth\ ilk. 3l;rr> land
June DOM. Public Health Scr\ 1c.c Congrcs\ionaI Rcpol-t\ (`c)c)rdiii;ltor. Ot`tlce ot'llcattl~
Planning UKI E\~;rluation. Ot`t`icc ot`thc .\\xl\t;tnt Sec~rctar-\ i(v tfcal~ll. M';l\llingtcw.
D.C.
Joanna Ebling. \+`or-d Proc~c\\lns S~LTI;I~I\~. 7`1~ CirL,Ic. Inc.. \l~~Lean. l'lrglnia
Pam Edward\. S!\tem Xdministrator. %lS;\. Inc.. Roth\ 111~. \lar- I;t~~cl
Rita Elliott. Technical Editor-. \c\r hlz\ico Tunior Rc:i\tl-! I ni\cl-\lt> rjt' \c\\
Mexico. Albuquerque. NW Xlc\icc)
Seth Errwnt. Ph.D.. Epidemic Intelllgcnce Ser\ ice Ot't'lca. 0t'l'lc.c on Smohtll~ ;111d
Health. CCDPHP. CDC. Roch\ille. \lar\l;~nd


Sharon K. Faupel, Staff Assistant, Office on Smoking and Health. CCDPHP. CDC.
Rockville, Maryland
Leanna Fernando, Administrative Assistant, New Mexico Tumor Registry, University
of New Mexico, Albuquerque, New Mexico
David Fry. Editor, The Circle, Inc., McLean, Virginia
Lynn Funkhauser, Word Processing Specialist, The Circle, Inc.. McLean, Virginia
Amy Carson, Student Intern, Office on Smoking and Health. CCDPHP. CDC. Rock-
ville, Maryland
Mary Graber. Secretary, University of California at San Francisco, School of Medicine.
Department of Family and Community Medicine, San Francisco. California
Gwen Harvey, Program Analyst, CCDPHP. CDC. Atlanta. Georgia
Patricia Healy, Technical Information Specialist. Office on Smoking and Health.
CCDPHP. CDC. Rockville, Maryland
Phyllis E. Hechtman. Editorial Assistant. The Circle, Inc.. McLean, Virginia
Timothy K. Hensley. Technical Publications Writer-Editor, Office on Smoking and
Health, CCDPHP. CDC, Rockville. Maryland
Julian Hudson, Courier. The Circle, Inc.. McLean. Virginia
Beth Jacobsen, Student Intern, Office on Smoking and Health. CCDPHP. CDC.
Rockville. Maryland
Renee Kolbe, Program Specialist. Office on Smoking and Health, CCDPHP. CDC.
Rockville, Maryland
Matt Kreuter, Public Information Specialist, Office on Smoking and Health, CCDPHP.
CDC. Rockville, Maryland
Peggy Lytton, Editor, The Circle, Inc., McLean, Virginia
Diana Lord, Research Psychologist, Department of Medical Psychology. Uniformed
Services University of the Health Sciences. Bethesda. Maryland
Daniel F. McLaughlin, Editor, The Circle, Inc., McLean. Virginia
Jackie L. Meador, Desktop Publishing/Word Processing Specialist. The Circle. Inc..
McLean, Virginia
Elaine Medoff-McGovern, Medical Secretary. Division of Preventive and Behavioral
Medicine, Department of Medicine. University of Massachusetts Medical School.
Worcester, Massachusetts
Nancy A. Miltenberger, M.A., Production Editor, The Circle. Inc.. McLean. Virginia
Rebecca Mosher, Staff Assistant, New Mexico Tumor Registry. University of New
Mexico, Albuquerque, New Mexico
Millie R. Naquin, Research Assistant. Office on Smoking and Health, CCDPHP. CDC.
Rockville. Maryland
Thomas E. Novotny, M.D., Chief, Program Services Activity. Office on Smoking and
Health, CCDPHP, CDC, Rockville, Maryland
Cathie M. O'Donnell. Project Director, The Circle. Inc., McLean, Virginia
Christine Pappas, Editorial Research Assistant, The Channing Laboratory, Harvard
School of Public Health. Boston, Massachusetts
Stacey M. Parcover, Secretary, Office on Smoking and Health, CCDPHP. CDC,
Rockville. Maryland
Lida Peterson, Computer Systems Manager. The Circle. Inc., McLean. Virginia


Renate J. Phillip\. Graphic .Arti\t. D&top Puhli\hln 2 Desipnrr. The Circle. Iric..
McLean. Vir~~ini~t `
Margaret E. Pickerel. Public Int'ormation and PubIicatlons SpeciaIi\t. ~t`t`icc 011 SIII~~-
ing and Health. CCDPHP. CDC. Rochville. Mq land
EliAmh Precup. Student Intern. Office on Smohtng and Health. CCDPHP. CDC.
Rochville. Maryland
Cary R. Prince. Editor. The Circle. Inc.. McLean. Virginia
Dick Ray. Director of Computer Sm ice\. The Circle. Inc.. IlcLean. Virginia
Nancy J. Rhodes. Editor. The Circle. Inc.. McLean. Virginia
Rose Mary Romano. Chiet`. Public Int'orm;Ltion Branch. Oft`icr m Snlohing and Health.
CCDPHP. CDC. Rocl\\.ille. Mar! land
Lisa Phelph. Computer S>3tern\ Anal! \t. The Circle. Inc.. hlclcan. \`irginia
Sel Semler. Sccreta~-1. Oi`ficc on Swrhing and Halth. CCDPHP. CDC. Roth\ 111e.
Maryland
Jane\ S1in.a. Student Intern. Otl`ice on Smohin 2 imi Health. CCDPHP. CDC. Roch-
ville. Marshland
Mattie Smith. Srcrrtar!, . CCDPHP. CDC. Roch\,ille. hl;rr> Ixnd
Linda R. Spiegrhmn. Administrative Oft`iccr. Office on Smohin: and Health.
CCDPHP. CDC. Roth\ ilk. Mar> Imd
Traion C. Stallinys. Project Sectmar>. The Circle. Inc.. McLean. C'irsinla
Sophia Stewart. Student Intern. Ofl`icr on Smohing and Htxtlth. CCDPHP. CDC.
Rock\~illr. Maryland
D:tniel R. Tich. Director of Publications. The Circ~lc. II~c~.. LlcLean. \`iyinia
Anne Trontell. M.D.. Epidemic Int~lligencr Stm ice Otfiwr. Ot`t`icc on Smohing and
Health. CCDPHP. CDC. Roth\ ilk. Mar! land
Karen T\,lrr. Cont'erenct` Coordinator. The Circle. Inc.. ZlcLwt. I'tt-ginta
Godfrey R. Vw. h1.D.. Student Intern. Ot`ficc on Smohing and Hcal~h. CCDPHP. CDC'.
Rock\ ilk. Mar> land
Su~n Von Bratmberg. Ini'ormaticm Speci;tli\t. The Circle. lw.. \lcLcarl. Virginl;r
Elyse Watwn. Adminiaxtt~c :\\\imnt. Nrn ?,le\ico TUII~~I- RcFi\tr>. L.ni\cr\lt! ot
New Mexico. Albuquaque. UC\+ Llcxico
Michael F. White. .A \sociate Dirt`ctor for Progr-am De\ ~~lopncn~. C`C`DPHf'. C`DC.
Roth\ ilk. Rlx~ land
Chxlex WIggin\. Xl.S.P.11.. E~~l~l~~liiologl\t. Xc\\ \lc\~co 1~t11iior RC~I\II-!. I 11i\ C`I.\II\
Of Neu Rle-ilco. .~lhlK~llmp'. Kl?\\ l\tc\tcr,
Louiw G. Wist`nxtn. TcchnicA Information Specul~s~. Ott`icc on Snlohlng and tlcalth.
CCDPHP. CDC`. Koch\ tllc. \l;rr> I;mcI
Rebecca B. b'olt'. Progrm .Inal! st. 0t`t'ic.c ot` Progrant Planning ,~nd I!\ ;rlu,ltioll. C`D(`.
Attanta. Gccwgia
S. Tannc~- Wra!. Technical Inter-matioll Spcclall\t. Ot't~cc 011 Snlohlng ad llcalth.
CCDPHP. CDC. Rtrch\ilk. IlarylmA


TABLE OF CONTENTS

Foreuord  ...........................................................  i

Preface  ............................................................. I

Acknowledgments  .................................................. xiii

ListofTables  .................................................... ..xx v
ListofFigur&  ....................................................  xxxi

1.  Introduction. Overview, and Conclusions  ............................. I

2.  Assessing Smoking Cessation and Its Health Consequences ..............  17

3.  Smoking Cessation and Overall Mortality and Morbidity ................ 7 1

4.  Smoking Cessation and Respiratory Cancer-5 ......................... IO3

5.  Smoking Cessation and Nonrespiratory Cancers  ...................... I43

6.  Smoking Cessation and Cardiovascular Disease  ...................... 1 X7

7.  Smoking Cessation and Nonmalignant Respiratory Diseases  ............ 175

8.  Smoking Cessation and Reproduction  .............................. 367

9.  Smoking, Smoking Cessation, and Other Nonmalignant Diseases  ........ 425

10.  Smoking Cessation and Body Weight Change ........................ 469

1 I.  Psychological and Behavioral Consequences and Correlates of
  Smoking Cessation  ............................................. 5 I7

Volume Appendix.  National Trends in Smoking Cessation  ................ 579

Glossary ........................................................ ..617

lndex.............................................................61 9


Xklll


LIST OF TABLES

Chapter 2

Table 1. Measures of false reports of not smoking from studies using
nicotine and cotinine as a marker . .  3X
Table 2. Measures of false reports from studies using CO as a marker  1 I
Table 3. Examples of potential methodologic problems in investigating
the health consequences of smoking cessation 17

Chapter 3

Table 1. Summary of longitudinal studies of overall mortality ratios
relative to never smokers among male current and former smokers
according to duration of abstinence (when reported I 76

Table 2. Overall mortality ratios among current and former smohers.
relative to never smokers. by sex and duration of abstinence at date of
enrollment. ACS CPS-II . . . . . . . . . . ,  7x
Table 3. Estimated probability of dying in the next 165year interval for
quitting at various ages compared with never smohing and continuing
to smoke. by amount smoked and sex . . .  x3
Table 4. Summary of overall mortality ratios in intervention studies in
which smoking cessation was a component . . . , . 8-t

Table 5. Summary of studies of medical care utilization among smokers
andformersmokers . . . . .._..................................

Table 6. Relation of smoking cessation to various measures of general
health status . . . . . . . . . . . .._..................................

Table 7. Age- and sex-specific mortality rates among never smokers.
continuing smokers. and former smokers by amount smoked and
duration of abstinence at time of enrollment for subjects in ACS
CPS-II study who did not have a history of cancer. heart disease. or
stroke and were not sick at enrollment . . . , . .

Table 8. Estimated probability of dying in the next 165year interval
(95% Cl) for quitting at various apes compared with never smohing
and continuing to smoke. by amount smohed and sex .

xx



90

. 95





97

\\\


Chapter 4

Table I. Histologic changes (?/ ) in bronchial epithelium by smoking
status .___.____.___.,,....._.__,.._._._...,.._.,....,..._._

Table 2. Relative rishs of lung cancer among never, fomter. and current
smokers in selected epidemiologic studies . .
Table 3. Lung cancer mortality ratios among never. current. and former
smokers by number of years since stopped smoking (relative to never
smokers). prospective studies . . . . . . .
Table 4. Relative risks of lung cancer among former smokers. by
number of years since stopped smoking. and current smokers. from
selected case<ontrol studies . . . . . .

Table 5. Relative risks of lung cancer among never. current. and former
smokers. by number of years since stopping smoking and histologic
type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 6. Relative risks of lung cancer among never. former. and current
smokers by types of tobacco products smoked  . . . . . . . . .
Table 7. Standard mortality ratios of lung cancer among former smokers
in ACS CPS-II (relative to never smokers) by years of smoking
abstinence, daily cigarette consumption at time of cessation. and
history of chronic disease . . . . . . .
Table 8. Histologic changes in laryngeal epithelium by smoking status
Table 9. Relative rishs of laryngeal cancer by smokin_e status

Chapter 5

Table I. Studies of oral cancer and smohing cessation . . .
Table 2. Studies of esophageal csnccr that have examined the effect of
smoking cessation . .
Table 3. Studies of cancer of the pancreas and smohing cessation .
Table 3. Studies of bladder cancer and smohing cessation  
Table 5. Bladder cancer risk according to smoking dose. duration of
smokitq. and smohing status
Table 6. Studies of cervical cancer and smohing cessation
Table 7. Studies of breast cancer and smoking cessation
Table 8. Studies of cancer at selected sites that have examined the effect
of smoking cessation .

I20

IX)

I32

I33

I18

153

I56

I60

165

167

I70

17-7

xxvi


Chapter 6

Table 1. Case-control studies of CHD risk among former smokers .
Table 2. Cohort studies of CHD risk among former smokers . . .
Table 3. Estimated probability of dying from ischemic heart disease in
the next 16.5year interval (95% CL) for quitting at various ages
compared with never smoking and continuing to smoke. by amount
smokedandsex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

201

. 206

Table 4. Intervention trials of smoking cessation and CHD risk . . .
Table 5. Studies of the effect of smoking cessation on persons with
diagnosedCHD.................................................231

Table 6. Studies of smoking cessation and risk of death due to aortic
aneurysm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...242
Table 7. Case-control studies of smoking cessation and risk of stroke . . . 247
Table 8. Prospective cohort studies of smoking cessation and risk of
stroke.........................................................253

Chapter 7

Table I. Percentages of subjects in cross-sectional studies with
respiratory symptoms. by cigarette smoking status and gender . . .    289
Table 2. Percentages of subjects in cross-sectional surveys with
respiratory symptoms by smoking and occupational exposure status .    . 297
Table 3. Change (o/c) in presence of respiratory symptoms. longitudinal
studies, by cigarette smoking status . . . . . . . . . . . . . . . .    .300
Table 4. Percentage of subjects with respiratory symptoms by smoking
status, 1961 and 197 1, in a cohort of middle-aged, rural Finns . . . 305

Table 5. Age-standardized mortality ratios for influenza and pneumonia
for current and former smokers compared with never smokers . .
Table 6. Association between cigarette smoking status and FEVI levels
in selected cross-sectional studies of adult populations . . , . . .
Table 7. Spirometric studies of participants in smoking cessation
programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 8. Studies of closing volume (CV/VC%), closing capacity
(CC/TLC%), and slope of alveolar plateau (SBNl/L) among
participants in smoking cessation programs . . . . . . . . . . . . . .
Table 9. Population-based longitudinal studies of annual decline in
pulmonary function . . . . . . . . . . . . . . . _ . . . . .
Table 10. Decline of FEVt (mL/yr) in subjects in the Copenhagen City
HeartStudy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table I I. Mortality attributable to COPD, United States. 1986 .

309

.3ll

. 320

. 334


. 330



337

342


Tahlc 12. Prwpectiw \tudic\ of COPD mortalit) in relation to cigarette
smol\inf 413tus. . . . . . . . . . 313

Table 13. Standardized mortalit> ratio\ for COPD among current and
former smoher\ hrohen down h) y;Lr\ of ah5tinence .

Chapter 8

Table 1, Possible mechanisms for effect of smohing on pregnant!' and
pregnancy outcome ,......._........................., . . .
Table 2. Summary of studie\ of fertility among smokers and former
smoker\ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Table 3. Summary of studies of perinatal and neonatal mortality in
smokers and nonsmoker\ during pregnanq  . .
Table 3. Estimated relative risk of fetal plu\ infant mortality for maternal
smoking in several birthweight groups. adjusting for maternal marital
statu\. education. age. and parity . . .
Table 5. Summary of studies of perinatal mortality in wloher\
throughout pregnancy. smohers who quit in the early month\ of
pregnancy. and nonsmokers during pregnancy  
Table 6. Summary of studieh of mean birthweight. b>, smoking statuh .
Table 7. Summar\, of nonexperimental studie\ of smoking cewttion
after conception. mean increase (+) or decrease (6) in birthueight (g)
according to timing of cessation
Table 8. Summary of nonexperimental studies of relative risk of IOU
birthweight for smoking ceaation after conception  
Table 9. Summary of birthweight outcome in randomized trials ot
smohing cessation in pregnancy . . . .
Table IO. Smoking and smoking! cehation during pregnancy. summq
of results of two wrveys of national probability \ample\
Table I I. Patterns of smoking cessation during pregnarq among
selected population4 . . .
Table 12. Summary of \tudit`s that estimated relative rish of \ariou~
pregnancy outcome\ for \mohing based on ;t "SJ nthe\ih" of the
literature. and attributable risk percent based on several estimate\ of
the prevalence of smohing during pregnancy . 3%

Table 13. Summary of studies reporting relationship of cigarette
smoking and age at natural menopause . . . 3'97
Table II. Summary of studit`\ of age of natural menopause among
former smoker5 . . . . . . . . . 399

Table 15. Sexual performance among male former smoher\ 104
Table 16. Sperm quality among smokers and nonsmokers 406

xxviii


Table 17. Estimated relative risk of azoospermia or oligospermia among
smokers versus nonsmokers or never smokers . . . . . . . . 408
Table 18. Sperm quality among former smokers . . . . . 409

Chapter 9

Table I. Percentage of healed duodenal ulcers among smoking and
nonsmokingpatients . . . . . . . . . . . . . . . . . .._..._...._..._........_ 433
Table 2. Results of statistical analysis of pooled data from Table I  . 437
Table 3. Recurrences of duodenal ulcer in smokers and nonsmoker\ in
clinical trials _ ~. . . . . . . . . . . . . . . . 43X
Table 4. Recurrences of gastric ulcer in smokers and nonsmokers in
clinical trials . . . . . . . . . . . . . . . . . 442
Table 5. Summary of studies of smoking and bone ma\< . . 445
Table 6. Summary of case<ontrol studies of smoking and fractures . 450
Table 7. Summary of cohort studies of smoking and fractures . . 454

Chapter 10

Table I. Summary of prospective studies on smoking and body weight . 374
Table 2. Details of prospective studies in which change in weight
relative to continuing smokers was reported . . . . . . . . . . 477

Table 3. Mortality ratios for all ages combined in relation to the death
rate of those 9Q109% of average weight  . . . . . . . . .
Table 4. Mortality ratios for all ages combined according to smoking
status in relation to those 90-109% of average age . . . .

. 393




. 494

Chapter 11

Table I. Diagnostic categorization and criteria for nicotine
withdrawal-Nicotine-induced organic mental disorder . . . .
Table 2. Prospective studies of quitting-related changes in mood,
anxiety. stress reactivity, perceived stress. self-image. and
psychological well-being . . . . . . . . .
Table 3. Summary of data from 1985 NHIS. behaviors of never. former.
and current smokers aged 20 and older . . . . .
Table 4. Summary of data from 19X7 NHIS. behaviors of never. former.
and current smokers aged IX and older . . . . . .
Table 5. Summary of data from 1987 BRFSS. behaviors of former
smokers and current smokers aged IX and older . . . . . . . . . . . 550

  536
. _



  548
. _


. 539


Table 6. Summary of data from I987 BRFSS. bchav iors of former
smohers aged IX and older by, duration of abstinence .
Table 7. Pet-cent distribution of persons aged IX and older by tobacco
product and use status. according to gender and cigarette smohing
status. United States. 1987 . .

Table 8. Physician visits and medical tests vv ithin the past y'ear amon?
AARP members ayed SO and older. by smoking status

SS?

557



563

Volume Appendix

Table I. Quit ratio in selected States. by age group and gender-BRFSS.
198X..........................................................5X6

Table 2. Cigarette smoking continuum by year. percentage of ever
cigarette smokers. by NHISs, United States. 1978-X7. adults aged 20
and older . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .     5x9
Table 3. Trends in quit ratio (`;/( ) (percentage of ever cigarette smokers
who are fomrer cigarette smokers). by age and by education. NHISs.
United States. 1965-87. adults aged 20 and older     592
Table 4. Effect of adjusting for use of other tobacco products on quit
ratio (percentage of evjer cigarette smokers wlto are former cigarette
smohers). 1987. NHIS. United States . . . . . . . . .     59-I
Table 5. Selected measures of quittin g activity (V t. NHISs. United
States. adults aged 20 and older     600
Table 6. Percentage of those intending to smoke in 5 years. by gender.
AUTSs. United States. 1964-86. current smokers aged 21 and older 609
Table 7. Percentage who report having ever received advice to quit from
a doctor. by smohing status and gender. United States. 1964-87. adults
aged2landolder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...610

xxx


LIST OF FIGURES

Figure I. Cyclical model of the stages of change . . 73
Figure 2. Hypothetical examples of disease incidence rates for current.
former, and never smokers, by age . . . 55

Chapter 3

Figure I. Compared with never smokers. relative risk of mortality in
current and former smokers aged 50-54. 60-63. and 70-74 at
enrollment, by amount smoked and duration of abstinence . . Xl
Figure 2. Estimated probability of dying in the next 16.5yr interval for
quitting at ages 55-59 compared with never smohing and continuing to
smoke.by sex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9X

Chapter 4

Figure I. Rish of lung cancer by number of cigarettes smohed per day
before quitting. number of years of abstinence. sex. and histologic types
Figure 2. Relative risk of lung cancer among ex-smokers compared with
continuing smokers as a function of time since stopped smoking.
estimated from logistic regression model, pattern adjusted for smoking
duration compared with pattern unadjusted for duration . .
Figure 3. Incidence of bronchial carcinoma among continuing cigarette
smokers in relation to age and duration of smoking and among never
smokers in relation to age. double logarithmic scale . . . . . .

. I21

. I23






 I17

Chapter 6

Figure I. Hypothetical effects of smoking cessation on risk of CHD if
mechanisms are predominantly rapidly reversible . . . . . . . . . . . . . . 19X
Figure 2. Estimated relative rish of MI after quitting smoking among
men under age 55. adjusted for age . . . . . 304
Figure 3. Mortality ratios due to coronary artery diseases; rates for men
who have stopped smoking are compared with those for men who
never smoked and those for men still smoking in 1952 2 I J
Figure 4. Mortality ratios for all cardiovascular diseases and CHD. by
daily cigarette consumption. US Veterans Study. 195449 2 I9
Figure 5. Mortality ratio for current and fomter cigarette smohers by,
years of smoking cessation. US Veterans Study. 1954-W . 770

\\\i


Figure 6. Effect of smoking cessation on survival among men with
documented coronary atherosclerosis; pooled survival among quitters
tN=1.390) and continuers (N=2.675) . . . . . . . . . . . . . .
Figure 7. Mortality ratios for stroke for current smokers and ex-smokers
compared with never smokers, by daily cigarette consumption, US
VeterdnsStudy,l954-69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 8. Survival free of stroke in cigarette smokers. never smokers,
and former smokers, aged 60, using Cox proportional hazard
regression model. among men and women  . . . . . . . . . . . . .

Chapter 7

Figure I. Nonproportional Venn Diagram of the interrelationship among
chronic bronchitis. emphysema, asthma, and airways obstruction . . .
Figure 2. Theoretical curves depicting varying rates of decline of FEVt
Figure 3. Hypothesized mechanisms by which airway
hyperresponsiveness may be associated with developing or established
COPD without necessarily being a preexisting risk factor  . .
Figure 4. Symptom ratio (number of observed symptoms to number of
possible symptoms) in nonmodifiers, modifiers, and quitters at each
test period; symptoms are cough, sputum production. wheezing. and
shortness of breath  . . . . . . . . . . . . . . .
Figure 5. Prevalence of cough and phlegm by smoking group . . .
Figure 6. Prevalence of dyspnea by smoking group . . . . .
Figure 7. Sex-specific mean height-adjusted FEV I residuals versus
pack-years for current and ex-smokers. and distributions of number of
subjects by pack-years . . . . . . . . .
Figure 8. Mean values FVC and FEV 1. expressed as a percentage of
predicted values. in IS quitters and 32 smokers during 30 months after
2 smoking cessation clinics  . . . .
Figure 9. Mean values for the ratio of CV/VC. of CC/TLC. and slope for
phase III of the single breath N? test (Nfi). expressed as a percentage
of predicted values in IS quitters and 42 smokers during 30 months
after 2 smoking cessation clinics . . . .
Figure IO. Percent-predicted diffusing capacity (%pDL) by pack-years
of smoking. current smokers and former smokers. in a study of adults
inTucson.AZ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure I I. Mean AFEV t values in never smokers, consistent
ex-smokers. subjects who quit smoking during followup, and
consistent smokers in several age groups . . . . . . .
Figure 12. Effects of quitting smoking during followup among men aged
5~9.....................................................



23x




252




259








280

`XI




2x4

2x7

293

295

317

322

336

xxxii


Chapter 8

Figure I. Perinatal. neonatal. and fetal mortality rates by birth&eight in
singleton white males. 19x0 3X0

Chapter 11

Figure 1. Performance on a meter (i.e.. visual) vigilance task.

Perfomrance on the continuous clock task. a visual vigilance tash 517
Figure 2. Self-reported withdrawal discomfort among abstinent smokers  53 I
Figure 3. Drinking relative to smoking status for men. 19X3 THIS  SSX
Figure 4. Drinking relative to smoking status for vvomen. IYX3 NHIS SSY

Appendix

Figure I. Trends in the quit ratio. United States. 1965-X7. by gender . . SYO
Figure 2. Trends in the quit ratio. United States. 1965-87. by race . SYI
Figure 3. Flow chart of quitting history. attempts lasting longer than I
year. NHEFS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..SY7
Figure 4. Estimated duration of abstinence on first l-year or longer quit
attempt, product-limit method, N=3,363 . . 59X
Figure 5. Percentage of ever smokers who never tried to quit. by
education. United States, 1974-87 . 601

Figure 6. Percentage of persons smoking at I2 months prior to the
survey interview who quit for at least I day during those I2 months,
United States, 197X-80. 1987. by education . . . . . . . 602
Figure 7. Percentage of ever smokers who had been abstinent for less
than I year. United States. 1966~87. by education 603
Figure 8. Percentage of ever smokers who had been abstinent for IL-I
years. United States. 1966-X7. by education 60-t
Figure 9. Percentage of ever smokers who had been abstinent for 5 years
or more. United States. 1966-X7. by education . 605



       CHAPTER 1
INTRODUCTION, OVERVIEW, AND
      CONCLUSIONS


CONTENTS

Introduction . . . . . . . . . . . . . . . .._._..__._.__.____.___._____.____._

MajorConclusions . . .

Development of the Report . . . .

ChapterConclusions  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chapter 2: Assessing Smoking Ceswion and Its Health Conwquences
Chapter 3: Smoking Cessation and Overall Mortality and Morbidit!
Chapter 3: Smoking Cessation and Respiratory Cancer5
Chapter 5: Smoking Cessation and Nonrespiratory Cancers
Chapter 6: Smoking Cessation and Cardiovascular Diseaw
Chapter 7: Smoking Cessation and Nonmalignant Respirator) Diwa\e\
Chapter 8: Smoking Cessation and Reproduction .
Chapter 9: Smoking. Smoking Cessation. and Other Nonmalignant Diwaw\
Chapter IO: Smoking Cessation and Body Weight Change
Chapter I 1: Psychological and Behavioral Consequences and Correlate\ ot
   Smoking Cessation . . . .
Volume Appendix: National Trend\ in Smoking Ceaation  

References . . . . . . . . . . . . . . . . . ..__..___..__.........._...__......_

  5
.


 x


 x


 Y

 Y

 Y
IO
IO
IO
II
II
I2
I7

I3
I3

15


INTRODUCTION

The 1964 Report of the Surgeon General's Advisory Committee on Smoking and
Health (US PHS 1964) concluded that cigarette smoking is a cause of lung cancer and
laryngeal cancer in men. a probable cause of lung cancer in women, and the most
important cause of chronic bronchitis. Other diseases, including emphysema and
cardiovascular disease, also were found to be associated with cigarette smoking.
although the evidence available at that time was not viewed as sufficient to establish
the associations as causal. Even in 1963. however, the evidence for adverse health
consequences of cigarette smoking was sufficient for the Committee to conclude that
"cigarette smoking is a health hazard of sufficient importance in the United States to
warrant appropriate remedial action" (US PHS 1964. p. 33).

Subsequent reports of the Surgeon General on smoking and health expanded and
strengthened the conclusions of the 1963 Report on active smoking and documented
the benefits of smoking cessation. (See US DHH S 1989 for review.) For some
diseases, such as cardiovascular disease. newer evidence warranted a determination that
associations with cigarette smoking were causal. Further associations of cigarette
smoking with disease were identified, and involuntary (passive) smoking was found to
be a cause of disease in nonsmokers (US DHHS 1986). Although cigarette smoking
has been investigated intensively since the 1950s. new associations of smoking with
adverse effects continue to be identified. For example. in a recent study smoking was
associated with cataracts (West et al. 1989).

Evidence substantiates cigarette smoking as a cause of disease in smokers and,
through involuntary smoking, in never smokers as well. This evidence has motivated
the implementation of diverse and far-reaching programs for smoking prevention and
cessation. The proportion of U.S. adults who smoke decreased substantially since the
1964 Report. In 1965.29.6 percent of persons who had ever smoked had quit; by 1987.
this percentage had increased to 44.8. representing more than 38 million adults. As the
numbers of formerly smoking adults increased in the United States and other countries
(US DHHS 1989), epidemiologic and clinical studies provided increasingly extensive
information on the health benefits of smoking cessation. Thus, the 1964 Report noted
that former smokers had lower overall mortality rates and lower lung cancer risk than
current smokers, but the cited evidence was limited. Scientific data are now available
on the consequences of cessation for most smoking-related diseases. Major benefits
have been shown for overall mortality and for many specific diseases. Although past
reports have considered much of the evidence, these data have not received a com-
prehensive and unified review. This Report systematically reviews the findings on the
health benefits and consequences of cessation.

This Report includes a Foreword by the Assistant Secretary for Health and the
Director of the Centers for Disease Control, a Preface by the Surgeon General of the
U.S. Public Health Service, and the following chapters:

Chapter 1. Introduction, Overview, and Conclusions

Chapter 2. Assessing Smoking Cessation and Its Health Consequences


Chapter 3. Smoking Cessation and Overall Mortality and Morbidity

Chapter 4. Smoking Cessation and Respiratory Cancers

Chapter 5. Smoking Cessation and Nonrespiratory Cancers

Chapter 6. Smoking Cessation and Cardiovascular Disease

Chapter 7. Smoking Cessation and Nonmalignant Respiratory Diseases

Chapter 8. Smoking Cessation and Reproduction

Chapter 9. Smoking. Smoking Cessation, and Other Nonmalignant Diseases

Chapter 10. Smoking Cessation and Body Weight Change

Chapter 11. Psychological and Behavioral Consequences and Correlates of
Smoking Cessation

Volume Appendix. National Trends in Smoking Cessation

A key to acronyms and terms used throughout the Report is found at the end of the
volume.

Other publications of the Public Health Service have reviewed determinants of
smoking cessation and abstinence (US DHEW 1979: US DHHS 1980. 19x8, and
methods of smoking cessation and relapse prevention (Schwartz 1987; US DHHS
1988); hence, these topics are not covered in this Report.

Beginning with the 1964 Report. the evidence on active smoking and disease has
been reviewed for causality to evaluate the associations of smoking with disease. The
explicit criteria used in this evaluation include the consistency, strength. specificity.
temporal relationship, and coherence of the association (US PHS 1964: US DHHS
1989). These criteria have provided a consistent and effective framework for examin-
ing the epidemiologic. clinical. and experimental data on active smoking. Although
the criteria cannot be applied in the same fashion to associations of smoking ce\\ation
with change\ in disease occurrence. the criteria of consistency. an appropriate temporal
relationship. and coherence must be maintained bith evidence on smoking cessation
and health.

Thus, thi5 Report examines data for consistency among investigations of the associa-
tions of cessation with disease occurrence and other outcomes. and considers the
biologic plausibility of the hnown or presumed associations in the context of the
mechanisms by which cigarette smokin g is known or thought to cause disease. The
appropriate time sequence of cessation Lvith its effect is evident: cessation must always
precede its presumed effect. In an observational study. [hi\ sequence may k reversed
by the tendency of persons with initial symptoms of a cigarette-related disease or with
frank di\eace to reduce cigarette consumption or to stop smoking (Chapter 1). The
findings of longitudinal studies among former smokers document high mortality rates
among short-term former smokers. which ic consistent with reversal of the causal

6


sequence of cessation followed by, reduced di\ea\e occurrence: that is. diseajc has
caused a change in exposure (Roget attd Murray 19X0).
Cigarette smoke in its gaseous and particulate phajej contain\ thousand\ of agent\.
many of u hich can damage tissues and cause disease (US DHEW IY7Y: US DHHS
IYX6, 198')). The pathogenetic mechanisms by which cigarette smoking cause\ disease
are divJer\e. ranging from longer term proce\\es. such as carcinogenesi\. to shorter term
processes. such a< interference with tissue oxygenation by carbon monoxide. Thu\. the
biologic context in w,hich the ev)idencc on cessation is considered must be disease-
specific: a unified biologic framework for evaluating the e\ idence on ce\\vtion cannot
he offered.
For example. cigarette smoking causes emphysema. an irreversible destruction of the
ga+exchanrina structure of the lung. and permanent oronly partialI\ rever$ible damage
        c c
to the airways of the lung. Little improvement of lung function after cessation would
be anticipated for a long-term smoker with disabling chronic obstructive pulmonary
disease (COPD) and extensive irreversible damage to the lung. However. ces&on
would benefit a smoker who has less extensive damage by slowing the rate of lung
function decline and thereby reducing the likelihood of clinically significant impair-
ment. By contrast with COPD. smoking cessation following myocardial infarction has
both relatively immediate and longer term benefits. The immediately decreased ri$k
of death in those who stop smoking in comparison with those who continue to smoke
may reflect a decrease of blood coagulability. improved tissue oxygenation. and less
predisposition to cardiac arrhythmias after cessation.
The findings of studies on the health consequence\ of smohing cessation also pro\ ide
evidence relevant to determining the causality of associations of active smoking with
disease. A decline in disease incidence after cessation needs to k considered a\ :I
positive indication of such a causal association. However. the pattern of changing risk
after cessation must be interpreted in the context of the mechanism of disease causation
by active smoking.
In interpreting individual studies on the consequences of smoking cessation. difficult
methodologic and conceptual issues must k considered. Chapter 2 addresses these
issues in depth. Because smoking cessation is a dynamic process. often involving
multiple relapses to active smoking, accurate characterization of the former smoker is
difficult and best accomplished by longitudinal observation. MisclasGfication of
cigarette smoking status may lead to biased estimates of the consequences of smoking
cessation. In observational studies and trials some rubjects may report that they are
former smokers. even though they continue to smoke: the resulting misclassification
tends to result in underestimation of the benefits of cessation. Unraveling the conse-
quences of smoking cessation from the effects of other factors determining the occur-
rence of disease poses a substantial analytical challenge. In reviewing individual
reports on the consequences of smoking cessation, the approaches to these potential
methodologic issues were assessed (Chapter 2).


MAJOR CONCLUSIONS

More than 38 million Americans have quit smoking, and almost half of all living
adults in the United States who ever smoked have quit (Volume Appendix). Neverthe-
less, more than SO million Americans continue to smoke. This Report reviews in detail
the health consequence5 of smoking cessation for those who have quit and for those
who will quit in the future. The following major volume conclusions summarize the
health consequences of smoking cessation for those who quit smoking in comparison
with those who continue to smoke:

1. Smoking cessation has major and immediate health benefits for men and
women of all ages. Benefits apply to persons with and without smoking-
  related disease.

2. Former smokers live longer than continuing smokers. For example, persons
who quit smoking before age 50 have one-half the risk of dying in the next
15 years compared with continuing smokers.

3. Smoking cessation decreases the risk of lung cancer, other cancers, heart
attack, stroke, and chronic lung disease.

4. Women who stop smoking before pregnancy or during the first 3 to 4
months of pregnancy reduce their risk of having a low birthweight baby to
  that of women who never smoked.

5. The health benefits of smoking cessation far exceed any risks from the
average ii-pound (2.3-kg) weight gain or any adverse psychological effects
that may follow quitting.

DEVELOPMENT OF THE REPORT

This Report was developed by the Office on Smoking and Health (OSH). Center for
Chronic Disease Prevention and Health Promotion. Centers for Disease Control, Public
Health Service of the U.S. Department of Health and Human Services, as part of the
Department's responsibility under Public Law 91- 222 to report new and current
information on smoking and health to the U.S. Congress.

The scientific content of this Report was produced through the efforts of more than
I30 scientists in the fields of medicine. psvchology. the biologic and social sciences,
and public health. Manuscripts for the Report. constituting drafts of chapters or sections
of chapters. were prepared by 26 scientists selected for their expertise in specific content
areas. An editorial team. including the Director of OSH. a medical psychologist with
the Uniformed Services UnivJersity of the Health Sciences. and four non-Federal
experts. edited and consolidated the individual manuscripts into chapters. These draft
chapters were subjected to an intensive outside peer review. with each chapter reviewed
by an average of five indivsiduals knowledgeable about the chapter's subject matter.
Incorporating the reviewers' comments. the editors rev,ised the chapters and assembled
a draft of the complete Report. The draft Report was then submitted to 15 distinguished


scientists for their review and comment on the entirety of its contents. Simultaneously.
the draft Report was submitted to 10 institutes and agencies within the U.S. Public
Health Service for review. Comments from the senior scientific reviewers and the
agencies were then used to prepare the final draft of the Report. N hich was then
rev!iewed by the Office of the Assistant Secretary for Health and the Secretary,
Department of Health and Human Setvices.

CHAPTER CONCLUSIONS

Chapter 2: Assessing Smoking Cessation and Its Health Consequences

1. Most former smokers have cycled several times through the process of smoking
cessation and relapse before attaining long-term abstinence. Any static measure of
smoking status is thus a simplification of a dynamic process.

2. In studies of the health effects of smoking cessation. persons classified as former
smokers may include some current smokers. Consequently. the health benefits of
smoking cessation are likely to be underestimated.

3. In contexts other than intervention trial\. self-reported smoking status at the time of
measurement and concurrent biochemical assessment are highly concordant. This
high concordance supports self-report as a valid measure of smoking status in
observational studies of the health effects of smoking cessation.

Chapter 3: Smoking Cessation and Overall Mortality and Morbidity

I. Former smokers live longer than continuing smokers, and the benefits of quitting
extend to those who quit at older ages. For example, persons who quit smoking
before age 50 have one-half the risk of dying in the next I5 years compared with
continuing smokers.

2. Smoking cessation at all ages reduces the risk of premature death.

3. Among former smokers, the decline in risk of death compared with continuing
smokers begins shortly after quitting and continues for at least IO to 15 years. After
IO to 15 years of abstinence, risk of all-cause mortality returns nearly to that of
persons who never smoked.

4. Former smokers have better health status than current smokers as measured in a
variety of ways, including days of illness, number of health complaints, and
self-reported health status.


Chapter 4: Smoking Cessation and Respirator! Cancers

1. Smoking cessation reduces the rijk of lung cancer compared with continued smok-
ing. For example. after IO year\ of abstinence. the risk of lung cancer is about 30
to 50 percent of the risk in continuing smokers: with further abstinence. the ri\h
continues to decline.

9. The reduced risk of lung cancer among former smokers is observed in males and
females, in smokers of filter and nonfilter cigarettes. and for all histologic types of
lung cancer.

3. Smoking cessation lowers the risk of laryngeal cancer compared with continued
smoking.

4. Smoking cessation reduces the severity and extent of premalipnant histologic
changes in the epithelium of the larynx and lung.

Chapter 5: Smoking Cessation and Nonrespiratory Cancers

1. Smoking cessation halves the risks for cancers of the oral cavity and esophagus.
compared with continued smoking. as soon as S year\ after cessation. with further
reduction over a longer period of abstinence.

2. Smoking cessation reduces the rish of pancreatic cancer. compared uith continued
smoking. although thi\ reduction in ri\k may only be measurable after IO year\ of
  abstinence.

3. Smohinp i\ a cause of bladder cancer: cessation reduces risk by about SO percent
after only a few years. in comparison with continued smoking.

4. The risk of cervical cancer i\ substantially lower among former smokers in com-
parison with continuing smoker\. even in the first feu years after cessation. This
finding supports the hypothesis that cigarette smokin, 0 is a contributing cause of
  cervical cancer.

5. Neither smoking nor smohing cesjution are associated with the rish of cancer of the
  breast.

Chapter 6: Smoking Cessation and Cardiovascular Disease

I, Compared with continued smoking. smoking cessation substantially reduces risk of
coronary heart disease (CHD) among men and women of all ages.


2. The excess risk of CHD caused by smoking is reduced by about half after 1 year of
smoking abstinence and then declines gradually. After 15 years of abstinence. the
risk of CHD is similar to that of persons who have never smoked.

3. Among persons with diagnosed CHD. smoking cessation markedly reduces the rish
of recurrent infarction and cardiovascular death. In many studies. this reduction in
risk of recurrence or premature death has been SO percent or more.

4. Smoking cessation substantially reduces the risk of peripheral artery occlusive
disease compared with continued smoking.

5. Among patients with peripheral artery disease. smoking cessation improves exercise
tolerance. reduces the risk of amputation after peripheral artery surgery. and
  increases overall survival.

6. Smoking cessation reduces the risk of both ischemic stroke and subarachnoid
hemorrhage compared with continued smoking. After smoking cessation, the risk
of stroke returns to the level of never smokers; in some studies this has occurred
within 5 years, but in others as long as 15 years of abstinence were required.

Chapter 7: Smoking Cessation and Nonmalignant Respiratory Diseases

1. Smoking cessation reduces rates of respiratory symptoms such as cough. sputum
production, and wheezing, and respiratory infections such as bronchitis and
pneumonia, compared with continued smoking.

2. For persons without overt chronic obstructive pulmonary disease (COPD). smoking
cessation improves pulmonary function about 5 percent within a few months after
  cessation.

3. Cigarette smoking accelerates the age-related decline in lung function that occurs
among never smokers. With sustained abstinence from smoking, the rate of decline
in pulmonary function among former smokers returns to that of never smokers.

4. With sustained abstinence, the COPD mortality rates among former smokers decline
in comparison with continuing smokers.

Chapter 8: Smoking Cessation and Reproduction

1. Women who stop smoking before becoming pregnant have infants of the same
birthweight as those born to never smokers.

2. Pregnant smokers who stop smoking at any time up to the 30th week of gestation
have infants with higher birthweight than do women who smoke throughout
pregnancy. Quitting in the first 3 to 4 months of pregnancy and abstaining


throughout the remainder of pregnancy protect the fetus from the adverse effects of
smoking on birthweight.

3. Evidence from two intervention trials suggests that reducing daily cigarette con-
sumption without quitting has little or no benefit for birthweight.

4. Recent estimates of the prevalence of smoking during pregnancy, combined with an
estimate of the relative risk of low birthweight outcome in smokers, suggest that 17
to 26 percent of low birthweight births could be prevented by eliminating smoking
during pregnancy: in groups with a high prevalence of smoking (e.g., women with
less than a high school education) . 29 to 43 percent of low birthweight births might
be prevented by elimination of cigarette smoking during pregnancy.

5. Approximately 30 percent of women who are cigarette smokers quit after recogni-
tion of pregnancy, with greater proportions quitting among married women and
especially among women with higher levels of educational attainment.

6. Smoking causes women to have natural menopause I to 2 years early. Former
smokers have an age at natural menopause similar to that of never smokers.

Chapter 9: Smoking, Smoking Cessation, and Other Nonmalignant Diseases

I. Smokers have an increased risk of development of both duodenal and gastric ulcer.
and this increased risk is reduced by smoking cessation.

2. Ulcer disease is more \evere among smokers than among nonsmokers. Smohers are
less likely to experience healing of duodenal ulcers and are more likely to have
recurrences of both duodenal and gastric ulcer\ within specified timeframes. Moat
  ulcer medications fail to alter the\e tendencies.

3. Smokers with gastric or duodenal ulcers who stop smoking improve their clinical
  course relative to mohers &ho continue to smoke.

3. The evidence that smohing increu\es the rish ofosteoporotic fractures or decreue\
bone ma\s is inconclusive. Hith many conflicting findings. Data on smoking
cessation are extremely limited at present.

5. There i\ evidence that smohing i\ a\3ociated u,ith prominent facial skin wrinkling
in whites. particularl) in the periorbital ("crou `\ foot") and perioral areas of the
face. The effect of cessation on ,hin hrinhling is unstudied.

Chapter 10: Smoking Cessation and Bad! Weight Change

1, Average weight gain after making cessation is only about 5 pounds (2.3 kg). This
weight gain pose5 a minimal health risk.

I?


2. Approximately 80 percent of smokers who quit gain weight after cessation. but only
about 3.5 percent of those who quit smoking gain more than 20 pounds.

3. Increases in food intake and decreases in resting energy expenditure are largely
responsible for postcessation weight gain.

Chapter 11: Psychological and Behavioral Consequences and Correlates of
             Smoking Cessation

I. Short-term consequences of smoking cessation include anxiety. irritability. frustra-
tion. anger, difficulty concentrating, increased appetite, and urges to smoke. With
the possible exception of urges to smoke and increased appetite. these effects soon
disappear.

2. Smokers who abstain from smohing show short-term impairment of performance
on a variety of simple attention tasks. which improv!es with nicotine administration.
Memory, learning, and the performance of more complex tasks have not been
clearly shown to be impaired. Whether the self-reported improvement in attention
tasks upon nicotine administration is due entirely to relief of withdrawal effects or
is also due in part to enhancement of performance above the norm is unclear.

3. In comparison with current smokers. former smokers have a greater perceived ability
to achieve and maintain smoking abstinence (self-efficacy) and a greater perceived
control over personal circumstances (locus of control ).

4. Former smokers. compared with current smokers. practice more health-promoting
and disease-preventing behaviors.

Volume Appendix: National Trends in Smoking Cessation

I. By 1987. more than 38 million Americans had quit smoking cigarettes. nearly half
of all living adults who ever smoked.

2. The percentage of ever cigarette smokers who are former cigarette smokers (quit
ratio) has increased from 29.6 percent in 1965 to 44.8 percent in 1987 at an average
rate of 0.68 percentage points per year. The quit ratio has increased among men
and women, among blacks and whites, and among all age and education subgroups.
Between 1966 and 1987, the rate of increase in the quit ratio among college
graduates was twice the rate among high school dropouts.

1. About one-third of all former cigarette smokers who have maintained abstinence
for at least I year may eventually relapse. As the duration of abstinence increases.
relapse becomes less likely.


4. Quitting activity, as measured by the proportion of people smoking at I2 months
before a survey who quit for at least I day during those 12 months. has increased
slightly over time. Between 1978 and 1987. this proportion increased from 27.8 to
3 I .6 percent.

5. Female smokers were more likely than male smokers to have quit smoking cigarettes
for at least I day during the previous year: however, there were no gender differ-
ences in the proportion abstinent for I to 4 years. Men were more likely than women
to have been abstinent for 5 years or more. These findings do not take into account
the use of tobacco products other than cigarettes.

6. Black smokers were more likely than white smokers to have quit for at least I day
during the previous year. Blacks, however, were less likely than whites to have
been abstinent for I year or more.

7. Younger smokers (aged 20 to 44) were more likely than older smokers to have quit
for at least I day during the previous year.

8. Smokers with less education tend to be less likely to have quit for at least I day
during the previous year compared with those having more education. In addition.
those with lower levels of education are less likely to have been abstinent for I year
  or more.

9. In 1964. about three-fourths of all current smokers predicted that they would
"definitely" or "probably" be smoking in 5 years. In 1986, fewer than half of all
current smokers felt the same way. Moreover, while more than 20 percent of current
smokers in 1964 predicted that they would "definitely" be smoking in 5 years, only
about 7 percent of current smokers in 1986 so predicted.

IO. Current smokers in 1987 were more than three times as likely as current smokers
in 1964 to report having received advice from a doctor to stop smoking.

14


References

ROGOT. E.. MURRAY. J.L. Smoliing and causes of death among U.S. veterans: 16 bears ol
observation. P&/ic, Hc~ulth RP/JOIY.\ M(3):? 1%272. May-June IYXO.
SCHWARTZ. J.L. Kcr,irn, w(/ tw//rwrio,r /)f SnroXir~y Cc\.\tr/i/w Mc,/lro<l\.  L:,riwt/ Stcrfc,.\ ti/i</
Ctrrwkr. /Y78-/YXi. U.S. Department of Health and Human Scrviccs. Public Health Scn ICC`.
National Institutes of Health. NIH Pubhcation No. X7-29lO. April 10x7.
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. 7.//c Hcci//h C`o/~.wqu~v~~ c\ CJ/`
StwXiq jiw u O,?,C,1. A Kqwr of tlw .%,,yw1 Golcwl  L:.S. Departn~cnt of Health and
Human Services. Public Health Service. Office of the Assrstant Secretq for Health. Otfice
on Smoking and Health. 19X0.

U.S. DEPARTMENT OF HE.4LTH AND HUMAN SERVICES. 7`lw I/w/r/, C`<w\c,r/w/~( <`\ of
I~rwlr~/~~trr:\ SmoXiu~. A Rqww~ of rhc Sw~cvw Gcwr-crl. U.S. Dcpartmen~ of Health and
Human Services. Public Health Service. Centers for Disease Control. DHHS Publication No.
(CDC) X7-X39X. IYXh.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. 7`1rc //c,tr/r/i Co/r.qw/~r (`< o/
S~~rdi~r,q Mic.c~i~c Adclic,~io,~. A Rcpor~ c!f`t/w S~rrqc~on G`c~~wr~d. /(IS%`. U.S. Department of
Health and Human Services. Public Health Service. Centers for Disease Control. Center fw
Health Promotion and Education. Office on Smohmg and Health.  DHHS Puhltcation No.
(CDC) 8X-X406. 1988.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. Rcchrc~i,r,q t/w Hrwlrh C`orr.w
yI~cI?c<`.s of .G?di/l,~.  25 Yeur3 of' P/Y~<LyC~.\.\.  A Rc~/wr-/ of fhc .Gr:gcv~i G~vwr~//. U.S.
Department of Health and Human Services. Public Health Service. Centers for Disease
Control. Center for Chronic Disease Prevention and Health Promotion. Office on Smohmz
and Health. DHHS Publication No. (CDC) X9-X41 I. IYXY.
U.S. DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE. SnioXiq (I/ICI Hc,tr/rlr.
A Rr~por~ c~~rhc,S~r~;~e,~,r Gcwr.tr/. U.S. Department of Health, Education. and Welfare. Public
Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health.
DHEW Publication No. (PHS) 79-50066. 1979.

U.S. PUBLIC HEALTH SERVICE. Smokiq a& Hculth. Repwt of /hr Ad~i.co/~v Coninri/tw
fr) l/w .Sw,qron Gcnewl ofthe P uhlk Heul/j~ Scr.\,icr. U.S. Department of Health. Education.
and Welfare. Public Health Service, Center for Disease Control. PHS Publication No. 1 103.
1964.

WEST, S.. MUNOZ. B.. EMMETT, E.A.. TAYLOR. H.R. Cigarette smoking and risk of
nuclear cataracts. Archi\v.s c!f'Oprl?u/nlo/o,~~ 107(X): I 166-l 169. August 19X9.

15


          CHAPTER 2
ASSESSING SMOKING CESSATION AND ITS
    HEALTH CONSEQUENCES


CONTENTS

Introduction . . . . . . . . . . . .    . . . . . . . . . . . . . .._............ ?I

Part I. Assessing the Dynamic Process of Smoking Cessation . 1 . . 72

The Process of Smoking Behavior Change  ...............
Behavioral Measures  ................................
Self-Report: Questionnaires and Interviews  ............

   Temporal and Frequency Issues  .....................
   Improving Self-Report Measures  ....................
  Alternative Behavioral Measures  ......................
  Surrogate Assessments ...............................
Nonbehavioral Measures  ...............................
  Physiologic Measures  ...............................
  Biochemical Markers ................................
   Terminology  ....................................
    CarbonMonoxide  ................................
   Thiocyanate  .....................................
    Cotinine  ........................................
  BogusPipeline.. ...................................
  Contextual Issues Affecting Biochemical Assessment ......

Part II. Assessing the Consequences of Smoking Cessation  .....
Study Designs Used To Assess the Consequences of Cessation
  Overview of Study Design ............................
  Ecologic Studies. ...................................
  Cross-Sectional Studies  ..............................
  CohortStudies  .....................................
  Case-Control Studies ................................
  Intervention Trials  ..................................
Methodologic Issues ...................................

Introduction  .....................
Statistical Considerations ...........
Bias ............................
Analytic Issues in Observation Studies

Summary  ...........................

Conclusions  .........................

References  ..........................

.............

.............

.............

.............

.............


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.

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.

. .

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.

. . .

22

. 25

. 25

. 27
2x
29
30
31

. 32
33
33
34
35

. 36

. 37
37

. 46

. 46
46
47

. 47
48
49

. 50
51

. 51

. 52
52

. 5s

. , 57
~~
. 58

. , . 59

19


INTRODUCTION

Smoking cessation is a dynamic process that begins with a decision to stop smoking
and ends with abstinence from cigarettes maintained over a long period of time.
Typically, initiation of regular cigarette smoking occurs at a young age. usually during
the teenage years (US DHHS 198Y); cessation may be contemplated and initiated at
any age. The spectrum of factors motivating cessation is diverse: some smokers quit
before being adversely affected by cigarette smoking whereas others quit as a result of
developing smoking-related disease. Most attempts to quit are temporarily successful.
and most smokers attempting to quit return several times to regular smoking before
achieving 1ong:tet-m abstinence.

For the purpose of health research, smoking status (i.e.. never. former. or current
smoker) can be evaluated by using an interview or questionnaire to query subjects about
their smoking behavior. However, self-reports may not fully characterize the process
of cessation in individual smokers, particularly if information is collected retrospec-
tively or cross-sectionally. Moreover, persons who are smoking may falsely report
themselves as former or never smokers. Biochemical markers. such as cotinine and
thiocyanate (SCN-) levels in body fluids. provide complementary measures of tobacco
product use.

However, reliance solely on biochemical markers of smoking also may lead to some
misclassification. For example. intake of some foods can result in high SCN- levels
unrelated to smoking behavior. Individuals who accurately report being quitters may
fail to participate in the validation process and therefore may be misclassified as
continuing smokers if nonparticipants in biochemical testing are assumed to be smok-
ing. Because proper classification of smoking behavior is critical for conducting
research on the health consequences of smoking cessation and for evaluating the results
of such research, it is important to consider how smoking status is assessed.

The health consequences of smoking cessation have been studied using conventional
approaches of epidemiologic and clinical research: ecologic study. cross-sectional
study or survey, case-control study, cohort study. and intervention trial. Each design
has well-described advantages for studying causes of disease and preventive factors
among human populations (Kleinbaum. Kupper, Morgenstern 1982). In addition. each
design type is subject to the three types of bias potentially affecting any epidemiologic
study: selection bias, information bias, and confounding bias (Rothman 19X6) (Chapter
2, Part II). Misclassification resulting from information bias is of particular concern in
studies of smoking cessation: misclassification is addressed in detail in this Chapter.

These conventional research designs have been used successfully to characterize the
adverse effects of active cigarette smoking and to amass the scientific information on
smoking cessation reviewed in this Report. For example, the evidence on smoking
cessation and mortality derives from cohort studies (Chapter 3); evidence on cancer
comes largely from case-control and cohort studies (Chapters 4 and 5): and information
on respiratory morbidity and mortality is based primarily on cross-sectional and cohort
studies (Chapter 7).

This Chapter establishes a methodologic framework for interpreting the evidence on
smoking cessation obtained from observation studies and intervention trials. Part I


describes the process of smohing cessation and the methods used to assess smoking
behavior. Part II reviews research methods used to study smoking cessation as well as
the potential limitations of data obtained from observational studies and intervention
trials including biases that may affect the results.

PART 1. ASSESSING THE DYNAMIC PROCESS OF SMOKING
               CESSATION

This Section describes the dynamic nature of smoking behavior. the various measures
of smoking status applied in observational and intervention studies. and the effect of
these measures on classification of smoking status.

The Process of Smoking Behavior Change

Smoking behavior in U.S. populations has been changing. and three-fourths of all
smokers have attempted to quit (Volume Appendix). The proportion of adult former
smokers in the population is now about the same as the proportion of current smokers.
These population changes have provided opportunity to describe the consequences and.
thereby, the benefits of cessation.

Progressing from smoking to former smoking is a complex, dynamic process and not
a one-time event. Retrospective. cross-sectional. and longitudinal studies of hou
people quit smoking on their own have demonstrated that smokers move through a
series of stages in theircessation efforts ( DiClemente and Prochaska 1982: Lichtenstein
and Brown 1980: Prochaska and DiClemente 1983; Prochaska et al. 1985; Rosen and
Shipley 1983). These stage\ have been labeled motivation and commitment. initial
change. and maintenance by Brownell and coworkers (lY86): contemplating change.
decidingt change. short-term change. and long-term change by Horn ( 1976): motivation
and commitment. cessation and possible relapse. and maintenance by Marlatt and
Gordon (1985): precontemplation. contemplation. action. and maintenance and/or
relapse by Prochaska and DiClemente ( 1983): and initial decision. initial control. and
maintenance by Rosen and Shipley (1983).

The stage model of Prochaska and DiClemente ( 1983: Prochsska et al.. in press) has
generated the most research and is described in more detail below (Figure I ). Pre-
contemplation is a period in which smokers are not thinking about quitting smoking.
or at least not about quitting uithin the next 6 months. The basis for the 6-month
timeframe is the assumption that 6 months into the future is as far as most people plan
a specific behavior change. Contemplation is the period in which smokers seriously,
consider quitting smoking within the next 6 months. Action is the period that begins
when actual cessation occurs and continues for 6 months after stopping smoking.
Maintenance is defined as the period beginning 6 months after cessation occurrence.
In all of the proposed stage models. differentiation is made between short-term
(generally up to 6 months) and long-term (generally 6 months and longer) change or
between initial cessation and maintenance of cessation. Maintenance continues until
relapse to regular smoking. or until a return to regular smoking is of minimalor no
concern and "termination" of the behavior occurs for the confirmed ex-smoker.

22


Less risky life
of terminators

Avoid further failure

Riskier life of
precontemplators

FIGURE l.-Cyclical model of the stages of change
SOURCE:  Pmchaka et ill. (III prw,

On any single cessation attempt (action stage). the majorit! of \moher\ relapse and
return to regular smoking. A National Heart. Lung. and Blood Institute con>rnsu\
conference defined relapse as at least one puff per day for 7 da! 4 and recommended
that this definition be applied uniformly (Shumaker and Grunbt'rs 19X61: however. thi\
definition is not used in all studies. Any return to \mokin~ that i\ Ic\s than the criterion
for relapse is considered a "lapse" or a "slip." n,hich may or may not C;ILI~ a return 10
regular smoking (Brownell et al. 19X6: Marlatt. Curry. Gordon. 19Xx1.

Although 75 to X0 percent of relapse occur> at 6 month Y and before (Hunt. Barnett.
Branch 1971: Hunt and Bespalec 1973: Hughes ct al. 19X1: Gar\c\. Hcinold. Rohncr
1989). individuals who maintain abstinence for 6 montll\ continue IO rclap~ b\ 12
months and beyond. For example. in a re\,ieu of IO ctudies III u hich minimal or no
intervention occurred (i.e.. \elf-change htudieb). relap~c' rate\ at 12 rnontl~~ i'or wmhw
who had previously maintained abstinence t'or ;II 1~41 6 mcmth\ ranged t`rom 7 to 35
percent (Cohen et al. 1989). Data from the National lical~h and Nutrition t!\;tmin;111011


Survey I (NHANES-I) Epidemiologic Follouup Stud) demonstrate that even after I
year of prolonged abstinence. relapse continues to occur 111 about one-third of former
smokers. Relapse continues to occur at a much lovver rate after 2 years (Volume
Appendix). In the Multiple Rirh Factor Intervention Trial (MRFIT). a multifact~~t
intensive intervention study, Ochene and colleagues (19x2) found that among smokers
who had stopped with the aid of intensive intervention. relapse continued to occur
throughout the 6 years offollowup. However. relapse has at a much higher rate in the
first year than in years two through six. Kirscht and colleagues ( lYX7) reported that Y.5
percent of adults who had been abstinent for 2-l to I I9 monthsreported smohing again
in a followup survey. Even after I10 months. 1.3 percent of fomrer smokers reported
smoking again.
Research would be simplified if the probabilrty of remaining a former smoker were
100 percent after a prolonged period of abstinence. If this were the case. then there
would be no concern about future misclassification of these confirmed former smokers.
However. the continuous nature of the relapse process and the curv'es that represent this
process indicate that the probability of maintained cessation u ill never be I00 percent.
The available data (Garvey. Heinold. Rosner 19X9: Ochene et al. 19X2: Cohen et al.
1989: Volume Appendix) suggest that for most research purposes. 2-l months of
continuous abstinence can be used as a practical criterion for categorizing individuals
as confirmed former smokers. However. use of this timeframe is often not feasible or
applicable in many research studies, and as a general fuideline for interpreting out-
comes-the longer the duration of continuous abstinence. the greater the probability
that individuals will remain former smokers.
Cessation is a cyclical. not linear. process: smokers cm enter or leave the process at
any point (Prochaska and DiClemente 1983: Prochasha et al.. in press) (Figure I).
Research on self-change approaches to smoking cessation suggests that the average
smoker cycles three to four times through the stages before attaining long-term
continuous abstinence and becoming a confirmed former smoher (Prochasha and
DiClemente 19X4. 1986: Marlatt. Curry. Gordon I YXX; Schachter 19X2). In a review
of self-change studies. Cohen and colleagues ( 19x9) found that onI> -l.3 percent of the
participants in the rev iewed studies shifted immedtately, from current smokers to former
smokers without experiencing any lapsesor relapses. Most smokers M ho relapse return
to a point where they think about stopping again. that is. the contemplation stage. A
smaller proportion lose their motivation to change and regress back to the pre-
contemplation stage (Prochaska and DiClemente 19X-l).
In summary, because of the dynamic nature of change in smohing behavior. an>
categorization of smoking status at a single point in time becomes a simplification. A
group of former smokers aill include individuals who have stopped recently or who
have been abstinent for varyin g lengths of time; some bill maintain abstinence. and
some will relapse. Knowledge of the dynamics ofsmohinp cessation and its usual time
course can help invtestigators minimize misclassification by choosing the most ap-
propriate methods for assessing smoking behavior and the appropriate sampling pro-
cedures (e.g. number of measurements made and time betueen repeated measures ot
smoking status).


Behavioral Measures

Self-Report: Questionnaires and Interviews

For health research purposes. smoking status is usually assessed by using self-
administered questionnaires or interviews.  However, other behavioral methods. sur-
rogate assessments, and nonbehavioral methods such as biochemical assessments are
also used as sources of smoking data.  These other sources will be reviewed in
subsequent sections. (See also rev,iews by Pechacek. Fox et al. lYX3 and Marsh et al.
IYXX.)

Questionnaires and interviews may include information concerning smohing at the
timeoftheassessmentorconcernin~acompleteorpartial retrospective lifetime history,.
Assessment can be made once or serially over time, thus providing more valid data
regarding cessation and possible relapse. Infortnation gathered from an intervieu or
questionnaire about smoking categorizes respondents as never. current. or former
smokers. Two standard items used in the National Health lntetvieu Survey (Volume
Appendix) to classify smoking status are "Have you smoked at least 100 cigarettes in
your entire life?" and "Do you smoke cigarettes now?" Someone responding "yes" to
the first question and "no" to the second would be classified as a former smoker. Such
a broad definition for former smokers combines persons who experimented with
smoking enough to have smoked lOOcigarettes with individuals who may have smoked
during their entire adult life and quit in the week prior to being interviewed.

The commonly used item. "Have you smoked at least 100 cigarettes in your entire
life?" has an advantage of counting as never smokers those individuals who experi-
mented with 1, 2. or quite a few cigarettes. Only those who have smoked at least 5
packs of cigarettes in their lifetime are counted as ever smokers. The arbitrariness of
this definition reflects the lack of accepted and standardized definitions for ev'er
smokers and never smokers. A definition of never smokers that requires only minimal
or no use of tobacco may result in many individuals with extremely low exposure to
cigarettes being classified as former smokers. which in general would not be biologi-
cally appropriate.

Another commonly used type of item. as in the Medical Research Council (MRC)
National Survey of Health and Dev,elopment (Britten 19X8). for defining ever smokers
is "Have you ever smoked as much as 1 cigarette a day for as long as I year'?" This
item is used by the American Thoracic Society. Division of Lung Disease in its Adult
Respiratory questionnaire: however. two other choices are added- "or 20 packs of
cigarettes" or "12 ounces of tobacco" (Ferris 1978). A comparable questions is "Have
you ever smoked at least 5 cigarettes per week. almost every week for at least I year'?"
(Petitti. Friedman. Kahn 19X I ). These items that are used to classify ever smokers are
based on a combination of the amount of cigarettes smoked (e.g.. 365) and the duration
of smoking (e.g.. at least 6 or I3 months).

The particular question used to differentiate between ever smokers and never smokers
can directly affect categorization of individuals. For example. Petitti. Friedman. and
Kahn ( 19X I ) found that with a more specifically defined question such as "Have you
ever smoked at least 5 cigarettes per weeh almost every week for at least I year'!" M hich



require\ wme period 0f"re~ular" smoking for an individual to be clawificd as an t`ver
maker. 12% of?i:! individuals reported being neler smoker\. However. when assessed
concurrently ti ith another questionnaire in which regular smoking was not defined and
the respondent self-defined waking. 7 percent fewer subjects t II9 of 252) reported
being never smokers.
Thus, the use of more clearly defined questions. wch as specifying 100 cigarettes in
;1 lifetime. or 1 cigarette per day for I year. or 5 ci_rarettes per week for I year. Mill
reduce misclaGtIcatlon. However. some misclassification will still occur for thaw
individuals who hmohed for relatively brief periods during their lives but cannot
accurately remember hou long they smoked or accurately estimate the number of
cigarettes they smoked.
Attention also must be paid to defining current or former smokers. Some studies.
such as the Cancer Prevention Study I (CPS-1) (Hammond and Garfinkel 1969). define
current smokers as those who respond affirmatively to the question "Have you smoked
within the past year?" Other studies u$e smoking in the past 6 months as the guideline
for current smokers (Coultas et al. 1988). The criteria for questions identifying current
smoker\ can range from having smoked in the past year. to the past 6 months. to the
past week. or to an unspecified period. A few additional questions will enhance the
specificity of the definitions of current smokers and former smokers. These items. or
comparable ones. have been used in previous surveys. for example. the 198X Baseline
Prevalence Survey for the Community Intervention Trial for Smoking Cessation.
funded by the National Cancer Institute: `.At what age did you start smoking on a
regular basis?": "On the average. about hou many cigarettes did you smoke per day
during the lact I?. months you smohed?": and for former smokers. "When did you quit
smoking cigarettes'?" (recorded to exact date if possible). These item\ provide udd-
tional information for defining ever smohers. or stratifying by levels of exposure. and
for determining the period of abstinence.
The dynamic nature of smoking ce\\ation highllghts the importance of being aware
that any categorical definition of former smoker in relation to the health effects of
smohing cessation will include former woher\ who h:r\,e been abstinent for \,arying
period\ of time. Optimally. questions on smohin, ~7 historv should ascertain the duration
                                         _
of abstinence for former \moher\. and if possible. abstinence period\ should be treated
aj continuous or categorized vuriablc\ in an anal>si\. thus avoidins the problem ot
treating former smoher\ ;IS ;1 single group.  Howewr. benefit\ of ce\\ation are still
clearly observed in spite of the limitation\ of using categorical data.
The mo\t common minimum period\ ofabstinencc u$ed for defining former smoking
statu\ are 2-l hours. 7 days. and 30 da\\. The National Interagency Council on Smoking
and Health ( 1973) recommended using ;I minimum of 7 da> s ofab\tinence for defining
cessation. However. becuuw of the nature of mokin g. usin_r ;t short abstinence period
to define former smoher\ i\ not optimal in epidemiologic studies. The degree of
misclassification of former smoker\ M ill depend on the minimum duration of abstinence
u\ed to define former smokers and the criterion wed to consider determine relapse.
Many studie\ do not specify a minimum duration of abstinence for indi\,idual\
classified 3s former smohers at ;I particular point in time. Data from such \tudie\ on
the aswciation of smohin, 17 ce\\ation L+ ith health and disease outcome\ mu\t bc


interpreted cautiously. For example. in the reports of the Whitehall Civil Servants
Study (Rose and Hamilton 197X; Rose et al. 1982). the criterion used to define
abstinence is not indicated. The only information provided is that the smokers reported
that "they were then smoking no cigarettes at all" (Rose and Hamilton 1978).

Regardless of the criteria used to define abstinence. the methodology for assessing
smoking status, including questionnaire items. needs to be carefully described by
investigators. Optimally these items should enhance the process of obtaining informa-
tion regarding the duration of abstinence. making it possible to fully determine the
relationship of smoking cessation to health and disease outcomes. When reviewing
studies of the health effects f smoking, the definition of the former smoker must be
carefully assessed, and the effect of the definition on the findings must be carefully
examined.

Temporal and Frequency Issues

Studies vary according to whether smoking is assessed retrospectively or prospec-
tively and whether a single assessment or a series of assessments is used. The category
of never smokers can be assessed retrospectively. usually relying on a single assess-
ment. Requiring subjects to reconstruct more detailed smoking histories can be very
demanding. Nevertheless, simply classifying individuals as former smokers or current
srnl  i reveals very little about the amount of smoking exposure experienced. More
pen. .Lnt questions regarding exposure include "How) long have you been abstinent
from cigarettes`?`: "At what age did you start smoking`?": "How many cigarettes did
you smoke during different periods of your life'?": "How many times did you stop
smoking'?"; and "How long did you remain abstinent during each of these occasions'?"
A series of repeated assessments can result in inconsistencies such as some in-

dividuals reporting smoking at one assessment and later reporting that they never
smoked. In a followup study in England. for example, Britten (198X) found 1.296
participants aged 36 who claimed that they had never smoked. Of these. 232 ( IX.7
percent) previously had reported smoking less than I cigarette per day, and 102 (7.9
percent) previously had reported smoking at least I cigarette per day for at least I year.
Of the 102 who reported previously that they had been regular smokers, 93 percent
reported that the last time they had smoked was at least IO years prior to the survey.

If the Britten study had used only one retrospective assessment of the subjects at age
36.323 percent of the 1,296 subjects would have been classified as never smokers and
32.6 percent as former smokers. Assuming that reports at a young age were more
accurate because memory bias was less likely to occur, the serial assessment indicates
that a more accurate categorization would be 29. I percent for never smokers and 36.5
percent for former smokers. Britten (1988) estimated that misclassification of this
magnitude, when applied to a study by Friedman and colleagues ( 1979). would result
in only a S-percent increase from 2.41 to 2.53 in relative risks of death for former
smokers compared with never smokers.

Krall and colleagues ( 1989) found that of 87 middle-aged adults. X7 percent accurate-
ly recalled their smoking status of 20 years earlier. but only 71 percent accurately
recalled the amount that they had smoked. Furthermore. underestimation of the amount

-77


smoked was tu ice as common for 20 years earlier ( I7 vs. 9 percent) and six times more
common for 32 years previously (37 vs. 6 percent). Persson and Norell (1989) found
that in a random sample of 9.394 individuals in Sweden. retrospective information
obtained 6 years later resulted in a strong tendency to overestimate previous cigarette
consumption among individuals who had increased their smoking (69 percent over-
estimated) and to underestimate among individuals who had decreased their smoking
(39 percent underestimated). Subjects with unchanged cigarette consumption showed
the highest levels of agreement (X9 percent) between original and retrospective infor-
mation. Rather than reconstructing full smoking cessation histories that are subject to
biased reporting. many retrospective studies rely on more limited categorization such
as never. former, and current smokers.

Retrospective studies enable researchers to assess long periods of smoking abstinence
without the need to observe the subjects over a long period of time. as would be
necessary in prospective studies. Case+zontrol studies. for example. can compare cases
with smoking-related diseases with controls with histories of being abstinent for IO to
20 years: in a prospective study. it may be impractical or impossible to study health
consequences of cessation with more than IO to 20 years of abstinence (Chapter 2. Part
II).

Prospective studies have the potential for more reliable and valid measures of
smoking status over time. especially when using a series of assessments, than do
retrospective studies. In intervention trials, for example. all subjects enter the trial as
current smokers. Following intensive intervention. subjects are identified as continuing
smokers or former smokers (abstinent). By assessing subjects at specified intervals
such as every 1 or 6 month\ over a series of years. especially when paired with
biochemical verification (Chapter _. ' see section on Biochemical Markers). researchers
can reduce the measurement bias and he more confident in the reliability and validity
of measures classifying continuing and former smokers and specifying length of
abstinence for former smohers. In MRFIT (Ockene et al. 1990) for example. a series
of4month followups over 6 year\ enabled researchers toclassify participants into three
categories: persistent quitters (continuous abstainers since the initial intervention).
intermittent quitters (abstinent for periods of time since the initial intervention). and
continuous smoherx (not abstinent during any of the followup periods). Such precision
in measurement is generally not possible or necessary in epidemiologic studies.

Prospective stud& may use 3 single assessment to categorize current. former. and
never smokers. These studies then prospectively, examine the categories to detect
differential rates of morbidity~ and mortality.. As discussed above. the assumption that
individuals vvill not change their smoking status maybe a tlavv, with \uch single
as\es\ments.

Improving Self-Report Measures

Ideally. assessments of smoking statu\ need to include standardized questions to
determine smoking status. that is never. current. and former smokers. For example. to
be categorized as a never smoker. the necessary response bould be "no" to a standard
question such as. "Have you ever \mohed at least I cigarette per day for at least I year?"

28


Whenever possible. questions should be used that allow continuous rather than
dichotomous scales for rejpon$e. A question such as "Do you smoke regularly?" results
in a dichotomous response scale. This scale provides much less information than does
a continuous scale. such as the question. "On the average. how many cigarettes do you
smoke per day`?" which can range from 0 to 20. 40. 60. or more. Multiple questions
such as. `* Have you smoked even a puff of a cigarette in the past 7 days?": "How many
cigarette% do you typically smoke each da),`?": and "How many cigarettes do you
typically smohc each weeh'l" can be used to refine a category such as current smokers.
Inclusion of other indices. such as biochemical markers of smoking (e.g.. sali\,acotinine
levels). can also be used to describe smoking statu\.

In a followup study. measures of smoking status optimally should be repeated over
multiple occasions. especially for dynamic categories lihe current smokers and former
smokers. which are open to change over time. Repeated measure\ over a series of
occasions provide further reliability and validity for assessments and alw provide
greater statistical power for detectin g differences betueen groups.  Nevertheless.
studies with only a single or a few assessments of smohing behavior have been
extremely informative.

Alternative BehaGral Measures

As a measure of smoking, self-report by questionnaires and interviews is the most
common. the least expensive. the easiest to use. and the most feasible in epidemiologic
studies (Frederiksen. Martin. Webster lY7Y: Pechacek. Fox et al. 1983). However.
other behavioral measures have also been used in clinical studies. Because these
measures are generally not used in large-scale epidemiologic studies. they w*ill be
presented only briefly m this Chapter.

Self-monitoring by the smoker. a measure of smoking commonly used in intervention
studies. involves recording by paper. pencil. and mechanical counters each cigarette as
it is smoked. The monitoring itself may be a reactive measure and alter the behavior.
depending on the nature of the monitored behavior and motivation (Abrams and Wilson
1979: Frederiksen. Martin. Webster 1979; Lipinski et al. 1973: McFall 1978: Orlean\
and Shipley 1982). It is an intrusive measure that is normally restricted to small \tudie\
of high intensity. Other behavioral measures, such as direct observation. collecting and
counting cigarette butts (McFall lY78). and measurin f their length (Auger. Wright.
Simpson 1979). are even more costly and intrusive and less appropriate for
epidemiologic and large intervention studies.

Alternative types of behavioral reports for validation of smoking status include
verification by an informant (Shipley I981 J. by self-report measure\ tising multiple
questions about smoking behavior or status as part of the same interview or question-
naire (see above). and by samplin 2 on multiple occasion\. Examples of the latter
usually involve long periods of time and often rc\ult in multiple sources of di\-
crepancy. (See Lee I9XX for summary.)


Surrogate Assessments

In some circumstances researchers may need to obtain information from sources other
than the index subjects. With some study designs, for example a case<ontrol study of
lung cancer, some subjects are unavailable to answ'er questions because of illness or
death. In cohort studies. or intervention studies with mortality endpoints, surrogate
interviews are sometimes required to assess smoking during the interval preceding
death.
Failure to obtain surrogate reports can cause considerable bias in some instances. In
a case+ontrol study of oral cancer. Greenberg and coworkers ( 19X6) obtained inter-
views with I I2 cases (67.9 percent) and surrogate reports for 23 cases ( 13.9 percent).
Cases needing surrogate report3 had more advanced stages of disease at the time of
diagnosis and were more likely to be black and less educated than cases interviewed in
person. Cigarette smoking and drinking hard liquor were more common among these
cases. Therefore, failure to include surrogate reports would have resulted in under-
estimates of the strength of association between cigarette exposure and hard liquor and
the risk of oropharyngeat cancer.
Pickle. Brown and Blot (1983) found that siblings of index subjects provided the
most complete data about smoking in the subject's family of origin and early life events.
Spouses and offspring supplied the most complete data about smoking history during
adult life. Incomplete data generally increased with the amount of detail requested. so
that there were considerably higher nonresponse rate\ for a detailed smoking history
(approximately SO percent) than for the history of a broad smoking status. such as never
smoker (approximately IS percent). Surrogates beyond a spouse or close relative
prov,ided much higher nonresponse rates for almost all questions in all statuses.
McLaughlin and colleagues ( 19X7) examined the reliability of retrospective surrogate
reports obtained IO years after initial reports and compared these with retrospective
self-reports using data from the NHANES-I (Cornoni-Huntley et al. 19X3). Correct
identification of previous smoking status was generally provided by most types of
surrogates. except siblings of male decedents. The combined level of agreement for all
surrogates ranged from X5 to 95 percent and was remarhably similar to that from
self-reports of living subjects. Thirty-five percent of the surrogates could not provide
data on when smoking began compared with I percent in self-reports. Surrogates who
responded tended to provide a later age for starting. Surrogates did. however, provide
estimates of years smoked that vvere comparable to the original reports. In this study.
siblings and other surrogates provided less reliable report\ than spouses. offspring. or
parents of subjects.
Lerchen and Samet (19X6) interviewed widow\ of lung cancer patients who had
supplied theirow>n smoking histories vvhile alive. They found that of 77 uiv,es of current
smokers, all supplied information about the cases' cigarette smoking status (ever/never)
that was in perfect agreement with the information supplied by the cases themselves.
Sixty-six (X6 percent) w'ere able to supply complete responses about their husbands'
smoking behavior. For those who responded. however. mean values reported by cases
and their wives were not significantly different for age at which cases started smoking.
years smoked. or average number of cigarettes smoked per day. Wives tended to report


20 cigarettes smoked daily even when their husbands smoked substantially more or
fess. Pershagen and Axelson (1982) also reported perfect agreement regarding
smoker/nonsmoker status when information was obtained from a close relative (parent.
wife. or child) for I4 lung cancer cases compared with information that had previously
been obtained from the cases by the physician. Blot. Akiba. and Kato (19X4) also
interviewed next of kin in a case<ontrol study of lung cancer among atomic bomb
survivors who had previously provided information regarding their own smoking
behavior while they were alive.  The investigators found that only I percent of
surrogates reported that a subject had never been a smoker while the subject reported
that he or she had smoked. suggesting that the identification of never smokers by next
of kin is very accurate. There was poorer agreement regarding those who smoked. with
I3 percent of surrogates indicating that a subject had smoked while the sub.ject had
reported never smoking.

Sandler and Shore (1986) examined the quality of data provided by adult offspring
on parents' smoking and drinking. The data were from 5 IX cancer cases and 5 IX
healthy controls aged IS to 59. When possible, mothers provided data on their own
smoking and their husbands' smoking. Of 9X2 subjects who had lived with their natural
mother, 97 percent provided data on their mothers' smoking status. Of those whose
mothers reported never having smoked cigarettes , 2.7 percent were reported as ever
having smoked by the adult child. Of those mothers who reported ever having smoked.
8.8 percent were reported as never smokers. Of those fathers reported by the mother
as never smokers, 17.2 percent were reported by subject5 as ever smokers. Of those
fathers reported as ever having smoked cigarette\ . 2 I. I percent were reported as never
smokers by their adult children. Even with the quantity of cigarettes collapsed into
categories to include answers of less than I pack, I pack. and more than I pack. the
proportion of mothers and subjects whose responses exactly agreed was X2.0 percent
for mothers and 49.2 percent for fathers.

Humble, Samet. and Skipper (1984) interviewed 46 subject-spouse pairs, waith 2
people in each of 38 of these pairs acting as the subject and as a surrogate for his/her
spouse, thus producing X4 total subject-surrogate pair\. For the 30 current or previous
cigarette smokers whose spouses gave complete smoking data regarding the subjects.
the subjects reported a mean use of 17.8 cigarettes per day compared wjith 14.3 reported
by their spouses. The difference was not significant.

Investigations indicate that useful information on smoking can be obtained in
epidemiologic investi&ations that must rely on surrogate information (McLaughlin et
al. 1987). Although greater misclassification occurs wshen surrogate reports are used
compared with self-reports. consideration of variables \uch as the relationship of the
informant, length of time he or she had known the case. the topic of the questions. and
complexity of the data gathered from the informant can add to the validity of the data
(Roget and Reid I975 ).

Nonbehavioral Measures

Methods other than self-report have been used to assess smohing status. Some
researchers have cxprecsed concern that sell`-report Ls hen used alone can bc an 111.


accurate measure that underestimates the amount of cigarettes smoked (Haley and
Hoffmann 1985: Marsh et al. 19Xx; Warner 197X) because subjects often underreport
levels of cigarette consumption or misrepresent themselves as former smokers (Luepker
et al. 19X9: Murray and Perry 19X7: Windsor and Orleans 19X6; Russell 19X2: Stookey
et al. 1987). Underreporting also has been linked to "digit bias." that is. subjects tend
to report in terms of multiples of ten and underestimate actual consumption (Pechacek.
Fox et al. 19X3; Vogt 1977: US DHHS 1989).

Between 1974 and 1985. estimates of U.S. cigarette consumption based on \elf-report
accounted for only about 70 percent of consumption estimates based on cigarettes taxed
and sold (Hatziandreu et al. 1989). This ratio has remained relatively stable. Most of
this discrepancy is lihely to be due to underreporting or a "rounding down" to the nearest
multiple of a half-pack of daily cigarette consumption (Kozlowski 19X6). although
misreporting of smoking status may play a role as well.

Validation of self-reports with measures such as biochemical assessments represents
a possible means of decreasing misclassification due to misreporting (Luepker et al.
1989: Windsor and Orleans 1986). However. some researchers note that biochemical
validation techniques present different problems that also cause misclassification. thus
favoring the use of self-report (Assaf et al. 1989: Crossen. Dougher. Belew 1983:
Hansen, Malotte. Fielding 1985; Hatziandreu et al. 19X9: Kornitzer et al. 19X3: Petitti.
Friedman. Kahn 19X I ). As noted above. sensitivity and specificity of the biochemical
measures are not perfect. In addition. the procurement of biochemical measures from
a large majority of self-reported quitters is not as feasible in large-scale interv,ention
trials or observational studies as it is in smoking studies of a smaller scale and a more
clinical nature. Subjects in the population samples do not have the same commitment
to studies that volunteers have to clinical studies. and the former are more likely to leave
the study area. which makes validation difbcult (Ockene et al. 1989). Validation aI40
requires more personal contact than is generally employed in observational or large-
scale field studies, and the additional contact may not be acceptable to the subjects or
feasible in the context of the study.

The section below on physiologic measures discusses methods other than behavioral
measures that have been used to a\ses'r cigarette smoke exposure. These measures are
then contrasted with self-report. and the varying needs for biochemical measurement
among different populations are considered.

Physiologic Measures

Smohing behavior has been assessed by measuring physiologic changes that result
from smoking (Pechacek. Fox et al. 19X-4). Smohing and smohe exposure are reflected
in a variety of acute and chronic physiologic measure\ primaril) because of the strong
pharmacologic effects of nicotine. These effects include changes in heart rate. blood
pressure. hand tremor. and skin temperature.  Each of these measures has a wide
variability under normal conditions and is affected hy man\ factor\ other than smohin~.
thu\ limiting usefulness ;I\ a measure ofsmohing (Pechaceh. Fo\ ct al. 19X1).

32


Biochemical Markers

Cigarette smoke i\ a complex mixture of chemicals. some of w hich are present in the
tobacco leaf and some of v. hich result from chemical reactions during either the curing
procec\ or smoking (US DHEW 1979: US DHHS 1986. 1989). Three chemical
constituents of tobacco smohe, carbon monoxide (CO). hydrogen qanide (HCN). and
nicotine. pass through cigarette filters and are pre\ent in inhaled tobacco smoke in
concentrations high enough to be absorbed and detected in persons who smoke. These
chemicals are measurable as intact compounds or as metabolic products.

Exposure to CO can be assessed in the blood a\ carbo\yhemoglobin (COHb) or as
CO in expired alveolar air. Method\ are a\,ailable for measuring cotinine. the primary
metabolite of nicotine, and SCN-. a metabolite of HCN. in urine. blood, and za1ib.a.
Other measures. such as skin+urface sampling for nicotine (Naliji and Lawrence 19X8)
are not as well established.

Extensive review\ of the literature on the use of biochemical markers as measures of
smoking status are provided by Bcnowit/ ( 1983). Haley and colleague\ ( 1986). Lee
( 198X). Pechacek, Fox. and colleagues ( 1981). and Windsor and Orlean\ ( 19X6).
Cummings and Richard ( 198X) supplied a review ofoptimal cutoffs for the biochemical
measures discussed here. This Section i\ not intended to provide an indepth review of
the variability and biochemical rationale for these meajure5 and will only provide an
overview of the use of biochemical assessments for smoking status.

Terminology

Sensitivity and specificity. characteristics of a test such as a biochemical assessment.
are measures of validity, the extent to which the test measures truth (Fletcher. Fletcher.
Wagner 1987). Typically. sensitivity and specificity are determined by comparing the
test results against a reference or "gold" standard. For smoking. self-reported status
has most often been used as the standard for assessing biochemical markers. The
sensitivity of a biochemical test for smoking exposure is the proportion oftrue smokers
who are classified as smokers by the biochemical test. The specificity of a biochemical
test for smoking exposure is the proportion of true nonsmokers who are classified as
nonsmokers by the biochemical test. A test of 100-percent sensitivity and lo(-percent
specificity would perfectly discriminate true smokers from true nonsmokers. However.
this degree of validity is not reached by any presently available biochemical marker.
In addition, the standard to which biochemical measures are compared. typically
self-reported smoking statu\. may be of limited validity. and thereby cause apparent
sensitivity and specificity to be reduced.

When continuous measures are used to test for smoking status. a cutpoint must be
chosen such that those individuals whose test value exceed\ the cutpoint are classified
as smokers and those with values below the cutpoint are classified as nonsmokers
(Cummings and Richard 198X). The level at which the cutpoint is set determines the
sensitivity and specificity of the test. Lowering the cutpoint improves the sensitivity
at the expense of specificity. Raising it will improve specificity at the expense of
sensitivity (Cole and Morrison 1980; Browner. NewJman. Cummings 198X). Selecting


a cutpoint depends on the relative importance of mislabeling an actual smoker as a
nonsmoker with a very insensitive but specific test versus mislabeling an actual
nonsmoker as a smoker with a very sensitive but nonspecific test. This tradeoff between
sensitivity and specificity is discussed in more detail elsewhere (Fletcher. Fletcher.
Wagner 1987).

An important contextual issue concerns the validity with which the biochemical
measure classifies individuals. When the test is applied to a population of smokers and
nonsmokers. the proportion of the persons who test positive. that is. above the specified
cutpoint. who are actually smokers becomes an important concern. This issue. distinct
from the question of w/hat proportion of smokers are above the cutpoint. is the crucial
measure of how much misclassification occurs. This proportion. the positive predictiv{e
value of a test, depends not only on specificity and sensitivity but also on the prevalence
of the condition in the population being tested (smoking in this example). The less
prevalent smoking is in the screened population the lower the positive predictive value
of a test (Browner. Newman. Cummings 198X).

The relative misclassification rates for smoker\ and nonsmokers. determined in part
by the estimated prevalence of smoking in the population to which the cutpoints are
applied, are particularly important in studies which use biochemical tests to verify
self-reported smoking cessation (Cummings and Richard 1988; Ruth and Neaton. in
press). For example. the pressure to quit smoking that is present in formal smoking
cessation programs may result in a high proportion of continuing smokers who report
not smoking. The use of cotinine validation in such circumstances (high prevalence of
false reporting) result\ in a high positive predictiv,e v*alue, as opposed to the lower
positive predictive value when the $ame test is applied to self-reported former smokers
identified in a population-based survey (low prev)alence of false reporting).

In biochemical validation studies. such as those reported in a subsequent section of
this Chapter. after optimal cutpoints are set using \elf-report in one population as the
gold standard. the biochemical marker then becomes the gold standard against which
self-reported smoking status is measured in another population.

Carbon Monoxide

High concentrations of CO are present in cigarette smoke (US DHEW 1979: US
DHHS 1986. 1989). Absorbed rapidly into the bloodstream during smoke inhalation.
CO has a half-life of-t to 5 hours in sedentary adults (Stewart 1975). Direct measure-
ments of CO can be taken from exhaled alveolar air or estimated by measuring the
percentage of hemoglobin combined with CO (COHb) (Stewart 1975).

Sensitivity of exhaled CO for classifying active smoking is generally in the range of
80 to 85 percent but can be affected by diurnal variability as well as other factors
(Benowitz 1983). Given the short half-life of CO. levels are influenced by time of day
and time elapsed since last cigarette. Measurements tahen late in the day, standardized
from time since last cigarette. are likely to give the best estimates of CO levels
(Frederiksen and Martin 1979: Horan, Hackett, Linberg 1978: Hughes. Frederiksen.
Frazier 1976). Using self-report of recency of smoking can increase sensitivity
(Bauman. Koch. Bryan 1983). Sensitivity is poor for light smokers (Fortmann et al.

34


1984: Vogt 1982). and specificity can be reduced by exposure to CO present in the
environment as a result of industrial and automobile pollution, environmental tobacco
smoke, indoor combustion sources. and use of products such as marijuana (Biglan et
al. 1985: Frederiksen and Martin 1979; Stewart 197.5). In spite of this. only 2 to 5
percent of nonsmokers in general populations will exceed I percent COHb (Janzon et
al. I98 I ; Kahn et al. 1974). tising COHb levels from a national probability sample.
the Radford and Drizd (1982) reported the 95th percentile for COHb to be I .77 percent
in nonsmokers, aged I2 to 74. If a 2-percent cutpoint is applied to this sample. 3.6
percent of nonsmokers would be incorrectly classified as smokers.

Thiocyanate

High concentrations of HCN. a toxic gas. are present in cigarette smoke. HowevJer.
HCN is very active chemically and is rapidly detoxified by the liver into SCN-(Langer
and Greer 1977: Boxer and Rickards 1952). Because SCN-accumulates in body fluids.
such as saliva. urine, and blood, it is used as a biochemical measure of exposure to
tobacco smoke. The biologic half-life of SCN- has been found to vary quite a bit (Bliss
and O'Connell 1984) although the length of time usually noted is between IO and I4
days (Langer and Greer 1977; Vesey 1981). Salivary SCN- can be measured most
reliably in parotid gland secretions (Shannon. Suddick. Dowd 1974): however. parotid
gland secretions show some seasonal and diurnal variability (Shannon. Suddick. Dowd
1974). When serum and saliva samples are compared, the levels are IS to 20 times
higher in saliva than serum (Langerand Greer 1977; Pechaceh et al. 1979: Vesey I98 I ).
However, saliva levels are more variable (Pechacek et al. 1979).

The increment of SCN- in light smoker5 is low, and there is much overlap of SCN-
levels in light smokers compared with nonsmokers (Fortmann et al. 1983: Neaton et al.
I98 1; Vesey et al. I98 I ). However. detection of light smoking in adults using SCN-
levels is better than in adolescents (Windsor et al. 1985). This is likely to be related to
the fact that adolescents are often in the process of learning how to smoke and inhale.
and they may not have an established pattern of smoking (Pechaceh. Murray et al. 19X-t).
For example. among younger adolescents only one-third or less could be identified on
a single assessment (Hunter, Webber, Berenson 1980: Luepker et al. 1989: Pechacek.
Murray et al. 1984). Specificity represents a more severe problem than sensitivity. A
large number of food products are sources of either cyanogenic giycosides (e.g..
almonds, bamboo shoots, sugar cane) or naturally occurring SCN- (e.g.. caulitlow~er.
broccoli, beer) and can produce levels of SCN- in saliva equivalent to the average levnels
of smokers (Langer and Greer 1977: Neaton et al. 19X I; Pechacek et al. 1979: Swan et
al. 1985).

The relatively low specificity and sensitivity of SCN- testing compared with cotinine
and CO make SCN- a less useful outcome measure for smoking cessation studies
(Gillies et al. 1982; Fortmann et al. 1984) unless adjustments are made using carefully
collected dietary and environmental exposure data. A prime advantage of using SCN-
for biochemical validation of smoking abstinence is its long half-life compared with
other biochemical measures (Fortmann et al. 1984; Steinman 1985; Murray et al. 1987;


Pechacek. Fox et al. 19X1). \vhich i\ of particular interest in population surveys where
longer term ub5tinence i5 of concern.

Cotinine

Cotinine. a metabolic byproduct of nicotine. i\ distributed throughout extracellular
fluid and is excreted through the kidnqs and salivary gland\ (Benowitz 19X?). About
15 to 20 percent is eliminated in the urine unchunsed. and the re\t is metabolized
(Benowitz 1983). The half-life estimates ofcotinine are variable and range from IS to
30 hours (Carey and Abram\ IYXX: Knight et al. 19X5: Greenberg et al. 19X-l: Haley
and Hoffmann 19X5: Haley et al. 19X7: Scpkovic. Haley. Hoffmann 19X6). The
differences in estimated half-life for cotinine reflect not only individual difference\ in
metabolism but also difference5 between \mohers and nonsmohers (Haley. Sepkovic.
Hoffmann 19X9: Sepkovic. Haley, Hoffmann I YX6: Hale} et al. I Y87). Cotinine le\ cls
vary with the diurnal cycle and are best asse\\ed late in the day (Benowitz 19X.3).
Methods are available for measuring cotinine in saliva. urine. and blood. Urinary le\,els
have been suggested to be too variable (Pechacek. Fok et al. 1981). and plasma or herum
levels appear to be the most hpable (Benou itz I983 ). However. sampling saliva because
of ease of procurement and accuracy in classifying smoker\ and nonamohers ha been
recommended as a useful. noninvasive method that can be applied to large-zcale
intervention trials (Abrams et al. 19x7).

Because nicotine is unique to tobacco. cotinine is a highly valid marker for almost
any tobacco use (Haley. Axelrad. Tilton 19X3: Rus~ttll et al. 19x1: Wald et al. 19X1:
Zeidenberg et al. 1977). Although nicotine has been aaessed in home studies. it is
recommended that cotinine be used because it ha\ a more enduring and stable blood
level (Langone. Gjika. Van Vunaki\ IY73). Detecting regular smoher\ by analysis of
cotinine in blood. urine. or saliva ih almost certain. and even light smokers and
intermittent smoker5 are caily detected (Benowitf lYX3: Haley. Axelrad. Tilton 19X3:
Paxton and Bernacca 1979: Zcidenberg et al. 1977: Carey and Ahrams IYXX: Williams
et al. 1979). In one investigation. Y5 percent ofadole~cent e\er smokers were detected
by cotinine (William\ et al. lY7Y). Specificity i\ al\o high: regular smokers typicall!
have blood cotinine levels of 200 to 100 ng/mL. light smoker\ have -IO to 50 ngiml.
and nonsmokers are typicsll>, helo\{ IO ng/mL. When nonmohers are aaeshed. the\
rarely have any detectable cotininc' (Benowit~ IYXi: Hale!. Axelrad. Tilton IYX3:
Sepkovic and Hale) IYX.5: Zeidenbers et al. 19771.

In comparative studieb of different biochemical measures of smoking. cotinine ha3
emerged a$ the measure of choice (Abram\ et al. lYX7: Hale). .4xelrad. Tilton 19X3:
Jarvis et al. IYX-I. 19X7: Knight et al. 19X5: Pojer et al. 1YX-l) because of itz superior
senGtivity and specificit!.  However. it i\ more expensive and more analytically
complex than the other biochemical measure\.

The value of biochemical meaures is limited to short-term abstinence and cannot be
used to document continuous abstinence in long-term \tudie\. CO. with a half-life of
3 to 5 hours. can validate self-reports of not having smoked in the pact 23 to 3X hour>
(Benowitz 19x3). Cotinine. with a half-life of I5 to 40 hours. would have limited
application for validation beyond a few day\. SCN-. ivith a half-life of 10 to l-1 day\.

36


has been used to validate self-reports of not having smoked in the past 7 days and may
be useful to validate up to 3 to 4 weeks. However. specificity of this measure is low
compared with cotinine and CO.

Bogus Pipeline

The bogus pipeline, an assertion to subjects that biochemical assessments will be used
to assess smoking status when they will actually only be collected but not evaluated. is
used mostly in research with adolescents. One of the reasons given by researchers for
continuing to use biochemical verification for at least some proportion of the total
subjects is the assertion that if the subjects believ,e biochemical validation will occur.
they will be more likely to provide valid responses to self-report measures. This "bogus
pipeline effect" was first presented by Evans. Hansen. and Mittelmark ( 1977) from the
work of Jones and Sigall ( I97 I ) concerning smoking among adolescents. It is believed
that there is great pressure among adolescents to misreport smoking activities, Murray
and coworkers ( 1987) provided an estensiv#e review of this aspect.

Murray and Perry (1987) attempted to determine the conditions under which a bogus
pipeline will be effective by manipulating conditions ofanonymity. They demonstrated
that a bogus pipeline for adolescents is more likely to have an effect if there is an
expectation that subjects would otherwise perceive large amounts of pressure to report
not smoking and there is a credible pipeline message. However, their findings suggest
that an effective procedure to ensure anonymity can reduce this pressure and likewise
reduce the need for the pipeline.

Contextual Issues Affecting Biochemical Assessment

The accuracy of self-report measures, the desirability for behavioral or biochemical
validation of self-report. and the type of assessment needed are issues that need to be
considered in the context of the type of study. the nature and size of the study sample.
and possible refusal problems.

The nature of the subject sample can affect the likelihood of misreporting and
therefore the desirability of validation by biochemical assessment. In Table I. studies
demonstrating misreporting rates for individuals who report cessation but who are
assessed to be smokers by cotinine or nicotine measurement are classified into three
types of subjects: untreated volunteer samples. intervention samples, and high-risk for
disease and/or medical patients. Table 2 presents a similar classification of studies
demonstrating misreporting with CO validation. The tables are adapted from Lee's
work (1988) with the inclusion of additional studies. In cases where multiple cutoff
criteria are recorded, the values closest to the optimal cutoff are reported. Several
studies should be viewed as outliers and are noted in the tables,. These studies reported
unusually high rates of individuals who reported not smoking but were above the
cutpoint and also employed cutoff criteria far below optimum cutpoints (Cummings
and Richard 198X).

For untreated volunteer samples. the mode for individuals classified as smokers by
biochemical assessment who reported not smoking is zero, and no sample exceeds 5

37


TABLE I.-Measures of false reports of not smoking from studies using nicotine and cotinine as a marker

Wllll;nrl\ 1'1 d
I lY7Y 1

H;tlcy. AxclwJ.
TlllWl ( IYX3)

WaltI c, aI , I YXJ)

Nm )l und
l.a&ncc ( I'JXX)

I'icrce cl ill. ( I YX7 J

0 (O/27)

2 (2/0X)



0 (O/IX)



0.`) (2/Z I )



I .3 ty2.32,
2.1 (S/2.32,


2.2 (33/1,?60)



2.5 (20/X0X,
1.2 (34/X()X)

0 (O/43,


1.0(3/h?.!)


TABLE I.--Continued

Kwwll et al
c I')X7?

Stoohq 111 al.
,19X7)

Saltvary nIcoIine           7.1 (l/13)

Ilrtnary nlcotme           II=?. N<hO

3x.x ,57/l-17,


TABLE l.--Continued

No
No
No
No
No
No

tladdwv et al. (IYX7)    IJS pr~&!n;ltlt w,11111'11               No

:! pg/l(H) mL urinary nicotine or
10 pg/loO tnL urinary cotininc

13.7 ng/tnl. wum cot inine
14.2 ng/mL. uliv;tt-y cotitliw
397 ng/mL urinary cotinint'
21 .X ng/mL allvary ntcotine
7.3 ng/niL plnw~;i nicotine
5X.6 ng/tnL urtnary nlcotiw
IO ng/tnL wrum


TABLE 2.-Measures of false reports from studies using CO as a marker

No

NV

NU       IO ppm CO (cxpirctl atr)
No        l.7fh CO(llh)

No

6 ppm CO (eupiraI air)
X ppm CO (c\pved air)

x ppn1

YLY

No

YC\

x ppm CO

x ppn1

2'4 COHh
-lo; (`OHh
W/r (`Otlh

% (n/N)
False report\

Comments

1.x ( I/Z1 )

Ih(lY/l2l)
lXCl2/l'l,

0
3

0 (O/?O)

4.2 (37/XYO,

7o.ht22/1(17)
(J.3 t lO/lO7~
1.7 t51107r


TABLE 2--Continued

M:tlct,ln1 1`1 a.
( 19x0)" h

Ra\r et al. ( 19X0)

YC\

O.X'd (`OHh

I% (`OHh

(`0

I .h'i (`OHh

(`0 or (`OHh

(`0

YL%        (`0 0, (`()I Ill

x.x ( v3.l I

0(0/33,

I3ct \* cc`,,
I .-I ( 117-l) ;md
4 7 I l/Z-l,

0 (O/X)


TABLE 2.--Continued

    Popul;ttion

1JK \moker\ nttendmg fetwrd
practitioners

US worhde 5moktng control study

Jamrwth. Fan ler
et al. (Ic)X?)"

Clwel et al.
(I'w.5)



Land0 and
McGovern ( 19X.5 1

Richmond and
Wch\tt`r ( 10x5)

UK wwker\ in trial of nicotine gum

French trial of acupuncture and
nlcotinc gum


IJS whjcct\ undergotnp variou\
treatmcnta for rliminattn~ wlohinf

Au\traltan wioker\ in a general
practtce: mndomi/ed tnitl ot
rttect\ of advice to five up

Ahram\ et al.
lI9X7)

Worh\ite cessation

(;l>nn. Gruder.       Chicago Lung Awxxttion
Jqxr\hl ( I'MI       ce\\i111011 wiy

Part 111. titFh-rt\h/mc~lic;tl patient\

Told to      Criterion for titlw
pivz up    reports of not vllohirtg


Some group\    7 ppm co



  YC\       IO ppm (`0



  Ye\       I 2 ppm <Y 1



  Ye5       5 pptn(`0

Q (n/N)
False wport\


About 37



0 (O/J)


2x.0 (7/35)



0 (O/14,

Ye\

Te\t group

Ye\



Yt3

IO ppm CO (exp~retl ;ur)    15.ht7/45,

3-mo to I -yr followup

6.tno ti~llowup

Sample ot \tuJy
parttclp:tnt\tN=23):
I -yr followup

C!p to 2.mo fdlowup

Criteria not \tnted:
h-t110 follow~up


TABLE 2.--Continued


percent for either cotinine or CO. For intervention studies, values are typically 2 to 5
percent for cotinine and 0 to IO percent for CO. High risk/medical samples appear to
have the highest rates of misclassification of former smokers with the rates exceeding
20 percent. For example. as shown in Table I, Jarvis and colleagues ( lYX7) reported
very low rates ( I percent) of false reporting in vascular patients who were not advised
to quit compared with the rate in high-rish patients uho here advised to quit ( I7
percent). It is likely that the pressure to stop smoking influenced the accuracy of patient
reporting.
Observation studies in which no intervention occurs. or intervention studies in which
there is minimal intervention or interaction M ith smokers. are less lihely to prompt false
reports of smoking cessation than studies in which intensive inter\.ention does occur.
In the former types of studies. in which no or low-intensity inter\,ention occurred. there
was a much lower prevalence of subjects reporting a 2-l-hour quit attempt during the
past 6 months or current abstinence (Prochasha et al. lYX5) than in intensiLe interven-
tion studies. making misreporting less likely. A greater tendency to misreport in no or
low-intensity intervention studies might occur with adoleccents. for whom pressures to
report not smoking may be omnipresent (Pechsceh. Murray et al. 19X-I: Chapter 2. see
section on Bogus Pipeline). A similar pressure might occur in some other instances.
such as worksites in which a ban has been placed on smoking. where no intervention
occurs but there may still be pressure on individuals to misreport. However. no studies
have looked at the possibility of misreporting in such instances. The context in which
the study tahes place is likely to influence the degree of misreporting. Data currently
being collected from smoking cessation programs in a wide variety of contexts may
help to clarify this issue.
Clinic interventions and intensive interventions. on the other hand. typically ask
participants to set a quit date. Close relationships are developed with the counselors,
and self-reports of quitting are often given initially in a peer group. Under these higher
demand conditions. biochemical verification may be needed to decrease the mis-
reporting of current smokers as former smokers. For example. in MRFIT, special
intervention subjects claiming to be former smokers at followup examinations had mean
SCN- levels between those of never smokers and continuing smokers (Ockene et al.
1982). Similar discrepancies between reported and validated cessation rates did not
occur for the usual care men who had not received intensive intervention.
The use of biochemical tests for validating self-reports in epidemiologic studies has
a number of limitations. The tests do not have perfect sensitivity and specificity: their
half-lives do not necessarily fit the timeframe to be covered: and not all subjects are
willing to provide the necessary samples for assessment. A very sensitive test may
misclassify subjects as smohers if they have heavy passive smoke exposure (DiGuisto
and Eckhard 19%: Haddow. Palomaki. Knight lYX6: Haley et al. IYXY: Jarvis et al.
1985). smoke occasionally (i.e., I or 2 cigarettes on isolated occasions) (Williams et al.
1979). and/or use nicotine in some other form. such as nicotine polacrilex gum or
smoheless tobacco (Cohen et al. IYXX: Slattery et al. IYXY). Biochemical marhers are
also limited because they assess relatively short-term cessation (less than 2 weeks). and
in studies concerned with the impact of cessation on health. there is more interest in
evaluating consequences of long-term cessation.


In large-scale studies. use of biochemical assessments is generally not feasible; thus.
mandatory use of such assessments and subsequent classification of refusers as smokers
(as suggested by home investigators involved in clinical intervention studies e.g..
Windsor and Orleans 1986) would result in an unacceptable distortion of the outcome
data. In addition, some subjects may drop out if validation is required. The effect of
lost subjects on study results may be difficult to estimate. In contexts other than
intensive intervention trials. self-reported smoking status at the time of measurement
and concurrent biochemical assessment have been demonstrated to be highly concor-
dant (Fortmann et al. 1984: Petitti. Friedman, Kahn I98 I) (Tables I and 2). This high
concordance supports the use of self-report as a valid measure of smoking status in
observation studies of the health effects of smoking cessation.

PART 11. ASSESSING THE CONSEQUENCES OF SMOKING CESSATION

Study Designs Used to Assess the Consequences of Cessation

Overview of Study Design

Most evidence on the health benefits of smoking cessation derives from studies of
human populations and not from animal studies or other types of research. Research
on humans can be classified as experimental (the investigator assigns subjects to be
exposed or not exposed to the risk factors or preventive factors of interest) or observa-
tional (the investigator does not determine whether subjects are exposed or not exposed
to the factors of interest; exposure reflects the subjects' choices or some other process).
Intervention studies include randomized or nonrandomized community-based inves-
tigations and clinical trials. The clinical trial. involving randomization of subjects to
be exposed or not exposed to an intervention, has been used to investigate the effects
of smoking cessation in patient groups and in populations. The observational designs
include the ecologic study, the cross-sectional study. the cohort study. and the case-
control study.

The biases potentially affecting these studies can be broadly classified as selection
bias. information bias. and confounding bias (Table 3) (Kleinbaum. Kupper. Mor-
genstern IYE). Selection bias refers to distortion of an exposuredisease relationship
by the mechanism through which subjects are selected. Information bias arises from
the incorrect categorization of subjects as exposed or not exposed or as diseased or not
diseased. The resulting misclassification of subjects on exposure or disease status may
occur in a random or nonrandom fashion (Chapter 2. Part I ). Confounding bias refers
to the distortion of the apparent effect of an exposure on risk caused by association with
other factors that affect outcome (Last 1988). In the subsequent review of the study
designs used to assess the benefits of smoking cessation. sources of bias most relevant
to each design are highlighted.

46


TABLE 3.-Examples of potential methodologic problems in investigating the
     health consequences of smoking cessation

Con\equenceh

Current smoker\ developing symptom\ of
disease qutt smoking

Apparent benefn\ ofcr\\ation are reduced

Self-reported former smoker\ are actually
mohtng (information bia\)

Apparent benefit\ of ce\%ttw are reduced

Former \moher\ tend to have smoked less
than per\tstent smokers (confounding htah)

Fatlure to xxount for the dlfferencr ma)
exaggerate the appsrent benefit\ of
ceaation

Former smoker\ tend to have a healthier         Failure to account for the dlfferrnce ma!,
lIfestyle than persistent \moher> tconfoundmg      exaggerate the apparent benefit\ 01
hia\)                               ceaatmn

Smoking practtce\ and the presence of
smoking-related direases affect panicipntton
in btudtes (selection hias)

.4pperent benefit\ of cr\wtlon ma) hr
mcreawd or decrrawd

Small number of wbject\ in a stud)

A heneficlal effect ofcrsttion may not
reach sttisttcal stgntficancr

Ecologic Studies

Ecologic studies represent a descriptive approach for examining the relation between
risk factors and disease. Groups, rather than individuals, are the unit of analysis in
ecologic studies. For example, changes in lung cancer mortality rates for selected
countries have been examined for correlation with changes in measures of smoking for
those countries. such as the percentage of smokers or per capita cigarette consumption
(US PHS 1964; Cairns 1975: Cummings 1984; Doll and Peto I98 I ). Ecologic studies
often have the advantage of being performed inexpensively and feasibly by using
already available data. This design has well-described limitations related to the
estimation of exposure and control of confounding, and may yield seriously biased data
on exposuredisease relationships (Kleinbaum, Kupper, Morgenstern 1982: Rothman
1986).

Cross-Sectional Studies

In a cross-sectional or prevalence study, exposure and outcome are assessed at the
same point in time among individuals in a population. Because cross-sectional studies
measure exposure and outcome variables simultaneously. the true temporal relation
between exposure and disease may be obscured (Rothman 1986). However. cross-
sectional studies can be readily performed and have supplied much of the evidence on
smoking cessation and nonmalignant respiratory diseases (Chapter 7).

47


Cross-sectional studies may be affected by selection hia\. Because cigarette smoking
is a strong cause of disease and death. groups studied cross-sectionally may not
accurately reflect the natural history of smoking. smoking cessation. and the develop-
ment of smoking-related illness. The proportion of heav ier smokers and more suscep-
tible smokers may be reduced compared with the original birth cohorts giving rise to
the cross-sectional study population (McLaughlin et al. 1987). Former smokers who
stopped because ofthe development ofdisease may be underrepresented. whereas those
who stopped to reduce the rish of illness may be overrepresented.

Information bias is also of potential importance in cross-sectional studies. Pre-
existing conditions in survey participants may affect recall of past smoking or may alter
the approach used by interviewers to gather smoking information.  However. as
summarized in Tables I and 7. cross-sectional surveys generally demonstrate low rates
of misreporting of smoking status when compared with cotinine and CO levels.

As mentioned previously. a single observation on smohing behavior may lead to
misclassification of smokers because of the dynamic nature of smoking behavior.
Former smokers are typically a heterogeneous group with periods of abstinence ranging
from days to years. For example, in the 1986 Adult Use of Tobacco Survey (US DHHS
1989). the subjects' responses were classified in IO categories. -l of which included
former smokers. Of the former smokers. 12.5 percent had quit within the past 3 months.
7.X percent had quit in the past 3 to 12 months . 77.3 percent had quit in the past I to 5
years. and 57.4 percent had quit 5 or more y'ears earlier.

Cohort Studies

In a cohort study. the \ubjrcts are selected on the basis of exposure status (e.g..
smoking behavior) and observed for de\.elopment of disease. Observation may be
forward in time (prospective). backward in time (historical or retrospective). or both.
Correct conclusions can usually be made about the temporal relation between exposure
(smoking cessation) and outcome (reduction of morbidity, or mortality). With the
cohort design. multiple health outcomes can be considered simultaneously. For ex-
ample, the CPS-I and CPS-II conducted by the American Cancer Society (ACS)
examined the effect of smohing bells\ ior on total mortality and specific causes of death.

In a study of \mohing cessation. selection bias could affect the findings of cohort
studies if subjects lost to observation were more or less lihely to benefit from smoking
cessation than subjects remaining under observation (Greenland 1977). For inten,en-
tion studies and cohort studies. the rate of sub,ject loss provides an index of the potential
selection bias.

In a cohort study of smohin, 0 ccs\ation. some Ini\cla\zification of exposure may be
introduced if the classification of smoking status is based on a single assessment.
Although the categorization of smohing status may' be correct at the time the informa-
tion is collected. inevitably some former smoker\ will resume smoking and some
current smokers will stop. The extent of the resulting error will increase with the
duration of followup. The resulting misclassification will tend to underestimate the
effects of quitting because those who relapse to become current smoker\ would not be
expected to experience beneficial effects attributable to quitting.

48


For example. in ACS CPS-I involving nearly I million people. Hammond and
Garfinkel ( 1969) studied changes in smoking status over a Z-year period. Male former
cigarette smokers in 1959-60 who reported that they were smoking in 196142 varied
according to duration of prolonged abstinence reported in the lYS9-60 survey. For
respondents abstinent le5s than I year in 1959-W. 37.3 percent reported smoking 2
years later; of those reporting abstinence for I to 2 years. 19.1 percent were smohing :!
years later; and of those reporting abstinence of more than 2 years. 1.6 percent were
smoking 3 years later. For all males who were former smohers in 1959~60. I I .3
percent reported smoking 2 years later. For all female former smoker\ in 195Y-60. 6
percent reported smoking 2 vears later. In the U.S. Veterans Study (Roget and Murq
IYXO: Kahn 1966). male veterans itt a cohort of 23X.X16 were classified based on
responses to questionnaires administered in 1954 or in 1957 (if the 1951 questionnaire
was not returned) and then folloued for 16 years to determine the relationship betbeen
tobacco use and mortality. Undoubtedly, many of the original current smokers became
former smokers as a result of the strong trend of smoking cessation among U.S. males
durin_g the followup period (US DHHS lYX9).

Repeated assessment of smoking status in a cohort stud) can mitigate misclassifica-
tion due tochanges in smoking status over time (Chapter 2. Part I). Repeated measures
are often feasibly made in cohort studies to minimiLe the effects of misclassification.
Alternatively. validation substudies can be conducted within the cohort to quantify
misclassification errors (Greenland I9XX).

Case-Control Studies

Casexontrol studies involve selection of study suqjects based on the presence (cases)
or absence (controls) of a disease. Exposure and other attributes of cases and controls
(e.g.. smoking status or lifetime cigarette consumption) are then measured. The groups
are compared with respect to the proportion having the attribute of interest to calculate
the exposure odds ratio. which estimates the relative risk associated with exposure.
Case-control studies can generally be conducted in les\ time than cohort studies or
intervention studies and are less expensive to perform. Case+ontrol studies are well
suited for evaluation of disease\ with low incidence rates.

Case+zontrol analyses may be affected by information bias and selection bias.
Case+ontrol studies are prone to information bias if lifetime exposure histories are
collected by interview (Schlesselntan 19x21. Retrospective lifetime histories of smoh-
ing or other exposures obtained from ill or elderly sub.jecth may introduce misclassifica-
tion. SimilarI\.. studies that rel\, on reports from surrogate\ to assess smohing ma).
misclassify exposure. If individuals classified as cases recall more accurately or less
accurately than those classified as controls, differential misclassification result\ (Gordix
1982). Differential misclassification may also be introduced ifre\pondent~ deliberateI>
falsify answers or if interviewers differentialI> gather information from cases and
controls (interviewer bias): interviewer\ not blinded to case-control \tatu\ may probe
more intensely for a putative causal exposure in cases than in controls (Sachett I Y79).
Blinding is often not feasible. and meticulous attention must be directed to training
interviewers and to designing questionnaire\ to rcmovc the po\\ibilit!, of intervieuer


bias. Although selection bias may affect any case-control study that is not population
based. it is unlikely to be of particular importance in most casexontrol studies of
smoking cessation.

Intervention Trials

Intervention trials are designed to test a hypothesized cause-effect relationship or the
benefits of a preventive program by modifying the putative causal or preventive factor
and measuring the effect on relevant outcome measures. Intervention trials may be
directed at individuals or groups. such as communities. Regardless of the unit of
observation. the trials may be conducted wsith (e.g.. a clinical trial) or without ran-
domization to the intervention.

Clinical trials are most commonly used to assess therapeutic interventions. but this
design has also been used to evaluate preventive interv,entions. such as smoking
cessation. A clinical trial includes one or more comparison groups in which subjects
receive the control intervention: subjects are randomly assigned to the treatment and
comparison groups to ensure that the groups are comparable with respect to charuc-
teristics potentially affecting the outcomes of interest. Individuals or groups such as
communities can be the units of randomization. Within the limits of chance. random
assignment makes the intervention and control groups similar at the onset of study.

Although widely used to test smoking cessation methods. clinical trials have been
used infrequently to assess the health benefits of smokin, 0 cessation. In comparison
with observation studies. the clinical trial design offers the potential for eliminating or
more tightly controlling bias from the selection of subjects and from confounding.
However. for many health outcomes, both a large sample size and a lengthy followup
period may be needed to have sufficient statistical pow'er. Moreover. in a study of
smoking cessation. the power of the trial also depends on the extent of the reduction in
smoking in the intervention group. in comparison with the control group. In the
reported smoking intervention trials. only ;I minority of participants attained continuous
or prolonged abstinence following most cessation interventions (Hunt. Barnett. Branch
1971: Hunt and Bespalec lY73: Ockene et al. 1990). Even with intensiv,e. prolonged
inten entions. as in MRFIT. only 42 percent of smokers within the special intervention
group were not sntohing at h-scar follow up. and only 76 percent of baseline smobers
                     2
had been continuously abstinent from cigarettes over this prolonged period (Ockene et
al. IYYO).

Only a few clinical trials provide information relevant to the health benefits of
cessation (Chapter 3). In the Whitehall Civil Servants Study, (Rose et al. 19821. the
investigators randomly intervened in smoking with advice from a phy,sician in a group
of men at high rish for cardiopulmonary disease. In MRFIT. smoking intervention w'as
one component of the rish factor intervention program directed at the special interven-
tion group (MRFIT Research Group IYX3).

In tnost clinical trials that assess the effect of cessation on disease outcomes. such as
the Whitehall Civil Servants Study (Rose et al. 1982). the tn\,estigators did not monitor
longitudinally the persistence of quitting or levels of biochemical markers. The only
clinical trial that has provided these measures is MRFIT (Ochene et al. lY90). Although

SO



maintained cessation rates were significantly greater in the special intervention than in
the usual care group, to date the difference has not been large enough to provide
adequate statistical power to assess the effect of smoking cessation alone on differences
in morbidity and mortality between the intervention and control groups (Chapter 3).
However, MRFIT was designed as a multifactor trial and did not assess the impact of
smoking cessation alone. Because MRFIT results indicated the greatest difference in
smoking cessation between special intervention and usual care subjects compared with
any other clinical trial and still lacked the power to detect outcome differences from
smoking cessation. it is unlikely that smaller trials would have sufficient power to
demonstrate an effect of cessation on morbidity and mortality (Chapter 3) (US DHHS
198.3).

Compared with observational studies which place few demands directly on subjects.
the use of interventions for smoking cessation in clinical trials increases the probability
of misreporting smoking status at postintervention followup because of the expectations
of the participants and the investigators. Typical periodic followup in clinical trials.
however, reduces the chances of misclassification related to relapses or to delayed
action to quit smoking-phenomena that are often not adequately recorded in observa-
tional studies. Routine followup also allows for more accurate measurements of the
duration of prolonged or continuous abstinence and the opportunity to validate with
biochemical testing.

Intervention trials other than clinical trials also provide information on the health
consequences of smoking cessation. A number of studies are in progress involving
interventions of varying intensity within a community. The North Karelia project
conducted in Finland is such a community trial: a comprehensive, community-based
intervention program was conducted to reduce cardiovascular disease (CVD)
(Tuomilehto et al. 1986). Mortality rates in North Karelia were compared with those
in other areas of Finland.

Methodologic Issues

Introduction

Epidemiologic studies have been the principal source of information on the health
benefits of smoking cessation.  Although the resulting data have provided strong
evidence for the benefits of cessation, the data need to be interpreted with consideration
of potential sources of bias and of other methodologic issues. This Section considers
the methodologic issues potentially affecting interpretation of studies of the health
consequences of smoking ceshation. The criteria for causality have served as a basis
for evaluating all of the evidence relevant to a particular association (US PHS 1963:
US DHHS 1981. 1989). However. associations found in individual studies must also
be assessed carefully. In any epidemiologic or clinical study. association may result
by chance, as the result of bias. or through a causal mechanism. Thus. this Section
presents an overview of statistical considerations relevant to studies of smoking
cessation and the most prominent sources of bias in such studies-information bias and


confounding hia\. It also considers the potentially complex problem ofanal!~ing data
on the effects of smohing cessation.

Statistical Considerations

Statistical significance testing addresses the likelihood that an observed association
has occurred by chance if. in fact. exposure and disease are unassociated (the null
hypothesis). By convention. probability (p) L alues less than 0.05 are generally accepted
as "statistically significant"; that is. chance is considered an unlikely explanation for
the association. For example. if the p value is less than 0.05. the probability that chance
explains the association is less than 5 percent. Confidence intervals describe the range
of effects compatible with the data at some specified level of probability. for example
95 percent.

Some studies find associations that do not attain statistical significance. "Negative"
investigations must be interpreted in the context of an investigation's sample size: a
small sample size may not provide sufficient information to test associations in the
range of interest. Such small sample sizes often provide inadequate statistical power
to test for the anticipated effects of smoking cessation. and such studies are uninforma-
tive as a result. In interpreting associations not achieving statistical significance.
confidence limits describe the range of effect compatible with the data.

Bias

In an)' epidemiologic study. associations may be affected h> bias. Biases from
misclassification and from confounding need to he considered in interpreting the
findings of studies of the consequences of smoking cessation. This Section focuses on
the effects of these biases in studies of smohing cessation.

Categorizing the dynamic process ofsmohing cessation poses ;I substantial challenge
to epidemiologic researchers (Chapter 2. Part I ). hlorrovcr. subject<niq not accurateI>
report their o\\ n sniokin, 17 beha\,ior. and reliance on surrogate sources of information
on smohing. LIS ma\ bt~ nc:ccssar!. in casc`+control studIt`\. ma\ also introduce error.

The c~~scqucnces of misclassi~c~~tion in obser\ ation studies ha\,c recei\ 4 substall-
tialcon~ideratic,n in the rpidcmiolog~c litt'rature (Copeland et al. 1977: Greenland 19X0:
Fleiss 1% I: Klcinhaum. Kuppcr. I\lor~enstcrn 19X2: Schlc~sclman 19X7: Kothm;r~~
19X6). Misclassiticatiorl c;m oc`c~ir in classif! in; either e\pc)surc` or outcome. Onl!
exposure inisclllssific~ltic~il. that is smohing \t;ltus. will he considered in this Section
(Chapter 2, Part I ).

Miscl~!s\it`ic~ltiorl nl;~> be cla\sified ;I\ nondifferential (or random) or 215 differential:
both types of miscl~rssit'ic~ltion ;!I-e potentialI> relet ant to studies of \mohing cessation.
~0ndit`ferentiA misclasslfic~ition occurs r:uidonil\ In relation to disease or ourcome
status. \rhercas diffcrcntial iiiiscl3\sificati(,n al`fects exposure information in a pattern
that varies u ith outcome status.  For c\;unple, differential ini\classification \roulJ
occur in a case+control stud! of lung cancer if cast`s tended to minimize the extent of
past smohing in compari\on u ith the information 5 "ii en h\ controls: elderI\ cases and
                                          _


controls might introduce nondifferential misclassification from errors in recall of past
smoking.
The consequences of nondifferential and differential misclassification have been
addressed in the epidemiologic literature. Brass ( 1954) is credited with demonstrating
that random misclassification in a 2x2 contingency table diminishes an association that
exists between two variables: in general for such cross-classified data. nondifferential
misclassification of exposure biases toward the null value. indicating no effect of
eposure (Rothman 1986). For exposures classified into three or more levels. the
consequencs of nondifferential misclassification are not exclusively directed toward
reducing the degree of association. Differential misclassification may either strengthen
or weaken associations. depending on the direction of the bias in reporting exposure
(Kleinbaum, Kupper, Morgenstern 1982: Rothman 1986).
The information presented in prior sections of this Chapter describes the directions
that bias may take and allows some generalizations. First, some degree of nondifferen-
tial misclassification may affect studies of active smoking and of smohing cessation:
the extent of misclassification depends on the type of information collected. the choice
of respondents (index subject or surrogate). and the health and age of the respondents.
Second. because disease is present at the time of interview. nondifferential mis-
classification is particularly likely to affect exposure information collected in cross-
sectional studies and case<ontrol studies. but little empirical evidence is available.
Third, because of the dynamic nature of smohing cessation. some current and former
smokers will be misclassified in cohort studies and clinical trials unless smoking
behaviors are measured with sufficient frequency during followup.
For example. MRFIT data illustrate the potential for misclassification of current and
former smokers as smoking status changes over time if smoking status is not longi-
tudinally assessed (Ockene et al. 1990). The usual care group included 3.09 I smohers
at baseline with 13.7 percent reporting quitting by the first annual folloclup visit. Of
those first-year quitters. only about half or 6.3 percent of all usual care smokers
maintained abstinence for the entire &year followup period ("continued stoppers").
However in each year of followup. additional smohers quit ("new stoppers") at a
maximum rate of 7.5 percent between the first and second years. decreasing to the
lowest rate of 4.3, percent between the fifth and sixth years. Simultaneously. smokers
who quit and relapsed during the trial succeeded in quitting in subsequent followup
periods ("recycled stoppers"). Recycled stoppers increased from 5.3 percent of the
usual care baseline smokers in the third year to IS.3 percent at the end of the sixth year.
By the sixth year of the study. 25.X percent of the usual care group were classified as
former smokers: 6.3 percent stopped during the first year and maintained abstinence
for the remaining &year followup period: 15.3 percent stopped. relapsed. and stopped
again: and 4.2 percent stopped for the first time in the last year of followup. Although
the usual care group is not representative of adult malt smohers. these data illurtmte
the dynamics of smoking behavior and the potential for misclassification.
Incorrect categorization of some current smokers as former smokers and of some
former smokers as current smokers. if nondifferential. would tend to reduce the apparent
benefit of smoking cessation. as disease occurrence is reduced in the category of
apparent current smohers by the inclusion of former smokers and is increased in the


category of apparent former smokers by the inclusion of current smokers. Stratification
by the duration of abstinence may prov,ide some control of this type of misclassification,

The category of never smokers in an epidemiologic study may include some persons
who smoked in the past (Britten 1988: Persson and Norell 1%`)). In general. former
smokers who reported themselves as never smokers consumed fewer cigarettes than
those correctly categorizing themselves as former smokers. Nevertheless. the bias
resulting from the inclusion of some former smokers in the category of never smokers
would tend to reduce the apparent benefit of cessation when former smokers are
compared with never smokers.

The consequences of misclassification must be considered in the context of the
disease under investigation.  For example. in studying lung cancer and smoking
cessation, the failure of long-term former smokers to report a brief period of relapse has
little relevance. In contrast. unreported periods of relapse would be relevant in
assessing smoking cessation and occurrence of myocardial infarction or of respiratory
symptoms, conditions for which cessation has some short-term benefit.

Bias from confounding is also of concern in studies of the health consequences of
smoking cessation. Former smokers tend to differ from continuing smokers in the
earlier intensity of cigarette smoking and in other aspects of lifestyle that may determine
disease risk. Former smokers tend to have smoked fewer cigarettes per day and to have
started smoking at an older age than continuing smokers (Friedman et al. 1979 Garvey
et al. 1983; Myers et al. 1987; Volume Appendix). Thus. at any age. former smokers
have had less cumulative exposure to cigarette smoke. on average. than continuing
smokers. Failure to account appropriately for differences in cumulative exposure
between former smokers and continuing smokers may exaggerate the benefits of
cessation. Misclassification of smoking measures may limit the degree to which
confounding can be controlled (Greenland 1980: Rothman 1986).

Other differences between former smokers and current smokers may also influence
disease risk. Former smokers are more likely to be of higher socioeconomic status than
continuing smokers and tend to follow a healthier lifestyle than persistent smokers
(Chapter I I and Volume Appendix). Former smokers generally drink less alcohol and
less coffee. are more physically activ,e, and experience less stress. although their relative
body weight tends to be greater (Friedman et al. 1979: Kaprio and Ko\henvuo 1988:
Chapters IO and I I ). However. some persons may' stop smoking because a personal
combination of risk factors places them at increased risk for disease. In the British
Regional Heart Study. former smohers had higher blood pressure and total serum
cholesterol at entry than current or never smokers (Cook et al. 1986).

In fact, observed mortality rates for many diseases have been higher for former
smokers than current smokers during the first few years following cessation. Persons
with symptoms of incipient illness or with newly diagnosed illness may stop smoking
(Hammond and Garfinkel 1966). Consequently. mortality rates for former smokers
immediately following cessation may exceed those for current smokers.
In studies of the effect ofcessation on the course of established disease. consideration
must be given to the severity of the underlying disease in former smokers and persistent
smokers. For example. in a study of mortality following myocardial infarction, persons

54


who quit smoking were at greater risk for death than those who did not quit because of
more severe underlying disease (Vlietstra et al. 1986: Hermanson et al. 1988).

Analytic Issues in Observation Studies

Complex associations among disease risk. age. and duration of active smoking and
abstinence further complicate assessment of the health consequence\ of cessation.
Analytic approaches should represent these relationships in a biologically appropriate
fashion. The risks of many cigarette-related diseases (e.g.. cancer. CVD. and chronic
obstructive pulmonary disease) increase with age (Figure 2). Following cessation.
disease risk may change in diverse patterns. depending on the disease-specific
mechanisms through which cessation alters disease occurrence. Disease rish may be
unaltered (Curve A). decline quickly or slowly compared with that for never smokers
(Curve C). or decline to a level between that of nevjer and persistent smokers (Curve B)
(Figure 2). Comparing the disease risk for former smokers with the rish for persistent

FIGURE 2.-Hypothetical examples of disease incidence rates for current,
      former, and never smokers, by age


smokers describes the disease burden removed by cessation: whenever possible. this
Report provides this comparison. For many diseases. risks for former smokers do not
revert to those for never smokers. Relative rirhs for former smokers compared with
never smokers describe the persisting consequences of past active smoking.
Thus. in studies concerning the consequences of smoking cessation. the analytic focus
is on describing disease incidence after cessation in relation to either the incidence of
disease in never smohers or in smohers who do not stop smohing. Interest centers on
addressing several questions: In a population that started smoking at a given age.
smoked at the same rate. and then quit at a given age. how does the disease rate evo1v.e
as a function of time since quitting? In particular. how does the disease rate compare
with that of a population of lifelong nonsmokers of the same age or with that of a
population of smokers who continue to smoke at the same rate'? How does the disease
rate after cessation depend on such factors as duration of smoking. number of cigarettes
smoked daily, age at starting. or other factors? These analytic questions are generally
addressed by estimating either the attributable risk (the difference between the risks for
exposed and nonexposed) or the relative risk (the ratio of the risks in exposed and
nonexposed) and comparing former smokers with either never smokers or current
smokers.
A cohort study that observed subjects from birth to death could supply the data
requisite for meeting these analytic goals. Observations could be made concerning the
age at starting smoking. the amount smoked. the age at stopping smoking. the duration
of time since stopping smoking. and the occurrence of disease. Incidence rates could
be calculated and the attributable risk or relative risk considered as a function of time
since quitting. To assess the effects of such factors as duration or amount of smoking.
smoking cohorts with different durations and rates could be analyzed.
Typically, however. cohort studies enroll subjects at various ages. and the smoking
histories of the subjects span a broad range of ages at starting smoking. durations of
smoking. amounts of smoking. ages at stopping smohing. and ages at observation. In
analyzing data from a cohort study. stratification and multi\,ariate modeling are used
to describe the disease occurrence in former smohers in relation to the time interval
since cessation. New statistical methods have fdcilitated the analysis of longitudinal
data on cancer and other diseases (Breslow and Day 1987: Thomas 198X). The analytic
approach should pro\,ide control for the effect of changing disease risk Mith increasing
age: as duration of smoking abstinence increases. age and disease risk should be
compared with that of never or current smohers in the same age stratum.
HowevJer. some analytic approaches may introduce overadjustment for the timr-
related dimensions of smohing history and of age and obscure the benefits of cessation.
Age at starting smohing. age at observation. duration of smoking. and duration ot
abstinence are interdependent: specification of any three of these v,ariables fixes the
fourth. Assuming that current and former smokers of a given attained age started
smoking at about the same age. the duration of smoking among fomrer smokers must
be less than for current smohers. Thus. adjustment for duration of smoking in compar-
ing current and fonner smokers is incorrect. Methods that attempt to allow each ot
these four time-dependent factors to vary freely are inappropriate and provide biased
descriptions of the variation in risk folIoKing cessation (Brown and Chu lYX7).


Data from case-control studies can be used for the same analytic objectives. Infor-
mation on age at starting to smoke, duration of smoking. duration of abstinence. and
number of cigarettes smoked can be obtained retrospectively. Conventional analytic
methods enable calculation of odds ratios by time since quitting. which estimate the
ratios of incidence rates: the reference group for former smokers can be either never
smokers or current smokers.

Risk of disease for former smokers changes because exposure to active smoking
ceases: for some diseases, the exposure of interest in assessing the health consequences
of cessation is the subsequent tobacco exposure experienced by continuing users but
avoided by former smokers. Some analytic methods may not address adequately this
avoided exposure. For example, using variables for cumulative exposure combines the
additional exposure for the continuing smoker with the consumption to the point of
cessation for the abstinent smoker. If repair processes affect disease risk after cessation.
then the interval of abstinence is also a relevant exposure parameter. Thus. regardless
of the type of data analyzed, the method of analysi\ should properly represent the
underlying biologic process.

SUMMARY

Correct classification of smoking status is important to determine accurately the
effects of cessation. Smoking cessation is a dynamic process in which smokers progress
through a series of stages in an effort to quit smoking. These stages have been labeled
differently by various investigators. The model generating the most research refers to
the stages as precontemplation, contemplation. action, and maintenance and/or relapse.
Very few smokers progress through these stages linearly. because most smokers relapse
and recycle through the stages three or four times before attaining long-term main-
tenance.

Four common types of studies for assessing the health consequences of smoking
cessation are vulnerable to various sources of information bias leading to misclaasifica-
tion of smoking status. Cross-sectional surveys have a relatively low frequency of
misreporting: however. recall of duration of abstinence is vulnerable to error. A
case<ontrol study. because of its retrospective nature. is possibly more likely to have
misreporting of smoking status in diseased cases than in nondiseased controls. Cohort
studies are likely to have low rates of misreporting of initial smoking status but high
rates of misclassification due to changes in smoking status over time. Clinical trials
are likely to have high rates of misreporting for subjects receiving intensive clinical
interventions. However, such trials should have relatively little misclassification of
smoking status over time and provide more accurate assessment of duration of
abstinence when regular followups are maintained.

Misclassification of smokers as former smokers will have the effect of under-
estimating the benefits of smoking cessation when a true effect exists. The extent of
the bias is proportional to the degree of misclassification. Any specificity added to
measurement by validation mea\urej will diminish the r-ni~classificatiorl bias.


CONCLUSIONS

I. Most former smokers havte cycled several times through the process of smoking
cessation and relapse before attaining long-term abstinence. Any static measure of
smoking status is thus a simplification of a dynamic process.

2. In studies of the health effects of smoking cessation. persons classified as fomler
smokers may include some current smokers. Consequently. the health benefits ot
smoking cessation are likely to be underestimated.

3. In contexts other than intervention trials. \elf-reported smoking status at the time of
measurement and concurrent biochemical assessment are highly concordant. This
high concordance supports self-report as a valid measure of smoking status in
observational studies of the health effects of smoking cessation.


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69


        CHAPTER 3
SMOKING CESSATION AND OVERALL
  MORTALITY AND MORBIDITY


CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...75

Smoking Cessation and Overall Mortality in Cohort Studies . . . . . . . 75

Smoking Cessation and Overall Mortality in Intervention Studies .............. 8-I

Smoking Cessation and Medical Care Utilization ........................... X7

Population Projections  .............................................. X7
Observational Studies ............................................... X7

Smoking Cessation and Health Status .................................... X7

Conclusions  ........................................................ 92

Chapter3 Appendix  .................................................. 93

References . . . . . .._................................................. 90

73


INTRODUCTION

The overall risk of mortality among smokers has been discussed in several prior
reports of the Surgeon General (US PHS 1964. 1969; US DHEW 1979: US DHHS
I989 ). The 1989 Report estimated that approximately 390.000 Americans died in I985
from diseases attributable to smoking (US DHHS 1989). Another source (Mattson.
Pollack. Cullen 1987) estimated that 36 percent of heavy smokers aged 35 will die
before age 85. and 2X percent before age 75. from a disease caused by smoking. Prior
reports of the Surgeon General (L'S PHS 196X; US DHEW 1979: US DHHS 19X9) have
reviewed the association of smoking with overall morbidity. concluding that ov,erall
morbidity is increased among smokers.  Quantitative estimates of the amount of
morbidity attributable to smoking vary because of differences in the measures of
morbidity used.

Data from the aggregate of studies of overall mortality and morbidity among \mohers
and former smokers show that smoking causes increased risk of morbidity and mor-
tality. However. the temporal pattern of the reduced all-cause mortality after quitting
and the effects on mortality risk of quitting at variou\ ages have not been fully described.
In addition, questions about the benefits of smoking cessation for mortality have arisen
because of the results of studies involving interventions to promote smoking cessation.
The association of smoking with medical care utilization is a topic that has not been
addressed in detail in previous reports of the Surgeon General.

This Chapter reviews studies of overall mortality among former smokers, with
particular attention to the temporal pattern of decline in mortality after quitting and the
association of age at quitting with decline in mortality. Overall mortality in intervention
studies that include smoking cessation is discussed with attention to problems of
inferring the benefits of smoking cessation for the individual from these studies. Studie\
of medical care utilization by and health status of former smokers are described.

SMOKING CESSATION AND OVERALL MORTALITY
          IN COHORT STUDIES

Table I summarizes the results of major cohort studies comparing overall mortality
among never, current, and former smokers. The studies consistently showed a substan-
tially lower risk of mortality among former smokers in comparison with continuing
smokers. Compared with continuing smokers. former smokers had a progressive
decline in mortality risk as duration of abstinence increased. although risk in some
studies was increased for I to 3 years after cessation, almost certainly because some
people quit due to ill health (Chapter 2).

The durations of abstinence required for former smokers to reach the mortality risk
of never smokers differ among studies. The American Cancer Society (ACS) study of
I million American volunteers (Hammond 1966). also known as the 2S-State Study and
as the Cancer Prevention Study I (ACS CPS-I). found that after IO years, mortality rates
among former smokers of fewer than 20 cigarettes per day reached levels equivalent to
those of never smokers. Among former smokers of 30 cigarettes or more per day.

7s



TABLE I.--Summary of longitudinal studies of overall mortality ratios relative to never smokers among male current and former
     smokers according to duration of abstinence (when reported)

All









I ox

  Former smoker\
Duration ot ah\tinencc (yr )

    s-9            IO-15           >I5



    I.5             I.3            I I



    1.34             I.01
    1.3X             I.31


    1.x7             I.24           I 47
    7.0x             1 .xx           I .72

I .hO
I.55
I .5x

0.x-l

0.93
0.90
0 91


TABLE I.-Continued

Former wwhers
All tlurarion\

Study

Current
smokerc

Pcr\i\lent
uuIUcr\

California HMO'
(Friedman et al. 1981)

I .x2                                 I Sl             I.13


mortality risk was still higher than that of never smokers even after IO years of
abstinence.

The more recent ACS study. ACS CPS-II. is designed similarly to CPS-I. Re-
searchers enlisted 77.000 volunteers. who then solicited their friends. neighbors, and
relatives to participate in the study. Those enrolled completed a four-page confidential
questionnaire on medical history. health behaviors. medication use, and occupational
exposures (Stellman and Garfinkel 1986: Garfinkel and Stellman 1988). A total of
52 1,555 men and 658.748 women were enrolled: 4-year followup data ( 1982-86) on
the cohort were included in the 1989 Surgeon General's Report (US DHHS 1989).

In this Report, mortality rates for all causes of death from the ACS CPS-II were
calculated using updated data for the same 4-year followup period (Table 2). Rates
were calculated by gender in S-year age groups for current and former smokers
according to level of cigarette consumption ( l-20 cig/day, 22 I cig/day for males: I -I 9
cig/day, 220 cig/day for females). Rates for former smokers were further stratified by
years since smoking cessation (<I, 1-2.3-S. 6-10. I l-1.5, and 216). Slightly different
strata were used for men and women with respect to daily cigarette consumption in
order to provide suitable distributions of subjects across categories of smokers and
ex-smokers.

TABLE 2.-Overall mortality ratios among current and former smokers,
     relative to never smokers, by sex and duration of abstinence at date
      of enrollment, ACS CPS-II

       Former \mohrr\
Duratwn of abstmsncr at enrollment or)

Current
smohrr\

<I       l-2      3-s      6-10     I l-15     216

Male\
l-20 cigldlcy
>I! I cig/day

Female\
I-IO q/da>
20 <if/da)

7 -.-- 73     2.4Y     2.3x     2.03      I .h3      I .3x      I .06
2.13     2.77     7.M     2.25     7.04      I .77      I.27



I .hO      I 5x      I .Yh     I .Jl      I.14      I.10      I .(I I
z IO     3.3Y     1.5X     7 03      I .hO      I .3x      I.15

Currcm
\mohw

<I      IL2      3-s     610     I l-l.5     >Ih

Male\
I-20 q/da\
22 I cig/da>

Female\
I-IY cigiday
X0 q/da!

2.31     2.Oh     2.M      I .x9      I .4x      1.2')      I .o I
7.73      I x5     2 IS      I .YO      1.77      I fl.5      1.1')



I .x7     0.76     I.26     I .J2      I .OI      I .09      I .Oo
Z.Jh     7.33     2.15      I .-II      I 46      I.IX      0 YS


In this analysis, subjects who had quit smoking were assigned to the duration of
abstinence category appropriate for when they enrolled in the study. This method of
assignment tends to blunt the rate of decline of mortality risk according to duration of
abstinence when compared with never smokers because former smokers do not change
categories as duration of abstinence lengthens. No attempt was made in this study to
determine smoking status after enrollment. and persons who had quit at enrollment but
had resumed smoking were still considered former smokers. Likewise. persons who
smoked at enrollment but subsequently quit remain assigned to the current smoker
category. This probably leads to some degree of misclassitication and affects relative
risk estimates (Chapter 2).
Like AC3 CPS-I and other cohort studies. mortality ratios were substantially lower
among former smokers than continuing smokers for all durations of abstinence except
that of I to 3 years. With the exclusion of those subjects who had a history of cancer.
heart disease, or stroke and those who said they were "sick" at the time of recruitment.
mortality ratios were lower among former than continuing smokers for all durations of
abstinence, among males at all prior levels of cigarette consumption. and among
females who smoked fewer than 20 cigarettes per day before they quit.
The difference in the pattern of decline in overall mortality between all subjects and
the subset of subjects who were healthy at recruitment provides strong evidence that
recent quitters disproportionately include those who have quit because they are ill. In
contrast with ACS CPS-I. which was conducted in the early 1960s. mortality ratios
among both heavy and light smokers in ACS CPS-II remained substantially elevated
in comparison with those of never smokers IO years after quitting. This increase was
evident in all subjects and in the subset of subjects who did not have a history of cancer,
heart disease, or stroke and who did not state that they were "sick" when recruited.
Sixteen years after quitting, the mortality risk among male former smokers of fewer
than 2 I cigarettes reached that of never smokers but remained elevated among former
smokers of 21 cigarettes or more. Among female former smokers in both categories,
mortality was comparable with that of never smokers after 16 years of abstinence.
The results of ACS CPS-II are broadly in agreement with those of the British
Physicians Study (Doll and Peto 1976; Doll and Hill 1964a,b) and the U.S. Veterans
Study (Kahn 1966; Rogot and Murray 1980). In both, the overall mortality risk among
former smokers remained elevated in comparison with that of never smokers up to 15
years after quitting, although the risk was substantially less than among continuing
smokers.
An Australian study of petrochemical workers (Christie et al. 1987) appears to differ
from the other cohort studies in finding that overall mortality risk among former
smokers reached that of never smokers 5 years after quitting. This study is unique in
that subjects classified as former smokers were all persistent abstainers.
The differences among other studies in estimates of the duration of abstinence needed
for a former smoker to have the same overall mortality risk as a never smoker are likely
to be due to other smoking-related factors, such as age at smoking initiation, that differ
among study populations and over time (Chapter 2). Irrespective of the duration of
abstinence needed to reach the mortality risk of never smokers, former smokers have
substantially lower mortality when compared with continuing smokers.


For three reprc\entative age groups (NJ--54.60-64, and 70-74 yr). Figure I shows
the relative risk of death among current and former smokers compared with never
smokers based on recent ACS CPS-II data for the subjects who did not have cancer,
heart disease. or stroke and were not "sick" at recruitment. Complete data from ACS
CPS-II on mortality in current. former. and never smokers aged 50-74 years are
presented in Table 7 of the Chapter Appendix. Data are not presented for those aged
less than 45 years and greater than X0 years because there were fewer than IO deaths in
almost all of the categories of former smokers. In each of the age subgroups shown in
Figure I. among both sexes and among former light and heavy smokers, mortality risk
relative to continuing smokers decreased with increasing duration of abstinence.

Using a method described by Kleinbaum, Kupper. and Morgenstern (1982). the data
from ACS CPS-II were also used to estimate the effects of quitting at various ages on
the cumulative risk of total mortality in a fixed interval after cessation. Several
assumptions have been made in conjunction with CPS-II age-specific mortality data in
order to estimate as many as 16.5 years' risk of death from all causes for individuals
who continue to smoke and those who stop smoking. The first assumption is that
age-specific mortality mtes measured from 1982-86 CPS-II data remain constant for
the next 16.5 years. The first category of smoking cessation is l-2 years: that is. the
individual gave up smoking I to 2 years ago. It is assumed that. on average. respondents
in the I-2-year category pave up smoking I .5 years ago. Similarly. for the cessation
categories 3-S. 6-l 0, and I l-l 5 years, the average durations of abstinence are 1. X. and
13 years, respectively. It is further assumed that respondents are exposed to the
age-specific mortality rates of the age interval in which quitting occurs for I .5 years
and to each of the next three age intervals for 5 years each, making a total of 16.5 years.
For example. a quitter of the -IO-&-year interval would be exposed to the age-specific
mortality rates of the 301-t-year-olds for I .S years. to those of 4539-year-old\ for 5
years, to those of SG%-year-old\ for 5 years. and to 5%59.year-olds for 5 years.

The results of thi5 analysis. presented in Table 3 and in greater detail in Table X of
the Chapter Appendix. \how that the benefits of cessation for total mortality extend to
quitting at older age<. For example. a healthy man aged 60-63 years who smokes 21
cigarettes or more per day is estimated to have a chance of dying in the next 16.5 \`ears
of 56 percent if he continues to smoke and 5 I percent if he quits.  Quitting smoking at
younger ages confers even greater proportionate increasej in survival (\ee Figure 7 of
the Chapter Appendix ).

Framingham investigator\ recentI!, analyred data from their cohort (D'Ago\tino et
al. 19X9) and aI\0 found that the benefit\ of quitting apply to those who quit at more
advanced age\. These researchers estimated that mean additional life expectancy for
those who quit at ages 35 to 39 wah 5. I years for males and 3.2 years for females. For
those who quit at ages AS to 69. additional life expectancy was estimated to be I .3 years
for males and I .O year for females.

As discussed in detail in Chapter _ 7 and other chapters. smokers differ from non-
smokers in a variety of social. behavioral. and psychological characteristics. and
successful quitters differ from those who continue to smoke (Rode. Ross. Shephard
1972: Blair et al. 19x0: Haines. Imeson. Meade 19X0: McManus and Weeks 1982:
Billings and Moos 19X3: Gottlieb 19X3: Brod and Hall 19X-l: Seltzer and Oechsli 19X5:

X0


MALES

            Aged XL54

Current Smokers <l    l-2 3-5    6-10    11-15   216

Aged 60-64

Current Smokers ~1

l-2    3-5    610   11-15   216

Aged 70-74

Current Smokers <l    l-2 3-5     6-10   11-15    216

             Former Smokers
         Duration of Abstinence (yr)

* ??????????

Q 221 c&/day

FIGURE I.-Compared with never smokers, relative risk of mortality in
      current and former smokers aged 50-54,60-64, and 70-74 at
      enrollment, by amount smoked and duration of abstinence
SOURCE: Unpuhll\hed tabulalions, Anwrican Cancer Societ).

XI


FEMALES

                               I

w --  Current Smokers cl    l-2    3-5    610   11-15   216

Aged 60-64

Current Smokers <1




4.0

4.0 -

I-2    3-5    6-10   11-15   216



              Aged 70-74

Current Smokers ~1

l-2    3-5    610    11-15   216
  Former Smokers
Duration of Abstinence (yr)

I 1-19 c&/day      0 220 c ig/da y

F`I(;IRE 1. (Continued )--Compared u ith ne\er smoker\. relati\ e risk of
      mortalit! in current and former smokers aged 50-54.60-64. and
      70-71 at enrollment. b> amount smoked and duration of
        abstinence

x2


TABLE 3.-Estimated probability of dying in the next 16.5year interval for
     quitting at various ages compared with never smoking and
     continuing to smoke, by amount smoked and sex

Age at
quitting or
at 51art of
interv31

Female\

Age at
qutttmg or
at \tart of
interval

Never
\moher\

   x!o q/da\

Contmumg     Former
mohrr\     smoker\

1&`&l        0.03        0.06         0.03             (I ox        0.0-l
4519        0.04        0.0')         0.06             0.1 3        0.0
SO&S-l        0.07        0. l-l         0.07             0.14        (l.OY
55-s')        0.1 I        0.2 I         0. 12             0.27        (I. IS
60-64        0.1 x        0.30         0. I Y             (I.38        0.3'
65-6')        0.30        0.46        0.3Y             0.52        (I.32
70-7-1"        0.26        0.4 I         0.77             0.4S        (I.3 I

Kaprio and Koskenvuo 1988). These differences may exist among adolescents prior
to initiation of smoking (Seltzer and Oechsli 1985). For these reasons, interpretations
of studies comparing these self-selected groups (never smokers. smokers, and quitters)
must consider the problem of confounding (Chapter 2). Misclassification. which is
discussed in detail in Chapter A. 7 also must be considered. However, studies of smoking
cessation predominantly misclassify persons who are still smoking cigarettes as former
smokers, and this would tend to obscure the benefits of cessation in comparison with
continued smoking. Further. although the possibility of uncontrolled confounding
needs to be considered in epidemiologic studies of smokin, 0 cessation and mortality.
the totality of data must be interpreted with consideration of its consistency. To account
for the evidence of a benefit of quitting that derives from nonexperimental cohort
studies, confounders would need to be distributed quite differently among current and

x3


former smokers and would need to be strong predictors of mortality. There is no
substantial evidence that thih is the tax.

SMOKING CESSATION AND OVERALL MORTALITY IN
        INTERVENTION STUDIES

Five studies. four of which were randombed triak evaluated overall mortality in
relation to interventions that included smoking cessation 3s a component. The results
of these studies are aummurired in Table 1.

TABLE 4.-Summary of overall mortality ratios in intervention studies in
     which smoking cessation was a component

Otil!~ one stud! cxaminccl wlohin g inter\ c'ntion alone t Rwc and Hamilton 197X:
Rose et al. 19X2). Of I .145 IIMIC` mwk~~. aged 10 to 59 and at hish ri\h of coronaq
heart diNe;Iw (CHDI or chrotttc hronchttis. 7 t-I \+erc randomt~ a\\iyed to a11 interLen-
tion group and 73 I to ;I norm;tl cat-c group. hlcn in the inter\ ention group wcrc fi\ en
individual ad\ ice to quit \mohing. and if intereaxi III quittins. up to four additional
vi5it4 over 12 month\.  AI the c)-!car follow up. 55 pcrccnt of responder5 in the
intervention reported abbtincnce compared I+ itli 1 I percent in the normal care group.
After IO !eat-\ of 1'~~llo~~ up. there \\crc 123 death\ III the inter\,ention group and 1% in
the normal care group. The proportionatt' diffcrcnce in total mort;rlit! hewecn the
intervention group anti normal cxc group I-2 percent) \\a not \t;iti4icall\ stgnitkxnt.
but the confidence inter\;tl \\;I\ u I& 1-12 percent to +23 percent). There \\t're XI

X-l


smoking-related deaths in the intervention group and Y2 in the normal care group. The
proportionate difference in smohing-related deaths has -Y percent. Again the con-
fidence interval was wide (-31 percent to +20 percent). Twenty percent of the men in
the intervention group who quit smohing cigarettes tooh up pipe or cigar smohing
compared with 3 percent of the men in the normal care group. and to the extent that
pipe and cigar smoking are mortalit) rish factors. any benefit of cessation of cigarette
smohing is obscured.

This trial is largely uninformative as to the benefit or lack of benefit of smoking
cessation for total mortality because of the small number of subjects. The trial uas
further compromised by the relatively poor compliance of the subjects with the
intervention: the net reduction in mean cigarette consumption over the IO years of the
followup among the intervention group compared ti ith the normal care group was onI\
7.6 cigarettes per day.

Other intervention studies that allow assessment of the relation ofsmohing cessation
to overall mortality have involved multiple interventions aimed at reducing several
different factors for CHD. The ability to draw conclusions about the effect of smoking
cessation on overall mortality from these studies is quite limited for this reason.

The North Karelia study targeted a region of Finland that had the world's highest
CHD death rate at the time of the study's initiation (Tuomilehto et al. 19X6) and was
aimed at modifying smohing. cholesterol levels. and blood pressure. The rest of Finland
was used for comparison. In the IO years after initiation of an aggressive risk reduction
program. there was a 35percent decrease in smohing in North Karelia compared with
a I-percent reduction in the rest of Finland (Salonen et al. IYXY). Blood pressure and
cholesterol levels did not change significantly in the intervention area compared u ith
the rest of Finland. Total mortality in the intervention area in the IO years after the start
of the study declined more rapidly than in the rest of Finland. although the difference
in the rate of decline in overall mortality was not statistically significant.

For at least two reasons, interpretation of the North Karelis study is problematic with
respect to the effect of smoking cessation on overall mortality. First. the study was
nonexperimental. with conclusions based on a comparison of total mortalit\, in the stud)
area with that of Finland. During the study period. overall mortalit) also declined in
the rest of Finland, perhaps because of secular changes in other factors related to
mortality and to changes in medical care (Salonen et al. 19X9). Second. the study was
not designed to investigate smoking cessation alone. Because of the mixing of inter-
ventions for three CHD rish factors, it was difficult to isolate the impact of the smoking
cessation component.

The Oslo study (Hjermann 19X0: Hjermann et al. 1981; Holme 1982) involved 1.237
normotensive men at high risk for CHD because of their smoking behavior and
cholesterol levels. The men were randomly assigned either to recei\,e interventions
aimed at reducing both CHD risk factors or to a control group. Tobacco consumption.
including pipe and cigar smoking. fell 45 percent more in the intervention group than
in the control group.

There was also a mean difference of I3 percent in serum cholesterol between the
intervention and control groups over 5 years (Hjermann et al. IYX I ). The stud!, was
small. and it was not designed toexamine total mortality endpoints; only 42 deaths were

X5


observed. Nevertheless. the mortality rate in the intervention group was one-third lower
than in the control group (one-sided p value=O. 13). Because there were changes in both
smoking and cholesterol levels. the difference in mortality cannot be attributed entirely
to smoking cessation.
The World Health Organization (WHO) European Collaborative Group conducted
an intervention study in factories in four European countries (WHO European Col-
laborative Group 1983). The study involved random allocation of 66 factories that
employed 49,781 men aged 40 to 59 to an intervention program targeting smoking.
cholesterol level. and blood pressure or to a control group. After 4 years. the net
reduction in mean cigarettes perday in the intervention factories was X.9 percent (WHO
European Collaborative Group 1983). At 6 years. overall mortality in the intervention
factories was 3.04 percent: in the control factories. it was 4. IS. The difference was not
statistically significant.
The Multiple Risk Factor Intervention Trial (MRFIT) was a randomized study of
more than 12.000 American men. aged 35 to 57 at entry. who were at high risk for CHD
on the basis of their smoking behavior. blood pressure. and cholesterol levels (MRFIT
Research Group 1981). Men in the special intervention group received an intensive
intervention aimed at reducing hlood pressure and cholesterol and encouraging smok-
ing cessation. Men in the usual care group were referred to their physicians and
examined annually. The interventions continued over the entire course of the study.
At 6 years. q-l.3 percent of special intervention smokers and 3.X percent of the usual
care smokers reported cessation. In the 7-year followup data reported in IYXZ. there
was no difference in total mortality between the special intervention and usual care
groups (MRFIT Research Group lYX3). However. in the 10.5-year follow up data of
MRFIT participants. overall mortality for the special intervention participants was 7.7
percent lower than for the usual care group (one-sided p value=O. IO: YO-percent
confidence interval (Cl). -16.6 to +7.3) (MRFIT Research Group IYYO).
A subgroup of MRFIT special intervention participants. who were hypertensive. had
resting electrocurdiograrll abnormalities. and comprised 31 percent of the special
intervention group. may have suffered excess mortality as a result of an unanticipated
adv,erse effect of one of the antihy~pertcnsive drugs (Cutler. MacMahon. Furberg 19X9).
This has recently been sugested as an explanation for the absence of an overall
difference in mortality~ between the special intervention and usual care groups at the
7-year follow LIP (MRFIT Research Group. submitted for publication I. Furthermore.
Ockene and coworhers ( 1900) recently reported that at IO.5 years. MRFIT participants
who quit smohing had significantI\ lower death rates than those who continued to
smohe in both special inter\ cntion and usual care groups. Mo5t important. like the other
multifactor intervention trials. it is difficult to infer a benefit or a lath of benefit ot
smoking cessation for total mortality from this study.
In summary. studies in\,ol\ in? smohing cessation interventions include a randomized
trial in which smohing cessation was the sole interventton and three intervention studies
in M hich it was ;I component. The small six of the former and the mixing of a smohing
intervention with other interventions in the latter mahe it impossible to reach con-
clusions about the benefits of smohing cessation from these studies alone: however.


nonintervention (i.e.. cohort) studies described in the previous Section clearI! indicate
a benefit of smoking cessation on overall mortalit!,.

SMOKING CESSATION AND MEDICAL CARE L'TILIZATIO\

Population Projections

The relationship between smohinf cessation and medical care utilization is acomplcx
issue.  Data on differential disease and mortalit!, rates comparing smohers and
abstainers are abundant. and man\ in\,ectigators have used these data to pro,ject the
savings in dollars attributable to smohing cessation (Weinham. Roscnbaum. Sterling
IYX7: Leu and Schaub 1'3x3; Lute and Schweit/el- 197X: O\ter. Coldit/. Kelly IYXIJ.
Cenerall\~. these projections produce results that depend on the man> assumption\ ot
the models that create them. For example. Lute and Schweitzer ( I Y~XJ projected that
the total 1976 dollar cost of smohing in the United State\ was about 527.5 billion and
that excess medical care costs accounted for about SX.2 billion of tho\r costs.
Weinkam. Rosenbaum. and Sterling ( lYX7) and Leu and Schaub ( IYX3). both using
population simulation approaches. concluded that mohin, (7 does not. o\er a lifetime.
lead to increased medical care utilization. Thi\ is because the short-term higher levels
of utilization of smokers are approximateI\, balanced b) shorter longevity and the
resulting reduced need for medical care.

Oster. Coldity. and Kelly ( 19X-I) used population prcjjcctions to estimate the medical
care costs of smoking and the proportion of those costs that are potentialI> recoverable
depending on the age at which smokin g is riven up and the level of smohing prior to
                               c
quitting. Male light smokers (<I pack/dab) who quit between ages 35 and 39 uere
estimated to recover about 59 percent of their lifetime excess medical care costs. Even
if quitting ua\ delayed until age\ 7.5 to 79. Ii@ smohers were estimated to recover
one-third of the costs.  For heavy smokers, quittin, ~7 earlier was estimated to ha\c
somewhat more benefit. For both sexes and all levels of smoking. medical care cost
savings from smoking cessation were estimated to be substantial.

Observational Studies

Table 5 summarizes studies that directly measured utilization of medical ser\,ices b)
current smokers. former smokers. and never smokers. These studies suggest that
smoking is associated with higher utilization of hospital services and that former
smokersexperienced a brief period of increased utilization of hospital {ervicesjust after
quitting followed by declines in utilization to levels of never smokers. Modest increases
in outpatient utilization by smokers are to some degree offset by a decreased propensity
to use preventive care services (Marsden. Bray. Herbold IYXX; Vogt and Schueit;ler
19X5; Oakes et al. 1973).

SMOKING CESSATION AND HEALTH STATUS

Table 6 summarizes studies of smohing cessation and health status. The variety of
measures used makes direct comparison across studies problematic. Furthermore. in
most cases. only a comparison of measures for never. current. and former smoher< is
available. Because some smohers quit due to illness and because most studies fail to

x7


TABLE S.--Summary of studies of medical care utilization among smokers and
       former smokers

R~fW3lCY

Re\uk\

Ashford      75.500 re\ldent\ of
(1973)       Exeter

Oahe\ et al.
(1974)

2.557 HMO memher~
m California

Phqwinn
visit\.
ho\pitali/alion

No consiwznt difference\ in any
mearure ot uIiII7aImn between former
smoker\ and current \moker\.

Male former \moher\ have more
phywtan viGts than current smoker\:
female former \moher\ have more
physician visit\ than currenr smoker\.
Male former smohrr\ are less likelq than
current smoher\ to be hospitalized:
ho\pituliratlon among female former
smoker\ compared with currenr \moher\
varle\ uith age.

Phkhician
\,`isits"     Da)\
     hospilali/ed"

Non\moher\
Smoher\
~0.5 ppd
I PPd
2 I .5 ppd

2.41      0.6-i


2.37     0.x7
2.Sh     0.6X
3.16     0.44

identit`y the reawn~ for quittin y. the relation betMew quitting and health status may be
obwured in \tudirs that clasGt) prrwn\ ah t'ornw and current mohers (Chapter 2). A
few \tudie\ differentiate bet\vetm short-term abstainer\ (-c I 1 r) and long-term abstainer\
(>I yr). and thtw htudiek are highlIghted.

XX


Data from the National Center for Health Statistics (US DHHS 1980) suggest that
former smokers have fewer illness days than continuing smokers, particularly among
younger women. Gallop (I 989) found that former smokers have absentee rates between
those of current smokers and never smokers.
Segovia, Bartlett, and Edwards (1989) conducted a telephone survey of 3.300 adults
and found a strong relation between smoking status and the reporting of good health.
Persons who had quit smoking for more than 1 year reported good health with about
the same frequency as persons who smoked only I to 5 cigarettes per day, whereas those
who had quit for less than 1 year reported good health at a frequency comparable with
smokers of 16 to 20 cigarettes per day. Balarajan. Yuen, and Bewley ( 1985) examined
the associations among various levels of smoking, recent and former cessation, and
presence of acute and chronic illness, medical office visits, and doctor consultations.
Current smokers had a higher prevalence of acute and chronic illness. and rates varied
in relation to the amount smoked. Former smokers who had quit in the year prior to
the survey had higher rates of illness compared with continuing smokers. and former
smokers who quit more than 1 year prior to the survey had rates between those of never
smokers and smokers of 20 cigarettes or more per day.
Reed (1983) found no difference in general physical health status between current.
former, and never smokers, not otherwise defined. Seidell and colleagues (1986)
examined the number of reported health complaints, out of an inventory of 5 1 possible
complaints, by smoking status and found that male, but not female, former smokers
reported fewer health complaints than smokers.
Astrand and Isacsson (1988) found that male employees of a pulp and paper plant
who smoked retired at an earlier age than nonsmokers. Data from the 1979 National
Health Interview Survey indicate that smokers have more restricted activity days, more
bed disability days, more hospital days, more physician visits. and an increased
probability of being unable to work or keep house, than nonsmokers (Rice, Hodgson.
Sinsheimer 1986). Analyses of data for the 1976-80 Health Interview Surveys showed
that smokers have a 55 to 75 percent excess in days with respiratory conditions
associated with reduced activity (Ostro 1989). Smokers experience more school
absences (Charlton and Blair 1989; Alexander and Klassen 1988) and work absenteeism
(Andersson and Malmgren 1986; Coughlin 1987; Hendrix and Taylor 1987: Gallop
1989) than do never smokers. None of these studies reported information on former
smokers.
These studies are extremely heterogeneous, with some methodologic shortcomings
(Chapter 2). Furthermore, smoking is associated with other behaviors that may affect
health (Pearson et al. 1987; Stephens 1986). and the studies do not adjust for changes
in other risk variables, such as increased exercise, that might be associated with smoking
cessation. Taken together, however. the studies are consistent with the hypothesis that
smoking cessation produces improvements in health status. This conclusion is evident
particularly when considering that smoking-related morbidity is a powerful motivation
to quit smoking and that recent quitters are likely to be sicker than continuing smokers.


TABLE 6.-Relation of smoking cessation to various measures of general health status

Sell-rcpofl ol ~llne\\ and   (`hronic ilIne\\
ph!\lcian VI\I~\        Acure illW\\
            Outpatient vl\n
            PhyGcian
                conwlliition

I.0-r' 1.31" 1.76"
I .03   I .OY   I.29
I .46   I .46   I .43
I.12   I .0x   I .OY

Gig/day
<IO   210

0.X2h
0.79
0.Y I

I .Olh
0.97
I .os


032'

o.X6h
0.7Y
I .oU

0.7Yh
O.Xh
0.66


0.49'

Quit   Quir
>I yr  <I yr
- -
I .43"  I.?h"
I.1 I    I 4x
I .40    I.75
I.10    I .47

I .(I"
I A)"
I .o"
I .o"

Y.6    I I.6
9.0    Y.6

IO.2
6.X

9.0
7.3


TABLE 6.-Continued

Reference

Population

Health status
measure

           Re\Ult\

Current smoker\       Former smoker\        Never smokers

   Gig/da!         CJUll   Quit

Ii-15 21-3  >??I      51 yr  >I yr
                  --

Segovia,
Bartlett.
Edwards
(IYXY)

Telephone survey of
representative sample
us adults

Self-report of "good health"            4. IX< 1.00" I .a'      3.42'   5.13"          6.13"

Gallop
(19X9)

Workers in the
pulp/paper industry

Work absence\

I.3'           I .OY'            I .otf


CONCLUSIONS

1. Former smokers live longer than continuing smokers, and the benefits of quitting
extend to those who quit at older ages. For example, persons who quit smoking
before age 50 have one-half the risk of dying in the next 15 years compared with
continuing smokers.

2. Smoking cessation at all ages reduces the risk of premature death.

3. Among former smokers, the decline in risk of death compared with continuing
smokers begins shortly after quitting and continues for at least IO to 15 years. After
IO to I5 years of abstinence, risk of all-cause mortality returns nearly to that of
persons who never smoked.

4. Former smokers have better health status than current smokers as measured in a
variety of ways, including days of illness, number of health complaints. and
self-reported health status.

92


CHAPTER 3 APPENDIX


TABLE 7.-Age- and sex-specific mortality rates among never smokers, continuing smokers, and former smokers by amount
     smoked and duration of abstinence at time of enrollment for subjects in ACS CPS-II study who did not have a history
      of cancer, heart disease, or stroke and were not sick at enrollment

4s 1')

so s4

55- SY

hOM4

hS-hY

70-73

75-74

I Xh.0        42Y.2

25.5.6        702.7

44x.9       1.131.4

733.7       I .YX I. I

I.1 IY.4       3,(H)3.0
2.070.5       3.6Yl.S

3.675.3       7.340.6

Current

Former wwher\ (22 I cie/d;tv)


TABLE 7.-Continued

Females



Age

Never
\mokrr\

<I

l-2

Former smokers (l-19 ctg/day)

Duration ofabtinence (yr)

  3-s         b-10

4SAY

so-s-l

55-w

6044

hS-hY

70-7-l

7s-7')

Females

Age

125.7        225.6

177.3        353.x

244.X        s42.x

3Y7.7        x5x.0

hY2. I       I .4Y6.2

l.lhO.0       2.0x4.x

7.070.x       2.3IY.5

Former smokers (Z20 cidciav)

Duration ofabstinence (yr)

<I           l-2           3-5         h-10          I I-IS         Zlh

4s -4')                    `77.Y           266.7         IO?.7          17X.6         224.7         142.1         I3X.X

SC& s4                    5 17.`)           13x.7         -%6.X          270. I         190.2         116.X         x3.0

55-s')                    x23.s           473.6         hO?.O          361 .o        4.543         412.2         1x2.1

6044                  I ,302.Y          I.1 14.x        X62.1          6YY.h        541.7         373. I        356.4

654,`)                  I .Y34.Y          2.219 h       I ,250.o        I ,hXX.O        X2X.7         7Yl.Y        SXI 3

70-74                  2.x77.0         4,635.X       2517.2        I ,6X7.2       2.X4X.7        I .62 I .?       I.ih3.4

75-79                  4,273. I          2.4OY.6       5.76Y.2         3.125.0       2.Y7X.7       2.x03.7       2.lYS.4


TABLE %-Estimated probability of dying in the next 16.5year interval
     (95% CI) for quitting at various ages compared with
     never smoking and continuing to smoke, by amount smoked and sex

Age at
quittlng
or at start
of interval

Never
smokers

          Males

    I-30 q/day
Continumf       Former
smokers        smokers

   22 I cig/dq

Contmuinf       Former
smohers       smoker\

4&44       0.01,
       (0.04&0.05)
4549       0.07
       ~0.07-0.08)
5&53       0.1 I
       (0.1 l4t.12)
F-59       0. I X
       (O.l7~.lY)
h&64       0.30
       (0.28-0.3 1 )
65-69       0.46
       (0.43~.4X)
7G-74"       0.40
       (0.384l.43,

  0.11
(0.10~).12)
  O.IX
to. 174.19)
  0.27
lo.zbwx)
  0.39
(0.7X%0.41 )
  I)..54
(0.52Kt.57)
  0.68
(0.64-0.72)
  0.61
lO.SfFo.65)

  0.05
(0.oGo.06)
  0. IO
(0.080. I I )
  0.17
to.ls~).lY)
  0.2X
to.`s4if)
  0.46
(0.4-0.50,
  0.5')
(0.5 14.67)
  0.55
(0.4S-o.64)

Female\

  0. I4
(0.13~).15)
  0.22
10.21LO.23,
  0.3 I
(0.3%0.33)
  0.46
(0.434.4n)
  056
(0.S 1~1.61 1
  0.67
(0.57-0.78~
  0.58
(0.444.7 I 1

  0.07
(O.OM.09)
  0.1 I
(0.10-0.13)
  0.2 1
tO.lX4.23)
  0.33
(O.xLO.37)
  0.51
(0.48<)..57)
  0.64
(0.5 I-0.77)
  0.5 I
10.32-0.72)

Age at
outtting

1-l') clg/day             ~20 ctg/day

1 L
or at start     Never     Continumg      Former      Continuing       Former
of interval    smoker\       smokers       smokers        smokers       smokers

4tx44       0.03
       (0.03-0.03)
4.549       0.04
       (0.04-0.04)
50-54       0.07
       (O.O&O.O7)
55-59       0.1 I
       (0.11-0.11)
6cM4       0.18
       (0.1%0.19)
65-69       0.30
       (0.29xI.3 I )
70-74"      0.26
      (0.25-0.27)

  0.06
(0.054.06)
  0.09
K~.O%O.O9)
  0.14
(0.13415)
  0.2 I
(0.I9-0.22)
0.30
(0.27wI.33)
  0.46
(0.41Hl.52)
  0.4 1
(0.35-0.47)

  0.03
(0.02-0.04)
  0.06
(0.o;co.07)
  0.07
(0.05-0.09)
  0.13
(0.0%0.16)
  0.19
iO.13-0.25)
  0.39
(0.26-0.52)
  0.27
(0.094.46)

97


30





2a

I-







l-






l-






b-





I-

Continuing smokers

:;:::
cl
;:;i;; Former smokers
.
0 Never smokers

WOMEN

FIGURE 2.--Estimated probability of dying in the next 16.5yr interval for
     quitting at ages 55-59 compared with never smoking and
      continuing to smoke, by sex
NOTE: Continuing and former \mokzrs include only thaw wlohing 2 I (men) or 210 (women)
c&c/day. Vertical bar\ represent 05% CI: the interval fur female never xmokw ih not shown hecauw it is
extremely narrtrw I I I-I I'% j. Bawd on Amwcan Cancer Society Cancer Prrvrntion Study II data fur
perwn, wthout a hl\tory of cancer, heart dlwaw. or stroke wjho were not "\ick"nt rnrollment.
SOUKCE: I!npuhlished tahulatwns. American Cancer Swiety, (we Table Xl.


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WORLD HEALTH ORGANIZATION EUROPEAN COLLABORATIVE GROUP. Multi-
factorial trial in the prevention of coronary heart disease. 3. Incidence and mortality results.
E1rr-o~p~c1/7 Her/u ./~lltl-,7lJ/ 4: 14 I-1 37. 1983.

102


          CHAPTER 4
SMOKING CESSATION AND RESPIRATORY
          CANCERS


CONTENTS

LungCancer ....................................................... 107
Pathophysiologic Framework. ....................................... 107
  Smoking and Histopathology of the Airways  ......................... IOX
  OtherChanges  ................................................. 109
Smoking Cessation and Lung Cancer Risk  ............................. I IO
  Pattern of Changing Risk After Cessation ............................ I IO
  Effect of Antecedent Smoking History  .............................. 122
   Duration of Smoking .......................................... 122
   Daily Cigarette Consumption  ................................... I23
    Inhalation Practices  ........................................... 123
    Different Tobacco Products ..................................... I24
   Effect of Age at Cessation ...................................... I25
Multistage Modeling  .............................................. I26
Cessation After Developing Disease  .................................. I29
Cessation After Diagnosis of Lung Cancer ............................. I29

LaryngealCancer.. ................................................. I31
Pathophysiologic Framework ........................................ I3 I
Smoking Cessation and Laryngeal Cancer Risk  ......................... I3 I

Conclusions  .................. YT.rTTZTT. .................... I-. -135

References  ........................................................ 137


LUNG CANCER

Epidemiologic studies have provided overwhelming evidence for a causal association
of cigarette smoking with lung cancer (US PHS lY63: US DHEW 1979: US DHHS
1989). The plausibility of this association is supported by the presence of numerous
carcinogens in tobacco smoke. Compared with the risk among never smoker\. the risk
of lung cancer for smokers may be increased twentyfold or more for heavy smokers
(US DHHS 1989). Risk of lung cancer increases with the number of cigarettes smoked
daily and the duration of cigarette smoking; risk declines after cessation (US DHHS
1982, 1989). For example, in an analysis of data from the British Physicians Study.
Doll and Peto (1978) indicated that among sub.jects w,ho persisted in smoking. lung
cancer incidence increased with the fourth or fifth power of the duration of smoking
and with approximately the square of daily cigarette consumption. In 19X5. estimated
attributable risks of lung cancer from cigarette smoking were 90 percent for males and
79 percent for females in the United States (US DHHS 1989).

This Section considers the effects of cigarette making on the epithelium of the
airways of the lungs. the site from which most lung cancers stem. and the evolution of
the smoking-related change, after cessation. The epidemiologic evidence on lung
cancer risk after smoking cessation is comprehensively reviewed; the change in risk
over time following cessation is described; and factors modifying the effect of cessation
are considered. The Section includes discussion of the application of multistage
modeling to data on smoking cessation.

Pathophysiologic Framework

Previous Surgeon General's reports have provided extensive reviews on carcinogenic
components of tobacco smoke and on experimental carcinogenesis with tobacco smoke
(US DHEW 1979; US DHHS  I98 2. 1986). Tobacco smoke contains numerous
carcinogenic agents with both initiating and promoting activity. Although the specific
mechanisms of respiratory tract carcinogenesis by tobacco smoke are not yet fully
characterized, the plausibility of the smoking-lung cancer relation has been considered
to be well supported by the available information (US PHS 1964: US DHHS 1982).

Carcinogenesis in the respiratory tract is widely considered to be a multistep process
involving sequential changes in a cell from the normal to the malignant state. Extensive
experimental and human evidence is consistent with the multistage hypothesis. and
application of the new molecular and cellular biology techniques to the study of lung
cancer is providing further insights into the genetic mechanisms underlying the
development of this disease (Birrer and Minna 1988). Experiments with animals have
shown that agents may initiate or promote cancer. In animal experiments involving a
sequence of exposures to agents, those agents that cause cancer when administered
initially are referred to as initiators, whereas agents that promote the growth of initiated
cells are referred to as promoters.

Diverse multistep models of carcinogenesis have been developed (Farber 1983). The
age-incidence patterns for epithelial cancers such as lung cancer. which show that the
rates usually increase as a power of age. are also consistent with a multistage process

107


(Doll 1971: Doll and Peto 1978: Peto 1984; Day 1984). The bronchial epithelia of
sustained smokers show a progression of abnormality (Saccomanno et al. 1974). The
pseudostratified. ciliated epithelium becomes metaplastic and then dysplastic. Car-
cinoma in situ may develop and eventually become invasive (McDowell, Harris,Trump
1982). To the extent that cigarette smoking affects late as well as early stages in this
process, smoking cessation would be expected to have beneficial consequences on lung
cancer incidence. The epidemiologic evidence provides strong support for the an-
ticipated benefits of smoking cessation.

Cigarette smoking is associated with changes in the large and small airways, in the
respiratory epithelium and parenchyma. and in the numbers, type. and functional
capacities of inflammatory cells. The reversibility of these changes after smoking
cessation is germane to respiratory carcinogenesis and to the health consequences of
smoking cessation. This Section focuses on studies that have examined the effect of
smoking on the respiratory epithelium and on the cells in the lungs of current, former,
and never smokers. Additional relevant information is reviewed in Chapter 7 and in
previous reports of the Surgeon General (US DHHS 1984. 1986).

Smoking and Histopathology of the Airways

Extensive histopathologic evidence is available on the effects of smoking on the
airways of the lung. The association between smoking and premalignant changes in
the bronchial epithelium has been addressed by many investigators (US DHHS 1982).
Based on sequential examinations of exfoliative cytologic specimens from uranium
miners over a period of many years. Saccomanno and colleagues ( 1974) reported
evidence of squamous metaplasia progressing through increasing atypia to carcinoma
in situ and invasive bronchogenic carcinoma. Detailed observations have been made
on the histopathology of lung specimens obtained at autopsy (Auerbach et al. 1957.
1962a.b. 1963. 1964, 1972: Auerbach. Garfinkel. Hammond 1973).

In 1962. Auerbach and coworkers (1962a) reported that the frequency and intensity
of epithehal changes increased with the number of cigarettes smoked daily. In addition.
the$e investigators assessed changes following smoking cessation in postmortem
bronchial epithelial specimens from 72 ex-smokers and controls matched individually
with 2 controls per case (Auerbach et al. 1962b). One control was a current smoker
matched with an ex-smoker on age. occupation. residence. and smoking history. The
second control was a lifetime nonsmoker also matched with an ex-smoker on age.
occupation. and residence. Some type ofepithelial abnormality was found in 98 percent
of histologic sections from current smokers. 67 percent from ex-smokers. but only 26
percent from never smokers. Thi$ pattern persisted for many specific types of epithelial
abnormalities including absence of ciliated ceils. presence of atypical cells. and
presence of hyperplasia and goblet cells in glands (Table I ). The occurrence of
unciliated atypical cells. the most severe change before invasive carcinoma, was similar
among ex-smoker\ and never smokers but was considerably greater among current
smokers. The number of cells with atypical nuclei was reported to decrease with
increasing number of years since smoking cessation. When current smokers were
matched with former smoker5 of the same age at time of cessation. former smoker\

108


TABLE I.-Histologic changes (8) in bronchial epithelium by smoking status

showed fewer lesions. suggesting that the number of lesions decreased rather than
merely failed to increase after cessation of smoking.

Auerbach and colleagues (1964) also reported that among cigarette smokers. there
was a high degree of association between all types of histologic changes in the bronchi
and in the lung parenchyma. However, the lungs of ex-smokers were more similar to
those of never smokers than to those of current smokers with respect to cells with
atypical nuclei. In this study of 46 ex-smokers. 3 2 had few atypical cells in their
bronchial epithelium. Auerbach and associates (1964) suggested that with cessation of
smoking.cells with atypical nuclei gradually disappeared from the bronchial epithelium
and were replaced with normal cells.

Other Changes

Several reports have described levels of DNA adducts formed by the combination of
chemical carcinogens or their metabolites with DNA in the tissues of never, former,
and current smokers. Decline of DNA adduct levels in human lungs after smoking
cessation has been reported by Phillips and coworkers (1988). These investigators
utilized autoradiographs of chromatograms of "P-postlabeled digests of DNA from
lungs of current. former. and never smokers.  A linear relationship was observed
between number of cigarettes smoked per day and DNA adduct levels (Pearson
correlation coefficient. r=0.72, p<O.OOl). In addition. ex-smokers who had quit smok-
ing I to 3 months previously had adduct levels typical of the current smokers (12-14
adducts/lOx nucleotides), whereas those who had not smoked for 5 years or more had
adduct levels similar to those of never smokers (I .7-4.9 adducts/l OR nucleotides).
These investigators suggested that the reduced risk of lung cancer among ex-smokers
may be due to loss of the promutagenic lesions that initiate the process, in addition to
late-stage effects.

Randerath and colleagues (1989) also used a "P-postlabeling assay to study DNA
damage in relation to cigarette smoking. Adduct profiles and levels were determined
in nontumorous surgical specimens taken from patients with lung or laryngeal cancer.


Characteristic profiles were found in the laryngeal and lung tissues; levels of adducts
tended to increase with the amount of cumulative smoking. The study included only
three long-term former smokers with duration of abstinence ranging from IO to I4 years.
These subjects had low levels of adducts compared with current smokers.

Smoking Cessation and Lung Cancer Risk

Pattern of Changing Risk After Cessation

Numerous cohort and caseqontrol studies have documented a reduction in the
relative risk of lung cancer among former smokers compared with current smokers,
The findings of selected studies are presented in Table 2. Former smokers in these
studies experienced a IO- to 800-percent increase in risk of lung cancer compared with
never smokers; however. compared with current smokers, former smokers showed a
20- to 90-percent reduction in risk.

The relative risk estimates provided in Table 2 group former smokers with varying
durations of abstinence from smoking. However, the number of years since cessation
has a strong effect on risk of lung cancer among former smokers: in studies assessing
risk by duration of abstinence. the reduced risk has been evident within 5 years of
cessation compared with continued smoking. and the benefit of cessation has increased
as the duration of abstinence lengthened. However, in most of the studies, the risk of
lung cancer among former smokers remained elevated above the risk among never
smokers. even in the longest periods of abstinence evaluated. In many studies. risks
among former smokers were higher than among continuing smokers during the first
few years after stopping smoking. This pattern of risk reflects cessation by individuals
who quit smoking because of symptoms and illness before the clinical diagnosis of lung
cancer (Chapter 2; Haenszel. Loveland. Sirken 1962; Doll and Hill 1964; Kahn 1966).

Table 3 summarizes standardized mortality ratios of lung cancer among former
smokers by years of abstinence. as reported in five cohort studies: British physicians.
U.S. veterans. Japanese males, and the American Cancer Society Cancer Prevention
Studies. ACS CPS-I and ACS CPS-II. These studies varied in the length of followup.
the extent of information obtained on smoking history. and the number of lung cancer
cases. Compared M ith never smokers. former smokers who had been abstinent for JO
to 20 years or more showed a varying extent of risk. reduction among the studies. In
the British Physicians Study. U.S. Veterans Study. and ACS CPS-II, former smokers
who had been abstinent for IS yearj or more showed an 80- to 90-percent reduction in
risk compared with current smokers. The percentage reduction in risk was slightly
lower among the Japanese cohort and higher in AC'S CPS-I.

Results from selected ca\e-control studies are shoun in Table 3. As in the cohort
studies, former smohers who had been abstinent the longest experienced increased rish
compared with nevter smokers. but substantially reduced risk in most i;tudies compared
with current smokers.

Thus, reduction in risk of lung cancer after smoking cessation has been observed in
numerous cohort and caseecontrol studies conducted in the United Kingdom (Doll and
Peto 1976: Alder\on. Lee. Wang 1985). the United States (Kahn 1966: Hammond 1966:


TABLE 2.-Relative risks of lung cancer among never, former, and current smokers in selected epidemiologic studies

Hammond ( IYhh)

Kahn t 1966)

Canadian Department of
National Health and Welfxe
( IYhh)

Population







ACS CPS-I

US veteran4

Canadi;m malea

Suhg'oup

Never \mohcr\







    I .o

    I .o

    I .o

Former smoker\



I-IY     20
clp/day   c igiclay
- -
2.0      7.`)

     3.7

     h. I

Cederlof et 31. t 1975)

Doll and Pet0 ( I Y7h)

Doll et ill. t IYXO)

Wigle. Mao. G-xc
(IYXO)

wu Cl al. t IYXS)

Carstewa Perd~npen.
Ehlund t IYX7)

ACS
tunpubli\hed
tabulation\)

                Melrs                  I .o                0. I                7.X
                Ft3dt3                 I .o                I .5                45

British mule phywians                         I .o                4.3               I0.J

Brtti\h female phyclclan\                        I .o                3.?               6.4,'

Alkrtic (Canada) cancer   Male\                  I .o                6.5                IO.4
patlent\             Female\                 I.0                7.1                5.2

Lo\ An@\ (CA) white\  Squamou\                I .(I                7.7               35.3
                 Adcnoc:lrcillonta            I .o                1.2                1. I

Swrdl\h males                              I .o                I.1            1.5"


ACS CPS-II           Male\                  I .(I                X.Y               21.3
                Female5                 I .o                4.x               17.1


TABLE 3.-Lung cancer mortality ratios among never, current, and former smokers by number of years since stopped smoking
     (relative to never smokers), prospective studies

                                    Smokmg ttatu\

Referwce              Populatwn

and yr \ince
uopped rmokmg

Mortality ratios (N)"

Doll and Pcto t I Y7h)

Roget and Murray t I YXO)

Never smoker\
Current moher\
Former smoker\
       l-4
       S-Y
      IO-14
        >I5

Current smoker\
Former woher\
       IL.4
       S-Y
      lOLl4
      15-l')
        x!o

Current waker\
Former smoker\
       l-4
       S-Y
        >I0

I .o (7)
15.X(123)


lh.O(l5)
S.Y(l')
5.3 (Y)
7.0 (7)

11.3(2.6OY)


1x.x (47)
7.7 (X6)
4.7 (I(H))
4.x (I IS)
2.1 (123)

3.x


4.7
2.5
I .4

IY.Sl-71,Dyr followup:
data on former smoker\ In
wmmary form

195449, 16-yr followup


TABLE 3.-Continued

Reference              Population

Smoking status
and yr since
stopped wloking

Hammond ( 1966)

ACS CPS-I male%

Never wwkerh
Current v~x~k.er~
f%mer \moher\
        <I
       ILit
      S-Y
        >I0

ACS (unpuhll\hcd
tuhulatlww)

ACS CPS-II malrb

Never w~ohers
Current smokers
Former smoker\
        <I
       I-?
       3-s
       &IO
      I l-15
        >Ih

Mortality ratio5 (N)"

Comments

I-l')
up/day

IYSY-67. 7.5.yr followup.
men aped SO-69

I .o (32)       1.0(37)
6.5 (X.01      13.7(351)

7.7 (`I)       2Y.I (73)
4.6 (5)       12.0(3X
I .o ( I )       7.2 (22)
0.4 ( I ,       I.1 ts,

I-20           221
cig/dny       clg/d;ly

I.0 (XI)       I .o (XI,
1x.x (60X)      X.9(551)

26.7 (32)      50.7 (63)
??.4 (7 I )      31.2(117)
16.5 (X2)      20.`) (Yh)
x.7 (X01      IS.0 ( IOh)
h.0 (6Y 1      I?.6 (Y5)
3.1 t I441      5.5 (I 121


TABLE .X-Continued

Never \mohcr\
<`urrcnt wiokw
I%rmcr \mohcr\
        <I
       l-2
       3-s
       610
      I l-l.5
        Zlh

l-1')          >20
+/day      Cl@i)

I .o ( IX l )
7.2 ( 145)

7.Y (3
9.1 (13,
2.0 (7)
I .o (4)
I.5 (6)
I .4 (23)

I .o ( IX I )
16.3 (334)

34.3 (3 I I
IY.5 (42)
14.6 (42)
Y.I (32)
5.Y (20,
2.6 (IX)


TABLE 4.-Relative risks of lung cancer among former smokers, by number of years since stopped smoking, and current
      smokers, from selected case-control studies

Reference

Popuhtion

Definition of
former smoher

Smoking status
and yr \ince
wpprd



Graham and Levin
(1971)

New York          At hospital admission

Never smoker\
Current vnokers
Former smoker5
       0-03
     >().%I
      >I-.?
      >3-IO
       >I0

Wigle, Mao, Grace
(1980)

Correa et al. (1984)

Alberta. Canada, cancer
patient5

At mtervww

NR

NWCI- \mohcln
Current \moher\
Former amohers
      3-s
       6X
       >20

Rewlts

Aci.juatment"

Male\

Crude

I .o
X.X

     42 2
     z 3 3
     IO.0
     3.3
      I.3

Mole\     l+males

  0. I       0.1
  I 0       I .o

3.4       0.9
0.7       0.s
0.7       0.5
0 2       0.4

M;lle\ d f?nlule\

     I .o
    I2 h

77
7.0
3.9


TABLE 4.--Continued

Deflnltlon of
former maker

Smoking status
and yr since
stopped

Results

Adjustment'l

AItl~r\~~n. Lee. W;rnp
(19X.5)

(;;I0 c, al , I')XX)

NK

Never makers
Current \mokrr\
Former smoker\
       I-2
      5-10
       >I0

Never smoker\
Current \mokrr\
Former smokers
       IL4
       s-9
       2 IO



Never smohw
Former smokers
       <IO
      1%19
      ?(k-?9
       230



Current smokers
Former smoker\
       I4
       >5

Mules
0. I
I .o


I .x
0.4
0.3

Female\
0.2
I .o


2. I
0.7
0.3

Males     Female\
) .o       I .o
3.9       2.9


6.9       7.2
3.1       3.9
LI       3.2

   Male\
     I .o


    I I .9
     6.1
     3.7
     I .9

Males     Femall3

I .o       I .o


I.?       2.0
0.6       0.9

Age

Age and
educatwn

At lrab~ I yr at time
of lntervleu

NK

Duration of
\mokmg


TABLE 4.--Continued

Reference             Population

     Defimtion of
    former \moher
~-.__~

    Smoking %13tu\
     and yr Gnce
      stopped
-~~~ __. ~~

Lubin et al. (1984a)

Pathak et al. (1986)

European casexontrol
study

New Mexico

At interview

Current smoker\
Former hmokerk
       1-4
      s-9
      l&l4
      IS-19
     2%?4
       x.5

AI least I yr before
interview

Current smoker\
Former smoker\
       S
      IO
      20



Current smokers
Former smokers
       I-S
       6-10
       >I0

Damber and Larson
(19X6)

Swedenh

NR

Males
I .u

I.1
0.7
0.6
0.4
0.4
0.3

Female\
I .o


0.9
0.7
0.4
0.5
0.5
0.3

Duration of
smoking

  Male\
S6.5      >hS
I .o       I .o


0.5       0.7
0.2       0.5
0. I       0.3

  Male\
    9.S


    73
    3.0
    2.0

Number of
q/day

Age


Graham and Levin I97 I; Pathak et al. 1986). Canada (Wigle. Mao. Grace 1980). Europe
(Lubinetal. 1984a;DamberandLarsson 1986).Asia(USDHHS 1982:Gaoetal. 1988).
and Latin America (Joly. Lubin. Caraballoso 1983). Although only a few studies had
information on female former smokers, the pattern of risk reduction was similar to that
observed for males. Decrease in risk after smoking cessation also has been reported
for each of the major histologic types of lung cancer (Wynder and Stellman 1977; Lubin
and Blot 1984: Benhamou et al. 1985: Higgins and Wynder 1988) (Table 5 and Figure
I ). Higgins and Wynder ( 1988) found that the decline in risk after cessation was more
consistent for Kreyberg I tumors (primarily squamous cell, small cell. and large cell
cancers) than for Kreyberg II tumors (primarily adenocarcinomas and bronchiolo-
alveolar carcinomas) (Figure I ). Smokers of filter and nonfilter cigarettes (Wynder and
Stellman 1979: Lubin et al. 1984b) and of other tobacco products (Joly. Lubin.
Caraballoso 1983: Lubin et al. 1984b; Damber and Larsson 1986; Higgins, Mahan,
Wynder 1988) have reduced lung cancer risk following cessation (Table 6). Although
the findings of the reviewed studies uniformly indicate lower risk among former
smokers. the magnitude and rapidity of the risk reduction with smoking cessation varies
among the studies. This variation has several potential explanations.
First, years of abstinence among those who stopped smoking for the longest time
interval varied from 5 to 25 years or more. Second, although former smokers have a
risk of lung cancer between those of continuing smokers and never smokers. the pattern
of declining risk as duration of abstinence lengthens has not been fully characterized.
The small number of former smokers in some studies limits the precision with which
the decline in risk can be described, particularly for the longer durations of abstinence.
Third. aspects of the active smoking history. including cumulative smoking exposure
up to the time of quitting. age at initiation. years of smoking. number of cigarettes
smoked per day. inhalation practices. types of cigarettes and other tobacco products
smoked, age at smoking cessation. and the reason for stopping, may modify the risk of
lung cancer after cessation (Chapter 4. see section on Effect of Antecedent Smoking
History). The varying extent to which these factors havJe been considered in analyzing
the effect of cessation may partially explain the differences in risk observed in former
smokers among the studies. As discussed below. failure to adjust for previous smoking
history may exaggerate the benefit of smoking cessation. but adjustment for cumulative
smoking history also may result in overadjustment of the risk estimate (Chapter 2).
Fourth, the studies vary in the definition of former or es-smohers and in the analytic
treatment of former smohers u ho have recently stopped smoking. In the case<ontrol
studies. former smohers have been defined as individuals who were abstinent at the
time of interview. at the time of cancer diagnosis. or at some other reference point (e.g..
I year before diagnosis of lung cancer and a comparable time for controls).
To reduce the bias introduced by quitting because of illness. fomler smokers who
stopped smoking after developing symptoms ordisease may be excluded from analysis.
Information on the reason for cessation was collected only in some studies. and persons
with symptoms at cessation have not been handled unifomlly in the published literature.
Finally. results of the relevjant studies are not totally comparable because the risks of
former smokers were compared u ith those of never smokers in some studies and with
continuing smokers in others.


TABIX S.-Relative risks of lung cancer among never, current, and former smokers, by number of years since stopping smoking

   Malt!\
Krq hcrf I> ,I?
I        II
I .o       I .o
31.3      IO 7

  Ft!lll;llt2\
Kreyherg type
I       II
I .o      I .o
10.5      4.4

52.X      I-t.?             13.6      6.7
74.0       5.0             6.2      3.6
17.1       6.6             5.1      4.1
13.7       5.-J             x.x      5.6
5.0       I.7                     O.`J
   Mnh
Krc?tm$ t>t>c
I        II
I 0       I .o


.I-&.(>       6.1
I'.'       2.1
IO 9
0.J       I .o
4.2

M;Itc\                 I;CllldC\
ADEN           sy    ADENO
    I .o              I .o      I 0

t 0
0.x
0.6
0.0
0.5

I.1      0.7
0.0      I .o
0 4      0.4
0.4      I .7
0.3      0.3


TABLE &-Relative risks of lung cancer among never, former, and current smokers by types of tobacco products smoked

Never smoker\

Former smokers

Current smoker\

C`Igarettc~ only                 I .o              6.Y             16.0
CIg;ir\ only                   I .o              2.5             3.1
Pipes only                   I .o              0.7              I .9
Clfars and pipe\                t .(I             2.4             x.5
Mixed woher\                I .o              S.1             10,s

Y r Gnce stopped
I4       2.5

0.6       0.7
4.4       0.0
2.0       0.Y
t .2       0.8

I .o
t .o
I .o
I .o

C`lgarelte\ only"
Plp13 only

Y r since \topped
t-10      >I0

S.0       1.2
5.0       4.5

9.5
x.0


KREYBERG I (N-330)

MEN

30


25


20

15


10


5


0

E

L

i4 t KREYBERG II (N=204)
Y 15
d             n    r-l r

35


30


25


20


15


10


5


0


15


10

9  10
F:
25
20

5

0

1  -   11  -  21  -  31  -  241
NUMBER OF CIGDAY

Yr of abstinence

WOMEN

KREYBERG I (N-951

KREYBERG II (N=lOO)

01-4 05-9 810-19 sl20-29 * >30

FIGURE l.-Risk of lung cancer by number of cigarettes smoked per day
     before quitting, number of years of abstinence, sex, and histologic
       types

SOC'RCE: Hlggn\ and W>ndrr (198X)


Although this review has emphasized the results of cohort and casexontrol studies.
descriptive data on lung cancer mortality in the United States are consistent with a
beneficial effect of the declining prevalence of cigarette smoking. Devesa. Blot, and
Fraumeni ( IYW) described declining mortality rates for lung cancer at ages belov, 15
years. The decreases were greatest among white men but also occurred among white
women and blacks of both sexes.

Effect of Antecedent Smoking History

The preceding Section reviewed epidemiologic studies describing the pattern of lung
cancer rish following smoking cessation.  This Section considers factors related to
smoking that plausibly could modify the effect of cessation on lung cancer risk: these
factors include the duration of smoking. daily cigarette consumption. inhalation prac-
tices, types of tobacco products smoked. and age at cessation.

Duration of Smohing

Duration of smoking prior to cessation is a potentially important modifier of the
pattern of risk reduction in ex-smokers. Graham and Levin (1971) examined the rish
of lung cancer associated with increasing durations of abstinence and with stratification
by duration of smoking (130 or 23 I years and 5-I-10 or 231 years). The decline in risk
associated with stopping v~as greater for those who had smoked for shorter periods than
for those who had smoked for longer periods. Similar results were reported by Lubin
and colleagues ( 19x41). who determined the rish of developing lung cancer by time
since stopping hmohing (0. I--1. 5-Y. and 210 years) and total duration of smoking
( I-19. 20-N. 404Y. and 23) Jears). In each category of smoking duration. the rish
of developing lung cancer decreased as the number of j'ears since stopping smohing
increased. but the rate of decline LI as greater among those who had smohed for a shorter
time. Among men who had smoked for I to IY years. the rish ofdeveloping lung cancer
after IO ycurs of abstinence dropped to Ie\s than one-third of that among current
smohers. On the other hand. t'or men 1% ho had smohed 50 ! ears or more and stopped
for at least 10 \`ears. the rish M as still YO percent otthat t`or men LI ho continued to smohe.
This analysis. which matched for age and controlled for both duration of smoking and
length of abstinence. introduces too man! \anahlcs i'or the temporal dimensions 01`
cifarette use (Chapter 7). B! simultaneously considering attained age. duration ot'
smohing. and length of abstinence. the anal> tic model incorrect11 forces former
smohers to ha\,e ;I ! oungcr age of starting to smohe than current smohers.  Ill ;I
case--Control stud!, in Sweden. Dambcr and Lars\on ( I YX6) also found higher rt'lati\.e
risks among t'onncr smohcrs of pipes and cl,,
                   `o,lrettes u ho had smohrd longer.
Brown and Chu ( lYX7) ~ggestcd that t'ailure to ad.iu\t for pre\ ious duration ot

smohing ma\ result in rish e\timatc\ i'or former smohers that are too ION and thus
exaggerate the henei'ith of smohing cessation. Based on reanalysis of data from the
large European case<ontrol stud!. Brou II and Chu ( I 1~x7) reported that the correlation
between duration ofsmoking and time since stopping smohing fore\-smoker\ M a-0.6.
indicating that men u ho had stopped \mohin, (1 t`or man\ \ ears had also \mohcd t'or le>s
                                       _ .


\
\
\
\
%
  `4 4

`\\
           \
            \
             \
      `A---- --&\
WITHOUT ADJUSTMENT FOR  ' \ \
  SMOKING DURATION           \ \ \

-  "' I
     0   k   lb   1;   $0   2k   io :
   YR SINCE QUIT SMOKING

FIGURE 2.-Relative risk of lung cancer among ex-smokers compared with
     continuing smokers as a function of time since stopped smoking,
      estimated from logistic regression model, pattern adjusted for
     smoking duration compared with pattern unadjusted for duration
SOCiRCE. Hroun and Chu (101171

time than men who had stopped for a shorter time. The relative risk of lung cancer
continued to decrease sharply with increasing years of abstinence without adjusting for
smoking duration. whereas the decreasing relative risk plateaued when adjusted for
duration of smoking (Figure 2). The difference in this pattern was most noticeable for
increasing years of smoking abstinence. For those who had stopped smoking for 27
years or more, the relative risk compared with continuing smokers was 0.30 when
adjusted for duration, but 0.17 when no adjustment was made. However. control for
previous duration of smoking (or cumulative previous smoking history) in determining
the risk of lung cancer among former smokers may constitute overadjustment if age
and duration of cessation also are included in the model (Chapter 2).

In summary, only limited analyses address the effect of duration of previous smoking
on the decline in risk following cessation. The data point to less decline of relative risk
following cessation, comparing longer term with shorter term studiej. but additional
investigation is needed.

123


Daily Cigarette Consumption

Previous smohing intensity or number of cigarettes smoked per day also affects the
pattern of risk reduction after smoking cessation. In the U.S. Veterans Study. the
mortality ratios for lung cancer were 1.3 I, 3.37, 8.31. and IO.05 for ex-smokers who
smoked I to 9. IO to 20.2 I to 39. and 40 cigarettes or more per day, respectively (Kahn
1966). The pattern of lung cancer rish reduction by years of smoking abstinence and
number of cigarettes smoked has been reported for several studies. In ACS CPS-I and
ACS CPS-II (Hammond 1966: Garfinkel and Stellman 1988). the decline in risk with
stopping smoking showed a comparable proportional reduction in risk among those
who had smoked less (Table 3). In the European case<ontrol study (Lubin et al.
1984a). men who had stopped smoking for IO years or more, but had previously smoked
30 cigarettes or more per day. had a M-percent risk of developing lung cancer
compared with corresponding current smokers. whereas men who had smoked 1 to 9
cigarettes per day had a 67-percent risk compared with corresponding current smokers.
Similar result\ were observed for female ex-smokers (Lubin et al. 1984a). As pre-
viously discussed. duration of smoking was considered in these analyses. Thus, heavier
smokers have less reduction of lung cancer risk following cessation than smokers of
fewer cigarettes per day.

Inhalation Pmctices

The pattern of lung cancer risk hy year\ of \mohing abstinence and by inhalation
practices (i.e.. frequenq and depth of inhalation) has examined by Lubin and col-
leagues ( 1983a). Their analysis indicated :I somewhat greater reduction in risk for those
ex-smokers who had inhaled le\s often or less deeply. Among men who had stopped
smoking for IO year, or more. relative risk by reported frequency of inhalation
compared with current smokers was lowest for those uho had rarely or never inhaled
(relative risk (RR)=0.30) and for those whose depth of inhalation was reported a\ onl!
slight or not at all (RR=O.37). In comparison. the relative risk after 10 bears or more
of abstinence was highest for those who had inhaled all the time (RR=O.50) and for
those uho had inhaled deeply tRR=O.47). The same pattern ~\as ob\er\,ed among
women.

Different Tobacco Products

Differences in the reduction in ri\k folIoMing cessation also have been investigated
by types of cigarette\ smohed. A loner ri\h of lung cancer has been obser\,ed fol-
mohers of filter cigarettes compared with smohcrs of nonfilter cigarettes (US DHHS
lYX7. IYXY: Wynder and Kubat IYXX). a pattern suggesting that the reduction in ri4h
among former smoher\ ma\' be more apparent for filter cigarette \mokerh,. Ho&ever.
no significant difference> in the trend of ri\h reduction by years of hmohing abstinence
(0. 14. 5-Y. and 210) and b>, type of cigarettes moked (filter. mixed. nonfilter) \\erc
observed by Lubin and coworher\ ( 19XlhJ in the European case-i'ontrol stud>. Among


men. the relative risk for former smokers after stopping smoking for IO lears or more
has 0.4 for filter cigarette smokers. 0.3 for nonfiitercigarette smoher5. and 0.5 for mixed
filter and nonfilter cigarette smokers.  These data were collected in five western
European countries from 1976 to IYXO: the tar yields of the products smohed were
relatively high in comparison with cigarettes currently smoked in the Ilnited States
(Lubin et al. IYX3b).

In most studies, cigar and pipe smokers have louver lung cancer risks compared with
cigarette smokers (US DHHS IYX2). Former smohers of only pipes or cigars also
showed an intermediate risk of lung cancer compared v. ith current smokers and never
smohers of these tobacco products (Table 6). In the U.S. Veterans Stud). the lung
cancer mortality ratio. compared with never smohers. was I .67 among current smokers
who used only pipes or cigars and 1 .SO among former smoker\ (Kahn lY66). In a
case-control study ofsmoking-related cancers conducted in the United States. Higgins.
Mahan. and Wynder (1988) reported that ex-smokers of cigars only showed a relative
risk of 1.5 compared with 3.1 among current smokers of cigars only. The relative rish
was 0.7 among ex-smoker\ of pipes only compared with I.Y among current pipe
smokers only. Analysis of the pattern of risk among ex-smokers of cigars and pipes
only by considering the amount and duration smoked prior to smohing cessation
revealed similar patterns of risk reduction among light and heavy smokers.

Lubin. Richter. and Blot ( 1984) also examined the pattern of risk reduction by years
of smoking abstinence (0. I--1, 25 years) and types of tobacco smoked (cigars onI!,.
mixed cigar and cigarette smokers, pipes only. and mixed pipe and cigarette smokers).
No apparent differences were observed in the estimated rishs. ivhen analyred by
tobacco products. among those who had stopped smoking for at least 5 years. but the
numbers of cases who smoked cigars only and pipes only were quite small. On the
otherhand. Damber and Larsson ( 1986) reported that the decrease in relative risk among
ex-smokers was less pronounced in smokers of pipes compared with cigarette smoker\
only in a case-control study conducted in Sweden. However. in this population. the
risk of lung cancer for pipe smokers (RR=6.9) was similar to that of cigarette smokers
(RR=7.0).

In summary, these analyses. limited by the sample sizes within strata of types of
products smoked, do not characterize precisely the changing lung cancer risk following
cessation for smokers of various tobacco products.

Effect of Age at Cessation

Several researchers have suggested that the reduction in rish after smoking cessation
may differ by age at cessation. Wynder and Stellman ( 1979) reported that the reduction
in risk after cessation was appreciably greater for people aged 50 to 6Y than for those
70 or older. However. only data for those aged SO to 69 were presented in this
publication. Pathak and associates (1986) also reported a strong interaction between
age and duration of cigarette smohing. Risk of lung cancer among ex-smokers was
compared with that of current smokers with adjustment for the amount smohed. For
ex-smokers less than 65 years of age. the estimated relative risks compared u ith current
smokers declined to 0.39. 0.14, and 0.06 for 5. IO. and 20 years of smoking abstinence.



respectively. For those aped 65 or older. the corresponding estimated relative risks
were 0.73.0.54. and 0.29. respectively. These two studies suggest that the risk of lung
cancer may decline less steeply with increasing abstinence for older ex-smokers.

Multistage Modeling

Multistage models provide a conceptual framework for facilitating understanding of
the relationship of lung cancer incidence with amount smoked, duration of smoking.
and time since cessation. These models. proposing theoretical constructs of fundamen-
tal biologic mechanisms. have been useful for evaluating epidemiologic data in a
biologic framework and thereby furthering the understanding of tobacco carcino-
genesis. However, fitting these models to epidemiologic data cannot establish the
veracity ofthe underlying biologic theory. Multistage modeling approaches have been
used to describe respiratory carcinogenesis and to assess smoking cessation and lung
cancer risk. Although a number of different mathematic models of carcinogenesis have
been proposed (e.g.. two-stage. multicell, multistage). this discussion primarily ad-
dresses the Armitage and Doll (1954. 1957) multistage model, which has been used
most extensively in studies of lung cancer.

Based on a series of studies examining age-specific mortality rates for various
cancers. Armitage and Doll (1954. lYS7) proposed a multistage theory of carcino-
genesis. Their model assumes that a single cell can generate a malignant tumor only
after undergoing a certain number of genetic changes. Animal studies also support the
multistage model. Multistage theories also predict the age pattern of occurrence of
many tumors induced in experimental animals by continuous exposure to chemical
carcinogens. Experimental regimens involving initiation and promotion provide direct
evidence of the effect of early- and late-stage events in the carcinogenic process
(Stenback. Peto. Shubik 198la.b.c).

Using data from the British Physicians Study,. Doll (197 I ) showed that when the
incidence of lung cancer in cigarette smokers was plotted against duration of smoking.
incidence increased approximately in proportion to the fourth powerofduration. similar
to the slope of the regression line when incidence in never smokers is plotted against
age (Figure 3). Thu\. a first-stage effect uas implicated because the excess lung cancer
risk among smokers increased with the same power of duration of smoking as the risk
with ape among never smokers. Moreover. the lung cancer mortality rates among
ex-smoker:, decreased someu hat initially and then increased ,Iowly in beeping with the
increase in rish among never smohers vv ith age (Doll I97 I ). Armitage ( 197 I) noted
that the stabilir.ation of excess lung cancer risk at the level when smoking stopped
suggested that smoking also affected a late stage. namely. the penultimate stage in the
carcinogenic process.

Day and Brown (IYXO) conducted a detailed analysis of the pattern of change in
cancer risk after cessation of an exposure. The results supported the Arnmitage-Doll
model. In addition. Day and Brown proposed that the stage affected by the agent and
the relative magnitude of the effect of the agent on early and late stages of the
carcinogenic process are critical in the determination of risk subsequent to cessation of
an exposure. To quantify the magnitude of smoking et'fectj on the two stages. Brown


1,000









100









10









  1

X-X  Cigarette smokers by duration of smoking
x ---a#  Cigaretie smokers by age
.-.  Never smokers by age

I             I         I       I      I     I    I
20          30      40     50    60   70  80

YEARS

FIGURE 3.4ncidence of bronchial carcinoma among continuing cigarette
      smokers in relation to age and duration of smoking and among
      never smokers in relation to age, double logarithmic scale
SOCRCE  Doll c I')7 I), xlth LO~XC~K~ (11 prIntin; ~`rrw m the w~yn,d figure

and Chu ( 1987) reexamined data on ex-smokers from the European case+zontrol stud)
of lung cancer (Lubin et al. lOX4a) and concluded that smoking had an almost double
relative effect on late-stage events compared with first-stage events. Using data from
a case<ontrol study in New Mexico, Whittemore ( 198X) developed a predictive model
for lung cancer that showed a twofold stronger effect on late-stage than on early-stage
events; the model overpredicted cases among ex-smokers and under-predicted cases
among current smokers. Therefore. Whittemore suggested that smoking may have an
even stronger effect on late-stage events than was assumed in the model.

.4lternative models and interpretation of data on former smohers and lung cancer ha\,e
also been suggested in several recent studA. Freedman and i%a\ idi ( 19X9) tested the


fit of the multistage model to data from ACS CPS-I and the U.S. Veterans Study. These
researchers observed that crude rates of lung cancer decreased u ith increasing years of
smoking abstinence although the trend w'as less steep when average amount of smoking
and ages when smoking started and stopped were considered in the analysis. Moreover.
the observed lung cancer rates among ex-smokers were compared with the expected
rates. which w)ere computed in three ways-risk at the time of quitting. risk at current
age with excess risk frozen at the time of quitting. and never smokers of the same age.
For each comparison approach. the ratio of observed to expected rates decreased u ith
increasing years of smoking abstinence. Freedman and Navidi ( 1989) concluded that
this pattern was incompatible with the multistage model. which predicts \tabiliration
of excess risk when an individual stops smoking.
Gaffney and Altshuler ( 1988) reexamined data from the British Physicians Study and
found that the best-fitting model among current smohers predicted an increase in the
excess incidence amon ex-smohers. which &as inconsistent with the obsened
decreased rates. These researchers found that a two-stage model fit the incidence of
lung cancer in both current smohers and ex-smohers. Gaffney and .i\ttshuter ( 1988)
then proposed a two-stage model with clonal growth in R hich cigarette smoke induced
the initial transition and promoted clonal grouth in these cells initiated by cigarette
smoke. Moolgavkar. Dewanji. and Luebeck ( 1989) questioned the biologic plausibilit\,
of the proposal by Gaffney and Altshuler ( 198X) and noted that their model oni) fit part
of the British physicians data set. did not consider each age-smoking le\,el. and
discounted the possibility that making affected two transition rates in the carcinogenic
process.
Moolgavhar. Dewanji. and Luebech ( IYXY) reanalyzed the British Physician\ Stud>
within the framework ofthe two-mutation. recessive oncogenesis model. Ba\ed on this
model. the second-mutation rate would be affected by \mohing. and a sudden decline
in risk after cessation of smohing v.ould be predicted. HoNever. this model implies
that smoking affect\ the last stage in a multi$tape process. contrary to current con\ider:t-
tions.
In summary. multistage models have been used to describe the interrelationships
among number of cigarettes smoked dail>. duration. time \inctz e\posurr ended. and
lung cancer incidence. Several In\,c\tigators hale interpreted the data on rish among
former smokers in different ~a> \. The epidemiologic data clearI> indicate that the rish
among former smohers i\ between that of continuin, (1 smoher\ and nekrr smohers.
Various models can be fit to the different data ~1s. The expected pattern ofrith among
former sniohers is sensitive lo the model \clectrd and dependent on the relati\ e
magnitude of the effect of smohing on earl> \ er\u\ late stage\ of the proces\ ot
carcinogenesis. Lsing multistage models. the data on t.ormer smohcr\ are insufficient
to allow precise quantification of the relati\ c cffcct\ of \mohin, 0 on the earl\ and late
stages of the carcinogenic proce\\. H hich smokin, (7 i4 assumed to affect. Ne~ertticle\\.
data indicate that \mohing ha\ an dt'cct on the late \tagt'\ of the carcinogenic proce\c
and that cessation reduce\ lung cancer occurrcncc.


Cessation After Developing Disease

Individuals who stopped smoking are not a randomly selected group in most studies
(Chapter 2). Often. smohers quit as a result of developing symptoms of a life-
threatening disease or immediately after diagnosis of cancer. This phenomenon is
ev id,enced by the increase in risk of lung cancer in the immediate period after cessation.
Sotne studies have grouped these former smokers with the continuing smohcrs or have
excluded them from the analysis.

A few epidemiologic studies have assessed the risk of lung cancer among those who
quit for health reasons and for non-health-related reasons. In the U.S. Veterans Study.
about 10 percent of the smokers quit because of a doctor's orders: these smokers here
presumably ill. The lung cancer mortality ratio relative to never smohers for es-
smokers who stopped because of non-health-related reasons MLIS 3.43 compared with
5.83 among ex-smohers who stopped on a doctor's orders and X.98 among continuing
smohers (Kahn 1966). In the European case-control study. Brown and Chu ( I YX7)
reported that the relative risk of lung cancer for those who stopped smoking because of
health reasons compared with those who stopped for reasons other than health uas 1.3
(p<O.OOl ). Moreover, the percentage who stopped for health reasons decreased uith
increasing years of abstinence. Among those who had stopped for I year or less. 95.X
percent stopped because of health reasons compared with 65.7 percent of longer term
ex-smokers. In ACS CPS-II, men and women who did not have a history of heart
disease. stroke, or cancer at the time of interview showed a decreased risk of lung cancer
in the first 2 years after smoking cessation when compared v+ ith continuing smokers.
In contrast, the risks for all subjects combined (i.e.. those with and without a history of
previous chronic disease) were increased during the first 2 years after smoking cessation
when compared with continuing smokers. The lower risks among the group with no
history of previous disease compared with the total group persisted for subsequent
periods of smoking abstinence (Table 7).

Cessation After Diagnosis of Lung Cancer

Two studies examined the relationship between smoking status and treatment out-
come of patients with small cell lung cancer. In the study by Johnston-Early and
associates ( 1980). survival was prolonged in patients who were ex-smokers or who had
stopped smoking at diagnosis, whereas no difference in survival by smoking status was
detected in the study by Bergman and Sorenson ( 1988).

The study by Johnston-Early and colleagues (1980) involved I 12 patients with small
cell lung cancer: 20 had stopped smoking before diagnosis; 35 had stopped at diagnosis;
and 57 continued smoking. Therapies included chemotherapy with radiation therapy.
with or without thymosin fraction V. The three patient groups were similar in disease
extent, pretreatment performance status, pack-years smoked, and age and sex distribu-
tion. The patients who had stopped smoking prior to diagnosis had the best survival,
followed by those who had stopped at diagnosis, and finally by those who continued
smoking; the median survival for the three groups was 70. 52. and 47 weeks. respec-
tively. Overall survival differences remained after individually adjusting for disease


TABLE 7.--Standard mortality ratios of lung cancer among former smokers in
     AC!+CPS II (relative to never smokers) by years of smoking
     abstinence, daily cigarette consumption at time of cessation, and
     history of chronic disease

I-20         >?I
erg/da\     q/da\

7.4        i-l.3
Y I        19.5
7 Y        11.6
I .(I         Y. I
I .5         SY
1-l         26

extent. performance status. and type of protocol treatment. Similarly. statistical sig-
nificance was maintained after simultaneous adjustment for both thbmosin and radia-
tion therapy.

The study b> Bergman and Sorenson ( IYXX) involved 153 small cell lung cancer
patients who received combination chemotherap>. Thirty-two had stopped smohing at
least 6 months before the initiation of treatment or had ne\`er smoked. 51 patients
stopped smoking less than 6 months prior to the start of treatment. and 71 patients
continued to smoke during the treatment period: the median survival was 39. 42. and
30 weeks. respectively. Reasons for differences in results betbeen the two studies are
not clear. Overall. patients in the study hy Bergman and Sorenson ( 1988) had smoked
fewer pack-years. but the median survi\,al and performance status of each of the three

130


smoking status groups were poorer than for the comparable smoking status groups in
the study by Johnston-Early and associates ( 1980).

LARYNGEALCANCER

Pathophysiologic Framework

Smoking has been firmly established as a cause of laryngeal cancer (US DHHS 1982.
1989) based on numerous epidemiologic studies. These studie, have employed diverse
methodologies and have been performed in different countries and covered various time
periods. Tobacco smoke exposure has been measured by number of cigarettes smoked
per day. number of years of smoking, age when started to smoke, type of cigarettes
smoked. and depth of inhalation (US DHHS 1982).

In the larynx, as in the bronchus. a sequence of histologic changes occurs with
continued smoking. These changes progress from cells with atypical nuclei. to car-
cinoma in situ. to invasive carcinoma. Autopsy studies show that recovery of the
laryngeal epithelium can follow smoking cessation. Auerbach, Hammond. and Gar-
finkel (1970) studied postmortem specimens of laryngeal epithelium from 942 men
(644 current cigarette smokers, 94 cigar and/or pipe smokers, I I6 ex-cigarette smokers.
and 88 never smokers). Ex-smokers in this study had stopped smoking for at least 5
years. Compared with current smokers, ex-smokers showed fewer histologic changes:
75 percent of ex-smokers and never smokers showed no cells with atypical nuclei.
whereas almost all current smokers showed some cells with atypical nuclei.

Similar findings were reported by Muller and Krohn ( 1980). who obtained laryngeal
epithelial specimens from autopsy. Of the 148 cases in the study. 24 were never
smokers and 24 were ex-smokers who had stopped smoking for at least 5 years. Table
8 shows the relative distribution of selected histologic features by smoking status.
Occurrence of all histologic changes was lowest among never smokers, intermediate
among ex-smokers, and highest among current smokers. However. the histologic
findings of ex-smokers in this study were more similar to those of light current smokers
(<lOcig/day) than to those of never smokers.

Smoking Cessation and Laryngeal Cancer Risk

A few studies provide data on the relationship between smoking cessation and risk
of laryngeal cancer (Table 8). Former smokers are at less risk than current smokers.
but have about six times the risk of never smokers. The relative risk of laryngeal cancer
is higher immediately after smoking cessation (i.e., l-3 years after quitting) compared
with continuing smokers. However. after approximately 3 to 3 years of smoking
abstinence, former smokers show lower relative risks with increasing years of smoking
abstinence (Table 8). Based on a case-control study of laryngeal and hypopharyngeal
cancer conducted in Europe, Tuyns and colleagues ( 1988) suggested that the benefit of
smoking cessation seemed to appear sooner after cessation for cancer of the
hypopharynx/epilarynx than for the larynx.

131


Risk reduction pattern by years of smoking abstinence and number of cigarettes
smoked daily was examined in a few studies (Table 9). In the U.S. Veterans Study. the
risk of death from laryngeal cancer was lower among ex-smokers upho smoked 10 to
20 or 71 to 39 cigarettes per dav than among current smokers. but it was not lower
among those smoking 1 to 9 or 30 cigarettes or more per day. However. there were
very few laryngeal cancer deaths in the lowest and highest consumption levels (two and
one. respectively) (Kahn 1966). In ACS CPS-II. es-smokers u ho smoked less than 2 I
cigarettes per day showed a greater reduction in laryngeal cancer mortalit) for all
durations of smoking abstinence compared with ex-smokers uho smoked 31 cigarettes
or more per day relative to current smokers. In a case<ontrol study conducted in the
Texas Gulf Coast region (Fall\ et al. 1989). there uas no consistent pattern of greater
proportion of reduction in risk among those who had smoked fe\s#er cigarettes per dab
prior to smoking abstinence. Moreover. there was still a threefold increaKed risk among
those who had smoked more than 30 cigarettes daily after IO years of smoking
abstinence (Table 9).
The effect of smohing duration prior to smohing cessation M as not considered in the
studies mentioned above. There is some indication that the average age at which the
ex-smoher developed clinical laryngeal cancer was about IO years older (6X.7) than
that of the current smoker (Wnder et al. 1976).
Alcohol has been shown to have an independent effect on risk of iqngeal cancer,
but the relationship is weaher than the one betu,een smohing and laryngeal cancer. The
relative risks forjoint exposure to alcohol and tobacco are consistent with a multiplica-
tive interaction of the two agents (Flanders and Rothman 1982: Elwood et al. 19X-l:
Olsen. Sabroe. Fasting 19X5). In this revie\* of the literature. no studies were found
that accounted for the effects of alcohol intahe in examining rish of laryngeal cancer
after smoking cessation.


TABLE 9.-Relative risks of laryngeal cancer by smoking status

Reference

Population

Kahn ( 1966)           US veterans

Never smoker\
Current \mohrrs
Former wloher\

WI+, Mao. Grace
(19X0)

Alberta. Canada. cancer
patlent\

Never rmoher\
Current vnoherr
Former \moher\

ACS (unpublished
tabulations)

AC-S CPS-II

Never \mohrr\
Cut rent winher\
Former \mohcr\

Fall\ et al. (1089)

TCXl\

Never winher\
(`urrent smoher\
Former \moher\

(y \mce stopped)"

3-Y
>I0

I IO

3.11
2.x

I .o
Y.5
7.2

I .o
7.x
(1.3

Malt\      I~cnl;tle\
I .o         I .o
17.x         Y.5
(7.7         6.5

I .o
0.0

3.2
  (`lg/d;l)
II 70     `I 30     31 40     >40

3.0       J.(I       72       0.Y
I.2       I .I)       .3 I       3.5


TABLE 9.--Continued

`l`U> II\ ct XI
(IYXX)

Former vnoher\
(yr \incc 4loppetl)
        I-3
       44
       7-10
       II-15
        >Ih
Cutrent wider\
Never w~oher\

Relative risk\

Malea


17.9
8.5
3.0
3.4
1.5
I4 3
  I .I)

Female


h.Y
2.6
  -
X.X


I1.h
  I .o

Entlolnry nx
I .5 I


CONCLUSIONS

I. Smohing cessation reduces the risk of lung cancer compared M ith continued \moh-
ins. For example. after 10 years of abstinence. the ri\h of lung cancer is about 30
to 50 percent of the rish for continuing smokers: with further abstinence. the ri\h
continue\ to decline.

2. The reduced risk of lung cancer among former w~ohers i\ oh3erved in male\ and
females. in smokers of filter and nonfilter cigarette>. and for all histologic types of
luns cancer.

3. Smohing cessation lower\ the risk of larynyxl cancer compared with continued
smoking.

1. Smohing ce\\ation reduce\ the severity and extent of premalignant histologic
changes in the epithelium of the larynx and lung.


References

ALDERSON, M.R.. LEE. P.N.. WANG. R. Risks of lung cancer. chronic bronchitis. ischaemic
heart disease. and stroke in relation to type of cigarette smoked. .lou/.rwl of E/?/d'nriolo,~~ trrrtl
Con7/777//7i7~ Hcr~ltlr 3Y(4):2Xh-293. December 1 YXS.
AMERICAN CANCER SOCIETY. Unpublished tabulations.
ARMITAGE. P. Discussion on paper hy R. Doll. .lorrr-/rt/l of 7hc R(JJU/ S~c17i.s//c~c/I Soc.ret?.
A134:155-156. 1971.

ARMITAGE. P.. DOLL. R. The age distribution of cancer and a multi-stage theory of
carcinogenesis. British ./07//77~1/ c$Cu/7wr 8: l-l I . 195-t.
ARMITAGE. P.. DOLL. R. A two-stage theory of carcinogenew in relation to the age
distribution of human cancer. B/-iris/7 .lor/r/7ct/ ofC~w7wr I I : I6 I-164,. 19.57.
AUERBACH. 0.. GARFINKEL. L.. HAMMOND. E.C. Relation of smoking and age to
findings in lung parenchyma: A microscopic study. Cl7cw 6% I t:2Y-35. January 1974.
AUERBACH. 0.. GERE. J.B.. FORMAN. J.B.. PETRICK. T.G.. SMOLIN. H.J.. MLIEHSAM.
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256(3):97-104. January 17, 1957.

AUERBACH. 0.. HAMMOND. E.C.. GARFINKEL. L. Histologtc changes m the larynx in
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AUERBACH. 0.. STOUT. A.P.. HAMMOND. EC.. GARFINKEL. L. Changes in bronchial
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AUERBACH. 0.. STOUT. A.P.. HAMMOND. E.C.. GARFINKEL. L. Bronchial epithelium
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1054. November 14. 1963.

AUERBACH. 0.. STOUT. A.P.. HAMMOND, E.C.. GARFINKEL. L. Interrelationships
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BENHAMOU. S.. BENHAMOU, E., TIRMARCHE, M.. FLAMANT. R. Lung cancer and use
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BERGMAN. S.. SORENSON. S. Smoking andeffect ofchemotherapy in small cell lung cancer.
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BIRRER. M.J.. MINNA. J.D. Molecular genetics of lung cancer.  SPnri/7tri~.\ i/7 O/,r n/o,g~
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BROWN. C.C., CHU. K.C. Use of multistage models to infer stage affected by carcinogenic
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CANADIAN DEPARTMENT OF NATIONAL HEALTH AND WELFARE. A Cur7udim7
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1966. 137 pp.

137


CEDERLOF. R.. FRIBERG. L.. HRI'BEC. Z.. LORICH. L;. 1/w Kc/~rr/r~/r\/r//, of S,,~oX/,,;; c//r</
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ELWOOD. J.M.. PEARSON. J.C.G.. SKIPPEN. D.H.. JACKSON. S.M. Alcohol. smoking.
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FLAbDERS. W.D.. ROTHMAN. K.J. Interaction of ;Ilcohol and tobacco in larl,n~~al c;Lnct'r.
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13X


GARFINKEL. L.. STELLMAN. S.D. Smoking and lung cancer in women: Findings in a
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604. April 19X6.


PETO. J. Early- and late-stage carcmogene\is in mouse \kin and In man. In: BGrzs(inyi. M..
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RANDERATH. E.. MILLER. R.H.. MITTAL. D.. AVITTS. T.A.. DUNSFORD. H.A..
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140


U.S. PUBLIC HEALTH SERVICE. S,voX/,i,q tr/rt/ H~wlrh. Rc/~~wI of I/W AC/I isor:\. Cor~rnrirrc~c~
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377. March lY7Y.

I11


     CHAPTER 5
SMOKING CESSATION AND
NONRESPIRATORY CANCERS


CONTENTS

Introduction . .

Review of Specific Site\
Oral Cancer. .
Esophageal Cancer .
Pancreatic Cancer
Bladder Cancer .
Cervical Cancer .
Breast Cancer
Endometrial Cancer
Other Cancer Sites

Multiple Primary Cancer<
Summary . .

Conclusion5 . .

References . .





.....................


.....................





.









......


......

. . . 117

147

 l-17

 IS2

. IS5

 IS9

 I65

. 16Y

 I69

. I72


. 176

177

. 17X

. . . l7Y


INTRODUCTION

Lung cancer. the first neoplasm causally linked to cigarette smoking, has been the
cancer most thoroughly studied with respect to exposure-response relationships and
benefits of cessation (US DHHS 1982). Subsequently, cigarette smoking has been
established as a cause of cancer at diverse other sites. For some sites (e.g.. oral cavity ).
the target cells are exposed directly to the various constituents of tobacco smoke. For
other sites (e.g.. urinary bladder). absorption. transport. and metabolic activation of
carcinogens in tobacco smoke result in exposure of target tissues. This Chapter reviews
the evidence on smoking cessation and cancer risk at various nonrespiratory sites. The
sites selected for review are those for which cigarette smoking has been determined to
be a cause of cancer. or contributing cause. or those for which evidence indicates a
possible association.

Methodologic issues encountered in inferring causality on the effects of smoking
cessation have been discussed in Chapter 2 and will not be reviewed in detail in thts
Chapter. Potential confounding by differences in prior tobacco exposure at the time of
quitting. and by differences between former smokers and continuing smokers in other
cancer-related risk factors may pose a greater obstacle to causal inference for the
nonrespiratory cancers than for cancers of the lung or larynx: the smoking effects are
generally smaller for nonrespiratory cancers. and the potential confounding factors are
more numerous.

REVIEW OF SPECIFIC SITES

Oral Cancer

Tobacco use is a major cause of oral cancer (US PHS 1964: US DHHS 1982. 1989).
An exposure-response relationship has been identified between the amount of tobacco
consumed and the risk of cancer of the oral cavity after considering the effects of alcohol
consumption. The proportion of 1985 oral cancer deaths attributable to cigarette
smoking in the United States has been estimated to be 92 percent for men and 6 I percent
for women (US DHHS 1989). The oral cavity, like the lung. receives direct exposure
tocigarette smoke. Presumably, the causal association of cigarette smoking with cancer
of the oral cavity reflects this contact and the same initiating and promoting agents that
are considered to determine the development of lung cancer.

Table I summarizes studies that have examined the relationship between smoking
cessation and oral cancer risk. In these studies, the risk of oral cancer among current
smokers ranges from 2.0 to 18.1 times (median of approximately 4) the risk among
never smokers. Oral cancer risks for women who are currently smoking seem lower
than those for men in studies conducted prior to the mid- 1970s. but little difference by
gender has been noted in more recent research. This gender pattern may be because of
the initiation of smoking at an older age among earlier birth cohorts of women (US
DHHS 1989) born during this century and the resultant low cumulative lifetime
exposure of such women.

I17


4.4

12

3'
3-t
I 0


3.X
7.2
I.-l
0.6
0.x


I 7

NP

Exclude\ "doctw .\ ordw"
qutttee
<`anccr mortalit)


TABLE I.--Continued

Wifle. M:w, Grsce    Alherra. Canada
( IYXOI           (lY71-73)

(`t~wxontrol
(x3:l,lwJ
(4 I .h74)

Houwm. TX
(IYX5-X7)

Blot c, al
(I'JXX)

Frsnco Cl d.
( I YXY )

Rrwil
( I `)X&XX,

X.7       2.5
3.3       0.X

4.5"       h I
        2.2
        I 0

Nf'
N t'

<5
5-l 1
?I5


TAHIX I.--Continued



In each study summarized in Table 1. the ri4 oforal cancer U;I\ lower atnong former
smokers after the first few years of abstinence than for current \moLer\. After 3 to 5
years of \mohing abstinence. oral cancer ri4 decreased b!, SO percent. In ;I study in
Argentina (Isco\,ich et al. IYX7) and in the large multicenter stud) conducted b! the
C.S. National Cancer Institute (NCI) (Blot et al. IYXXJ. the ri\h of oral cancer among
tormer mohers after IO year\ of abstinence WLII comparable u ith that among ne\ t`r
mokerh. Thi\ observation has been interpreted as an indication tha[ the greatr\t effect
ot` smohing on oral cancer rich ma)' be in the later (postinitiation) stage\ of carcino-
genesi\ (Blot et al. IYXX).
Although it is isell hnonn that stnoheless tobacco (ST) increaec the rish of oral
cancer (Winn et al. IYXI: US Dl1HS 10X6) and that stopping the u\e of' ST reduce\ the
prevalcncc of premalignsnt tissue change\ in the mouth (Gupta et aI. IYX(1). there i\
little information on the ri\h of oral cancer in former u\er\ of' ST.
Compared wjith current smoher\. t'ormer makers ma\' ha\ c different alcohol drinhing
habit\ het'ore and after >mohing cehhation. and thu\ comparison\ olri\h berireen current
and former smoker\ map' he conf'ounded b>, alcohol consumption (Chapter I I 1. In three
investigation\. the effect of smoking ce\hation w;t\ examined and past alcohol coti-
\umption was controlled by multiple logistic regression (Blot et al. IYXX: Kabat and
Wjnder IYXY: Kabat. Hebert. Wynder IYXY ). In the three htudics. estimate\ ol`relatt\e
ri\h\ t'or both current and t'onner hmoherh were similar to those observed in studies in
which alcohol was not included ;I> an adjustment factor. The stability of the relative
rich estimate\ for stnohing with adjustment for alcohol intahe suggests that alcohol doe\
not substantially confound the relationship befueen oral cancer ri\h and cigarette
smohing status and that the lower risk of former smohet-\ cannot be explained b> lower
levels ofalcohol consumption (Chapter I I ). One stud) was sufficiently large to permit
detailed stratified analysis of the modification of the smohing effect by alcohol
consumption (Blot et al. 198X). In thi:, study. former smoher\ were observed to have a
lower risk than current smohers for both men and women at each of five levels ofalcohol
consumption.
The U.S. Veterans Study (Kahn lY66) demonstrated that at each of three levels of
past cigarette smoking exposure. former smokers had lower rich of oral cancer than did
current smokers. Kabat. Hebert. and Wynder (IYXY) controlled for past cigarette
exposure by tnultiple logistic regression and found that relative rihk estimates. which
were adjusted for past alcohol and cigarette consumption. did not difftr from the crude
estimates for fortner smohers ( 1 .O vs. 1 .O relative to never smohers).
Second primary cancers of the mouth and pharynx occur commonly in person\ v. ith
an initial primary cancer in the mouth. pharynx. or larynx. Several studie\ ha\,e
addressed the incidence ofhecond primaries ofthe mouth. pharynx. or larynx in relurion
to smoking status after diagnosis and treatment of the first prima-\. The finding\ ot
these studie\ are inconclusive. w)ith some indicating reduced rihk of a second primq
af'ier cessation (Moore lY65; Moore 1971: Wynder et al. 196Y: SiI~erman. Gorshb.
Greenspan 19X3) and others showins no clear benefit of cessation (Castigliano IYhX:
Schottenfeld, Gantt. Wynder IY71: Chapter 5. 5ee section on blultiple Pi-imaE.
Cancers).


The result\ of t&o studies indicated that continued \mohinp after diagnosic of oral
cancer may reduce survival. particularly in combination with alcohol consumption
(Johnston aid B;tll;tntyne I Y77: Stevens et al. 1983 ). These analyses. however. did not
aci.iu\t for the tnore advanced stage of cancer among u$cr\ of alcohol and tobacco at
presentation (Johnston and Ballantynr 1977).

The rehulth of studA of oral cancer and cigarette smoking cessation indicate that
former smohers experience ;I lower ri\h of oral cancer than current hmohers and that
this lower rish does not appear to be ;I result of confounding by alcohol or level of
cigarette consumption prior to ces4on. The rish of oral cancer has been shoun to
drop substantially within 3 to 5 years ofce\sation.

Esophageal Cancer

Smoking i4 a major cause of esophageal cancer (US DHHS 1981. 19X9). In the
United States. the proportion of esophageal cancer deaths attributable to tobacco has
been estimated to be 7X percent for men and 75 percent for women (US DHHS 19X9).
.A5 for cancer of the oral cu\,ity. cigarette smoking is an independent risk factor for
esophageal cancer but can also act in conjunction with alcohol to increase cancer risk.

Table 7 summarixe~ the studie\ that have esatnined the relationship between smoking
cexttion and esophageal cancer rish. In these studies. the risk of esophageal cancer
for current stnoher\ range\ from I .7 to 6.4 titnes the risk among never makers (median
of approximateI> 5). These tindinfs are Gmilur to those for oral cancer as shown in
Table I. The risks for \mohinf and esophageal cancer uere similar among male\ and
females.

Three year\ after cessation. former smohers sho\sed lower ri\h\ than current smoher\
in each study summarized in Table 2. \sith the exception of the Swedish prospective
\tud\; (Cederlofet al. 1 Y75) in M hich mohin, -associated risk\ were considerabl\ IOU er
than in any other stud). tio\\ever. in follo~up of this cohort. more dramatic elevarionx
in tnale mortalit> from s\ophageal cancer uere ohser\txi in current \moker5 relative 10
never mohcrx standardized mortalit! ratio\ were I I for I to 7 2 tobacco per ci;t~. 4.5
for X to I5 g tobacco per &I> . arid 5.4 for more than I5 g of tobacco per da (Car\ren\en.
Pershqen. Ehlund 10X7). For fomxr moherh. the st;tndardi/ed mortality ratio ~34
I .i. Approximalel> 3 to 5 bear\ after ces\;ttion. rish ol'e~phngeal cancer ua\ reduced
hq approximatcI> 50 percent in the t\\o \tudie\ ptxxtdin, (7 information b> duration of
ahtincnce (Table 2 I. Data are \ er! \cmt about the effect\ of cesation on the ri\h ot
esophafc~il cancer o\er long period\ of abstinence. The L'.S. Veteran\ Stud) shoued
that the ri\h among former \mohrr\ \<;I\ lo\+c'r at each of four le\,els of pat number\
of cigarette\ 3mohcd per da>.

A multivariate anal> \i\ in whtch Itfetime alcohol consumption M ;I\ irxluded ;I\ an
adjustment factor (La Vecchia. Liati el al. IYX6) produced relati\ e ri\h\ for current and
former \tnoher\ that \bcre similar IO those oh\er\ed in other \tudie\. In thi\ \tud!. the
crude relative ri\h f'or ex-smohcrs LIH\ nexl! identical to one that ~34 xiju\ted for
alcohol con\utnption (2.7 \\. 3.01. u,,
             \ ocTe\tiiig that ~rlcohol u:ih not 3 confounder in the
estimates of the benefits of cc\\ation. X \tud\ that ~a'r limited to nondrinher~ (La
Vecchia and Negri I YXY) ;tIw produced rish estimate\ for \mohiq that aerc \er!

152


TABLE 2.-Studies of esophageal ranter that have examined the effect of smoking cessation


TABLE 2.--C'ontinued


similar to those derived from other studies. supporting an earlier observation of elevated
risk for esophageal cancer in nondrinking smokers (Tuyns 1983 ).

This review of past research on esophageal cancer and cigarette smoking cessation
indicates that former smokers experience a lower risk of esopha_peal cancer than do
current smokers. and that this lower risk is not because ofconfounding by lower alcohol
intake among former smokers.

Pancreatic Cancer

The association. noted for many years. between smoking and cancer of the pancreas
is considerably weaker than that between smoking and oral or esophageal cancer (US
DHHS 1982). Although the causal mechanisms underlying this association are unclear.
smoking has nonetheless been regarded as a contributing factor in cancer ofthe pancreas
(US DHHS 1982. 1989). In the United States in 19X5. the proportion of pancreatic
cancer deaths attributable to smoking has been estimated to be 29 percent in men and
33 percent in women (US DHHS 1989).

Table 3 summarizes studies of the relationship between pancreatic cancer and
smoking cessation. In these studies, current smokers had risks ranging from I .O to 5.3
times (median of approximately 2) the risk among never smokers. Risks for pancreatic
cancer associated with smoking were similar for males and females.

Former smokers generally had lower risk than current smokers for pancreatic cancer.
but the available data do not characterize adequately the change in risk with duration
of abstinence. The large case<ontrol study conducted in Los Angeles, CA. (Mach et
al. 1986) would suggest that risk is not substantially reduced until after IO years ot
abstinence. whereas the smaller English study (Cuzich and Babiker 1989) suggests that
substantial risk reduction is more immediate among women than among men: risk
reduction may take as long as 20 years among men. This difference in the time course
of risk after cessation according to gender has no clear biologic explanation and may
be only a chance finding.

The question of potential confounding by differences in cigarette smoking exposure
prior to quitting was addressed in the analysis of the U.S. Veterans Study (Kahn 1966).
In each of four levels of past cigarette consumption. the risk among former smokers
was found to be lower than that among current smokers. In the study conducted by
Falk and colleagues (19X8), former smokers had a lower risk of pancreatic cancer than
current smokers at each of three levels of numbers of cigarettes consumed per day and
also at each of four levels of numbers of years smoked.

Because alcohol can cause insult to the pancreas and has been thought to be a possible
pancreatic carcinogen (Cubilla and Fitzgerald 1979). two investigators adjusted for
lifetime alcohol consumption in multiple logistic regression analyses (Falk et al. 198X:
Clavel et al. 1989). These analyses produced relative risk estimates similar to those
derived from other studies that did not adjust for alcohol and thus suggested that alcohol
consumption is not aconfounding factor in the smoking-pancreatic cancer association.

The results of epidemiologic investigations on pancreatic cancer and cigarette smok-
ing cessation indicate that there is a weak, but consistently observed. association
between smoking and pancreatic cancer and that former smohers experience a loner


`I'AHI,E A-Studies ot'c;~nwr of'the pancreas and smoking cessation

I 4
I \

I 7
I .A

I .o


TABLE: X--Continued

\I'
\I'

-
`JO
-1


twll;ltc      I 3"        0.x
                   t .(I
                   1.t

M;llC       2 5"        0.x

M:1lc        2.0        1.2
f-clll;llc      1.7        I .h

MAIC       32       t s)"

<IO
IO 20
>Z!O

<to
10~ 70
>70

NP


risk of pancreatic cancer than current smokers. This diminution of risk with abstinence
serves to strengthen the hypothesis that smoking is a contributing cause of pancreatic
cancer. Although alcohol does not appear to be a confounder in the assessment of the
benefits of smoking cessation. the possibility of confounding by other factors. \uch as
diet or amount of prior cigarette consumption. has not been adequately studied.

Bladder Cancer

As with pancreatic cancer. the relationship between bladder cancer ri\h and smoking
has been noted for many years. However. because relative rish\ have not been great])
elevated and because of uncertainty about the effects of unidentified confounding
factors in this disease. the causality of this association haj been considered less certain
compared with other diseases in earlier reports of the Surgeon General (US DHHS
19X2). Smoking has nonethelec\ been regarded a\ a contributing factor in bladder
cancer: in 1985, it was estimated that in the United State\ 17 percent of bladder cancer
deaths in males and 37 percent in females are attributable to smohinp (US DHHS lYX9).
A particular problem with causal inference in smokin, CT and bladder cancer arise\
because of the inconsistent finding of clear exposure-response relationship\ in all
studies. as has been observed between cigarette smoking and respiratory cancers.
However. the usual measures of exposure to tobacco smoke may not accurately index
the bladder's dose of tobacco-related carcinogens. The International Agency for
Research on Cancer (IARC) concluded. based on evidence available through 19x5, that
smoking of different forms of tobacco is causally related to cancers of the bladder and
renal pelvis (IARC 1986).

In addition to the studies reviewed in the 1982 Surgeon General'\ Report (US DHHS
19X2) and in the 19X6 report of IARC ( 19X6). more recent data document a consistent
association between cigarette smoking and bladder cancer. In an extended followup of
a cohort of 25,000 Swedish males, mortality rates for bladder cancer were increased
fourfold among ever smokers compared with never smokers (Carstensen, Pershagen,
Eklund 19X7). In current smokers,  the risk of death from bladder cancer was
approximately three times greater at all levels of consumption. The excess mortality
from bladder cancer among current smokers was comparable in the American Cancer
Society (ACS) Cancer Prevention Study II (CPS-II) (Table 4).

An extension of a large hospital-based case-control study, originally reported in 1977
(Wynderand Goldsmith I977), showed similar increases in risk among male and female
smokers (Augustine et al. 1988). The study included 1.3 16 male and 505 female cases
and 3.940 male and I.504 female controls interviewed in 9 U.S. cities between I969
and 1984. For current smokers, odds ratios increased to approximately 3.5 for male
and female smokers of 21 to 30 cigarettes per day. Odds ratios were lower among
former smokers, although the risk did not decline as the duration of abstinence
lengthened (Table 4).

The findings of a recent population-based case-control study documented similar
levels of bladder cancer risk associated with cigarette smoking (Slattery et al. 19XX).
Slattery and coworkers (19XX) assessed cigarette smoking and bladder cancer in 3.72
white male cases and 6X6 controls in Utah. The overall crude odds ratio for current


IL3
4-h
7.-IO
II-15
216

IL.1
341
7-10
I I-I.5
zth


TABLE 4.-Continued

Reference

Population (yr of       DeGgn
data collection)    (number ofwhjecr\)

(knder

Rl\h ret;ltwc to nwer
   wwher\


Currcm     Former
smohcr\    rmohen

Wynder and
Gotdamith ( 1977)

h US cities
( IYh%74)

Cavz:control
(574:56X)







(ls5:154)

Male

2.6
2.Y
I .s
I .h
I .2
I.1

2.5
I 2

Vineih et at
(IYX3)

Cartwrlght et al.
(IYX3)

Mornwn et al
(IYX4)

Italy
(lY7X-XI)

Erlgld
(lY7X-XI)

Ca\e:controt
(755:276)

Case:control
(Y.v:l.Jo')

(3'757Y,,

Bowm. MA
(107677)


Manchuter. UK
(1976-7X)
Nagoyii. Japan
(lY7~7X~

Caw:controt
t3'7:3', I )
(lfd:ll?l

t3vX:4Yo)
(lss:c!41)

(`x:44?)
(hh: 146)

MLlltT       6.0

Male       I .h


(`awxontrol
(5l?:s')h)

(SOS: 13(W)

Malt

Female

Mule

Fwl;ltc

3.4        3.0

t .CJ        I.2

7.v        2'
         t .h
         1.7
        I ..v

7.2        4.5
         I.8
         I .h
         I.1

2.2 .I       2.3'
       22'
        ?.I'
0.Y'       1.7'
        I.?
        1.2'

NP

NP


TABLE 4.-Continued

Slattery et al
(IYXX)

Claude. Frcn~el-
Brymr. Kuwe ( IYXX)
ACS CPS-II
(unpuhl~~hed
tshulathl\)

Hurch et al. (IYXY)

Utah
(lY77-x.31

C;mxia
(IY7Y-X2)

Case:control
(332:6x6)

Caaexonrrol
(531521)
Prwpective
(421.663)
(h0.5.75X)
Cohe:control
(627flO2)
(IYY:IYo)

Male       3.7        3.7
                  2.7
                  I .Y
                  1.X

MLlk       3.5        I .x

M;k!       2.`)        2.0
Fl!malc      2.X        2.0

Mde       27        I .7
km;de      2.6        I.1

0.557
X-IS
I6 29
?70

NI'

NP
Y P


smohing. compared M ith never smohing. was 3.69 (95-percent confidence interval (CI ).
2.5X-5.26). Ho&ever. an expoatre-response relationship u'a\ not evident with reported
average number of cigarettes smoked daily. The odds ratios for former smokers
declined only after X years or more of ab>,tinence.

Table 3 summuri~e\ finding\ from studies that have examined the relationship
between cigarette smoking cessation and risk of bladder cancer. Of all the non-
respiratory cancer \iteh. the relationship betwteen bladder cancer risk and cigarette
smoking cessation has been most extensively studied. In these studies. the risk among
current smokers ranges from I .O to 7.2 times the risk among never smokers (median of
approximately 3): rishs are similar among male5 and females. More recent studies
conducted since the mid-1970s tend to show> higher ri$kh for current smokers than do
the earlier studies. The higher ri5ks in more recent studies may reflect the earlier age
of starting to smoke of more recent cohorts of smokers (US DHHS 1989) or the presence
of a long latency period for the smoking effect to become fully manifest after initiation
in susceptible personh.

Beyond the first few years of abstinence. former smokers generally have lower risks
than current smokers. The study conducted in six U.S. cities (Wynder and Stellman
1977; Wynder and Goldsmith 1977) indicated an approximate SO-percent reduction in
risk after 6 years of abstinence. with risk returning to that of nonsmokers among men
after IS years. A similar return to nonsmoker ribh was also observed after 6 year\ of
abstinence in an English study (Cartwright et al. 19X3) and in an Argentine study after
20 years (Iscovich et al. 19X7). However. results from other studies (Howe et al. IYXO:
Vineis. Esteve. Terracini 19X-t: Hartge et al. 19X7: Burch et al. 19X9) indicated that the
reduction in rish in the first few years after ces;sation is followed by little subsequent
additional reduction. even beyond IOor I5 years ofabhtinence. These observations are
in contra\t to those for the other cancer site\ review,ed in this Chapter.

In some studiej. the analyse\ controlled for the possible confounding effect3 of lower
cigarette consumption among former smoker5 prior to cec\ation. The U.S. Veteran\
Study (Kahn 1966) showed no reduction in ri\h for former smokers. compared M ith
current smoher\. at level\ of past cigarette consumption of I pack or less per dab. There
wa\ an approximate SO-percent reduction in risk. however. for those former smokers
who had previousI) \mohed more than I pack per dab. Mo\t studies that included past
cigarette smoking exposure as a co\ ariatc in multiple logistic regression anal) se\
(Wigle, Mao. Grace IYXO: Howe et al. 19X0: Vinei\. Estete. Terracini 19X-l: Claude.
Frent;rel-Beyme. Kun,v IYXX: Slatter; t'l ;I]. IYXX: Burch et al. IYX9) show,cd relative
risks that were similar to those observed in studies in which no such adjustment M;I\
made.

A large multicenter study conducted b!, NC1 (Hartfe et al. lYX7) contained sufficient
numbers of subject\ for detailed subgroup analykrs. Table 5 displays the findings of
thi\ study when both average cigarette do\e per da> and duration of smokiq are
cross-classified for current and former \mohers. In each of these nine categories.
bladder cancer ri\k was lob,er among former smokers than among current smokers.
.A\ reviewed above. the amount of e\,idence supporting cigarette smohing as a cause
of bladder cancer has become increasingly compelling \ince the 19X2 Report of the
Surgeon General (US DHHS 19X3). which focused on cancer. Multiple studies of

I63


TABLE 5.-Bladder cancer risk according to smoking dose, duration of
      smoking, and smoking status

varying design conducted throughout the world have shown statistically significant
increases in risk of bladder cancer among smokers. Cigarette smoking. determined to
be a contributory factor in bladder cancer in past reports of the Surgeon General (L'S
DHHS 1983. 1989). can now be identified as causally associated with bladder cancer.
The evidence adequately meets the criteria for causality established in the 1964 Report
(US PHS 1964). The decline in risk of bladder cancer with cessation further supports
the conclusion that cigarette smoking causes bladder cancer. This diminution in risk
cannot be explained by confounding from lower cumulative consumption among
former smokers compared with continuing smokers.

Cervical Cancer

Recently, an association has been noted between cancer of the uterine cervix and
cigarette smoking (Williams and Horm 1977; Stellman. Austin, Wynder 1980: Lyon et
al. 1983; Hellberg. Valentin, Nilsson 1983: Berggren and Sjostedt 1983; Peters et al.
1986; Brock et al. 1988: Nischan. Ebeling. Schindler 1988). However, because of the
possibility of confounding by unidentified factors (in particular, a sexually transmitted
etiologic agent), this association has not been identified as causal (US DHHS 1981,
1989; IARC 1986). Components of tobacco smoke can be identified in the cervical
mucus of smokers (Sasson et al. 1985; Schiffman et al. 1987). These compounds have
been found not only to display mutagenic activity in this environment (Holly et al.
1986). but also to have the ability to impair local immunity by reducing the populations
of Langerhans' cells within the cervical epithelium (Barton et al. 198X). The reduction
in circulating levels of P-carotene caused by cigarette smoking is yet another
mechanism whereby cigarettes may increase the risk of cervical cancer (Harris et al.
1986: Brock et al. 198X; Stryker et al. 1988). Thus. the association of cigarette smohing
with cervical cancer is biologically plausible.


Table 6 summarizes findings from studies that have examined the relationship
between cervical cancer risk and cigarette smoking cessation. In these studies, the risk
among current smokers ranges from 1.0 to 5.0 times the risk among never smokers
(median of approximately 2). Smoking-associated risks for invasive cancer and for
carcinoma in situ are generally similar.

After the first year of abstinence, former smokers have lower cervical cancer risk than
current smokers in most studies. Exceptions include the study conducted in Milan (La
Vecchia, Franceschi et al. 1986). which showed risk reduction for invasive cancer but
not for carcinoma in situ among former smokers. and the study conducted in Central
America (Herrero et al. 19X9) in which no association with smoking was observed at
all, even for current smokers. The effect of time since stopping has not yet been well
studied for cervical cancer, but observations from a large multicenter study conducted
by NC1 (Brinton. Schairer. Haenszel et al. 19X6) suggested that risk reduction may occur
fairly rapidly after cessation. One study found that smokers tended to have a poorer
prognosis for survival after radiation treatment for invasive cervical cancer, but no data
were presented regarding smoking cessation (Kucera et al. 1987).

A major concern in studies of smoking and cervical cancer has been the potential for
confounding by factors that would predispose a woman to become infected with a
sexually transmitted agent that might be causally related to the disease, such as human
papilloma virus (Stellman. Austin. Wynder 1980; Winkelstein et al. 1984: IARC 1986).
Therefore, it is important to note that those studies that controlled for risk factors for
sexually transmitted disease (Trevathan et al. 1983: Greenberg et al. 1985: Herrero et
al. 1989: Slattery et al. 1989) produced relative risk estimates for current and fomler
smokers that were quite similar to those from studies that made no such adjustments.
The association of smoking and cervical cancer has been considered by some to be a
result of residual confounding by inadequately measured indicators of exposure to a
sexually transmitted agent. Although factors such as the number of past sexual partners
are only surrogates for a hypothetical etiolngic infectious agent, they are the very same
social correlates of tobacco smoking that would suggest this type of confounding.
Therefore. even though such factors as age at first intercourse and the number of sexual
partners are imperfect indicators of infection by a possible etiologic agent. their
inclusion as covariates in multivariate analyses may be sufficient to control confound-
ing to some extent in the analysis of the effects of smoking on cervical cancer ri&.

This review of the evidence on cervical cancer and cigarette smoking cessation
indicates that there is a consistently observed association between cervical cancer rish
and cigarette smoking and that former smokers experience a lower risk of cervical
cancer than current smohers. even after adjusting for the social correlates of smoking
and risk of sexually acquired infections.  Thi, observed diminution of risk after
cessation lends support to the hypothesis that smoking is a contributing cause of cervical
cancer. Based on a recent c0mprehensiv.e review of epidemiologic studies providing
data on smoking and cervical cancer. Winkelstein (1990) concluded that smoking is
causally associated vvith cervical cancer.

166


TABLE &--Studies of cervical cancer and smoking cessation

Reference

Location (yr of        Design
data collection)     (number of subjects)

Risk relative to never
   smokers


Current    Former
smokers    smokers

Yr
since
qwttmg

Comment\

Cederlof et al.
(lY7.5)
Clarke. Morgan.
Newman (1982)

Marshall ct al.
(1983)

Trevathan et al.
(IYX3)

Greenberg et al
(IYXS)

Brinton. Schairer,
Haenwel et al. ( IYXh)

La Vecchin.
Franccschi et al.
I IYXh)

Sweden
( 1963-72)

Toronto, Ontario
(1973-763

Buffalo. NY
(1957-65)

Atlanta, GA
(19X0-81)

England
( 1968-83)

5 US citieh
(19X?-X4,

Milan. Italy
(IYXI-X4)

Prospective
(27,700)

Case:control
( I785G.5)

Case:control
(5 13:4YO)

Caw:control
lYY:2KX)

Prospective
(17.032)

Caae:control
t4)30:7')73

Caaexontrol
(1X3:1X3)
(230:220)

s.0



2.3



I.6



4.2

3.0"

I.5

I.4h
1.7

3.0

I.7

0.x

2.1

0.7

2.2
I.1
I .o
I.1

2.5
0.x

NR

NR

NK

NR

NR

74
5-Y
>I0

NK
NR

Cancer incidence

Invawe cancer

(`arcinomu in \itu
Ad~uwxl for wxual partner\. birth control
pill\. SE.5

Inva\iw anccr incidence
Ad~uwd for age at marriage. birth control
pItI\, SES

Adjusted for sexual partner\. age at first
mttxcourw. SES


TABLE 6.--Continued


Breast Cancer

In general. prior research has shown little relation betvveen cigarette smoking and the
risk of breast cancer (Baron 1984: Rosenberg et al. 1984: Baron et al. 1986): however.
in recent years, several reports have raised the possibility that there might be a weak
positive association (Table 7). Because there has been considerable discussion about
the possible role of smoking in breast cancer in recent literature. the relationships among
cigarette smoking, smoking cessation. and breast cancer risk are reviewed. Cigarette
smoking creates a set of physiologic conditions that result in various antiestrogenic
effects (Baron 1984: Jensen, Christiansen. Rodbro 1985: Michnovicz et al. 1986). as
well as affecting body mass (Camey and Goldberg 1984: Hofstetter et al. 1986:
Chapters 9. IO, I I ). The relationship betvveen cigarette smoking and body mass is a
particularly important consideration in studies of breast cancer, because body mass has
a complex age-dependent association with breast cancer risk. with obesity being
protective in premenopausal ages but slightly risk-enhancing later in life (Willett et al.
1985).

Table 7 summarizes findings from studies that have examined the relationship
between breast cancer risk and the cessation of cigarette smoking. The risk of breast
cancer among current smokers ranges from less than I .O to 4.6 times greater than among
never smokers (median approximately I ). The relative risks of smoking do not
consistently differ in premenopausal and postmenopausal age groups. In addition, there
is little consistency regarding the change in risk observed after smoking cessation.
Former smokers have lower risks in some studies, but higher risks in others. Adjustment
for other breast cancer risk factors does not appear to completely remove the weak
association observed in some studies (Schechter. Miller, Howe 1985; Rohan and Baron
1989).

In one study it was found that smokers tended to have a greater prevalence of
tumor-positive axillary lymph nodes at the time of diagnosis than did never smokers
and former smokers, a finding that could not be explained by patient delay (Daniel1
1988). This association was not confirmed, however, in a recent report based on I O-year
followup of the Nurses Health Study cohort that included 1,373 cases with information
on extent of disease at diagnosis (London et al. 1989).

This review of breast cancer and cigarette smoking suggests that cigarette smoking
is not associated with breast cancer. Consistent changes in risk are not observed with
smoking cessation.

Endometrial Cancer

The relationship between cigarette smoking and cancer of the endometrium is unique
among the associations of smoking with cancers at various sites; of the sites for which
smoking has been associated with a change in risk, endometrial cancer is the only cancer
for which there is fairly consistent evidence of an inverse (protective) relationship
(Baron 1984; Lesko et al. 1985; Stockwell and Lyman 1987), an effect that may be
limited to postmenopausal women (Smith, Sowers, Bums 1984: Koumantaki et al.
1989). The reasons for the lower risk among women who smoke are not well under-.

169


TABLE 7.-Studies of breast cancer and smoking cessation

LocatIon (yr ot          DestJy
data collection)      tnumber of suhjcct\)

Menopau\al
XtatUS

Kisk relative to never
   smokers


Current     Former
smoker\    smoker\

Yr
since
ywtting          Commenrs

Cederlof et 31.
(lV75)

Schcchter, Mtllrr.
Howe (IYX.5)

Hiatt and Fireman
( I YXh)

Brinton. Schurer,
Stanford et al.
(10x6)

stochw~ll and
Lyman ( I YH7)

Brownson et 01.
(IYXX)

Adami et al.
(IWX)

Rohan and Baron
(19X'))

Sweden
(lYh3-72)

Canada
(IYXO~X2)

Northern Calil'omta
(IY6`~XO)

Untted State\
t 1973-75)

Flortda
(IYXI)

Missourt
( IY7Yw%)

Sweden and Norway
( Iox4-~x5 )

Awtralia
(IYK~X4)

Prospective
(27.700)

C~w:control
(4`): 134)
(7 I:?IY)

Proqxtnw
(X4.172)

Caae:wntrol
(447503)
thl4:XIX)

Caw:control
(4.01 1:2.`)52)

Ca~rxontrol
(1 14:20X)
(206:x72)

Cnbexontrol
(427,517)

Ca\e:control
(146: 132)
(2X0:2xX)

Pre
and pot

Pre
po\t

Prr
po\t

Pre
Po\t

Pre
Pwt

Pre
Pwt

Pre
and pwt

Pre
Pwt

0.6

4.6
I.1

I.2
I.1

I.1
I.1

1.3"
1.2"

2.3
1.2

I .o

I.3
I.5

0.4

1.x
0.x

I.2
I.3

I .4       NR
I .o       NR

0.9       NR
0.`)       NR

I.2
0.7

0.x

2.4
0.9

NR

Cancer incidence

>I
>_I

NR
NR

Adjusted for xveral breast cancer
risk factory

Cancer incidence

NK
NR

Relative risk calculated from
crude data

>I
tl

Adjusted fbr szveral breast cancer
ri& fnaor5


TABLE 7.--Continued

Reference

Location (yr of         Design
data collection)      (number ofsuh,jects)

Menopausal
\tatus

Kid relative lo never
   mohers


~`urrent     Former
smokers    smoherh

Yr
since
quitting

Comment\

London et al.
(19x0)

United State\
( IY7h-X0)

Prohpective
( I 17.557)

Pre
Post

I .O"        I.1        NR
1.1"        I.1       NR


stood. but may be due to smoking effects on estrogen production and metabolism.
including increased 2-hydroxylation ofestradiol in smokers (Michnovicz et al. 1986).
an earlier age at menopause in smokers (Baron 1981). and indirect effects of the body
weight differences between smokers and nonsmokers. such as the production ot
estrogens from precursors within adipose tissue (MacDonald et al. 197X: Chapters 8
and IO).

Table 8 includes a summary of findings from studies ofendometrial cancer that have
examined cigarette smoking cessation. Although the risk ofendometrial cancer among
current smokers in these studies is approximately 30 percent lower than that among
never xmohers. the risk among ex-smokers is similar to. or slightly greater than. that
among current smohers.

This review of past research on endometrial cancer risk and cigarette smoking
cessation sugests that current smokers are at lower risk of endometrial cancer than
never smokers. but it is not clear whether this protective effect of smoking on endo-
metrial cancer risk might be reversed soon after cessation of cigarette smoking.
Although further investigation of the mechanisms for the protective effect of smoking
on endometrial cancer is of scientific interest to better understand the effects of smoking
on hormones and of hormones on endometrial cancer risk, this inverse association with
smoking has no public health relevance, as the well-substantiated risks to other organ
systems from continued smoking far outweigh any potential benefits to the endo-
metrium.

Other Cancer Sites

The metabolic products of tobacco smohe can be found in ovarian follicular fluid
(Hellberg and Nilsson 198X). However. there i\ little evidence that smohing ih as-
sociated with cancer of the ovary (Byers et al. 1983: Baron 1983: Baron et al. 1986:
Stockwell and Lyman 1987; Whittemore et al. 198X: Mori et al. 1988). The rish of
ovarian cancer differs little for either current or former mohers. a\ indicated in the only
two studies that have examined the effect of cigarette smoking cessation on ovarian
cancer rish (Table 8).

Tobacco has been regarded as a contributing f;ictor for cancer of the kidne? (US
DHHS 1982. 1989). The U.S. Veterans Study (Kahn 1966: Repot and Murray 19X0)
and ACS CPS-II (ACS. unpublished tabulation\) qgest onI1 \msll difference\ in
mortality from renal cancer between current and former amohers (Table XI. A study of
renal pelvis and ureteral cancers in Copenhagen (Jensen et al. 198X). hob,ever. showed
a pattern of risk diminution with abstinence Gmilar to that observed in bladder cancer.
a site with the same histologic type of transitional-cell tumors.

Cancers of the anu1r and peni\ are considered possibly to result from infection by a
sexually transmitted agent in a v.aj analogous to cancer of the uterine cervix (Daniel1
1985; Daling et al. 1987: Hellberg et al. 1987). Smokers hake been found to be at
increased risk both for cancerofthe penis (Hellberg et al. 19X7) and anus (Daling et al.
1987: Holmes et al. 198X) in recent ctudie\. Only one study has examined the effect of
cessation on the risk of these cancers (Hellberg et al. 1987). This study found that

172


TABLE I.--Studies of cancer at selected sites that have examined the effect of smoking cessation

Cederlof et al.
(197%

Lrsko et al.
(1985)

Stockwell and
Lyman ( 19X7)

Cederlof et al.
(lY75)

Stockwell and
Lyman (19X7)

Franks et al.
(IYX7)

Kahn
( 1966)

Roget and Murray
I IYXOJ

Jensen et al.
(IYXX)

Sweden
( 1963-72)

X North American citte\
(1976-X3)

Florida
(IYXI)

Sweden
(1963-72)

Florida
(IYXI)

United Stab
(IWO-X2)

US veterans
(19.54&62)

[IS veteran\
(1954-6Y)

Copenhagen
( 1979~X2)

Proqxctive
(27.700)

Casexontrol
(50X:706)

Ca5e:control
(9Yo:?.Ys2)

Prospective
(27.700)

Case:control
(hwx2,YS2)

Cawxontrol

Prospective
(24X.lY.5)

Prospective
(293.YSXJ

(`nxexontrol
(Y6:`XX)

Endomctrtum

Endomctrnm

Ovary

Ovary

Kidney

Kldncy

0.5



l).x'l



0.x"



0.5



1.1"



I.1



I .4



I .`I



3.7

I .h

O,kJ

0.0

I .6

II.0

0.`)

I.5

I.2

I .4

N P

NI'

NI'

NI'

>I

NF'

NI'



NI'


TABLE X.--Continued

Kisk relative 1o never

Keterencc

Population (yr o!
data collectwn 1

   Design
(number of\uhject~

Cancer
site

   smoker\


Current     Former
smokers    \mokcr\

Yr
since
quitting

Comment\

Hcllhcrg et al.      SWd~ll
(I`JX7)         (NPI

Cederlof'ct 31.
(1')7S)

S\*cdcn
(lY63-77)

Rogol and Murray
( I YXO)

IIS veternn\
(lYS4dY)

Yu e1 al.
(14X3)

Lo\ Angclr\. CA
( l'J7Sm 70)

Kahn
( IYtx)

(`rdcrlof et a.
(l'J7.5)

Roger and Murray
(IYXO)

Nomura er aI.
(IYYO)

Kahn
( IYhh)

US veteran\
( l'JSJ~h2)

Prwpectivr
t17.300)

<`ahe:comrol
(76:76)

Prospeclive
(23X.195)

Prwpect ivc
(?7.3001

Pro\pective
(2YJ.YSX)

Prwpectwe
l7.YYO)

Plnqeclive
(74X.l'JS)

Pt!Ill\

Liver

Liver

Liver

Stomach

Stomach

Stomach

I .h



2.4



2.3


1.X"



I .4



I.3



I.5



2.7



I .J

I .7



I .o



I .X



I.1



I.1



0.7



I.1



I .o



I .s

NP



NP



NP



NP



NP



NP



NP



NP



N P

Cancer incidence in males

Cancer mortality

Abtnincr\ for 210 yr were
considered never hmokers

Excludes "doctor`s order\" quilter\
Cancer mortality

Cancer mcldence in males

Extension of US Verrran\ Stud)

Cohort identified 1065-6X and
followed through October 19x6

Exclude\ "dnctor`x order\" qulttw
Cancer mortality


TABLE &--Continued

Reference

Population (yr of
data collection)        Design
            (number of wbjects)

Cancer
Gte

Rihk relative to never
   \molLer\

Current     Former
wloherh    smokers

Yl
\ince
quitting          Comments

Cederlof et al.
(1975)

Roger and Murray
( I980)

Trichopoulos et al.
(1987)

ACS CPS-II
(unpublished
tabulations)

Sweden
(I 963-72)

US veterans
( 195449)

Greece
( 1976-84)

United States
( 1982-86)

Prospective
(27.300)
(27.700)

Proqxctive
(24X.ooO)

Case:control
( 104:454)
(X9:454)

Prospective
(42 I .623)
(605.758)

Leukemia
(Males)
(Females)

I.1
0.4

0.X
I .o

NP
NP

Cancer incidence

Leukemia

I .h

I.5

NP

Extcmion of US Veterans Study

Liver
HB,Ag
HR,Ag+

3.3"
I .6'(

2.x
I.3

NP
NP

Kidney
(Mules)
(Females)

NP
NP

Cancer mortality



current smokers had a penile cancer risk I .6 times that of never smokers. but the risk
among former smokers was similar to that among current smokers (Table 8).

Primary hepatocellular cancer has been associated with smoking in a number of
recent studies (Trichopoulous et al. 1980: Lam et al. 1981: Yu et al. 1983: Oshima et
al. 1984: Trichopoulos et al. 1987; Hirayama 1989). This association is of potentially
great public health importance because of the high incidence of primary liver cancer
and the epidemic of cigarette smoking worldwide, which is increasingly involving
countries in which liver cancer is the leading cause of cancer mortality. The mechanism
whereby smoking might affect liver cancer risk is unknown.  Although potential
confounding by alcohol consumption is of concern in interpreting this association. the
association of smoking with hepatocellular cancer has remained significant in several
studies after controlling for alcohol intake (Trichopoulos et al. 1980: Yu et al. 1983;
Oshimaet al. 1984; Trichopoulos et al. 1987). One case<ontroI study (Yu et al. 1983)
and two cohort studies (Cederlof et al. 1975: Carstensen. Pershagen. Eklund 1987:
Rogot and Murray 1980) have examined the effects of smoking cessation on liver cancer
risk. In all three studies. current smokers were found to have higher risks than either
never smokers or former smokers. In the case<ontrol study. potential confounding by
different alcohol consumption of current and former smokers was controlled (Yu et al.
1983). Many of the earlier studies (including the prospective studies reviewed in thi\
Chapter) did not exclude the possibility that cancer of the liver may have been primary
in another (smoking-related) organ. The possible role of hepatitis B as a modifier of
the effect of smoking on the risk of liver cancer is not clear (IARC 1986).

Tobacco has been associated with stomach cancer. but whether this association i\
causal remains unclear (IARC 1986: US DHHS 1982. 1989). Fe& studies have
considered the effect of cessation on the risk of stomach cancer. The U.S. Veterans
Study (Kahn 1966; Rogot and Murray 1980) and the Swedish study (Cederlof et al.
1975) indicate a reduction in stomach cancer risk after cessation. although the relative
risks among current smokers were small in these studies (Table 8).

Leukemia has recently been implicated as a smoking-related disease (Austin and Cole
1986: Severson 1987: Kinlen and Rogot 198X). hut this observation has not been
consistent (for review. see Kinlen and Rogot 1988). The U.S. Veterans Study showed
only a slight dose-response relationship formyelogenous leukemias. but there uas little
difference in risk between current and former smokers (Kahn 1966: Ropot and Murray
1980: Kinlen and Roget 1988 ). In the earlier presentation of these data. there was no
difference in risk among ex-\mohers. compared b ith current smokers. at any of four
levels of prior cigarette smoking (Kahn 1966). The most recent analysis of these data
indicated there was little difference in risk among fomrer smokers compared with
current smoker5 for any of the subtype\ of leukemia. One study demonstrated a poorer
prognosis for patients with myelogenous leukemia who were cigarette smohers (Ar-
chimbaud et al. I989 ).

MULTIPLE PRIMARY CANCERS

The occurrence of multiple primary cancers may reflect the effects of the same risk
factor\ in the pathogenesis of the multiple cancers. the effects of agent5 used in treating

176


the initial malignancy. or simply the consequence of chance (Schottenfeld 1982). Thus.
multiple primary cancers have been investigated with the goals of examining envJiron-
mental and host factors increasing cancer risk and of identifying adverse consequences
of cancer treatment. Tobacco use, including cigarette smoking. has been examined as
a risk factor for the development of a second primary cancer. after diagnosi\ of a first
malignancy at cigarette-associated and non-cigarette-associated \ites: the effect of
smoking cessation on the occurrence of second cancers has also been addressed in
several investigations.

Descriptive studie\ have shown that an initial malignancy at a smoking-a5sociatsd
site is followed by an increased risk for cancer at the same or another cigarette-
associated site (Wynder et al. 196% Schottenfeld 1082). In an early study of multiple
primary cancers. Berg. Schottenfeld. and Ritter (lY70) examined the risks of second
primary cancers in persons evaluated at Memorial Hospital for squamous cell cancers
of the respiratory or upper digestive tract or other histologic types of lung cancer.  In
comparison with expected numbers of cases based on incidence rates for New York
State. significant excesses wtere observed for cancer\ of the lip. oral cav,ity or pharynx.
esophagus, larynx, and lung.

Only limited evidence is available on the effects of smoking cessation on the
occurrence of multiple primary cancer\. Moore reported two studies ( 1965. I97 I ) of
second primary cancers in persons with an index malignancy of the mouth, pharynx. or
larynx: both showed reduced risk for a second primary cancer in persons who stopped
smoking after diagnosis of the first cancer. For I to IS years. Silverman, Gorsky. and
Greenspan (1983) observed I17 smokers who had a primary cancer of the head and
neck region. Thirty percent of continuing smokers developed a second oral primary
cancer compared with IS percent of those reducing smoking and I3 percent of those
completely stopping.

In contrast, an effect of cessation was not found in two other studies (Castigliano
1968; Schottenfeld. Gantt. Wynder 1974). Castigliano's 1968 study included 88
subjects with mouth or throat cancer who survived for at least 3 years without evidence
of recurrence. During a minimum followup period of 3 years, the occurrence of a
second primary cancer was not related to smoking status. Schottenfeld. Gantt, and
Wynder (1974) examined multiple primary cancers in 733 patients admitted to
Memorial Sloan-Kettering Cancer Center with a primary epidermoid carcinoma of the
Ordl cavity, pharynx, or larynx. During the .5-year followup period. the smoking status
of those developing and not developing a second primary did not differ significantly.

Interpretation of these studies is limited by the small numbers of subjects and the
limited duration of followup. Furthermore. the interactions of tobacco smoking with
other risk factors of cancers of the head and neck, particularly alcohol consumption,
complicate interpretation of these data.

SUMMARY

This review of the relationship between cigarette smoking cessation and the risk of
nonrespiratory cancers has shown that former smokers tend to have lower risk than
current smokers forcancers of the oral cavity, esophagus, pancreas, bladder, and uterine

177


cervix. This lower risk appears to be neither an artifact of a lower exposure to cigarettes
in former smokers prior to quitting nor a result of confounding by other known risk
factors for these cancers. This observation of a diminution in risk further supports the
hypothesis that cigarette smoking is a causal factor for cancers of many sites other than
the respiratory system. Although smoking is not as strong a risk factor for non-
respiratory cancers as it is for cancers of the lung and larynx, substantial numbers of
cases of many nonrespiratory cancers can be attributed to tobacco use (US DHHS 1989).
The patterns of diminution in risk with increasing duration of abstinence indicate that
smoking cessation provides a substantial reduction in the risk of nonrespiratory cancer.

CONCLUSIONS

I. Smoking cessation halves the risks for cancers of the oral cavity and esophagus.
compared with continued smoking, as soon as 5 years after cessation, with further
reduction over a longer period of abstinence.

2. Smoking cessation reduces the risk of pancreatic cancer, compared with continued
smoking, although this reduction in risk may only be measurable after IO years of
abstinence.

3. Smoking is a cause of bladder cancer; cessation reduces risk by about SO percent
after only a few years. in comparison with continued smoking.

4. The risk of cervical cancer is substantially lower among former smokers in com-
parison with continuing smokers. even in the first few years after cessation. This
finding supports the hypothesis that cigarette smoking is a contributing cause of
  cervical cancer.

5. Neither smoking nor smoking cessation are associated with the risk of cancer of the
  breast.

178


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I x0


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IXI


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and bladder cawr 111 Argentina. l~rtc,i-,rc~r/o/~o/.I~~r,,./i~// of'Ctr~w(~r -!Ot61:733-7-l0. December
IS. lY87.

JENSEN. J.. CHRISTIANSEN. C.. RODBRO. P. Cyarette \mohing. serum estrogens. and hone
locc during hormone-replacement therapy early after menopause. !Ye11. Eyy/o,rcl ./olrwci/ of
Mctlki,w 3 I3:Y73-Y75. IYXS.

JENSEN. O.M.. KNUDSEN. J.B.. MCLAUGHLIN. J.K.. SORENSON. B.L. The Copenhagen
case-control study of renal pelvk and ureter cancer:  Role of \mo)ling and occupational
exposure>. /r,lc,,.rfrrtiorfu/ .lor,,.,kr/ <$Crrrrc.rr. 3 I (3):557-S6 I. April 15. 19xX.
JENSEN, O.M.. WAHRENDORF. J.. BLEITNER. M.. KNUDSEN. J.B.. SORENSEN, B.L.
The Copenhagen case<ontrol study of bladder cancer: Role of smoking in invacive and
non-invasive bladder turnours. ./of/r-/,trl ~~~E/,i~lc,tlllo/,~,~? (1)1d Co,,rwfr,ri!\ Hca//h 4 I ( I ):3&
36, March 1987.

JOHNSTON, W.D.. BALLANTYNE. A.J. Proyostlc effect of tobacco and alcohol use in
patients with oral tongue cancer. Al/rc/?c till .lo~ow// of`S~o:q~~~y 133:141--147. 1977.
KABAT. G.C.. HEBERT. J.R.. WYNDER. E.L. Ri& factors for oral cancer in women. C</,rw~.
Rc.wtrrd~ 4% 10):2X133-2806. May IS. I YXY.

KABAT. G.C.. WYNDER. E.L. Type of alcoholic beverage and oral cancer.  I/lfe/.wlfi~wl
.lo~rrrlol c$Crrr,c (81' 332 ): 190-I 93. February IS. 19X9.
KAHN. H.A. The Dom study of smohing and mortality among US \ eteraw Report on eight
and one-half years of observation. In: Haenrel. W. (cd.) &/cl~r~rrt~/o,qi( (I/ A/>,nw~/c Ilt>.c lo r/w
Slrtrl~ of CU/iW/~ 1111d Orlrar CIlI~olllr~ Di\cw\c~.\.  NC1 Monograph 19. U.S. Department ot
Health. Education. and Welfare. L1.S. Public Health Service. National Cancer Institute.
January 1966. pp. I-125.

KINLEN. L.J.. ROGOT. E. Leukemia and \mohmp habIt\ among Cnited States wtcran\.
B~.rti.cll M&rr (I/ ./orcwtrl 207(66-l9):657-65Y. Scptcmber IO. I YXX.
KOUMANTAKI. Y.. TZONOL. A., KOUMANTAKIS, E.. KAKLAMANI, E.. ARXV,4N-
TINOS. D.. TRICHOPOULOS. D. A ca\e<ontrol btud!, of cancer of the endometrium in
Athem. /,rlr,,.,rclto~,,tr/ .lol/r,w/ ~/`CLIII(.LJI. -&it5 ):7Y5%7YY. Ma! 15. I YXY.
KUCERA. H.. ENZELSBERGER. H.. EPPEL. W.. WEGHALPT. K. The Influenceofnlcottnc
abuse and diahctes mellitus on the re\uIt\ ofprnna-> irradl:rtmn in the treatment ofcarcmoma
of the cervix. Ctrr~c,r,. hO( I ): 11, July I. 10x7.
LAVECCH1A.C.. FRANCESCHI. S.. DECARLI. A.. F.4SOLI. M..GENTILE. A..TOGNONI.
G. Cigarette smoklnf and the risk of cervical neoplu\ia. .-\rwrlc.o,~ ./orf,.~rtr/ of E/)/k,~rc~>/~~,q>
113 I ):27-2Y. January IYXh.

LA VECCHIA. C.. LIATI. P.. DECARLI. A.. NEGRELLO. I.. FR.4NCESCHI. S. Tar ) leld\
ofcigarette\ and the ri\h ofwqhagral cancer. /~~rc,~.,rtr/io,rr//.I,~rc/.,r~~/ofC~r,~~ c~r'iX:.3X I -3X5.
1086.

LA VECCHIA. C.. LIATI. P.. DEC.4RLI. A.. NEGRI. E.. FRANCESCHI. S. Coffee conwmp-
tion and rish of pancrcatlc cancer. /r,lr,.,ftrt,~jrrt,l ./r~l/,-,w/ o/`Ctl/lc (`I' 10:3OY%.3 13. September
IS. 19x7.

LA VECCHIA. C.. NEGRI. E. The role of alcohol in ocwphafca1 cancer in non-mohcrr. and
the role of tobacco in non-drinhcr\. //lrc~,-,/~///rj/r~// .I<),,, w/ /$Ct///c (`I' 1315 ):7X-&7X.5. Md!
IS. IYXY.

LAM. K.C.. YC. M.C.. LEUNG. J.W.C.. HENDERSON. B.E. Hepatltij B virus and cigarcttc
wiokmg:  Ri\h factor\ for hcp~ttocellular c;Lrcinomil in Hong Ken:. C`tr/rwf. Ro.wtr/-c Ir
-13 12):5116-52-1X. Deccmhrr IYX2.

IX?


LESKO. SM.. ROSENBERG. L.. KAUFMAN. D.W.. HELMRICH. S.P.. MILLER. D.R..
STROM. B.. SCHOTTENFELD. D.. ROSEh3HElY. N.B.. KNAPP. R.C.. LEWIS. J..
SHAPIRO. S. C&arette smoking and the rixh of endometrial cancer. !Vtr\t. E,!q/c/,I<l Jorrmul
cjfMedic i/w 3 13( 10):593-596, 19x5.

LONDON. S.J.. COLDITZ. G.A.. STAMPFER. M.J.. WILLETT. W.C.. ROSNER. B.A..
SPEIZER. F.E. Prospective study of smoking and the rish of breast cancer ./~~rr/.,~cll ,!f'tll[,
N~~~iorld Coui cr. lristiflrrr X1 (2 1 ): 1615-163 I. Kovember I. 19x9.
LYON. J.L.. GARDNER. J.W.. WEST. D.W.. STANISH. WM.. HEBERTSOK. R.M. Smok-
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562. May lYX3.

MACDONALD. P.C.. EDMAN. C.D., HEMSELL. D.L.. PORTER. J.C.. SIITERI. P.K. Effect
of obesity on conversion of plasma androstenedione to e\tronc in postmenopau\al women
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130:43x355. 197x.

MACK. T.M.. YU. M.C.. HANISCH. R.. HENDERSON. B.E. Pancrea\ cancer and amolin?.
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76( I ):49%60. January I YX6.

MACMAHON. B.. YEN. S., TRICHOPOULOS. D.. WARREN. K.. NARDI. G. Coffee and
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MICHNOVICZ. J.J.. HERSHCOPF. R.J.. NAGANLMA. H.. BRADLOW. H.L.. FISHMAK.
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ber 19X6.

MILLS. P.K.. BEESON. W.L.. ABBEY. D.E.. FRASER. G.E.. PHILLIPS. R.L. Dietap habit\
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MOORE. C. Smoking and cancer of the mouth. pharynx. and larynx. ./o~r~~rcd of`tlrc Anwr% m
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MORRISON, A.S.. BURING. J.E.. VERHOEK, W.G.. AOKI. K.. LECK. I.. OHNO. Y..
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NISCHAN. P., EBELING, K.. SCHINDLER, C. Smoking and invasive cervical cancer rish.
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NOMURA, A., GROVE. J.S.. STEMMERMANN. G.N.. SEVERSON. R.K. A prospective
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NORELL. S.E.. AHLBOM. A.. ERWALD. R.. JACOBSON. G.. LINDBERG-KAVIER. 1..
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.lo7rr77ul ofPuhk Hculrh 79(X ): IO1 6-l 019. 19X').

IX3


OSHIMA. A.. TSLIKUMA. H.. HIYAMA. T.. FI~JJMOTO. 1.. YAMANO. H.. TANAKA. M.
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IYX4.

PETERS. R.K..THOMAS. D.. HACAN. D.G.. MACK. T.M.. HENDERSON. B.E. Risk factors
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ROHAN. T.E.. BARON. J.A. Ctgarette smohtng and breast cancer.  AnM~r~/t~url Jolo-IlUl of
Epitkt77io/r~,q~ l29( I ):3632. January IYXY.

ROSENBERG. L..SCHWIKGL. P.J.. KAUFMAN. D.W.. MILLER. D.R.. HELMRICH. S.P..
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SASSON. I.M.. HALEY. N.J.. HOFFMANN. D.. WYNDER. E.L.. HELLBERG. D..
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SCHECHTER. M.T.. MILLER. A.B.. HOWE. G.R. Cigarette smohing and breast cancer: A
case-control study of screening participants. Anro-ic.trrr .lo~r~xcr/ of`E/,ir/c~n7iolr,,y~ I Z I t4):379-
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SCHIFFMAN. M.H.. HALEY. N.J.. FELTON. J.S.. ANDREWS. A.W.. KASLOW. R..4..
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SCHOTTENFELD. D. Multiple primary cancers. In: Schottenfeld. D.. Fraumeni. J.F. Jr. (eda.!
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January 19x3.

SLATTERY. M.L.. ROBISON. L.M.. SCHCMAN. K.L.. FRENCH. T.K.. ABBOTT. T.M..
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26l( I I ):lSu)-ISYX, March 17. IYXY.

SLATTERY. M.L.. SCHUMACHER. h1.C.. U'EST. D.W.. ROBISON. L.M. Smokmp and
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January IS. 19xX.

SMITH. E.M.. SOWERS. M.F.. BURNS. T.L. Effects ofsmohing on the development of female
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IYXX.

STELLMAN. S.D.. AUSTIN. H.. WYNDER. E.L. Cervtx cancer and cigarette smohing: A
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19X3.

184


STOCKWELL. H.G.. LYMAN. G.H. Cigarette wlohin, (1 ;ultl the rr\L 01. l'cm;~lr reproductnr
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WILLETT. W.C.. BROWNE. M.L.. BA1N.C.. LIPNICK. R.J.. STASIPFER. M.J.. ROSNER.
B.. COLDITZ. G.A.. HENNEKENS. C.H.. SPEIZER. F.E. Relali\e Meight and rish of breast
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19x5.

WILLIAMS. R.R.. HORM. J.W. Ahcocicltion ofcancer \ite\ with tobacco and alcohol conwmp-
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WINN. D.M.. BLOT. W.J.. SHY.C.M.. PICKLE. L.W..TOLEDO, A.. FRAUME~I. J.F. Snuff
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WYNDER. E.L.. DODO. H.. BLOCH. D.A.. GANIT. R.C.. MOORE. O.S. Epidemiologic
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WYNDER. E.L.. HALL. N.E.L. POLANSKY. M. Epidemiology of coffee and pancreatic
.

cancer. Cor7wr Rrwr~c./~ 13(X):390(-3906. August 19X.3.
WYNDER. E.L.. STELLMAN. S.D. Comparative epidemiology of tobacco related cancer\.
Ctr~cw. Rc.wcrr~c~/7 37( I ?):36OX--l622. December 1977.
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Hepatitis. alcohol consumption. cigarette wiohinf. and hepatocellular carcinoma in Lo\
Angele\. C`tr,rc.c~r- Re.~c~trrc~h 1.?( 12. Part I ):6077-h07Y. December 19x3.

IX6


     CHAPTER 6
SMOKING CESSATION AND
CARDIOVASCULAR DISEASE

IX7


CONTENTS

Introduction  ....................................................... IY I

P~tthopli~~iol(lfic Framen orb  ......................................... I Y I
Smohing and Development ot.CHD  .................................. I Y I
  .r\thcrosclero\i~ .................................................  I Y I
  Thrombosi\ .................................................... I Y,i
  Sp~lslll ........................................................ IYS
  .L\rrh~~thmia\  ................................................... I Y5
  Reduced Blood Os!sen Deli\,er!  .................................. IO.5
Smohing and Development of Peripheral Arterial Diwase ................. I Yh
Smohing and Development ofC~rebrc~\34cttl;tr Diseae  IY)h
Anticipated Effect\ of Smohin, cr Ce\ation on Ri\h of`Cardio\ acular Disca\e\
  Bawd on Knou ledge of Mech;tniwl\  ............................... 197

Smohing Ceaation and CHD  ......................................... 197
Cross-Sectional Studie\  ............................................ IYY
Studies 01` Smohing Ceh\ation and Ri\h of` MI Among Health! Person\  ...... 700
  Cax-Control Studies ............................................ 200
   Cohort Studie\  ................................................. 70.5
  Intervention Trials  .............................  ................ 22-1
Smohing Cexttion and CHD Ri\h Among Person\ With Diqywed CHD  ... 770
Summary of Smohing Ce\ation and CHD Rish ......................... 23Y

Smohing Cewttion and Aortic Aneur>wl ................................ 211
Studies of Smohing Cessation and Rish of Aortic Aneurysm ............... 211

Smohing Cessation and Peripheral Arterial Occlusive Di\ea\e  ............... 211
Smohing Cessation and Development of Peripheral c\rtery Di\ea\e Z-l.3
Smohinf Cessation and Prognosi\ of Peripheral Artery Disease Z-l.1
Surnmar~ ........................................................ 11-J

Smohing Cehation and Cerebrovascular Disease ..............  ........... 215
Studies of Smohing Cessation and Ri+ of Cerebrovawular Disease ......... 2-W
  Cro\s-Sectional Studic\  .......................................... 7-K
  Case-Control Studieh ...........  ................................ 7-K
  Prospective Cohort Studies  ....................................... 2IY
  Summary of Observational Studies  ........  ........................ 75 I
   Intervention Studie\ ............................................. 251
  Influence of Prior Levels of` Smohing  ............................... 25 I
   Effect of Duration of Abstinence ................................... 32
  Oral Contraceptives and Stnohing Cessation  ......................... 25X
  Effect of Smoking Cessation After Strohe  ....  ...................... 260
Summary ........................................................ 2hO

Conclusions ..................................................... ..~60

References ...................................................... ..26 I


IIVTRODLCTION

Cigarette smoking is firmly established as an important cause of coronary heart
disease (CHD). arteriosclerotic peripheral vascular disease. and stroke (US DHHS
1983. 1989). Eliminating smohing presents an opportunit) for bringing about a major
reduction in the occurrence of CHD. the leading cause of death in the United States.
Before examining the epidemiologic evidence relating zmohin, ~7 cessation and rish of
CHD and other forms of cardiovascular disease (CVD). the mechanisms by uhich
smohing leads to these diseases are briefly reviewed. The objectives in considering
these mechanisms are to address the plausibility that smoking cessation reduces rish of
CVD. to estimate the expected magnitude in rish reduction. and to assess the rapidit)
with which any risk reduction might occur. Whether these mechanisms are immedi-
ately reversible. irreversible. or slowly reversible i\ of particular rele\,ance to the
rapidity with which smoking cessation will reduce rich. The role of smohins in the
pathogenesis of CHD is discussed at length.  Th e etiologies of peripheral \ ascular
disease and stroke share several common features M ith CHD: thus. discussion focuses
on distinguishing features.

PATHOPHYSIOLOGIC FRAMEWORK

Smoking and Development of CHD

Pathogenesis of CHD. which includes the clinical manifestations of myocardial
infarction (MI). angina pectoris. and sudden death. is extremely complex and mediated
by multiple mechanisms and etiologic factors (Munro and Cotran 198X). At least five
interrelated processes are likely to contribute to the clinical manifestations of MI-
atherosclerosis. thrombosis, coronary artery spasm. cardiac arrhythmia, and reduced
capacity of the blood to deliver oxygen. Smoking appears to influence many steps in
the development of CHD. Although not all of these effects are proven fully. the
evidence for an influence on several mechanisms is convincing. The exact components
of cigarette smoke that are responsible are not known in each instance. but experimental
data have implicated nicotine and carbon monoxide (CO) in several processes. Other
products of cigarette smoking, such as cadmium. nitric oxide. hydrogen cyanide. and
carbon disulfide. have been hypothesized to play a rote. but their quantitative contribu-
tions remain unknown (US DHHS 1983).

Atherosclerosis

Atherosclerosis is the mechanical narrowing of medium-sized arteries by the
proliferation of smooth muscle cells. lipid accumulation. and ultimately. plaque forma-
tion and calcification (Munro and Cotran 1988). These lesions develop over decades
and are not immediately reversible; whether they are substantially reversible at all in
humans is a matter of current interest. Reversibility has been demonstrated in non-
human primates (Clarkson et al. 1984: Malinow and Blaton 1983) and huggested in
studies of humans using repeated arteriography (Blanhenhorn et al. 1987). Smohing is

I91


clear]) associated with the presence of atherosclerosis of the coronary arterie>, small
arteries of the myocardium. the aorta. and other vessels ;I\ demonrtrated in man!
autops) and angiographic studies (US DHHS lYX3). The development of athero-
sclerosis is complex. and several processes are likely to be important.
Endothelial damage is thought to play ;I primary role in the development of
atherosclerosis by exposing the arterial intima to blood lipids and white cells and bj
stimulating platelet adhesion. The endothelial damage can be an actual physical
denudation. but toxic functional damage may have similar consequences. In animal
studies. serum nicotine at levels similar to those of human smokers caused endothelial
damage (Krupshi et al. 19X7: Zimmerman and McGeachie 19X7). Evidence that
smoking has a direct toxic effect on human endothelium is provided by the observation
that smoking 9 tobacco cigarettes approximately doubled the number of nuclear-
damaged endothelial cells in circulating blood (Davis et al. 198.5. 1986): smoking
non-tobacco cigarettes had little effect. In addition. Asmussen and Kjeldsen (1975)
found pronounced degenerative changes of the umbilical artery endothelium at the time
of delivery among mothers who smoked: these changes were not present in the arteries
of nonsmoking mothers.
Smooth muscle cell proliferation is a primary feature of atherosclerotic lesions and
may result from several stimuli: the mo5t clearly demonstrated is platelet-derived
growth factor from adherent platelets. Smoking appears to increase the adherence of
platelets to arterial endothelium: blood draun from persons after smoking 3 cigarettes
results in a more-than-hundredfold adhesion of platelets to rabbit endothelium than does
blood drawn from persons before smoking or from ne\`er smohers (Pittilo et al. 19X1).
Platelets from chronic smohers have a greater tendenc) to aggregate on an artificial
surface than do those from nonsmokers (Rival. Riddle. Stein lY87). In minipig>. both
cigarette smoke and CO increase the adhesion of platelets to arterial endothelium
(Marshall I YX6). The intluence of smohing on platelet activity is discussed further in
the following section.
Lipid infiltration of the arterial intima. largely cholesterol, is another primaq feature
of atherosclerosis and is directly related to higher blood levels of low-densit!
lipoprotein cholesterol (LDL-C) and reduced blood levels of high-density lipoprotein
cholesterol (HDLC'). Smoking reduces the level of HDL-C. A strong inverse associa-
tion betv,eren daily cigarette consumption and HDL-C has been observed in man)
cross-sectional studies in the United States (Freedman et al. 19X7; Gordon and Doyle
19X6: Reichle!, Mueller. Hanis et al. lYX7: Willett et al. IYX3) and in other countries
(Assmann. Schultc. Schrleuer IYXI; Goldhourt et al. I9Xh: Gomo lY86; Jacobsen and
Thelle IYX7: Pellctier and Baher IYX7: Robinson et al. 19X7: Tuomilehto et al. 19X6).
In a longitudinal. community-based study. HDL-C decreased among persons starting
to smoke and increased among those &ho stopped smoking (Fortmann. Haskell.
Williams 19X6). In other prospectike studies. smoking abstinence ha\ been associated
M,ith substantial increases in HDL-C levels in both men and women (Hulley. Cohen.
Widdouson IY77: Hubert et al. 19X7: Rabhin 19X-t). In a stud) among young adults
in Louisiana. those \vho began smohing experienced substantial reductions in HDL-C
compared with those u ho did not start (Freedman et al. I%%). HDL-C increased among
I3 adult women who \uccessfully stopped smohing for 18 days. but decreased to its


previous levels among those vvho returned to smohing (Stamford et al. IYXh). Thus.
data indicate that smoking reduces the level of HDL-C. a potent protective factor against
CHD.

In a number of studies. smokers ha\,e been found to hav,e higher levels of triglycerides
(Freedman et al. 19X6: Jacobsen and Thelle 19X7; Gomo 19X6: Willett et al. lYX3):
however. the independent relation of triglyceride level with rish of CHD is not clear.
Smoking appears to have little. if any. relation with LDL-C level. Howsever. smokers
have approximately twice the level of serum malondialdehydt of nonsmohers (Nadiger.
Mathew. Sadasivudu lYX7): malondialdehyde can alter LDL-C and may promote its
incorporation into arterial wall macrophages (Steinberg et al. IYXY). In a metabolic
study among young men. smokers had a decreased cholesterol net transport from cell
membranes into plasma. which could partially explain the accumulation of cholesterol
in arterial walls (de Parscau and Fielding 19X6).

Thrombosis

Coronary artery thrombosis, resulting from platelet-fibrin thrombi, is a key element
in most cases of MI. Thrombi are visualized in a high percentage of coronary arteries
studied angiographically within hours of the onset of infarction (DeWood et al. I YXO).
and agents that lyse thrombi are effective treatments for MI (Stampfer et al. 19x7;
Loscalzo and Braunwald IYXX). The efficacy of aspirin. an antiplatelet agent. in
preventing MI further supports the role of thrombus formation (Steering Committee of
the Physicians' Health Study Research Group lYX9). The finding that smoking is
associated with history of MI even after controlling for atherosclerosis (Hartz et al.
19X I ) emphasizes the importance of mechanisms in addition to those that promote
atherosclerosis.

Platelets play a central role in thrombus formation in addition to releasing growth
factors that stimulate the proliferation of smooth muscle cells in arterial intima (Pack-
ham and Mustard 19X6). Platelets can form microthrombi that become incorporated
into the arterial wall, thus contributing to plaque formation and participating in
generation of larger platelet-fibrin thrombi that may acutely occlude a coronary artery.
Smoking cigarettes acutely increases spontaneous platelet aggregation in humans
(Davis et al. 1985) and in dogs with coronary artery stenosis (Folts and Bonebrake
19X2). Madsen and Dyerberg ( 19X4) observed that smoking 2 high-nicotine cigarettes
substantially reduced bleeding time among healthy young men, although ex vivo tests
of platelet aggregability vvere only minimally inhibited. In this study. smoking low
nicotine cigarettes and inhalation of CO had little effect on bleeding time. Shortened
platelet survival, an indirect indicator of activation. was observed in smokers and
reverted to normal after 4 weeks of smoking abstinence (Fuster et al. 19X I ).

Studies of smoking and platelet aggregation ex vivo in response to the typical stimuli
used in the laboratory. such as adenosine diphosphate (ADP) or thrombin. are incon-
sistent. Increased aggregation has been seen with platelets from chronic smokers
(Belch et al. 1984) and in blood drawn IO minutes after smoking I cigarette (Renaud
et al. 19x5; Renaud et al. 1984); in the latter study. aggregation was associated with
blood nicotine levels but not with carboxyhemoglobin (COHb) levels. However. in


other studie\. ex viva platelet aggregation was not related to cigarette smoking (Pittilo
et al. 19x3; Dotevall et al. 19X7: de Loyeril et al. IYXS: Madsen and Dyerberg 19X3).
In one large study. aggregation in response to ADP stimulation was actually somewhat
greater in nonsmoker\ (Meade et al. 19X5). Studies of the effect of smoking on platelet
production of thromboxane. which mediates the aggregatorv effect. have also been
inconsistent. In some studie\. smohing was found to acutely increase thromboxane
blood levels. which reflect the capacity to produce thromboxane in response to stimula-
tion. and urinary metabolitea. which reflect the normal steady-state production
(Toivanen. Ylikorhala. Viinihka 19X6: Marasini et al. 19X6: Fischer et al. 1986).
However. serum thromboxane B? level\ were found to be similar among chronic
smokers compared with nonsmokers in another study (DotevaIl et al. 19X7). The
serious limitation\ of cx vivo aggregability measurements in the evaluation of in vivo
platelet activity have been noted (Fitqerald. Oates. Nowak 19Xx). These researchers
meawred urinary excretion of a thromboxane metabolite and found elevated levels in
chronic smohers that were reduced to the level ofnon~mokers after aspirin administra-
tion. suggesting ;I platelet origin of the excess excretion (Nowak et al. 1987).
The luch of a consistent relation between making and ex viva te\ts of platelet
aggregability despite the demowtration that platelets of smoker\ adhere more readily
to endothelium has led to the suggestion that wioking inhibits the production in arterial
walls ofprostacyclin. an inhibitor of platelet aggregation (Mad\en and Dyerberp 1984).
Reinders and coworkers ( 19X6) demnnwated that the production of prostacyclin b)
cultured human endothelial cells is impaired by incubation with cigarette \mokc
condensate. Pittilo and colleague3 ( 1982) also found that smoking reduce\ endothelial
cell synthesis of pro\tacyclin in rats. Thu\. in \.i\o making-related effects on platelet
function may be mediated in part b>, an interaction with endothelium.
Fibrinogen levels have been found to be elevated among smoker\ in numerow
cross-sectional studies (Meade et al. 19X6: Kennel. D'Agostino. Belanger 19X7: Wil-
helm\en et at. 19x3: DotevaIl et al. 19X7: Belch et al. IYX3: Ballei\en et al. IYX5).
Fibrinogen levels. in turn. are \trongl!. related to ri\h ofCHD and stroke (Meade et at.
lYX6: Kannel. D'Ago\tino. Bel;inycr 19X7: Wilhelmwn et al. t9X4). Smohing ce\w
tion rewlted in ;I decrease in fibrinogen levels after 1 w,eeh\ among Y female moher\
(Harenberg et aI. t YX5) and after X LI eeh\ among I1 mule maker\ (Ernst and Matrai
1987). In the latter stud\. the level\ after X v,eeh\ \+eere similar to those among nc\`er
maker\. When fibrinogen M;I\ remeasured after 5 bears. \ alues had decreased to the
level\ofnever smoker\ among men u ho had stopped wiohin, L ~7 ,tnd had incren\ed amonp
thaw M,ho started or rrsumcd wiohing (Made. Imcson. Stirling 19X7). In multivariate
analk\e\ ofdata from the Fram~ngham Stud! (Kanncl. D'.Qo\tino. Belrmger 19X7) and
Northu ich Parh Stud! (Me& et al. 19X6) that both included cigarette smoking as uell
;I\ fibrinogen le\ttl\, fibrinogen retained a clear independent a\socistion \\ ith ri\h ot
CHD. whereas the effect of smohing \~a\ sub~tantiatt! reduced after the inclusion of
fibrinogen in the model. Thi\ anatysi\ wggest\ that elevated fibrinogen le\,els ma>
mediate a quantitativeI! important part of the effect ot` smoking on CHD rish.
Other clotting abnormrrlitie\. such as increuwd plasma viscosity and reduced red cclt
deformabilit>. that tend to promote thrombw formation ha\,e alw been obwrwd in
smohers (Belch et al. IYX-!). In addition. Iewls of plawiinogen. which promote\ I\\i\


of thrombi. are lower in smokers (Wilhelmsen et a). 1983: Belch et al. 1984). but the
levels increase after smoking cessation (Harenberg et al. 1985).

Spasm

Coronary artery spasm can cause acute ischemia manifested as angina pectoris and
may promote thrombus formation at the site of repeated arterial constriction (Felts and
Bonebrake 19X2). Both chronic and acute cigarette smoking have a demonstrable
vasoconstrictor effect on the coronary vasculature (Klein 1 YX3). Compared V. ith never
smokers. current smokers have an approximately twentyfold risk ofvasospastic angina
pectoris (Scholl et al. 1986). Coronary artery spasm has also been identified bl
angiography after smoking a single cigarette (Maouad et al. 1983). Smohing-induced
vasoconstriction has been demonstrated in patients with atherosclerotic coronary artq
disease (Martin et al. 19X3) that is mediated by an cx-adrenergic increase in coronary
artery tone (Winniford et al. 19X6). In addition. smokin, L 0 3cutely increases platelet and
plasma vasopressin (Nussey et al. 19X6) as well as the carrier protein of vasopressin
and oxytocin (de Lorgeril et al. 1985). In addition to causing acute arterial spasm.
cigarette smoking appears to be associated with a reduction in long-term coronary arter)
diameter independent of atherosclerotic plaque (Fried. Moore. Pearson 19X6). although
the mechanism for this relationship is unclear.

Arrhythmias

In some instances, arrhythmias can precipitate Ml by reducing cardiac output or
increasing myocardial demand. More importantly. arrhythmias are a major complica-
tion of infarction. Thus. reducing the threshold for serious arrhythmias tends to increase
the case-fatality rate of MI. Cigarette smoking was found to lower the threshold for
ventricular fibrillation in a study of animals (Downey et al. 1977) and was found to be
associated with a 2 I -percent increased prevalence of ventricular premature beats on
two-minute electrocardiographic rhythm strips obtained from IO. I I9 men (Hennekens
et al. 19X0). Smoking-related ventriculararrhythmias may contribute to the occurrence
of cudden death and to increased case-fatality ratios during the courre of MI.

Reduced Blood Oxygen Delivery

Cigarette smoking acutely increases myocardial oxygen demand b\, raising
peripheral resistance, blood pressure, and heart rate (Martin et al. 1983: Klein 1984).
Concurrently, the capacity of the blood to deliver oxygen is reduced by increased
COHb, greater viscosity (Galea and Davidson 19X.S). and higher coronaq vascular
resistance. Imbalance between oxygen requirement and delivery as a result of these
factors is not likely to be a cause of MI but may contribute to infarction in the presence
of significant atherosclerotic narrowing of vessels. Consistent with these mechanisms.
low levels of COHb exacerbate myocardial ischemia during graded exercise (Allred et
al. 19X9). and smoking is associated with more frequent and longer ischemic episodes
detected by ambulatory electrocardiographic monitoring among patients M ith chronic


stable CHD (Barr\ et al. 19X9). Blood and plasma 1 iscwities among former smokers
are lower than thaw among current smoker\ and Gmilar to thaw amon never smoker\
(Ernst and Matrai 19X7 ). In the wit stud>,. both blood and pluma viscosity decreased
after wioking ce\\ation and were similar to levels of never makers after X weeks.
Reduced oxygen delivery to the myocardium ma) play a role in lowering the threshold
for ventricular arrhythmias.

In addition to influencing the development ofCHD. smoking ha\ been hypotheGzed
to have direct toxic effect\ on the myocardium. Hartz and coworkers ( I9X-I) found ;i
nearly threefold increavzd prevalence of diffuse ventricular hypoLine\is among heavy
smoker5 compared with never makers within 3 population of patients undergoing
diagnostic coronary ungiography and ventriculogrsphy.

Smoking and Development of Peripheral Arterial Disease

The extremely strong aswcistion between smoking and peripheral artery disease is
likely to be mediated largely through the mechanisms that promote atherosclerosis
(Criqui et al. 1989). The peripheral \awcon\trictive effect\ of smoking. mediated bj
nicotine-stimulated release of catecholamines (US DHHS 19X3). are likely to play a
further important role (Lusty et al. 19X I ).

Smoking and Development of Cerebrovascular Disease

Cerebrovawulur diwae reprewnt\ a heterogeneous group of pathologic processes
that include infarction due to jteno\is and thrombo\i\ (referred to here a\ ischemic
stroke). embolism from the heart. and hemorrhage from medium-hized vessels in the
wbarachnoid space (wbarachnoid hemorrhage) and from microaneutyms of smaII
penetrating vessel\ (intracerebral hemorrhage).  The association of \mokinp with
ischemic strobe i\ likely to be mediated largely through the mechanisms that promote
atherosclerwis and thrombus formation. Associations between smoking and extent of
cerebral artery athcrowlero\i\ ha\ e been obher\ ed at Irutop\) among persons u ho haw
died of cauw\ unrelated to CVD (Reed et al. I9XX) and among volunteer\ in 3
crowaectlonal stud> evaluated b! ;I nonin\as~\.t` method (Rogers et al. 19X.3). Smoking
was a1w ;I strong predictor of the extent and w~erity of cerebral ve\\el atherowlcro\i\
in an Italian multicenter \tud> of rever\ible cerebral ischemic attack> fPas\ero et A.
19X7) and in an in\c\tiyation of 2X pair\ of Finnish tn in\ (Haapanen et al. 19x9).

The mechanistic ba\i\ i\ unhnoun for the strong relation hettieen smoking and
\ubarachnoid hemorrhage (US DHHS 19X9: Shinton and Beever\ 19X9). which is
thought to result mo\t commonl! from the rupture of a baccuI;Lr aneurysm. .Although
hypertension i\ a\sociatcd uith thij occurrence. chronic \mohing is unrelated to
w\tained elwation in blood prehwre.  A ueah and clinically unimportant inverse
relation with hypertension ha\ been \een in several studie\ ISchoenenbeqer 19X2; US
DHHS 1983). although the association betw,ecn cigarette smoking and risk of hyper-
tension was obser\,ed in 3 large pro\pecti\e ime5tigation (Witteman et al. 1990).


.Anticipated Effects of Smoking Cessation on Risk of Cardiovascular Diseases
         Based on Know ledge of Mechanisms

The possible effects ofsmohing cessation on the rish of CHD are illustrated in Figure
1. The incidence of CHD increases sharpI!, with age mm~, `7 both smohers and net CI
smokers: similar patterns are seen V. ith other smohing-related cardio\,ascular diseases.
At each age. the rates are higher for smohers. and the increase with age is more rapid
among smokers (US DHHS 19X3: ACS. unpublished tabulations). probabl\ because ot
the ongoing. cumulati\,e damage caused bj smoking. Thus. the absolute excess
incidence or mortalit>. (attributable rish) of CHD due to smohing. represented b> the
vertical difference bet&eeen the lines for- smokers and never smokers in Figure I.
increases u ith age. However. the relative rish. represented b!, the ratio of incidence or
mortality rates, tends to decrease with age.

Theoretically possible outcomes ofsmokinfcessation are depicted by lines A. B. and
C (Figure I ). Line A represents an immediate and complete reversal of the effect ot
smoking. so that the quitter ahnost instantly assumes the rate of the never smoher. Line
B represents the worst-case scenario: although the stimulus for progressive damage is
removed. no reversibility exists so that the former smoker assumes a constant absolute
excess risk above that of the never smoker. In this case. it is apparent that quitting
would still provide a substantial benefit compared with not quitting and that the relatiic
risk for a former smoker compared with a never smoker w,ould decline over time. An
intermediate effect of smoking cessation is depicted by line C: the effects of smohinp
are slow~ly reversed. and the rate for the quitter gradually approaches that of the never
smoker.

The effects of smoking on CHD are probably mediated by multiple mechanisms.
several of which are well established. Some of the effects of smoking appear to be
reversible within days or weeks, including the increase in platelet activation. clotting
factors. COHb, coronary artery spasm. and increased susceptibility to ventricular
arrhythmias. Other effects may be irreversible or only slowly reversible. such as the
development of atherosclerosis as a result of smooth muscle proliferation and lipid
deposition in the arterial intima resulting from lower HDL-C levels. Thus. persons who
stop smoking are likely to experience a component of rapid decline in risk compared
with those who continue to cmoke and another component that more slowly approaches
the risk of never smokers. Because the effects of smoking are multiple and complex.
the rapidity and magnitude of risk reduction achieved by smoking cessation can best
be estimated by empirical data based on epidemiologic studies in humans. Available
data are examined in detail in the remaining sections of this Chapter.

SMOKING CESSATION AND CHD

Epidemiologic evidence on smoking and CHD has been reviewed in detail in previous
reportsofthe U.S. Surgeon General (US PHS 1964: US DHEW 1971. 1979; US DHHS
1983, 1989). After an exhaustive review of the data, the 1983 Report of the Surgeon
General concluded that "cigarette smoking is a major cause of CHD in the United States
for both men and women" and "should be considered the most important of the knon n


CHD Mortality
(par 100,000 porron - yrrrd

700

800

600




400




300




200





100




0

1       I

40     46

I       I

60    66
Age

L       L

60     06

FIGURE I.-Hypothetical effects of smoking cessation on risk of CHD if
     mechanisms are predominantly rapidly reversible (A),
     irreversible (I!), or slowly re\ ersible (C ). (CHD mortalit! rates
      shown in solid lines are for men in ACS CPS-II, 198246.3

modifiable riA t`actors t'or CHD" I C'S DHHS 1983. p.6). O\erull. the Report noted that
smoher\ ha\e about a 70-percent e\c`c`\\ death rate t`rom CHD. and hea\ ier vwLer\
have an even greater eaces\ risk.

IYX


Since IYX3. additional e\,idence has accumulated to further support these con-
clusions. Some of these data were presented or summarized in the I YXY Report of the
Surgeon General (US DHHS IYXY). For IYX5. cigarette smoking was estimated to be
responsible for 71 percent of all CHD deaths in the United States among men aged 65
years or older and for 15 percent of CHD deaths among younger men. Tv.elve percent
of the CHD deaths among women aged 65 or older and -1 I percent of those in bounger
&omen were attributed to cigarette smoking. In 19X5. I I5.0()0 deaths from CHD were
attributed to cigarette smoking.

A large amount of data supports the vie\+ that active cigarette smohing substantialI!
increase5 risk of CHD. Data also indicate that former smokers have a lower risk ot
CHD than do current smokers. Despite methodolofic and geographic differences. the
studies are remarkably consistent in demonstrating a reduced risk of CHD among
former smokers. Much of this literature has been reviewed in earlier reports of the
Surgeon General (US DHEW lY7Y: US DHHS lYX.3) as dell as h> Kuller and
colleagues ( 1987).

This Section reviews the epidemiologic e\,idence of the effects of cigarette smohing
cessation on CHD rish. specifically MI and CHD death. The relevant studies ma\' be
divided into those that examine the effect among apparently healthy individuals
(primary prevention) and the effect among individuals already diagnosed uith CHD
for risk of recurrence or CHD death (secondary prevention). Cross-sectional studies of
the extent of coronary atherosclerosis also provide relevant information.

Cross-Sectional Studies

In a detailed study of coronary atherosclerosis. Auerbach and couorhers (lY76)
examined I .O% autopsied hearts from patients at the East Orange Veterans Administra-
tion Hospital and found that smokers had more severe disease than never smohers. with
past smokers having intermediate levels. Those who died from CHD or diabetes or
those who had hearts weighing more than 500 g were excluded. After aci,iustment for
age. current cigarette smokers had a prevalence of advanced CHD that ranged from
11.7 to 33.4 percent. depending on the number of cigarettes smohed per day. The
prevalence among never smokers was 5.3 percent compared with I I .O percent among
former smokers. The prevalence odds ratio of advanced versus no disease or minimal
disease was 2.4. when former smokers were compared with never smokers. In contrast.
among current smokers of I to 2 packs per day. the ratio was 6.7. A similar pattern was
observed for different pathologic manifestations of CHD.  The effect of duration ot
abstinence among former smokers was not analyzed.

Ramsdale and coworkers ( 1985) used arteriography to assess the extent of coronar)
atherosclerosis before surgery for valve replacement among 3X7 patients. All patients
provided a smoking history, including age at initiation of smoking and cessation of
smoking and average number of cigarettes cmoked per weeh. Among never smohers.
X7 percent had no stenosis greater than SO percent: only 60 percent of past smohers and
60 percent of current smokers were without this degree of stenosis. Of never smohers.
only 2.6 percent had three or more arteries affected compared with 10.6 percent of
former smokers and 13.2 percent of current smohers. Both current and past smoher-\


had more were coronary artery diseaw. The median xx~re among ne\er smokers and
current smokers was 0.2 and 7.X. respectively.  For pa\t smokers. the data were
prehented by duration since quitting. There was no evidence for a trend of decreased
effect by increasing time since cesation. The median score for those quitting within
the previou\ 5 year\ wa\ 5.0; for 5 to 10 year\. 5.0: and for IO year\ or more. 7.5.
Coronary atherosclerosi\ was positi\,ely correlated with lifetime number of cigarette\
smoked among both current or past smokers. In this study. past smokers had a slightly
worse coronary ri<k profile than other groups. No information v.a\ provided about past
or concurrent illness that may hwe motivated the former mokerh toquit. Nonetheles\.
this study supports the view that cigarette \mohing is a risk factor for atheroxlerohi\
and that a substantial duration of abstinence may be necesw! to appreciably reduce
its extent.

Weintraub and coworhers (1985) evaluated smoking history in I.339 coronq
arteriography patient\. Of thehe patients. YX1 had Ggnificant coronav diseae (7.5
percent or more obstruction).  Amount of current \mohing was not a si~niticant
predictor of serious obstruction after total pack-years were considered. On average. the
rish for such obstruction increased by about I percent per pack-year.

Cross-sectional studies ofarteriogrsphic finding\ can be difficult to interpret hecau\e
patient5 undergoins angiographs are clearl>~ not repre~entati\e of the general popula-
tion. Nonethelchs. the\e studies wpport the view that hmohing cause\ an increase in
atherosclerosi\ and that very recent quitting has little impact on coronar!~ \teno\i\.

Fried. Moore. and Pearson ( IYXh) studied the effects of \mohing h> a\he\Gng the
coronary diameter in 3 I men \\ho had normal coronar\' arteringrams. Men M ith an!
detectable \tenoGs in the main coronary arterie\ or more than 75 percent in an! coronq
branch were excluded to assess the effect\ of mohing on the caliber of coronary arterie\
in the absence of atherosclerosi\. These researcher\ found that after udjuhtment for
alcohol intahe (which i\ ;l\\ociated M ith u ider arteries ). current and former \moher\
had 10 to SO percent nxro~~er urterie\ than did neker smoher\. The pa$t \moher\ had
someuhat narrower arterie\ than current smokers although thi\ uas not stati\ticall!.
Ggniticant. Of the I I cx+mohcr\. 6 had quit in the previous year. This \tudg sugge\th
the po\\ihility of another per\i\ting effect of mohing. apart from promoting
atheroxlero\i\. not rapidI! raerwd b) cc\\stlon.

Studies of Smoking Cessation and Risk of MI Among Healthy Persons

Case-Control Studies

Table I wmmarizes data from ca\e+wntrol \tudie\ (Wlllett et al. 198 I : Rosenberg.
Kaufman. Helmrich. Miller et al. 1985: LaVecchia et al. IYX7: Rosenberg. Palmer.
Shapiro 1990). of men and Momen from the LInited State\ and abroad. Prospective
\tudie\ of CHD are generally considered lea prone to bias than ca\exontrol htudie\.
although casexontrol \tudie\ are probuhly 1~54 susceptible to mi\cla~sificntion rewlt-
in? from resumption of smohing mnong former smoker\. For example. an individual
diagnosed u ith a recent MI can probably recall his or her \mohing \tatu\ .just before
the infarction with cowiderable accuracy (Chapter 7). Thu\. c:l\exontroI \tudiek ma>



TABLE I.-Case-control studies of CHD risk among former smokers

Reference         Population

Number of
CBIC\

Willett et al.
(19X1)

Nurses Health Study: women
aged JO-55

263

5.260

Nested m cohort

2Y

Overall
I .o 10.7-1.h)

2.0 (7.34.0)

Quit I-4 yr
I .s (0.7-3. I )

Rosenberg.      Eastern US men aged 45      1.x73       2.775    Hwpitnl-bawd
Kaufman. Helmrich.
Shaptro (19x5)

Rosenberg.      &tern US women aped 40      5.55       1364    Ho\pitnl-bawd
Kaufman. Helmrtch,
Miller et al. ( 1985)

LaVecchia et al.
(10x7)

Italian women aged 45

IhX

2.51

34x

3s

@It S-4 yr
I.3 to.x-3.0)

Quit 210 yr
O.h(O.l-1.3)

I.1 (O.`J-1.4)

I 0(0.7-1.0)    I .A-7.0 depending 011
        cig/da,


TABLE I.--Continued

@IIt <?`I ,110
2.6 ( I .X-.3.X)


be quite v,aluable in assessing the time course for the decline in risk. However. the lack
of detailed data on fatal cases is a potential limitation of the case-control approach.

In a csse+ontrol study of women in the Nurses Health Study cohort. Willett and
coworkers (1981) identified 263 women who reported a nonfatal MI on the baseline
Nurses Health Study questionnaire in 1976 wjhen they were 30 to 55 years ofafe. Their
smoking histories were compared with randomly selected controls corresponding in
age with a case-control ratio of l:ZO. Women who were former smokers did not
experience increased risk of Ml. with a relative risk compared with never smokers of
I .O (9Spercent confidence interval (Cl). 0.7-I .6). In contrast. current smohers had a
significantly elevated threefold higher risk of MI. When duration of abstinence was
assessed. it appeared that those who quit either I to 3 or 5 to 9 years earlier had a
nonsignificantly elevated risk of IS, and those who quit IO years or more earlier had
a relative rish of 0.6. Because there were only 39 cases among former smokers. the
estimates for risk by duration of abstinence are not precise.

Rosenberg. Kaufman. Helmrich. and Shapiro ( 19X5) specifically analyred the impact
of smoking cessation on risk of first MI among 4.64X men less than 5.5 years of age.
using a hospital-based case-control design. Men with known preexisting heart disease
were excluded. The 2.775 controls were mostly persons with fracture or sprain. disk
disorders, and gastrointestinal disorders thought not to be related to cigarette smoking.
There were 1.X73 cases and 2.775 controls. For current smokers (smoked within the
past year). the age-adjusted relative risk w'as 2.9 (9Spercent Cl. 2.4-3.3) and for past
smokers overall, it was I. I (9Spercent Cl. 0.9-I .4). The relative risk for those who
had not smoked for I? to 23 months was 2.0 (9S-percent Cl. I. l-3.X). For those with
longer durations of abstinence. the relative risk was I. I (9S-percent Cl, 0.9-l .4) (Figure
2). The risk was increased for those smoking more cigarettes per day among current
smokers as well as recent quitters. For longer durations of abstinence. the amount
previously smoked appeared to have little impact. These investigators also examined
the effect of quitting within categories of other risk factors; in general. there were no
marked differences other than for diabetics among whom the benefits of cessation
appeared to be greater. The same group of investigators (Rosenberg. Kaufman,
Helmrich. Shapiro 1985) addressed the possibility that continuing smokers and former
smokers may differ in their underlying risk of heart disease. They found that those who
quit had a slightly higherrisk profile. Hence. the benefit of cessation in this study cannot
be attributed to overall better health among those who quit.

Rosenberg and associates ( 19X5) also conducted a hospital-based case+zontrol study
of first nonfatal MI among women less than SO years of age (Rosenberg. Kaufman.
Helmrich. Miller et al. 1985). Women who smoked in the year before admission were
classified as current smokers. Participants consisted of 555 cases and 1 .X64 controls
who were hospitalized for trauma, orthopedic disorders. and other conditions thought
to be unrelated to smoking. Current smokers had relative risks increasing from I .4 to
7.0, depending on the number of cigarettes smoked per day. In contrast. former smokers
(at least I year of abstinence) had the same risk as never smokers, with a relative rish
of I .O (9Spercent Cl. 0.7-l .h).

In a recent report, Rosenberg, Palmer, and Shapiro ( 1990) further examined the
decline in risk of MI among women who stopped smoking. Cases included 9 IO women

203


40

EX-SMOKERS

FIGURE 2.-Estimated relative risk of MI after quitting smoking among men
      under age 55, adjusted for age: 95% CIs are indicated by
      vertical line: relative risk for men who never smoked is 1.0
%OTE: MI=n~~wmii;ll 11113I.cII011. cI=Lmf`ld~rlic m,Lmal.

SOCRCE R~wntw~. Kauln~dn. Hdnwh. Shapmr t lW51.

with first infarction: their mohing hi\torie\ were compared with those of 2.375
hospitalized control\. Anion, Q ti,rmrr \mohers olersll. the relative rik of MI was I ..!
(%-percent Cl) compared L\ ith never mohers: for current smohers the relative risk wa\
3.6. When former smoker\ were subdivided according to duration of abstinence.
women who had stopped smohing within the previou\ 24 month\ had a relative r&k of
2.6 (95percent Cl, I .X-3.X ). The relative ri\k was I .3 for those who stopped smohing
14 to 35 months earlier. \f'ter 3 years of abstinence. relative risks ranged from 0.X to
I. I and were indistinguishable from that of women who had never smoked.


Cohort Studies

Data from prospective cohort studies are summuri/ed in Table 3. The British
Physicians Study of Doll and Hill ( 1955. lYS6) \~a\ one of the important earl! studieh
that established the linh betv.een smohing and rish of CHD and the health benefits of
cessation. The stud\ is based on a sur\eJ of40.637 British ph\,sician\ who responded
to a I YS I questionnaire inquiring about smohing behavior. A ~cond questionnaire uas
mailed to men in 1957-58 and to women in IY60-61: the response rate uas YX percent.
The IO-year followup (Doll and Hill lY61) u\ed the updated data to assess rich amo~~g
former smokers. Additional questionnaires were distri hured in lY66 and 1 Y72. u ith
response rates of96 and YX percent. respectlvel\,. The `O-year follou up of 31.W) me11
(Doll and Peto lY76) shohed ;I reduction in CHD mortalit! among former smohers.
The benefits were more apparent in the > oungcr age group. and the excess risk declined
with increasing duration of abstinence. In men aged 31 to 53 year\. the relative rish
among former smohers of I to 4 \ ears' duration M ;I\ I .Y compared u ith ne\ er smohers:
relative ri$k further declined to 1 .4 to 1 .3 with a maximum of 20 years' duration ot
abstinence. In contrast. persistent smohers had a relative rish of3.S. In this study. those
who quit had smoked about IO percent fewer cigarettes per day before quitting than did
persistent smokers.

The British Physicians Study also included 6. IY4 women. for whom the data \h'ere
reported sepsrately (Doll et al. 19X0). These women completedquestionnaires in IYS I.
I Y61. and 1973. In contrast to most studies among adults. a substantial minority of
nonsmoking women in this cohort initiated cigarette smohing between 195 I and 1961.
Thus. the rates of smoking-related diseases among thoe classified as never smokers
are likely to be overestimated because never smokers. defined according to the 195 I
data. included a proportion of subsequent current smokers. Overall. the relative risk of
CHD mortality among former smokers was 0.Y compared with I .O to 2.2 among current
smokers. depending on the amount smoked. Because there were only 26 cases among
former smokers. a detailed analysis was not performed.

The first large-scale American Cancer Society (ACS) cohort was assembled in 1952
when 1X7.783 men aged SO to 6Y. living in 9 States, completed a questionnaire related
primarily to smoking (Hammond and Horn 19SXa.b). The men were enrolled by over
22.000 ACS volunteers each of whom was asked to enroll IO individuals, excluding
those who were seriously ill. There was no further update of cigarette uce. These men
were studied for fatal outcomes for an average of 44 months. for a total of 667.753
person-years. Cause of death for 1 1,870 individuals was determined by death certifi-
cate. Compared with never smokers. the relative risk of death due to CHD among
current smokers of less than I pack per day was 1.75. Among former smokers of less
than I pack per day, those quitting within the previous year had a relative risk of 2.09.
those quitting 1 to 10 years earlier had a risk of 1 .S4, and those quitting for more than
10 years had a relative risk of I .09. A similar pattern was observed among smohers of
1 pack or more per day: among current smokers, the relative risk was 2.3: among
quitters within the past year. 3.00: among quitters of I to 10 years. 2.06; and among
quitters of more than IO years, I .60 (Figure 3). The authors speculated that the elevated

20s


TABLE 2.--Cohort studies of CHD risk among former smokers

Aged 55~64
Quit I 3 yr  I .9
  5 0 yr  I.4
lO~bl4yr  1.7
  ?I5 yr I.3

I.7

  Awl 26.5
   <
Quit I ~4 yr  I .O
  5 Vyr I.3
IO l4yr 1.2
  >lSyr I.1

I .3


TABLE 2.--Continued

Reference              Populallon         Followup

Numtwr of caes
  cinlollg
former smohers

Rcl:n~vc rd.\ compn~wtt \* irh
   nwcr w~,her\"

Ftrrmer        Currrm
\mohrrs        winher\

(`ommenl\

L)oll cl al. (10X0)

Brni\h phyxicinns: 6. IYl women

Hammond and Horn
(1YSt-h.h)

I X7.7X3 men aged SW50

44 mu for CUD denth\

2.3
x0
40

IX
fl4
40

Hammond and       ACS CPS-I: 35X.533 men free of
(iarflnhrl ( 1069)     diagnosed CHD

6 yr for CIID mortatlty

7')
57
SS
S2
70

0.01

Quit< I )r  2.OY
I 10>1- I.54
  >I0 y,- I.OY
Prevlou\ly >I ppd

Quit i I yr 3 (H)
  I-IOyr 7.06
   >I0 yr I .hO
Prevwu\ly I-t') clg/d:q

Qull cl yr I.hl
  I--l\r I.21
5 Yir I.26
IO 141, ().%I
  >20 \r I .IlX


TABLE 2.--Continued

Reldive ri\ks compnred with
   never smoker\"

Kelerrncc


tlalnmond ;md
(Llrllnhcl I IYW)
~C(IIltIIlUcd)

  anlonp
former wlokerr



    62
   IS4
   13s
   I33
    x0

   Former         Current
   wlnher\         wwkrrs       Comment\


                2.5s
Prevlou\ly 220 clg/dsy
Quit <I yr I.61      (7,X?? cn\e\)
   I4 yr l.Sl
  S-Yyr 1.16
  IO-13 yr I.25
  tlS yr I.05

AC`S (unpuhll\tlcd     AC`S (`I'S II. I 2 m1111on
I~ihul;lll~~rl\)        tllc'll ;1nd LIo,nc,,

l`l
4x
47
xx
00
3SY

Men ~2 I c~g/day
Quir <I yr I.43
  ILZyr I.hl
3-s ) I  I .-lo
6-IOyr I.2
I I-ISyr O.YY
Zlf)yr OXX

I .`)3

I 0
13
ih
67
71
IX'

Men 22 I clg/day
QUIZ <I yr 2.56
  I-lyr I.S7
2-Syr I.41
610 yr 1.6.3
I ILlSyr I.16
Zlhyr 1.00

2.02


TABLE 2.-Continued

ACS funpublibhed
tabulations)
(continued)

3
7
II
12
I7
X7

0
IO
I6
2-l
I7
32

Dom f I YSY ): Kahn
f IOhh); Roget and
Murray ( I YXO)h

US veteran\: 24X.046 men

Wnmen <x clg/`t:ly
Qu11 <I yr 2.13
  l-7 )r 0.X7
  3%5yr 1.31
h IO yr 0.74
I I IS yr I.20
  >lhjr 1.17

I 76

Women 220 L?r/d;l)
QW <I 41 I.41
  l-2)1 l.lh
  1-S yr O.Oh
h-104r I XX
I I-ISyr I.37
216yr I.12

2.77

I .5x


TABLE 2.--Continued

Keierencc


Darn ( IYSO): Kahn
( I YM ): Kogot pl
Murray ( 10X0)
tcontlnucd)

            Krlntive rid.\ compared with
Number r)fca\e\           never \moher\"

                 Former          Current
  ;m1w1g
linmcr \moher\        vnokers          vnoher~         Comrllrnt\

       Stopped (overnll)  I 16         I .5x        No update ot
             4 yr 1.40                wwking
            S-Y yr  I .40                   in format itrn
           IO-l4yr 1.30
           1% IO yr  I .20
            >Nyr 1.10

0.Y

I. I (W-2.7)

0.7

Aged 3Y40  I .Y
Aged SOL5Y  I. I

2.3        Only baseline
        kmohing data wed

2.0 3.0
depending on
amount mokrd

No data on
duratwn

I.3

Smohing
intirrm;ttion
upduted biennially

2.5


TABLE 2.-Continued

Number of case\

Rclativr ri\h\ compared wuh
   never vnohcr\"

Reference            Population

Followup

  among
former \moher\

Former
smoher\

Current
5moher~

Comments

Cederlofet al. (lY75)   Sample ofSl. 91 I Swedish      IOyr               07        Quit I-Y yr   I .s lOLlI    1.7
           men aged I X49                                                  Only hawlme
                                            Smoked <ZO cig/day   0.`)           stnohmg data uwd
                                            Smohed 220 cig/dny   I.6
                                                       X6        Quit 210 yr   I .o total
                                            Smoked GO cigiday   0.Y
                                            Smoked 220 cig/dn)   I.1

Fulleret al. (1983)

Whitehall ciwl servants:
IX.403 men aged Jo-h4

IO yr for
CHD deaths

Friedman et ai. ( 19X I )   25.4 I7 Kniwr-Permanrnte      4 yr for
             subacriher\ in the San Franciw)     (`HD death\
           area. aged IO- 79

20x

I7 I normo-glycemlc   I.3
13 glucow intoluant   0.7
     I4 diahetb   3.X

31                   0.Y

2.5
I.5
2.`)

I .h

Prevalent c`aw\ of
C`HD not omitted:
c'xcIu\~on ot thaw
cav3 tncreas2d
the apparent
henrfit ot qulttln&!


TABLE 2.--C'ontinued

3)

1.st1.0 1.1)

I .Y4

2. I I0.X
tlq~entllng on
amount vnohed

Strokcwlutlctl
hut prcvaknt
(`III) 1101
cxcludetf at
lxwline


TABLE 2.--Continued

5 y





4.7

I)

NR

(`I ID dc;llll\

2.1)

Nctrerwom and
Jucl t 14xX)

2.365 Dmi\h be driver\

7.75 !r tar Ml amI
(`HD tle;lth


EX-ClG4REnE
SMOKERS IN 1952

SlOI      stqcped St& WI
wnokii
in 1952    s&g smoking smoking
       cl yr   210 y'  in 195.2


        3.m

3.0

             still
           rm&i
2.5            in 1952

EX-CIOAAETTE
SMOKERS IN 1952

stoppd stqpd stw
smoking smoking Mkino
<l yr   I-1oyr 21oyr

2.09

Never Smoked  Smoked ~1 ppd       Smoked 21 ppd

so4       18 64
iz     r   Tl

40
25

FIGURE 3.-Mortality ratios due to coronary artery diseases; rates for men
      who have stopped smoking are compared with those for men
     who never smoked and those for men still smoking in 1952
NOTE: ppd=pach\/ds>.

SOURCE. Hammond and Horn ( lY5Xhl.

risk among recent quitters reflected the inclusion of men who stopped smoking because
of early symptoms of heart disease.

A second cohort study. the ACS Cancer Prevention Study 1 (CPS-I) (formerly called
the ACS Z-State Study). was undertaken between 19% and 1972. Recruitment was
by family, and eligible families had at least one person aged 35 or older. All family
members aged 3.5 or older wtere asked to participate in the study: more than I million
persons were enrolled. In a 6-year followup of 358.513 men free of diagnosed serious
illness. clear reductions in risk ofCHD mortality were observed among former smokers
compared with current smokers (Hammond and Garfinkel 1969). Among those smok-
ing less than I pack per day. the relative risk among current smokers was I .90. Among
those who stopped in the previous year. the relative risk v.as 1.61. and amon_e those


with 10 years or more of abstinence. the risk was nearly the same a\ that for never
smoher5. A similar pattern was observed among those smoking 1 pack or more per day.
Current smokers at that level had a relative risk of 2.55. Quitters of less than 1 year
had a relative risk of I .6 1. and those with between IO and 20 years of abstinence had
only a slightly elevated relative risk of I .2S. Because of the very large number of deaths
and the careful followup. the estimates of effect are relatively precise. In this period.
cigarette smoking declined substantially. especially in the predominantly white, mid-
dle- to upperclass groups represented by the study population. Hence. some misclas-
sification of the current smoking group may have occurred. but the relative risks among
former smokers. apart from the most recent quitters (some of whom inevitably resumed
smoking). are likely to be accurate.
In 19X2. a third ACS cohort. CPS-II. was initiated in SO States. The methods for
recruitment and the population enrolled were similar to CPS-I. but the cohort was larger,
vvith more than I .2 million participants (Chapter 3). Preliminary data based on 4 years
of followup were published in the 19X9 Surgeon General`s Report (US DHHS 1989).
Among men. former smokers aged 35 or younger had relative risks of CHD of 1.31.
those aged 36 to 63 had I .7S. and those 65 or older had 1.29; the relative rijhs among
current smokers were 1.94 . 3.X I. and I .62. respectively. A generally similar pattern
wa\ jeen among women.
When the data are examined by amount of previous smoking and time since quitting.
the pattern of changing risk is influenced by the presence of disease at enrollment.
When those who reported themselves a\ sick or as having previously diagnosed cancer.
heart disease. or stroke at baseline were not excluded from the analysis, men who
previou4y smoked fewer than 2 I cigarettes per day and who had quit smoking within
the previous 3 years experienced a CHD mortality rate that was about 6 percent higher
than that among current smokers. However, vvith increasing duration of abstinence, the
risk among former smokers came very close to that of never smokers: after I6 years or
more. the relative risk was 1.01 (US DHHS 1989). It is likely that the early peak in
mortality among recent quitters partly reflects the effect of having included those vvho
quit because of smoking-related illness.  After excluding those with cancer. heart
disease, and stroke at baseline, this early excess mortality is less apparent (Table 2). In
all categories. those who quit 1 to 2 years earlier had relative risks substantially lower
than those of current smokers. Findings are less consistent for those who quit within
the past year. presumably because of a high incidence of smoking resumption in that
group and the possible inclusion of persons who stopped smoking as a result of
symptoms due to undiagnosed illness. A very similar pattern was observed among men
who smoked 21 cigarettes or more per day, except that the relative risks were higher
for all but those with the shorter period of abstinence. The absolute rates were lower
for women, as expected, and the relative risks are thus statistically unstable. Neverthe-
less, the overall patterns among female smokers were generally similar to those among
male smokers.
To examine the effects of smoking cessation at different ages. CPS-II data on
cumulative mortality rates due to CHD were tabulated for 5-year categories of age at
cessation. (See Table 3 and Chapter 3 for a description of the methods used to calculate
these rates.) The mortality rates used for these calculations were based on subjects not


TABLE 3.- Estimated probability of dying from ischemic heart disease in the
     next l&5-year interval (95% CI) for quitting at various ages
     compared with never smoking and continuing to smoke, by amount
       smoked and sex

Age at quitting
or at start of
mterval

Never
smoker\

Continuing \moken            Former smoker\

<?I"        21"       -21"        271"

MEN

4044        0.0 I         0.03         0.03         0.0 I        0.02
          LOI-.Ol)      (.01-.03)      I .03-,043      I .0%02 1     I .Ol-.01)


4549        0.02         0.04         0.04         0.02        0.02
          l.OIL.02)      (.04-,051      I .04-.os J      LO-03)     (.OlL.03t

5u-54        0.04         0.07         0.06         0.04        0.04
          (.03-.03 I      ~.f&.O7)      (.06?07 I      t .03-.OS)     (.02-.OS)


55-59        0.05         0.10         0.09         0.0s        0.0x
          (.OS-.06)      I .0x-. I I ,      (.07-.lO)      t .0&.07 I     ( &.lO)

60-64        0. IO         0.14         0. I6         0. I2        0. IO
          (.09-.ll)      1.12-.l6J      t.Io-2I 1      I .OY- IS I     (.OC. IS,


65339        0. I5         0 20         0.13         O.IJ        O.I?
          t.1.v.171      I.16.?.?I      I .0x-. I Y 1      (.07-.2 I )     ,.I~.241

70-74h        0.13         0. I7         0. IO         0.19        0.1 I
           t.1 I-,141      1.13~.71,      I .o-. 16,      ,.llk.2Y,     I .02-.X),

sick at interview or givring a history, of heart disease. cancer. or stroke. For both women
and men. during the next decade-and-a-half cumulative CHD mortality for those who
stopped smoking before age 60 was about half that of those who continued to smoke.
This same pattern of reduced risk extended to those who stopped smoking between ages
60 and 64. After age 65. few persons stopped smoking. as indicated by wide confidence
intervals, so that no clear patterns could be determined.

Because the methods used in CPS-I and CPS-II are similar. it is appropriate to
compare the results of the two studies. In CPS-II. the relative risks of CHD for current
smoking among men and women are substantially higher at every age than those
observed in CPS-1. The higher relative risks for CHD and other smoking-related
diseases among women in CPS-II are possibly due to the earlier age of smoking

216


TABLE 3.-Continued

Age at quittmg
or at \tan of
inrerval

Never
smokers

Continuinp smokers

c20"       t2o'l

WOMEN

4044

4549

SOL54

Y-59

60-64

6549

70-7`lh

0.00
l.06.00)


0.W
(.Oo-.Ol)

0.0 1
(a-.()I)


0.02
(.02-.02)

0.04
(.03-.OJ)


0.07
(.07-.0X)

0.07
(.0&.07)

0.02
( .02-.O? )


0.04
(.O?-.os 1

0.06         0.0x
(.04-.07)      I.O&.lO)

0.11
(.07-,153

0.09
(.OS-. 13)

0.0 I
(.()I-.Ol I

0.03
(.O?-.03)

0.05
(.0&.06)

0. I?
( .07-. I 8 1

0.1 I
(.OS-,161

Former wwkrr\

0.00
LOO-.Ol )

0.00
C.(K)-.oo I

0.0 I
I .(%.02)

0.0 I
(.W.O'l

0.02
(.oo-.05)


0.12
(.03-.2 I 1

0.03
(.00-.0X)

O.ciJ
(.OOL.O I )


0.0 I
I .(K)-.o I I


0.0'
LO-.02)


0.02
LO-,041


0.04
I 0 I -.I%)


0.09
(.Ol-.17)


0.02
(.os-.OS)

NOTE. Brrsed on \ub~ect\ not \Ick at enrollment or givmf a hr\tory of cancer. hean dlreaw. or stroke. 9%
confidence interval (Cl) shown m parenthev%
* CigJday.
h E~runa~rs for qultlmg at thl\ age are e\mnate\ of the prohahllity of dyne in the next 12.5.yr interval
SOURCE: Unpublished tabulation\. American Cancer Sucx~q,

initiation in the more recent cohort (US DHHS 1989). The higher relative risks among
men are more difficult to explain because the age of initiation has not changed
substantially among men over time (US DHHS 1989).

The large size and careful methodology of the three ACS cohorts provide consider-
able evidence for the benefit of quitting in reducing risk of CHD. These studies also
provide strong evidence that there is some residual risk of CHD attributable to past
smoking that persists for a considerable duration after cessation.
The U.S. Veterans Study (Dom 1959: Kahn 1966; Rogot 1974: Rogot and Murray
1980) has also provided useful information on the health effects of smohing. The
population was drawn from 293.958 U.S. veterans who held Government life insurrlnce
policies in December lY53. In 1954. a total of 19X.820 individuals returned mailed


questlonnalres about their smohing behavior. and in 1957. an additional 49.226
responded. Those \vho stopped smoking on a ph>,sician's orders were excluded from
the analysis. Mortalit!, in this cohort uas monitored. and death certificates were
obtained to assess cause of death. Smohing status after the baseline questionnaire was
not ascertained. After 16 years offollo~up. quitters at enrollment when compared with
never smohcrs had relative risks of I. IS for all cardio\,ascular mortality and I. 16 for
CHD death specifically (Roget and Murray IYXO). In contrast. men who uere current
smokers at baseline had relative risks of 1.5X for these two categories. Among past
smokers. risk of death due to CVD increased with higher pre\,ious usual daily cigarette
consumption. The relative risks among past smohers. compared Gth never smohers.
ranged from I .02 for less than IO cigarettes per day to I .33 for 40 ciparettes or more
per day. This gradient M as more pronounced among current smokers I Figure 1).

A gradient was also apparent for decreasing rish with increasing duration of cmohing
abstinence. For both cardiovascular and coronary mortality. there was a moderate
decrease in risk with short duration of abstinence and a smaller. but consistent decline
in rish uith longer periods of abstinence (Figure 5).  After 20 years or more of
abstinence. the relative risk of CVD was I .04. and for coronary death. the risk M as I .05.

The major strength of the U.S. Veterans Study is the large numbers. M ith 2 I.1 Ii
deaths from CVD among smohers and 9.077 among former smokers.  The long
followup period without reclassification of smokin, (7 status is a limitation. \\ hich M ill
tend to lead to an underestimate of the effect of sustained smohing and an underestimate
of the benefit5 of quitting (Chapter 2). This source of potential bias ma! not ha\e
marhcdl~ distorted the estimates in this stud!: in the follo~up of this cohort (Roget
and Murray 19X0). the relative risk for cardiovascular mortalit\ associated M ith current
smoking at enrollment \\a\ I .h? at X.5 years and I .5X at I6 !ears: for coronar\ disease.
the relative rish U;I\ I .6l at X.5 years and 1.5X at I6 vex\. Thus. the impact of
misclassification of current smohers M ho quit (and therefore lowered their rish) as
persistent smohcrs appears to be slight.  A similar comparison of the relati\.e rishs
among former smohers is less int'ormati\e in assessing the impact ofmisclassificati~,n.
hfost quitters u ho resume smohins do 40 ~~ithin 2 years after cessation. Thcret'tore.
IniscI~Issit`ication of e\-smoher5 betuecn X.5 and I6 fears of cessation is likeI> to he
small. For both cardio\us~ular mortalit! and coronar! mortalit>. the relati\ e ri&\
among ex-smohers declined slightI> from I .2 I at X.5 hears of follo\vup to I. I5 and I. I6
at I6 yxrs of` follow up. This is consistent u ith the in\ crst` relation bet~reen duration
of smohing cessation ;und mortalit\' ratio.

Among current mohers In the l:.S. Veterans Stud!. the relati\.e rishs of coronar>
disease \\ere slightI> hisher after X.5 years of follow up (relati\ e rish (RR )= I .Y5 for >20
cig/da\ ) than after 2.5 \cai-s of follo~up (RR=1 .75 I tDom 10.54). As expected. tho\e
M ho stopped smohing on ;I ph\ slcian's orders v,ere at higher rish of death regardless
of their smohinf statu\.

An earl!, report of combined data from the Framinyham and Albany Heart Studies
(Do! Ie et al. I Yh2) included 4. I20 men free from coronq di\easc at entr) into the
stud!.. The Framingham Stud) data were bard on 6 lrars oft`ollouup and the Albany
&art Stud! data on X bears of follo\~up.  .4mong the 4 I I former smohers in the
combined cohort. the rcIati\t' rish of Ml (age-adiusted) U;I~ 0.Y compared u ith nt'\`cr

71X


<lo/day

lO-20/day

2139Iday

r40Iday

124

<lo/day    lO-PO/day

21-39/day

r40Jday

CIGARET'IES SMOKED
      I Ex-Smokers

O ?????*? ???????

FIGURE 4.-Mortality ratios for all cardiovascular diseases and CHD, by
    daily cigarette consumption, US Veterans Study, 1954-69
NOTE: Ex-smoker5 includes only former cigarette \moher\ who stopped smohmg for reawn\ othel
than physician's orders.
SOURCE: Rogot and Murray (1980).


All cardiovascular
diseases
(330-334, 400-468)

Coronary heart
disease
(420)

2.0



LO



0 i


2.0



1.0



0 i

  cufrentdgerm-
I Ex43gamesmokers

A: stoppedlessthan~yervS
B: stopped5-9yecm,
c: stopped m-t4 yews
D: st&xfd 15-19 yeCra
E: saopped2Ot~morSysarS

A B C 0 E

A   B C D E


M;I~ I. I (c)S-percent Cl. 0.5-2.2). Current smokers had significantI!, elevated relative
rich\ ranging from 3.0 to 3.0. depending on the amount smoked.

In a later report from the Framinghum Study based on I X year\ of follow up biennial
examination>. Gordon, Kennel. and McGee (1471) assessed the effects of \mol\ing
cessation. In thi\ analysis. anyone who smoked for I lear or more during the mo\t
recent ?-year interval between examinations was considered ~1 current moher. Ap-
proximately 20 percent of men who reported that they had quit smoking a~ entr! into
the studs resumed \mohing: about halfofthose smoked very little oronly intermittentI>
after resumption. Compared with current smoker>. former smokers had B 30.percent
reduction in fatal and nonfatal CHD (escluding angina): the relati\,e ri\h ;imong current
smokers compared w>ith that among never \moken was 1.3. Other coronary ri4 factor\
were examined in detail: there uere no \ipnificant difference\ between per\i\tent
smohers and those who quit. but those who quit Mere more likely to be ill. Hence. it
would be expected that acl.justment for confoundin, ~7 would have revealed even greater
benefit from cea\ation. The benefit of quitting seemed more marked in younger men.
However. there w'ere only 73 cases ofCHD amon? the quitter\ \o that a detailed analysi\
could not be performed.

The Western Collaborative Group Study monitored a cohort of 3.514 men for an
average of X.5 years for CHD incidence (Rosenman et al. lY75). Information collected
at baseline among men aged 3Y to 39 indicated that former maker\ had a relative rirh
of 1.9 compared with that of never smokers . 30 percent lower than among current
makers. For men aged SO to SY. former smokers had a relative ri\k of I. I compared
with never smokers. 40 percent less than among current makers.  Thih effect of
cessation wa\ slightly greater than that observed after 4.5 years of followup (Jenkin\.
Ro\enman. ZyLanski 196X). The difference between the age groups could be a true
effect or may reflect different levels of misclassification: it is possible that a greater
proportion of the quitters in the younger group than in the older group resumed smoking.

In 1963. a prospective <tudy of smoking and mortality was conducted in Sweden by
sending questionnaires to a probability sample of men aged IX to 6Y (Cederlof et al.
tY7S). .A total of 51 ,Y I I respondents provided some information: a \ub\ample of
I I .739 were sent followup questionnaires in 1969. In that interval. II percent of the
former makers had resumed cigarette smoking. and an additional X percent initiated
pipe or cigar smoking. The men were monitored for IO years for mortality and cancer
morbidity. Men u,ho quit within the past 9 years had a significantly elevated relative
risk (RR= I .5) that waj nearly as high as the relative rirk for current smokers (RR= 1.7 ).
In contra\t. those with a longer duration of abstinence had B relatib'e risk of I .O. Men
with diseases at baeline were not excluded. \o it is likely that the benefits of recent
cessation are obscured by the inclusion of men with disease-induced quitting.

The Whitehall Civil Servants Study (Rose et al. 1977: Fuller et al. 19X.1) i\ another
important source of data on risk factors for CHD. Between I967 and 1964,. a total of
I X.401 male civil servants aged 30 to 64 were examined. In the I Y-year follow up. the
age-adjusted CHD mortality rate amon g 17.05 1 persons with normal blood sugar was
SO percent lower for quitters than for current smokers. When compared with never
smokers. the relative risk for former makers among normoglycemics u as I .3. Among
the YYY men with glucose intolerance (but not diabetes). the ri\k for former smoker\

"I
--


was 30 percent lower than that for current smokers.  Overall. the 224 diabetic men
experienced a very high risk of CHD; among this group the risk for former smokers
was 30 percent higher than for current smokers (based on IO cases among the current
smokers). These data are generally consistent with other studies in the overall findings.
but suggest that smoking cessation may not have the same benefit for diabetics as for
the general population; however. this finding is based on small numbers, and the
severity of diabetes was not considered in the analysis. This study did not provide any
information on the time course of the decline in risk after cessation. It is also likely that
during the long followup period. a substantial percentage of current smokers quit
smoking.

The effect of differences in coronary risk factors other than smoking was examined
in quitters and persistent smokers by Friedman and colleagues (1979). As expected.
there were a number of differences between quitters and persistent smokers when they
were studied at a time in which individuals in both groups were smoking. A followup
analysis of this same population was conducted to assess the impact of quitting on risk
of CHD and to evaluate the effect of differences between these groups that might alter
CHD risk (Friedman et al. 19X1 ). Smoking was assessed by questionnaire at ap-
proximately annual multiphasic health checkups given at the Kaiser-Permanente Medi-
cal Centers in San Francisco and Oakland. CA. There were 9.394 persistent smokers.
1.856 persistent quitters (those who denied smoking at 2 sessions after an examination
when they were currently smoking), and 12.697 never smokers. The cohort has
monitored for an average of 4 years for a total followup of 1 XX.436 person-years. The
age-. sex-. and race-adjusted death rates (per thousand person-years) associated with
CHD were 2.6 among smokers, I .4 among quitters. and I .6 among never smokers.
After adjustment for baseline differences. quitters had a risk of fatal CHD that was 55
percent lower (YS-percent CI. 74-27) compared u ith persistent smokers. By excluding
individuals with frank coronary disease at baseline. a slightly hisher benefit for quitting
was demonstrated.  Further adjustment for measures of smoking intensity slightly
attenuated the reduction in rish to 47 percent. suggesting that only a small part of the
apparent benefit of quitting is attributable to the fact that quitters were less intense
smokers at initiation of smoking.  Only the number of cigarettes smoked had any
measurable impact: depth of inhalation and duration of smoking had no effect. Except
for uomen during the first half of this century. most smohers begin to smoke during
adolescence: thu\. duration i\ very highly correlated v.ith age in most populations.
These findings generally confirmed prev,iour results from the same study (Friedman.
Dale>. Ury lY7Y ).

The Seven Countrie\ Study (Keys IYXO) provided a valuable resource for analysis of
rish factors for CHD. A total of I6 cohorts of men. aged 40 to 59. living in 7 countrie\.
were examined and monitored for IO vear\ for CHD incidence. The cohorts were
assembled between lY5X and 1064. and consisted of I ?.OY6 men free from CVD. In
each rrouping of cohorts. former smohers had a lovver ri\h of CHD than did current
   c
mohers. Houever. only about 7X case\ of CHD death among former smokers were
reported: therefore. no detailed analysis w'as possible.
Data on the health effects of smoking cessation are also available from the Health
Insurance Plan of Greater Nevv York. The incidence of MI uas ascertained over a

17-J
---


3-year interval among I lO.OOO individuals (Shapiro et al. 196Y ). A total of 613 cake\
of MI were reported among men aged 35 to 6-l in this group. Compared u ith current
smokers. those who quit in the preceding 5 years had a %-percent lower risk: compared
with never smokers. the relative risk was 1.0. As in other studies. the percent reduction
in ri\k associated with smoking cessation tended to be lower in the older age group>.
but a decreased risk associated with quittin g wa\ apparent among all ages.
Many studies of smoking cessation have focused on middle-aged men and women.
Even as recently as the late 1970s. current smoking was considered to be a minor ri\h
factor for CHD beyond age 65 (US DHEW 1979 ). and the benefits ofce\sation among
older persons have been questioned (Seltzer 1971. 1975 ). Jajich. Ostfeld. and Freeman
(1984) assessed the effect of quitting among 7 2.674 recipients of public as\i\tance aged
63 to 75 in Cook County. IL. Of the 2.674 individual\ studied. 770 were paht \moher\.
873 were current smokers. and 1.248 were never smokers. Participant> were screened
at baseline and monitored for 4 years for CHD mortality. Overall. former smoher\ had
a relative risk of CHD mortality of I. 1 I (based on 20 exposed cases). whereas current
smokers had a relative risk of I .94. The number of cases was inadequate for a detailed
analysis of the effect of duration of abstinence. Perjon\ with heart problem\ \vere not
excluded at baseline. Approximately one-third of the CHD deaths were among those
with such a history: therefore, it is likely that the apparent benefits of quitting may be
understated because of the tendency of such individuals at high risk to quit because of
illness. These data provide some evidence that the benefit\ of cessation extend to older
adults.
The British Regional Heart Study (Cook et al. 1986) monitored 7.735 men aged 10
to 59 who were randomly selected from general practice lists in the United Kingdom.
The men were screened at baseline and studied for 5 to 7.5 years for incidence of fatal
and nonfatal CHD; in this interval, there were 336 CHD outcomes. Those with CHD
at baseline were not excluded. Compared with never smokers. quitters had a relative
risk of approximately 2.5: compared with current smokers. the relative risk u'a\
approximately 30 percent lower. Men who quit smoking within the previou\ 5 years
had a relative risk of approximately 3.3, compared with 3.6 among persistent smokers.
Those who had quit more than 5 years earlier had a relative risk of approximate11 2.3.
but there was no evidence for a trend of decreasing risk with increasing duration since
cessation. Even those who had quit 20 or more years earlier had an elevated rish. After
adjustment for other risk factors, the relative risk in this group was I .6 (p=O. I I 1.
As expected, the prevalence of CHD at baseline among quitters was significantI>
higher than for either current or never smokers. Presumably. the diagnosis of dihea\c
provided a motivation to quit. When these men waere excluded. the relative risks were
attenuated. Nonetheless. for those who had quit in the previous 5 years. the relative
risk was still elevated at 3.2. The total years of smokin, (7 w'as suggested ah the mo\t
important variable. It was also suggested that cessation lowered ri\k primarily b\,
preventing the accumulation of further years of smoking. It i\ noteworthy that although
results of this study are adequate to show an elevated risk among past \mhers. the
number of cases among former smokers is too small to provide precise estimates of rish
at the various durations since quitting. For example. there are only I I ca\es in the proup
that quit 20 or more year\ earlier.


Many studies of large cohorts examined the effects of smoking primarily among men.
However, the Nurses Health Study investigators reported on smoking and CHD in a
cohort of 12 I.700 women monitored through biennial questionnaires from I976 to 1989
(Willett et al. 1987). Women with previously diagnosed CHD were excluded from the
analysis. Compared with never smokers. former smokers had a relative risk of I.5
(9S-percent Cl. I .&2. I ). In contrast. current smokers had a substantially elevated
relative risk. ranging from 2. I for smokers of 5 to I4 cigarettes per day to 10.8 for those
who smoked 45 cigarettes or more per day. There w'as no further analysis for the effect
of duration of abstinence. The authors suggested that the slight elevation in risk of
ex-smokers was due. in part. to resumption of smoking by some fraction of the former
smokers. Adjustment for age: obesity; menopausal status; estrogen use: family history
of MI: and personal history of diabetes. hypertension. and high cholesterol in a
multivariate analysis led to an identical relative risk of 1 .S. demonstrating the absence
of confounding by these coronary risk factors in this population.

In another cohort study. Floderus. Cederlof. and Friberg ( 198X) monitored 10.945
twins born in Sweden between IX86 and 1925. Smoking behavior was ascertained at
baseline in I96 1, and the cohort was studied for mortality for 3 I years using matched-
pair analysis. Among the males. former smokers compared with never smokers had a
risk of coronary mortality of 1 .O (95-percent CI. 0.X-I. 1). In contrast. current smokers
had relative risks ranging from I .4 to I .8 depending on amount smoked. There were
no data on duration of abstinence at baseline. and there may have been changes in
smoking prevalence during the long followup that would tend to attenuate the relative
risk.

In a unique cohort design. Raichlen and coworkers ( 1986) examined progression of
atherosclerosis among 33 men who underwent coronary angriographies at least 7 years
apart. Among current smokers. progression of disease waj statistically significant and
was correlated with pack-years smoked during the interval. Among pa\t smoker\. the
degree of progression of atherosclerosi\ was far Ies\ than among current smokers: it
w'as not statistically different from lack of progression.

Several other cohort studies have reported on the relation of smoking cessation M ith
risk of CHD: however. the number of sub.jects was generally too small to contribute
substantially to knowledge in [hi\ area (Table 7).

Intervention Trials

In >everal clinical trials. an attempt has been made to ev aluatc the effect of altering
ri\h factors for CHD. including smohing (Chapter 3). !Uost of the trials including
smoking cessation have also incorporated interventions for other CHD rish factors
mahing it difficult to assess the independent effect of quitting. Nonetheless. the\e data
have extended the understanding of the effects of mohing ce\\ation on CHD rish.
AssesGng \elf-report of smoking cessation or decrease in cigarette consumption is
another potential difficulty. There may' be a tendency for sub.jects in a trial to seeh
approv.al and avoid ne gative feedbach by, reportin, 17 le\s cigarette use than i$ actually
the case (Chapter 2). Such a tendency would have the effect of miscI:t\\ification and
would yield an underestimate of the benefits of cessation (Table 1).

72-l


TABLE 4.--Intervention trials of smoking cessation and CHD risk

Rcferencc

Population

Intervention

oulcome

caw\ among
fwnmer moher\

  Effect of
wlohing ce\sttton
(nonrandom~~ed)

Hughe\ et al. ( I')81 );  MRFIT: I?,Xhh healthy US   Diet, reduction in weight.     CHD death\        I5       7% declme iI1        4J1k reduction
MRFIT Research   tnen aged 35-57 at high CHD  hypertenswn, and smoktng                    interventwn group    compared with
Group ( 1982. I YX6):   r&k                                                            peralwnt smokers
Grimm (19X6):

Ockene et al.     MRFIT: 7,663 participant
(IYYOI        smokers at entry

Diet. reduction in weight.
hypertension. and smohmg

(`HD dcnth\

33

Quitter\ had 42%
reduction t Ih~hO'% 1

MRFIT: h.Y43 participant
smoker\ at entry

Diet. reduction in weight,     CHD death5        I2
hypertrn~ion. and amohlng

Iljrrmann et al.
(IYXI)

Oslo study: I.232 healthy    Diet and wioking
Oslo men aged 4(WY 31 high
C`HD risk

Kornttxr et al.
(IYX.31

I Y.409 male Helgian tlctory
workers. aged 40-51)

Anti\moking.
hypcrtcn\ion control




The Multiple Risk Factor Intervention Trial (MRFIT) was designed to test whether
reduction of diastolic blood pressure. serum cholesterol. and cigarette smoking
decreases the incidence of CHD (Hughes et al. IYX I: MRFIT Research Group IYX6:
Grimm 19X6). Men aged 35 to 57 were screened: of those in the upper IS percent ot
CHD ri\k (based on coefficients from the Framingham Study ). but without overt CHD.
6.428 were randomized to special intervention. and 6.438 were a\\iyned to usual care.
Men in the special intervention group were given intensive instructions concerning diet
and hmokinp cessation and were treated for hypt'rtenxion. Thox in the usual care group
were referred to their regular source of medical care. The difference in total cholesterol
between the two groups was only half that expected: because of better than anticipated
hypertension treatment in the usual care goup. the difference in blood pressure w;ts
also substantially less than expected. At the outset. 5Y percent of the participants were
current cigarette smokers. After 12 months. 3 I percent of the smokers in the interven-
tion group had quit (verified by thiocyanate (SCN-) levels) compared with 12 percent
of the smokers in the control group. At the end of the h-year trial. 16 percent of smohers
in the intervention group had quit compared with 2Y percent in the control group.
Mortality resulting from CHD was only 7 percent lower in the special care group. a
difference that did not approach statistical significance. The authors suggested that the
small decrease in risk was due in part to the smaller than anticipated differences in risk
factor levels between the twogroups and that aomeofthe benefit in rich factor reduction
might possibly have been counterbalanced by an unfavorable response to antihyperten-
sive therapy in some of the hypertensive patients (MRFIT Research Group 1982).
Within the intervention group. those who quit in the first year had a multivariate-
adjusted relative risk SO percent lower than that of persistent smokers: in the control
group. adjusted relative risk 30 percent lower than that of persistent smokers. In thi4
trial, risk of sudden CHD death was reduced 65 percent among quitters compared with
persistent smokers. Because all participants were seen at least annually. the possible
misclassification of smoking status vvas minimized.

The lO.S-year followup data from MRFIT have recently been published (MRFIT
Research Group 1990). Deaths due to CHD were 10.6 percent lower in the special
intervention group (95percent Cl.-23.7 to 4.9) compared with the usual care group
(two-sided p value=0.24). This reduction in risk was largely attributable to a 24.3.
percent lower risk of death due to acute Ml (2-sided p value=O.o4). Total cardiovaxular
mortality was 7.1 percent lower after 10.5 years in the special intetvention group
compared with the usual care group (p>O.OS). In one analysis not based on randomized
groups. CHD mortality rates of smokers who had quit within the first I2 months of the
trial and of those who were still smoking at that time vvere compared (Ockene et al.
1990). Quitters had a 37-percent reduction in mortality. After adjustment for other
CHD risk factors. the reduction was 42 percent (95-percent Cl. 16-60). The slightly
greater benefit observed after adjustment for risk factors indicates that there w.as little
confounding and that it w'as in the direction that would tend to underestimate the benefit
of cessation. This analysis ignored any changes in smoking status after the first annual
examination. To the extent that either some of the quitters resumed smohing or some
of the current smokers quit. that analysis would yield an underestimate of the benefits
of cessation. A second analysis compared quitters who remained abstinent at the first

"7
--


three annual examinations u ith persistent smohers. In this analysis. which uould be
aft'ected to a lesser extent by misclassification. former smohers had a 65-percent
reduction in risk compared with persistent smokers (YS-percent Cl. 37-80).
A trial using a somewhat similar design was conducted in Oslo. Norway (Hjermann
et al. 1981: Hjermann. Holme. Leren 1086). Males aged 40 to 19 were screened for
coronary risk. and normotensive men at high risk of CHD due to elevated serum
cholesterol, smoking, and other risk factors were identified. The participants had no
clinical CHD at the time of randomization to the intervention or control group (N=603
and N=h?X. respectively). The intervention consisted of advice and instruction on
altering diet and reducing smoking. Participants Mere examined at least annually during
the 5 years of followup. After 5 years. fatal and nonfatal CHD was reduced in the
interventioryroup by 37 percent. There uas greater success in reducing cholesterol in
this trial than in inducing smohiny cessation. The mean serum cholesterol was ap-
proximately 13 percent lower in the intervention group than among the controls.
However. only 3 percent of the smohers in the intervention group and I7 percent in
the control group quit entirely. although many reduced the amount moked. There was
an inverse relation between CHD incidence and percentage change in tobacco con-
sumption. but this did not attain statistical significance. The authors calculated that
approximately 3 percent of the difference in CHD incidence betbeen the two youp\
was attributable to differences in smoking.
A second report (Hjermann. Holme. Leren et al. lY86) included fo`ollowup through
101 months. Statistically significant reduction\ among the intervention group com-
pared with the control group were seen for fatal coronary events (reduced 59 percent ).
total coronary events (reduced J-1 percent). and total cardiovascular events (reduced 61
percent).
The World Health Organiration European Collaborative Trial in the multifactorial
prevention of CHD M;IS conducted at several sites in Europe. Pooled results \rere
reported from center\ in the United Kingdom, Belgium, Itall. and Poland (WHO
European Collaboratik e Group I YXi ): separate reports have also been published from
centers in the United Kingdom (Row. TunstalI-Pedoe. Heller IYXi) and Belgium
(Komitler et al. 19X3 ). A total of 66 l`actories invoh ing 19.78 I men u ere randomi&
to a multitactorial risk t`actor reduction program or to the control group. The reduction
ot Ieve]\ of risk t`actor\ \ arictl considerahl\ among the center\. O\wal I. the reduction
in risk factor Ie~els \+:I\ modest. and there \+ ;I\ no significant decline in CHD endpoints
in the intervention group. The et`t'cct on CHD \$a\ broadI\ correlated u ith changes in
rish factors. There M as no qecitic anal! sic on the impact of smoking cessation.
The Belgian center M ;I) the Iaryst in the European Collaborati\ e Trial. Fifteen pair\
of factories uere rundoml! allocated IO the inttwention or control group\. u hich
included IY.-lOY men aged 10 to 5Y vearc. The intervention included ad\ ice about
smoking cessation and reduction of h!,pertension and clc\ ated cholesterol. Subjects
were screened as part of the trial. but referred to their ou n phb sicians for therap!,. After
6year\. there ~a\ a 24.5percent reduction in fatal and nonfatal CHD in the intrr\ention
group compared M ith the control 5 woup (p=O.O3) (Kornit/er et al. 19213). The rates in
the intervention and control groups continued to diverge throughout the follow up


period. No specific analysis wasconducted to assess the independent effect ofsmohing
cessation on risk of CHD.

The multifactor primary prevention trial in Gotebor,. 0 Sweden focused on reduction
of hypertension, elevated serum cholesterol. and smoking (Wilhelmsen et al. 19X6). A
random sample of 10.003 men aFed -IS to 5.5 years was included in the inter\.ention
group. and 2 other random samples of the same size were identified as controls. Ot
those invited to participate in the intetvention group. 7.3YS attended the first screening
examination. At the outset. w'ithin the interv/ention and control groups combmed. 70.6
percent were former smohers. After 1 years. the proportion of former smohers in
creased to 17.7 percent. and after IO years to 3Y.4 percent in the intervention group. In
the control group. the percentage of former smokers also increased-to 22.3 percent at
4 years and to 36. I percent at IO years. The differences achieved for other risk factors
between the intervention and control groups were also quite small. After IO y'ears. there
w'ere virtually no differences in fatal and nonfutal outcomes between the groups.

The center in the United Kingdom was also large (Rose. Tunstall-Pedoe. Heller
19x3 ). with I2 pairs of factories and I X.7 IO men aged 40 to SY years. There were only
very modest changes in risk factors other than cigarette smoking. The reported number
of cigarettes smoked per day in the intervention _rroup decreased by I6 percent. but the
proportion of current cigarette smokers decreased by only 4 percent. Rose and Hamil-
ton ( 197X) stated that whereas self-report ofcessation is likely to be reasonably accurate.
reported decreases in smoking are probably exaggerated. With such small net changes
in risk factors, it is not surprising that there was virtually no difference in the rate of
CHD between the two groups.

Only one trial has attempted to assess the effect of advice for smoking cessation
without intervening for other risk factors simultaneously. In theory. trials of this design
can provide the clearest indication of the effect of such advice in the absence of other
effects. Participants were selected from a cohort of 16.016 from the Whitehall Civil
Servants Study (Fuller et al. 1983). From this group. I .44S high-risk male smokers
aged 40 to 59 were randomized to a normal care group or the intervention group that
received antismoking advice. At year one, 5 I percent of the intervention group reported
that they were not smoking. and at year three. 36 percent reported the same. In the
normal care group. the corresponding percentages were IO and I3 percent. A third of
the quitters reported smoking cigars or a pipe. It is important to note that the question-
naire response rate at 3 years w/as 64 percent in the intervention group and 70 percent
in the normal care group (Rose and Hamilton 197X). The 9-year response rate was X3
percent. At that point. 55 percent of responders in the intervention group reported
quitting. as did 41 percent in the normal care group. Despite the similarity of smoking
prevalence of the two groups, at IO years CHD mortality decreased by IX percent in
the intervention group. This difference did not attain statistical significance (YS-percent
CL 43 to +I8 percent) (Rose et al. 1982).

Smoking Cessation and CHD Risk Among Persons With Diagnosed CHD

Studies examining smoking cessation and CHD risk among persons with diagnosed
CHD may be less prone to some of the methodologic pitfalls discussed in Chapter 2.


In many instances. studies are primarily of individuals who were smokers up to the time
of the infarction. Such a major health event can be a powerful motivation to quit
smoking permanently. Moreover. the timing of quitting often coincides with the
infarction and is therefore ascertained quite accurately. Because those with a prior
diagnosis of CHD are at such high risk for another event. the estimates of effect can be
relatively precise, even with a modest number of individuals under study. One
difficulty in interpreting these studies is in the comparison of quitters with never
smokers. Never smokers who suffer MI tend to have a worse CHD risk factor profile
(apart from smoking) than smokers (Mulcahy 1983). However. most of the other risk
factors are less amenable to change than smoking. After smoking is removed as a risk
factor among former smokers. the effect is often a better prognosis than that for never
smokers. Several of these issues and a review of the literature prior to 1983 are
discussed by Mulcahy ( 1983). This researcher found that studies were quite consistent
in showing that quitters had about half the risk of recurrent MI or CHD death compared
with persistent smokers (Mulcahy 1983). Nearly all studies of this issue have indicated
a benefit of cessation (Table 5).
A cohort of 113 patients who survived for 28 days a first attack of coronary
insufficiency or Ml was studied for 5 years (Mulcahy et al. 1977). Of these, I90 were
smokers at the time of the event. Of the 89 who stopped. the cumulative 5-year death
rate was 14.6 percent. Of the 32 who reduced cigarette use. the rate was 13.1 percent.
However, among the 59 persistent smokers. _ 78.8 percent died within 5 years. Nearly
all of the deaths were associated with CHD.
This study was extended by further accrual of patients and followup of 55 I men less
than 60 years of age (Daly et al. 1987). Of the 406 current smokers at the time of the
event. I40 had stopped by year two. Those quitters had a IO-percent reduction in risk
of sudden death and a lo-percent reduction in risk of total mortality compared uith
those who continued to smoke.
A 197X report from the Framingham Study (Sparrou. Dawber. Colton 197X) com-
pared the survival of 56 individuals who quit smoking after a first MI with I39 who
continued to smoke after the diagnosis. Within 2 to 3 years after diagnosis. former
smokers had a significantly better survival rate than persistent smokers. The 6-year
mortality rate (estimated by life table methods) wa\ IX.8 percent among quitters
compared with 30.4 percent among persistent smokers. When the risk of recurrent Ml
~`as a\se\sed. the authors found that former smoker\ had a lower risk than persistent
smokers. with a h-year reint`arction rate of IS.5 percent in quitters versu\ 2 I.5 percent
among smoker\. Howe\cr. with only eight reinfarctions among the quitter\. the
differences were not statisticull~ Ggnificant. The rate of decline in risk could not be
assessed because of the small \ampie\.
Framingham Study investigators (Hubert. Holford. Ktinnel 1982) conducted a long-
term followup study of I30 sub.jects uith angina pectoris. They found that smoking
statu\ at the examination ascertaining unyina ~a\ modestly associated with jubsequcnt
risk of a later. more \etious CHD outcome. Apparently. the change in smoking behavior
explained this findin:. Of the angina patients who smoked. 1-l percent quit between
the onset of disease and the biennial examination v, hen the diagnosis uas confirmed.
Another 29 percent quit during the follow up period. In this cohort. the heavier makers


TABLE S.-Studies of the effect of smoking cessation on persons with diagnosed C:HD

                                                            Rctlucl~on in r14

Population

Mulcahy et al.
(lY77)

I90 Dublin men aged 40 who
smoked at time of first coronary
inwfficlency or MI

Daly CI al. (1987)

373 men aged <60 who smohed at
mnr of first MI or unstable angina and
wrvwed ? yr

Sparrow. Dawher.
and Colton ( 107X)

Framingham Heart Study: lY.5 cohort
member\ who \mohed at time of first
MI

Hubert, Holford.   Framingham Hzxi Study: a~h~ject~
Karmrll ( IYX2)    with anpin;i

Average Y.4 yr:   NR
<16yr

6 yr

IO dcxh\

Qh yr

NR

Salonu1 ( IYXO)

North Karrlla. Finland: 523 men
aged 4.5 who smokc`d 31 first MI

3 yr

76 tlc;uh\:
71 (`HI) tlc;nh\


`I'AHLE S.--Continued

Followup

Keductmn ,n rl?k
compared with
persistent smoker\"

Comments

Aherg et al t 10x3)  YX3 (iotchorg n~lc wwher\        < 10.5 yr
             ;,I time ot MI

44 recurrent
nonfatal MI

NK

IO4 recurrent
nont`a~al MI: X0
CHD death\

33% reduction: X% in qumer\.
12% in per\iwnt \mokers

X0% (tormer and never      Former and never wwhw
\moher\ ~5. perhlhtent     consdrred together. not
hmoher5)           \epararcly

30%; dltterence klwren
groups increawd with tune

30% quitters had wow
predlcted prognwls at
hawline. no further
a\w~wvznt of smoking
kyond 3 mo after Initial MI

60% ovemll:
40% firct h yr:
X0% 7-l 3 yr

Followup kgan 2 yr after
MI. when smobmg status
was as\ewzd


TABLE S.--Continued

Reductmn in rlsh

Reference           Population

Followup

Cahes among
former smokers

compared with
per&trnt Amoker?

Johansson et al.
(198.5)

I56 Giitehorg women aged 565.
smokers at time of first MI

S yr

I? deaths

60% (X0-20)

Quitter\ had wow baseline
progno\i\: dlfferencea
hrtwren group\ were
apparent early and incrrawd
with time

Perkins and Dick
(10X5)

I IY UK patient\ who smoked at
first MI

S yr

Y death\

Vlietctra ct al.
(19X6)

I I.605 patients in CASS who woked   S yr      By risk quartile:
at time CHD was diagnwed hy
angiography                             the\11 I: 13
                                        2: ?I
                                        3: 44
                                 (wow) 4: 1.56
                                   ovel.illl: 234

Hcrmanson et al.
(IYXX)

3.045 CASS patients with CHD aged
x-54

5.3 yr for
Ml or death

35 54 y,: NR

I .X93 CASS patients with CllD aged
2.55

SS-SO yr: YY
6lMv-l yr: Y2
6%6Y yr: 4X
>70 yr: 1Y

Total mrwtality:

30%
40%
50%
20%
10% (X-20)

4O'X tso-20)

30% (SO `0)
30% (SO IO)
10% (60 0)
70(/r (X0-30)

Quitter\ had worw hawl~ne
prognw~\: e\cluwn of
thow H ith mixed amohinp
hchnvior and clwc' follouup
reduced lihelihood 01
nli\cla\\ificalion 01
cxpowrc: iilw.
ho\l~~t;~ll/atio~i for MI -a\
wh\lantially Ircduccd in
former \mohcr\

Rcanaly\,l\ of :I \uhwt ot
p;ltlent\ an;~ly/cd hy
VIIC`thtra ( IYXh)


TABLE S.--Continued

1 yr
5 yr
IO yr

YY%    YX'k
Y7%    X-l%
YS%    5 I %


v.ere more likely to quit than the lighter smokers. Former smokers had a lower rate of
subsequent CHD. There was a suggestion that older persons benefited less: however.
this finding could not he confirmed because only a small fraction ofthe 25 older smokers
actually quit.
Salonen ( 1980) monitored a Finnish cohort of men less than 6.5 yeaJ3 of age ~4 hose
smoking behavior \Y;IS assessed 6 months after MI. Of these. 352 were never smokers.
302 were persistent smokers. and 231 quit smoking u,ithin 6 months after Ml. Three
years after MI. quitters had a -K-percent reduction in risk of total mortality (95percent
CI. IO-60 percent) and ofCHD death (95percent Cl. IO-60 percent) compared uith
persistent smokers. The reduction in risk was more pronounced in earlier periods:
between 6 months and 1 year. mortality was reduced by 60 percent (95percent Cl.
IO-80 percent). It is possible that the apparent decline in benefit may represent
misclassification because current smokers continued to quit but were still analyxd as
current smokers. The benefits of quitting were strongest among those with the best
prognosis after infarction. Of post-MI deaths. 2X percent were estimated to be at-
tributable to continued smoking.
As part of the Norwegian trial of timolol use after Ml. mortality of the I.881
participants was ascertained over an average of 17 months according to smoking status.
Virtually no differences were observed (Von der Lippe and Lund-Johansen 1982).
Across both the timolol and placebo groups. 8 percent of the nonsmokers died.
compared with 8 percent of those who stopped smoking before entry into the trial. 7
percent among those who quit in the first month of the trial. and 8 percent amon?
persistent smokers. However, there was a reduction in reinfarctions, 8 percent among
those whoquit in the first month of the trial compared with 12 percent among persistent
smokers (Ronnevik. Gundersen. Abrahamsen 1985).
Shapiro, Howat. and Singh (1982) monitored 142 patients who survived a first MI
that occurred when the patient was younger than age 45. Of these patients, 50 who
continued to smoke more than 20 cigarettes per day had substantially higher mortality
rates (5%percent IO-year mortality by life table methods) than did the 61 never and
former smokers (12-percent mortality). The survival curves began to diverge I year
after MI. Unfortunately. data were not presented separately for former smokers. and
apparently there were only a small number of never smokers.
Aberg and colleagues ( 1983) studied 983 men aged 67 years or less who were listed
in the MI Register of Giiteborg between 1968 and 1977. The men were smokers within
3 months of their initial MI. who survived hospitalization. Not all men listed in the
Register were included in the study. but the selection process did not introduce bias.
Quitting was defined as not smoking 3 months after the infarction. Followup began at
that point and continued for IO.5 years. The 542 males who had stopped smoking by
3 months after infarction had a significantly worse prognosis. based on predischarge
characteristics. than did the 441 persistent smokers. Those who quit had substantially
more left ventricular failure and higher peak enzyme levels during hospitalization.
Based on these and other preinfarction and hospitalization variables. those vvho quit
had a predicted 2-year mortality that was 8 to 9 percent higher than that of persistent
smokers.  However. despite this slightly worse baseline prognosis. quitters had a
significantly lower mortality than did persistent smokers. Overall. the j-year mortality


was significantly reduced among quitters. with a cumulative mortality rate 30 percent
lower. The effect was somewhat stronger among those aged SO or older than among
younger men. but wa\ significant in both age groups. The cumulative S-year reduction
in recurrence of Ml was 30 percent. These estimates almost certainly underrepresent
te true effect of cessation for two reasons: quitters at baseline had a distinctly worse
prognosis. and smoking cessation was defined only at the point 3 months after
infarction. It is likely that some of the smokers quit at a later point: this would tend to
dilute the smoking group with ex-smokers who enjoy a lower risk. Thus. the rates of
mortality and reinfarction among truly persistent smokers would be underestimated in
this study. The two groups began to diverge for both endpoints after as little as I year
postinfarction. and the differences increased with time. This report confirmed and
extended initial findings from that study (Wilhelmsson et al. lY75).

Several studies have monitored patients with angiographically diagnosed coronary
disease. Kramer and coworkers (19X3) studied 37X men with sequential coronary
angiograms. These researchers found that neither cigarette smoking at the initial or
followup examination nor smoking cessation was predictive of progression of
atherosclerosis.

Daly and colleagues (I 9X3) studied 2 I7 men who stopped smoking after a first
diagnosis of unstable angina or MI and IS7 persistent smokers. Smoking status was
defined 2 years after the first diagnosis. As in the Aberp study ( 1983). those who quit
tended to have a more serious diagnosis than the persistent smokers. However, quitters
enjoyed substantial protection compared with persistent smokers. For total mortality.
risk was reduced by 60 percent among those who quit smoking compared with
continuing smokers: for fatal reinfarction. risk was also reduced by 60 percent. During
the first 6 years of follow up. the reduction in risk was 40 percent (95percent CI. IO-60
percent). but in the follouup period of 7 to I3 years. the benefits of quitting were more
marked. with a reduction in risk of 80 percent (C)S-percent CI. SO-90 percent). The
benefits of quitting were more marked among those with less severe initial disease. In
this study, quitters had a lower cumulative mortality than did never smokers with these
diagnoses. Those never smohers may havse had more coronary risk factors other than
smoking which may be less amenable to change than smoking.

In a later study with some of the same patients. Daly and covvorkers (1985) found
that I year after the initial event. 24 I quitters had a IO-percent lower prevalence of
angina compared with I33 persistent smokers. However. by 6 years of followup. the
prevalence of angina waj the \ame in both group\ and remained similar throughout the
followup pertod of I7 y'ears. Green ( 1985) noted that the prevalence of angina 6 months
after infarction among X5 I ex-smokers was equivalent to that among smokers. How-
ever. it is unclear whether the ex-smohrrs were smohing at the time of the event.

Mo\t studies of the effect of post-411 cessation have been conducted among men.
Johansson and colleagues ( lY85) examined I56 women in Goteberf. younger than 6.5.
who were \moher\ at the time of their first MI. The definitions and criteria were the
same as those in the study by Aberg and coworhers (1983). Three months after
infarction. 75 women continued to smoke and 8 I had stopped. As in the Goteberg Study
of men (Aberg et al. IYX3). women who quit had more severe infarctions. Despite the
worse prognosis normally associated with the higher enryme elevations and other

236


indication\ of severity. the quitters had a significant11 better \urvi\aI. The reduction
in rich compared with \mohers remained at 60 percent (95percent Cl. 20-80 percent 1.
and after adjustment for prognostic feature\ before and during the Infarction. the
reduction remained at 60 percent. When compared u ith never moher\. the relative
risk among quitters w'as I. I, The reinfarction rate ~`a\ \lightl>. though not \ignit`icantl>.
higher among persistent smokers.
Similar finding\ for a rapid benefit Mere observed in the small \tud> of Pcrhins and
Dick ( 1985). For S year\. these re\earchera monitored 53 paticnt~ (including I I
women) \h.ho stopped \mohing at the time of the infarction and 67 prrsi\tcnt \moher\
(of whom IX were women L Men u ho quit had ;I SO-percent reduced ri\h of death: for
women it was 60 percent loner.
As part of the Coronary .Artery Surgery Stud!. the effect of \mohing cr\\ation on rish
of clinical CHD outcome\ ua\ as\e\\ed in men with documented coronar!
atherosclerosis by angiography (Vtictstra et at. iYX6). The death rate\ among t .490
quitters were compared with those of 2.675 persistent makers and 2.Yl2 never
smokers. Men who were quitters at baseline but who \ub\equcntll resumed mohing
and those who were smokers initially but later stopped were excluded from the analysis.
Hence. this study was largely free of mi\clu\Gficstion. As in most of the other studie\.
the quitters had slightly worse prognoses than did the persistent smohers. At e\`ery level
of risk. however. quitters had a significantI>, better S-year survival.  Overall. the
reduction in risk (from Cox regression) was 10 percent (YS-percent Cl. N-SO percent).
The benefit was slightly more pronounced amon, 0 those uith the worst baseline
prognosis. Overall. the S-year survival rate among quitters uaz similar to that of never
smokers (85 vs. 87 percent. respectively). Nearly all the benefit was attributable to a
decreased rate of CHD death. After adjustment for prognostic score. the rate of
hospitalization for MI was substantially higher among persistent smokers than among
quitters (I I .3 vs. 7. I percent, respectively). For both fatal and nonfatal endpoint\. the
rates began to diverge substantially after about I year (Figure 6). Because of the careful
study design and the unusually large number of cases, the results of this study must be
accorded considerable weight.
In an extension of the analysis of survival data from the Coronary Artery Surgery
Study, the effects of smoking cessation were examined in a population of individuals
aged 55 and older with angiographically documented coronary disease (Hermanson et
al. 1988). As in the previous report, persistent smokers were defined as those I .086
smokers who did not quit throughout the 6-year followup period, and quitters were those
807 who stopped smoking I year before the baseline angiogram and who did not resume
smoking during followup. The experience of 3,045 younger subjects aged 35 to 53
years was also examined. At every age. quitters had better survival rates than did
persistent smokers, and there was no evidence that the benefit was attenuated with
increasing age.
Employing a different approach, Hallstrom, Cobb, and Ray (1986) studied a cohort
of 310 men who smoked and were discharged from the hospital after an episode of
out-of-hospital cardiac arrest. After the arrest. i 7 I9 men continued to smoke and Y 1
men quit. During the average 47.5 months of followup. 67 persistent smokers and IX
former smokers died of a recurrent cardiac arrest. After adjustment across baseline rish


3                                                   I

       1        2        3        4        5
TIME (YR)

0 Quitters     A Continuers

FIGURE 6.-Effect of smoking cessation on survival among men with
     documented coronary atherosclerosis: pooled survival among
      quitters ~3) (X=1,490) and continuers (A.) (N=2,675)
SOI'RCE: Vltrlstrn et `11. ( IYX6).

strata. this difference was of borderline significance in a life table analysis (p=O.O76).
After exclusion of crossovers ( 14 smokers quit 26 months after the arrest. and 2 quitters
resumed smoking). the benefit of cessation was slightly more pronounced (p=O.O48).

Analysis of data from a trial of practolol also provided information on the effects of
smoking cessation after MI (Green 1987). There were X55 never smokers. 1.344
persistent smokers. and X5 I individuals who quit smoking after the entry MI. Those
who stopped smoking had a worse outcome initially than persistent smokers. and the
benefit from cessation did not appear until 2 years after the event. When events in the
first 6 weeks after the index MI were excluded. the benefits of cessation appeared at
about 18 months. By 14 months, those who stopped had a 30-percent CHD risk
reduction. As in other studies, former smokers when compared with continuing
smokers tended to have more severe Ml. with significantly more pulmonary congestion
noted when x-rayed and significantly greater occurrence of faster dysrhythmia. Thi\
supports the view that those with a worse MI are more likely to quit. and it explains
why quitters in the study had a worse initial outcome.

In a trial of rehabilitation after MI. l-17 patients in a Sw,edich hospital were routine11
invited to participate in a rehabilitation program: IS8 patients in a comparable hospital
were not (Hedback and Perk 1987). The cardiovascular experience in the intervention

238


group was favorable, and when the specific effect of smoking cessation was examined
among the X7 patients from both groups who quit after MI. approximately IS.9 percent
died in the subsequent 5 years compared with 30.6 percent among the persistent smokers
and I I .X percent among the never smokers.

The influence of smoking cessation on frequency of restenosis after coronary angio-
plasty was assessed by comparing X4 persistent smokers with 76 individuals who
stopped at the time of angioplasty (Galan et al. 19Xx). Patients were reexamined
angiographically after an average of 7 months. Restenosis was significantly higher in
persistent smokers (55 vs. 3X percent. p=O.O3). Several other studies (Fleck et al. IYXX:
Vandormael et al. 19X7) failed to find an association between smoking at angioplasty
and subsequent restenosis. but those studies did not consider the impact of cessation at
the time of angioplasty. Although the mechanisms of restenosis are not clear. the
findings of Galan and coworkers (IYXX) are consistent with a fairly rapidly acting
process for decreased risk after cessation.

As part of the British Regional Heart Study described above. investigators also
monitored I ,S 15 men with evidence of CHD but without Ml and 42X men with evidence
of prior Ml at entry (Phillips et al. IYXX). Smoking behavior was assessed at baseline.
and the men, aged 40 to 59, were studied for an average of 7.5 years. There was no
update of the smoking information. After ad,justment for age and other risk factors. for
those with non-MI CHD at baseline. the relative risk comparing former with never
smokers was I .4: for current smokers, it was 2.1. For those with a history of MI. the
relative risk for former smokers was I .7: and forcurrent smokers. it was 1 .Y. The degree
of misclassification that may have occurred during the followup period is difficult to
assess. No information is available on the duration of abstinence or the degree of
severity of CHD as distributed by smoking status.

In acommunity-basedfollowupof 325 post-MI patients in Baltimore. MD. Goldberg.
Szklo, and Chandra (1981) found that after control for several clinical and
sociodemographic factors. survival among those who quit at the time of MI was
substantially improved. The I-. S-. and IO-year survival rates among those who quit
were 99. 97. and 95 percent, respectively; in contrast. the rates among persistent
smokers were 9X. X4, and 51 percent, respectively. Despite the lack of updates on
smoking behavior. there was a trend for diverging survival between the two groups.

Summary of Smoking Cessation and CHD Risk

Within the past 40 years. large amounts of data regarding the effect of smoking
cessation on CHD risk have been accumulated from numerous studies. However
diverse in design and location, these studies consistently find that the risk of CHD is
reduced among former smokers compared with those who continued to smoke. The
data are compatible with a rapid, partial decline in risk, followed by a more gradual
decline reaching levels of never smokers after a prolonged period. The initial decline
appears to occur within I year of cessation or perhaps even less and constitutes a
reduction of about one-half or more of the excess risk associated with current smoking.
The remaining decline in excess risk is more gradual. with the risks reaching those of
never smokers only after a number of years of smoking abstinence. This pattern of


decline in excess rish is compatible with multiple effects of smoking on the process of
developing CHD. including both short-term influences on platelets and other factors
relating to thrombosis which may be more rapidly reversible and long-term increases
in atherosclerosis which are only slowly reversible.

Persistent smokers may differ from those who quit in other ways that could affect the
risk of developing CHD. A number of investigators have examined whether such
differences would account for some or all of the decline in risk among those who stop
smoking. The risk profiles of quitters and persistent smokers vary among studies: In
some studies. there are no material differences; however. in other studies. quitters have
a healthier profile: the opposite is true for still other studies. In the studies of primary
prevention. none of these differences could explain even a minor portion of the
decreased risk among quitters. Most studies of cessation after an MI have found that
quitters had a higher baseline risk; however. their risk decreased compared with
persistent smokers. Thus. both in primary and secondary prevention studies. confound-
ing effects of other risk factors do not explain the apparent benefits of cessation. To
the contrary. in many studies. the decrease in risk is even more pronounced after
adjustment for baseline characteristics.

Only a few studies have examined the impact of smoking cessation in relation to
v'arious other CHD risk factors. No data are available to suggest that the relative risks
differ substantially in the presence or absence of other CHD risk factors: that is. the
percentage reduction in risk most likely occurs across risk factor categories. However.
because individuals at high risk for other reasons such as family history. hypertension.
or elevated cholesterol have higher rates of CHD. a given percentage decrease in risb
among these indivtiduals is a greater absolute decrease than among those with a lower
risk profile. Hence. it is ofespecially great importance to achieve high rates ofcessation
among individuals who are otherwise at high rish for CHD.

Most data on the effects of smohing cessation are derived from white males. but
sufficient information is available about women to indicate that the findings are similar
for both sexes. Less is hnown about the effects of cessation among minority groups:
however. there is no reirson to believe that the benefits of cessation would be any
different for these groups.

Several studies have examined the effect of smohinz cessation after age 60 on
subsequent CHD rish. Data are novv available that demonstrate that the benefits of
cessation extend to older adults ;ts well as to young and middle-aged adults for both
primary (Table 3) and secondary prevention (Hermanson et al. 19x8). Although the
relative rishs of CHD among current smohers tend to be loner among older persons
than among younger persons. smohing cessation among older persons can hav,e a greater
absolute effect because their rates of CHD are so much higher.

Considerable data address the effects of smoking cessation among individuals LI ith
diagnosed CHD. A reduction in risk of further CHD-related morbidity and mortality
that accompanies smohing cessation has been conclusi\,ely demonstrated. Cigarette
smoking is considered the leading modifiable CHD rish factor: over\\ helminp evidence
demonstrates that cessation reduces that rish substantially.

240


SMOKING CESSATION AND AORTIC ANEURYSM

Abdominal aortic aneurysm refers to the dilatation or expansion of the aorta because
of degenerative or inflammatory destruction of the components of the arterial wall.
Most abdominal aortic aneurysms are a result of atherosclerosis. although other
conditions cause abdominal aortic aneurysm\. The preponderance of evidence from
autopsy studies reviewed in the 1983 Report of the Surgeon General sugfects that
cigarette smoking aggravates or accelerates aortic atherosclerosis (US DHHS 1983 ).
In addition. epidemiologic studies published up to that time indicated that mohers had
elevated death rates from ruptured abdominal aneurysm compared with nonsmokers
(Hammond and Garfinkel 1969: Hammond and Horn 195Xa.b: Kahn 1966: Weir and
Dunn 1970). Mechanisms whereby smoking causes atherosclerosis are reviewed in this
Chapter.

Studies of Smoking Cessation and Risk of Aortic Aneqsm

Several of the larger prospective cohort studies reviewed above have reported results
for mortality by cause of death. The data on mortality among~ former smokers from
abdominal aortic aneurysms reported in five prospective cohort studies are summarized
in Table 6. A consistent pattern is seen among men in these studies, with an excess risk
of mortality approximately 50 percent lower among former smokers than among current
smokers. However, excess risk among former smokers has remained about two to three
times higher than that among never smokers. A similar pattern was also present for
women in ACS CPS-II. Although data for women are limited. Doll and associates
(1980) reported 11 deaths due to aortic aneurysm occurring during 32 years of followup
among 6,194 women. Overall. these data indicate that former smokers have a reduced
risk of death from aortic aneurysm compared with current smokers. More detailed
analyses by duration of smoking abstinence have not been presented.

SMOKING CESSATION AND PERIPHERAL ARTERIAL OCCLUSIVE
                   DISEASE

The peripheral arteries include those branches of the aorta that supply the upper and
lower extremities and the abdominal viscera. Most peripheral arterial occlusive disease
results from atherosclerosis. although other conditions may cause obstruction of these
arteries. Symptomatic atherosclerosis of peripheral arteries occurs most often in the
vessels of the lower extremities. The I983 Report of the Surgeon General reviewed
risk factors and epidemiologic data relating to the etiology of peripheral artery disease
(US DHHS 19X3). In that Report. an extremely strong association between cigarette
smoking and diagnosis of peripheral artery disease was observed (US DHHS 1983).
Cigarette smoking was the strongest risk factor for peripheral artery disease in the
Framingham Study (Kannel, McGee. Gordon 1976). In this Section. the impact of
smoking cessation on risk of developing peripheral artery disease is reviewed. In
addition, the influence of cessation on treadmill time, rest pain, progression to amputa-
tion. and survival among patients with diagnosed peripheral artery disease is discussed.

231


TABLE 6.-Studies of smoking cessation and risk of death due to aortic aneurysm

I)011 Cl <II. I I'JXOI


Smoking Cessation and Development of Peripheral Artery Disease

Two studies provide sufficient detail to calculate the risk of peripheral vascular
disease among former smokers compared with current smokers. Jacobsen and
coworkers (1984) compared a consecutive series of S3 patients with intermittent
claudication with age-matched controls free from symptoms of claudication. All
patients with claudication were either current or former smokers. Among former
smokers. the risk of developing peripheral arterial disease was 50 percent lower than
that of current smokers.

Hughson. Mann. and Garrod ( 197X) reported risk factors for intermittent claudication
among 54 patients and IOX controls. Smoking was the risk factor most strongly
associated with the development of intermittent claudication. Former smokers had an
estimated S&percent lower risk than that of current smokers.

Smoking Cessation and Prognosis of Peripheral Artery Disease

In a study of 91 men with mild intermittent claudication monitored for at least 6
months, patients who stopped or decreased smoking had slightly less progression of
symptoms during 2.5 years of followup. but this finding was not statistically significant
(Cronenwett et al. 1984). Changes in treadmill exercise tolerance were assessed among
41 patients suffering from intermittent claudication who continued to smoke during the
followup period and among I6 patients who stopped smoking after the first test and
remained nonsmokers until the end of study (Quick and Cotton 1982). The maximum
treadmill walking distance did not change significantly among continuing smokers (33
meter improvement, p=O. 17). However, among those who stopped smoking. the
improvement in maximum treadmill distance was statistically significant (86.2 meters.
p=O.O2). The two groups were not compared directly.

During a 6-year period, the risk of developing pain at rest was studied in 223
consecutive nondiabetic patients with intermittent claudication (Jonason and Ringgvist
1985). The cardiovascular risk profiles were almost identical for 30 never smokers and
34 patients who stopped smoking within I year after initial examination. These two
groups were combined and compared with 160 patients who continued to smoke. The
cumulative percentage of patients with pain at rest after 6 years was 8 percent among
those who had stopped smoking within I year after the initial examination or who were
never smokers; among smokers and those who stopped smoking more than 1 year after
the initial examination, 21 percent developed pain at rest (~~0.03 after adjustments for
difference in presence of multiple stenoses at baseline). These data are difficult to
interpret because never and former smokers were combined, but suggest that the rate
of development of rest pain is decreased among former and never smokers compared
with those who continue to smoke.

In a followup study of 60 patients who underwent operation for intermittent claudica-
tion, those who stopped or reduced smoking after referral had a much improved
prognosis (Hughson et al. 1978). At baseline. clinical characteristics or the number of
cigarettes smoked did not differ between those patients who decreased or stopped
smoking and those who continued to smoke during the followup period. The interval


between initial and repeat operations was significantly shorter in those who continued
to smoke (Mann-Whitney tz\t. p4.05). Those M,ho stopped or reduced smoking
attained a significant improvement in overall survival h!, I 2 months. A second series
of 160 patients was studied for X years after their first hospital admission. Those who
were smoking at the time of referral had ;I significantly poorer survival pattern than
those who had stopped smoking or had reduced smoking. Similar results were observed
by Jonason and Bergstriim ( 19X7) who studied 343 consecutive patients with intermit-
tent claudication and by Faulkner. House. and Castleden (1983) who studied I33
patients.

A retrospective record review was undertaken at Mayo Clinic to identify nondiabetic
patients with a clinical diagnosis of arteriosclerosis obliterans. and Jucrpens. Barker.
and Hines ( 1960) reported the survival and amputation rates among these patients. Of
IS9 patients who smoked at the time of diagnosis and who survived 5 years. XX
continued to smohe and 7 I abstained from smoking after diagnosis. Of the total number
of patients who continued to smoke. I 1.4 percent required an amputation within the
S-year period. In contrast. none of the abstainers required amputation during this
period.

In a recent retr0spectit.e 5-year folio% up study. Ameli and colleagues ( 1989) reported
the rates of amputation and patency of I36 arterial reconstructions performed for lower
limb ischemia. Of 17 I patients. 10.3 smoked before the operation. and of the smokers
43 postoperatively discontinued \mokiny. The 3-l patients who continued to smoke
more than IS cigarettes per day had ;I fivefold increase in risk for amputation at 1 years
and a threefold increase in rich for amputation at 5 years compared with the X7
nonsmokers (including never and former \mohers) and smokers of IS cigarettes or It's\
per day (p=O.Ol3 ). Five years after surgrrb. 2X percent of patients smohinp more than
IS cigarettes per da> had undergone amputation compared L\ ith 1 1 percent of the
patients ~4 ho were nonsmokers or jmohed I5 cisarettt'\ or less per da>.

The eft'ect of mohlng on the patenq. of fcmoropoplitcal \ rin b> pass grafts u\ed for
treating periphcrul arterial occlusion u a\ studied among 7 157 patients monitored for I
year (Wiseman et al. 19X9). Patients \4 ho continued to mohc. identified b> elevated
serum SCV. had a graft patent! of 63 percent after I bear compared u ith X-I percent
among nonmoher\ (p<O.O1). HoLtc\er. the anal! \is did not \eparate never smoker\
from those M ho stopped ymohin, ~5 ncx or at rhc time of surfer\ I p4.02 ). OnI\ serum
fibrinogen Ic`\.cI\ i4erc a strongt`r pi-cdlctor of= (`raft failure than serum SCN~.

Summar!

Overall. thehe studic\ 410~ ;I Io\\cr rish of pc`ripheral xtcr! disease among formel
smohers compared u ith currt'ilt \mohcr\ md :I consl\tent reduction In complication\ ot
peripheral \,ascul,lr di\easc amorl~ patient\ u ho stop \mohing. Those u ho quit ha\,c
Improved pertormancc and inipro\ cd o\ rrall \iir\ i\ al.


SMOKING CESSATION ASD CERERRO\`ASC1'LAR DISEASE

Stroke is the third leading cause ofdeath in the United States. It is also ;I major LTILIW
of morbidity. with approximately 400.000 Americans suffering strokes each !ear
(Gravies 19X9). The two major types of strobe are ischernic strobes due to occlusion ot
a vessel by an embolus or thromhus and hemorrhagic strokes resulting from suharach
noid or parenchy/mal hemorrhage. The terms cerebro\~ascuI;tr accident and strobe UC
nonspecific and usually refer to clinical syndromes resultin, ~7 from ccrchral in fat-ction
or hemorrhage. A thrombotic or emholic strobe rna\~ he ca~~wd by, uthcrosclerotic
disease of the extra- or intracranial blood I essels. Emboli/ation from the heart OI-
extracranial arteries is also an important cause of strohc. In the Framingham Stud!.
atherothrombotic brain infarction (referred to in this Chapter as tsc~hemic strohc)
accounted for S2.Y percent of strobes (Wolfet al. IYXX ). Improv cd diagnostic methods
have prov,ided a better categorization of the causes of strobe.

The I963 Report of the Surgeon General (L'S PHS 196-t) noted :I modcmte increase
in the mortality rate from cerebrovuscular disease in cigarette smohers compared with
nonsmokers in the original ACS Y-State Study (Hammond and Horn lYSXa.b) ;tnci the
L1.S. Veterans Study ( DOI-II IYSY). In the lY7 I Report. six m;t.jor prospecti\ e
epidemiologic studies were reviewed (US DHEW lY7 I ). Cigarette smohers in these
studies experienced increased stroke mortality compared with nonsmokers. The IYXO
Report noted that women who smoke have an increased rish of subarachnoid hrm-
orrhage (US DHHS 19X0). The 19X3 Report reviewed the data associating cigarette
smoking with strobe and found an increased rish of stroke among smohcrs that was
most evident amon younger age groups (US DHHS 1YX.i ). It aim noted that female
cigarette smohers have an increased risk of subarachnoid hemorrhage and that the
concurrent use of cigarettes and oral contraceptives greatly increased this rish.

The 19XY Report of the Surgeon General reviewed four additional large cohort studies
that addressed the relation between cigarette smoking and rish of stroke and concluded
that cigarette smoking is a cause of stroke (US DHHS 19X9).

In a recent meta-analysis, Shinton and Beevers (lYX9) summarized the relation
between cigarette smoking and stroke using 32 separate case+x~ntrol and cohort
studies. The overall relative rish of stroke associated with cigarette smoking 4435 1.5
(YS-percent CI. 1.3-I .6). Relatv*e risks differed considerably for the subsets ofstrohe:
cerebral infarction I .9. cerebral hemorrhage 0.7. and subarachnoid hemorrhage
2.9. Relative risks decreased vvith increasing age: for persons less than 55 years of age.
the relative risk was 2.9: for those aged 55 to 74 years. the relative rish was 1 .X: and for
those 75 years and older, the relative risk was 1.1. A dose-response relation was
observed between the number of cigarettes smoked and risk of stroke. and women had
a slightly greater relative risk than men (RR=l.72 vs. I .43).

Based on the data from ACS CPS-II, the IYXY Report of the Surgeon General
estimated that 51 percent of cerebrovascular disease deaths among men aged less than
65 years were attributable to cigarette smoking. and among women of the wmc age. 55
percent of cerebrov)ascular disease deaths were attributable to smoking (US DHHS
19X9). For persons 65 years of age or older. 24 percent of cerebrovascular disease


among men w;13 attributable to mohing: ;~mong women. 6 percent was estimated to be
attributable to smohinf.

Studies of Smoking Cessation and Risk of Cerebro\ascular Disease

In this Section. data from crohs-sectional. case+ontrol. prospective cohort. and
intervention studies are reviewed. A\ di>cus\ed in Chapter 2. miscla\Gfication of
former smoker\ because of recidivism during the followup period ih a general concern
in prospective studies.  However. ca\e+control studies of stroke are limited by the
relatively high fatality rate for incident cerebrovascular events. particularly for sub-
arachnoid hemorrhage. This often exclude5 man) incident cases or force5 the use of
proxy information from next of bin or other relatives. In all epidemiologic studies of
past smohing and ri\h of strobe. careful classification of stroke by pathophyiologic
type is important. Details of the relation between past smoking and risk of .strohe are
presented in Table\ 7 and 8 for each type of stroke reported bj investigator\.

Cross-Sectional Studies

In a cros\-sectinal analysis of 1.691 black 2nd u hite men and women admitted for
diagnostic evaluation ot' the carotid arterie\. Tell and couorkers ( 1989) reported ;I
Ggnificant relation between cigarette smohin g an the thichne\\ ofcarotid artery plsque
assessed using B-mode ultraonography. Ba\ed on self-report. patient\ were charac-
teri/ed as either nonsmoker5 (never smohed or quit more than IO bears earlier). former
hmoher\ (quit between IO !`ear\ and 1 month earlier). or current \moher\.  After
ad.justing for a patient'\ age. race. WX. and hi\torq ofdiabete\ mrllitu\ and hypertension.
the mean plaque score\ diftred Ggniticantl>, amon g the thrrc smoking group\. The
mean difference in plaque thichnc\\ compared M ith that M hich could be expected M ;I>
-0.3 I mm for non\moher\. 0.04 mm i'or former \moher\. and 0.31 mm for current
>moher\. The ah\olutc difi'erencc in mean plaque score\ between nonsmoher4 and
current mohers ~+a\ 0.63 mm (95percent Cl. 0.-154).X I mm). betueen non\moher\
and former \moker~. 0.35 mm (95percent Cl. 0. I7-0.51 mm ). and hetheen t'ormer and
current smohrr\. 0.27 mm (95.percent Cl. 0.0X-0.47 mm). The\r data jugge\t 11 4o\\er
rate ofproge\\ion ~lfutiic'rcl\clcrcl\i\ among person\ ~4 ho ha\ e quit \moking compared
with those who continue to \mohe.

In ;I cro\\-sectional \tud! of cerebral blood tloL4 IcLels in 26% neurologicalI! normal
volunteer\. Roger\ and co~orhcr\ ( I OX5 J obs?r\ ed that \ublects M ho quit smoking had
\ignificantl\ higher cerebral pt'rt'u\ion Ic'\el~ than subject\ i+ho continued to smoke.

Case-Control Studies

Case-control studies addreaing the relation bct\\een \mohing and ri& of \trohe are
\ummuri& in Table 7. In man! other publi4ed ca\e--ControI ctudies. t`ormer \moher\
have not been \pecificall> identified ac ;I distinct e\po\ure group. In those stud& that
identify former smoher\. the numberot`ca\e\ has been ver! mall or unspecified except
for the \tud\, by Donnan and collrague~ I 19X9). In \e\,eral \tudie\ (Bell and Ambro\c


TABLE 7.--Case-control studies of smoking cessation and risk of stroke

                                               Krldi\c rid. :b c01~~tx11cd n1111 ncvcr vrrcAc~\"


Qwt  <z yr
7-S yr
S-IO yr
>I0 yr

I .`)3           3.X')
2.52           3.72

I.11            I.IX
I.76           3.27

2.0(1.3 3.1)      3.7

3.2
3.1
2.1
1.7


I YX7: Taha. Ball. Illingvvorth I YX2: Bell and Symon 1974, ). population smoking rates
rather than a true concurrent control group were used for comparison purposes. Despite
these limitations, the risk of stroke among former smokers haj been consistently lower
than that among current smohers. Data for subarachnoid hemorrhage (Bell and Symon
1979; Taha. Ball. Illingworth 19X2) show a persistent elevation in risk among former
smokers compared with never smokers: however. this rish is lower than among current
smokers.

Prospective Cohort Studies

To date. a total of I4 prospective cohort studies have reported sufficient detail to
categorize former smokers as a specific subgroup monitored for incidence of strobe.
These studies have obtained information on smoking status at baseline through inter-
view or self-administered questionnaire and have observ(ed populations for 2 years
(Nomura et al. 1974) to 26 years (Wolfet al. IYXX). Other cohort studies have reported
the relation between cigarette smoking and stroke but have not included sufficient
details to categorize ex-smokers as a unique exposure group.

In each of the studies included in Table 7. the risks among former smokers and among
current smokers are reported compared with the risk among never smokers. The earlier
prospectivje studies tended not to show a positive relation between smoking and stroke.
and in several studies. the risk among past smokers was higher than that among current
smokers. In a multivariate analysis of data from the Whitehall Civil Servants Study
( IX.403 male British civil servants). the relative risk of stroke was 2.2 among current
smokers of IS cigarettes per day compared with never smokers. whereas the relative
risk among former smokers w/as I .S (Fulleret al. 1983). Among British women. current
smokers experienced a 3.0 relative risk of subarachnoid hemorrhage. and former
smokers experienced a 2.3 relative risk (Vessey. Lawless, Yeates 1983). Lower
elevations in risk were found among individuals experiencing ischemic strokes.

No excess risk of stroke was observed among 2.748 current or former smokers.
residents of Cook County. IL (Ostfeld et al. 1974) or in 47.423 residents of Washington
County, MD (Nomura et al. 1974). Doll and Peto (1976) studied 34,440 male British
physicians for 20 years and updated information on cigarette smoking after 6 and IS
years. These researchers used similar methods for studying female British physicians
among whom smoking status was updated after 10 years (Doll et al. 1980). Only slight
elevations in risks of stroke were seen among male current or former smokers, and no
excess risk was found among female current smokers. Similarly, Okada and colleagues
( 1976) found no significant elevation in risk of stroke among current or former smokers
in a Japanese population.

In I4 cohort studies published after 1980. the relative risks among former smokers
were lowerthan those reported for current smokers (Table 7). Rogot and Murray (19X0)
observed U.S. veterans and defined the population of former smokers as those who had
stopped smoking for reasons other than a doctor's orders. These former smokers had
a relative risk of I .02; current smokers had a relative risk of 1.32.
In a study of 7.895 Hawaiian men of Japanese ancestry (Abbott et al. 1986). 65X
smokers who quit in the first 6 years of followup were monitored for another 6 years:


their age-adjuwd relative rish for total strobe uas I .5 compared 1% ith never smokers
(Y5-percent Cl. l.(L2.3). Ri\h\ were similar for ischemic and hemorrhagic stroke$.
Concurrently. current smohers had ;I relative rish ot'3.5 compared with never \mo!-.er<.
Former >moLer\ had 3 cignificant reduction in ri\h oftotal \trohe compared with current
\moher\ (p4.05). Thi\ analysi\ wggests that after adjusting for other rkh factorh.
former wloher\ may be at increawd ri\h of \trohe. This residual rik may be due to the
irreversibility or slov, rcverGhilit> of the underlying mechanisms of' \mokins-
attributable \trohe. or the resumption of making among former smokers.

Welin and colleagues ( 19X7) followed 7XY men born in IYl3 for 18.5 years. Smoking
information H;IS updated during ;I follouup examination after 6 years. Investigators
then identified ;I wbgroup of former smokers who were monitored for I2 years. Among
these former\mnhers. the relative rish of stroke W;I\ 1. IX compared with I .67 forcurrent
smohers.

Wolfandcouorkerk ( IYXX) studied 1.255 men and women in the Framingham Stud!,
and updated cigarette smoking information at Z-year intervals.  Among current
smokers. the relative rishs of overall stroke were 1.33 for men and I.61 for women.
During the 26 year\ offollowup. SO percent of the normotensive smokers quit smohing
compared with 33 percent of the hypertensive smoker5 (p4J.05). Former \moher\ had
a Ggnificantly lower ri4h compared with current makers. This relation wa\ olxer\ed
among men and women in each of the blood pwsure categoric\. Benefit\ of mokinp
cessation were oh\erved in the hypertewiw and nonnotensive subjects.

In the Nurse, Health Stud!,. current smohing \\;I\ \trongl> awxiatrd \h ith rish ofhoth
wbarachnoid hemorrhage and thrcllnboemholic \trohe (RR=lO.3 and 3. I. re\pectivel!.
for 3 cigarette\ or more per da ) (Coldit/ et al. IYXX). The relative rish\ for former
smoker5 were sutxtantially Io~er.

A4 described in the IYXY Report of the Surgeon General. the relative ri\h\ of \trohe
for smokers \houed an increase when CPS-II data f`rom I YXZ to IYX6 Mere compurcd
uith CPS-I data from lY5Y to lY6S I US DHHS IYXY 1. The\e studies. using the same
design and method\. \houed an increaw in the relati\r rish ofdeath from strobe among
current \moher\ for men aged 33 to (11 \car\ from 1 .7Y in I Y5Y-65 to 3.67 in I YXLX6.
For women of the ~me age. the rel:rti\t' ri\L Incrcrcrwi l`rom I .Y2 to 1.X0. The number
of former wohers among ~~omcn in CPS-I M;I\ too small to report the\e data separateI!.
HoNever. t'or male\. the rcl;lti\e ri\h ot`\trohe among t'ormer smoher\ has \ho\\ n little
increase and remanned onI!, \lightl! higher than among nt'\`cr mohers.

The reawn\ are uncle;tr f`or the stronger a\soci;uion\ hetnce11 cigarette mohing and
ri\h of strobe noted in more recent \tudie\. tfoL\t'\t`r. this tendew! for higher relative
ri\h\ in the more recent \tudic`\ ha\ been documented t`or ;I u ide varier> of smohing-
related d\\ea~e\ (CS DHl1S IYXY). One lihcl~ e\pl;m;lticw i\ that the effect of\moking
i\ related to duration ot`\mohing. and the cohwt\ ot` pcrxon\ (e\pcciall> women) u ho
stxted smohing before ase 20 irr'e onI\ IIOU reachin, (7 middle and late xiulthood
(Garfinhel and Stellmxn I YXX). Control of h!yertenslon has lmpro\ ed in the L.nitetl
State\ during the Ia\t decade. and the incidence of 4trohe ha declined. Thu\. wiohing
ma\ iio~ pta!, ;I rrlativcl! cc wxtc'r role in the eti(~lw\ or thi\ d~waw than it did In t`xlier
                                    2 .
period\ u hen uncontrolled h\ perten\ion M ;I\ more con~~~mn.

250



Summary of Observational Studies

In a meta-analysis of cohort and case-control studies of cigarette smoking and stroke
(Shinton and Beevers 1989). the overall relative risk of stroke among former smokers
was I. 17 compared with never smokers (9Spercent CI. 1.05-l 30). This estimate is
based on a summary of I8 relative risks from 13 studies that separately identified former
smokers (Kahn 1966: Doll and Peto 1976: Abbott et al. 1986: Colditz et al. 1988: Ostfeld
et al. 1974; Kono et al. 1985: Khaw et al. 1984: Vessey. Lawless, Yeates 1984; Bell
and Symon 1979: Bell and Ambrose 1982; Bonitaet al. 1986; Bonita 1986; Taha. Ball.
Illingworth 1982). As observed for the relation between current smoking and stroke.
the risk among former smokers was greater when the analysis was repeated using only
those studies with stroke occurring before age 75 (RR= I .47.95-percent Cl. I. I S-l .X8
compared with never smokers). By comparison. the relative risks for current smokers
were 2.9 for those younger than SS years and I .8 for persons aged 55 to 74 years. Thus,
although a modest elevation in risk persisted among younger former smokers, this
relative risk was substantially less than that which was observed among current
smokers.

Intervention Studies

Intervention trials described above provide little direct evidence relating to change
in risk of stroke after smoking cessation. Only the trial of smoking cessation conducted
among I.445 British men used a single intervention (Rose et al. 1982). During IO years
of followup, five men in the normal care group died because of stroke, and seven men
in the intervention group died because of stroke. The small numbers in each group and
the small difference in smoking cessation rates between the intervention and control
groups limit any conclusion regarding the impact of smoking cessation in this popula-
tion.

Other intervention studies have included management of hypertension and
cholesterol as well as smoking cessation programs.  As discussed under randomized
trials of smoking cessation and CHD. these multiple interventions make drawing
conclusions difficult regarding the relation between smoking cessation and risk of
stroke (Steinbach et al. 1984: Wilhelmsen et al. 1986: MRFIT Research Group 1982.
1986; Salonen, Puska, Mustaniemi 1979; Hjermann 1980; Holme 1982).

In a nonrandomized intervention, Rogers and colleagues (1985) measured changes
in cerebral artery blood flow among volunteers who were encouraged to abstain from
cigarettes. Cerebral perfusion was improved after smoking abstinence.

Influence of Prior Levels of Smoking

Using data from the followup of 248,046 U.S. veterans monitored for I5 years, Rogot
and Murray (1980) reported the mortality ratio for stroke among former cigarette
smokers who stopped smoking for reasons other than a physician's orders according to
the level of prior cigarette smoking. Based on 1,279 strokes among past smokers, the
mortality ratio for stroke among former smokers relative to never smokers increased

75 I


with higher previous daily cigarette consumption from 0.94 for those smohing less than
IO cigarettes per day to I .33 for those smohing 30 cigarettes or more per day compared
with never smokers (Figure 7). Data from ACS CPS-II also address this relationship
(Table X). Within each level of previous smoking. the risk of stroke was clearly lower
for former smokers than for continuing smokers, except among men who smoked 2 I
cigarettes or more per day. Other studies have had too few former smokers to classify
them according to previous number of cigarettes smoked.

~10 cig/day   1 O-20 cig/day  2 l-39 ciglday   ~40 cig/day

O ??????????

m Current Smokers

FIGURE 7.-Mortality ratios for stroke for current smokers and ex-smokers
      compared with never smokers, b> daily cigarette consumption,
      US Veterans Study, 1954-69

Effect of Duration of Abstinence

The relation between duration of abstinence and rish of strohe has been addressed in
only a few studies. In a case<ontrol stud) that included 135 former smohcrs who
suffered strobe. Donnan and coworkers ( 19X9) observed that the relative rish of strohe
declined monotonically over the IO years following quitting: at the end of IO years. a
significant excess rish of strohe was still evident.

Using 5-year intervals. Root and Murra~~ (19X0) reported the mortalit>, ratios for
those who had abstained. Assuming that an individual classified as a former smoher at
the beginning of the study would remain a former smoher throughout the IS Iears of


TABLE S.-Prospective cohort studies of smoking cessation and risk of stroke

Population

OIlreId et al. (lY74)




NomLlra et al. ( 1074)

2.738 Cook Coun1y. Il.
rek.lcnt~ receiving old age
;I\\l\txlce aged 65-74

47.423 Washington Count).
MD rc\itlent~

O.Vlh    I 4 cl)!/`la): I .7v
    IO IV clp/day: 0.x5
     20 cIg/tl:ly. 0.x I
I .03"          0.7')
0.7')          0.X6
I .ot)          I ..I0
O.Y7          I).`)0

Doll and Pet0 (1976)

Brirlxh phykians: 3J.440
men

Ohada et al. ( lY7h)    4. I X6 Jnpanew

20 yr


h)l

NK



NK


TABLE S.--Continued

Relative risk compared with never smoker\"

Reference

Outcome

Former
smokers

Current
smohers

Doll e1 ill. ( IYXO)

British phy\Icl;ms: 6.lY4
vso"lell

Kogot and M way
(IYXO)

FullcreI al. (IYX7)

Whwhall CIVII wrvant\:
I X.403 men aged 40-64

Vea\ey. Lawleh5.     I7.000 l.lK women aged
Yelltea t IYX4)        2% 3Y

Abbott et al. ( I YXh)

Honolulu Heart Study: 7,XYS
men of Japanese orIgIn: hSX
\mokcr\ who quit In first 6 yr

Welin cI al. t IYX7)

7X0 men living In Gothrnhurg.
67X examined

Car\Iensen.
Pwhagen. Eklund
(IYR7)

?S.lSY Swede\

22 yr

IS yr

IO yr

It&l6 yr

l2yr:
6 Yr

IX.5 yr:
I I yr

Ihyr

NK

I.279

34

2
4


I I
3

NK

I24

DeaIh due to cerebral
thromboG%

Stroke ICD 336343
(7th revision)

Strobe mortality

Subarachnoid
NonhemorrhagIc

Thromboembolic
Hemorrhage
Total

Excluded subarachnoid
hemorrhage

Cerehrovascular mortality
ICD 43%43X

I.IX





I .02

I-14q/day:  0.03
14-24 cIg/day:  0.45
225 cig/day:  0. I Y


         I.32

I.52    I-Y rig/day: I .O'
    I%lYcig/day: 2.0
     220 cig/day: 2.3
2..Jh             3.0
I.3               I.4


I .6 (0.7-3.X)         3.00
1.X (0.4-9.0)         6.10
I.5 ( I &2.3)         3.50

I.IXh             1.67

1.10

I-7 g/day: 0.9
X-I 5 g/day: 0.9
>IS g/d/day: I.1


I'S I)tltis (I'JXY)    AC'S (`PS-I (2%St:lle Stud) )     h yr ( I OS--h.! 1     NR


TAHIX X.--Continued

Qwt <I yr 0.27        2.07
tL2yr  1.42
3 ~.s yr I .3Y
h to yr 2.27
II ISyr 2.34
>Ihyr l.Y)2

Qutt <I yr NR         I .77
I-2yr l.Y2
1-s yr 0.7')
h-t 0 yr 0.5')
t ILtsyyr 1.23
Zlhyr O.Y3


TABLE K-Continued


follo~up. the\e investigator\ reported mortalit> ratios clo\e to I .O for all durations
except for 5 to 9 years after quitting.

Based on 26 ye;irs of\tud!,ing 4.35 men and u'omttn in the Framingham Study (Wolf
et al. 19X8). the ri& of\troLe among person\ u ho stopped was significantly lower than
that among persons who continued to smohe cigarettes. Furthermore. persons u ho quit
smohing developed strobe at the mte of never smoker\ soon after discontinuing
cigarette smohing (Figure 8). Wolf and coworhers ( 198X) estimated that the risk of
stroke among smokers had decreased significantly ? yean after quitting and reverted
to the level of never smokers within 5 years. The\e results persisted after controlling
for age. blood pressure. serum cholestrol level. relative weight. left ventricular hyper-
trophy on electrocardiogram. and blood glucose level. Thu\. the reduction in risk after
smoking cessation is not attributable to differences in other rish factor\ for stroke
between those who quit and those who continue to smohe.
In the Nurses Health Study (Colditr et al. 198X). B lower ri\h of stroke was ohserved
with increasing time from cesation. Compared with the ri\h among never smokers.
the relative risk was 3.6 among women who had stopped for les\ than 2 j'ears
(95percent Cl. 1.11.7). However. among women who had stopped tbr 2 lears or
more, the relative rish was reduced to I .3 (9S-percent CI. I .O-2.0). Women currentI).
smoking IS to 14 cigarettes per day had ;I relative risk of 2.9 compared with never
smoker\. Again. the elevation of the relative risk during the first 3 year\ after cehation
is consistent with high recidivism among the\e women.
Prospective data from ACS CPS-II \ho\ved that among men who quit smoking. the
risk of \trokc returned to that of never smohers after I I year\ or more of smohing
abstinence for those originally smohing fewer than 2 I cigarette\ per dab. However. for
men who pre\,iousl\ smohed 21 cigarette\ or more per da\. the rish among former
smokers did not return to the level of ne\`er smoker\. even after I6 bears or more of
cessation. Among women who quit. the rate of decrease &;I\ much more rapid: h! 3 to
5 years after cessation. the ri\h of a-ohe wa\ 4milar to that of never smoher\ (Table
8).

Oral Contraceptives and Smoking Cessation

In two studies the risk of subarachnoid hemorrhage was augmented m~ong cigarette
smokers who also take oral contraceptive\ tPetitti and Wingerd IY7X: Collahorati\e
Group for the Study of Strohe in Youn, 17 Women 1975). In the Collaborative Group
Study of stroke among youn, ~7 women ( 1975 1. the cutegot-\ of former smoher\ was not
cleat-l), defined: rather. ;I group of"once regular \moher\" XI\ compared with "never
regular smoker\." In this stud\ there u :I\ no ;t\\oci;ltion between current smoking or
former smoking and risk ofthromhotic strobe. O\,erall. the relutiie rish for hemorrhqic
strobe was I .X among once regular moher\ and 3.3 anon2 current smoker\. Within
the group of once regular hmoher\. uomen currently usins oral contracepti\,e\ had
approximately twice the risk compared u ith women not u\in, ~7 oral contraceptives. The
Royal College of General Practitoner\ \tud! of oral contracepti\,e\ did not separate
former smokers from never smoher\ (Luyde. Beral. Kay I98 I ). Hence, data to address
the relationshipamongoral contraceptive\. smoking cessation. and risk of \ubarachnoid

258


--\
o ? o ? o ?

1        .        I

5     10    15     20     5     10    15     20


        Years of Follow-up

FI(;URE &-survival free of stroke in cigarette smokers (dotted line), never
   smokers (solid line), and former smokers (dashed line), aged 60,
   using 00x proportional hazard regression model. among men and
          women
SOtJK~`E. Wolt'rt al. I IYXX).


hemorrhage are not available from that study. Because oral contraceptive preparations
used today provide substantially lower doses. the risk of cardiovascular disease as-
sociated with their use and their interaction with cigarette smoking may be different
than observed for the early high-dose preparations.

Effect of Smoking Cessation After Stroke

In contrast with CHD. in which the focus after MI is prevention of recurrent disease.
the center of attention after a major cerebrovascular event is rehabilitation. For CHD.
substantial evidence shows the benefits of abstaining from smoking after onset of CHD.
Comparable data are not available on the benefits of abstinence after stroke.

Summary

Risk of stroke resulting from occlusion of the cerebral arteries and from subarachnoid
hemorrhage is increased approximately twofold to fourfold among current smokers
compared with never smokers. After cessation. the excess risk decreases steadily. In
some studies, the rish of stroke among former smokers becomes indistinguishable from
that of never smokers within 5 years: in other studies. this decrease did not occur until
after IO years or more of smoking abstinence. The reduced risk of stroke among persons
who stop smoking is independent of the amount prel iousl) smohed and other knoun
risk factors for stroke. Similar reductions in risk of stroke after cessation are seen
among men and women. but fev. data are available for minority populations.

I Compared with continued smohing. smoking cessation substantially reduces rish ot
coronary heart disease (CHD) among men and women of all ages.
2. The excess risk of CHD caused by smoking is reduced by about half after I qear ot
smoking abstinence and then declines t ~~raduall>. .After I5 years of abstinence. the
risk of CHD is similar to that of persons u ho ha\e never smohed.
3. Among persons u ith diagnosed CHD. smohinf cessation murkedl! reduces the risk
of recurrent infarction and cardiovascular death. In many studies. this reduction in
risk of recurrence or premature death has Hun SO percent or more.
3. Smohing cessation substantialI!, reduces the rish of peripheral artery occluG\e
disease compared M ith continued smoking.
5. Among patients N ith peripheral arter? disease. smohing cessation impro\ es exercise
tolerance. reduces the risk of amputation after peripheral arter! turgq. and
  increases overall survival.

6. Smoking cessation reduces the risk of both ischemic strobe and subarachnoid
hemorrhage compared M ith continued smoking. After smoking cessation. the rish
  of strohe returns to the Iehel of never smohers: in some studies this has occurred
within 5 years. but in others as long as IS bears of abstinence were required.


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          CHAPTER 7
    SMOKING CESSATION AND
NONMALIGNANT RESPIRATORY DISEASES



CONTENTS

Introduction  ..................................................... ..27 0
Part I. Smohing Cessation and Respirator) Morbidit!  ..........  ........... 2X5
Respiratory Symptom\ ............ , ................................ 2X5
  ClinicalStudies  ................................................ 2x3
  Cross-Sectional Studie\ of Population\ .............................. 2XX
  Occupational Groups  ........................................... 2%
  Longitudinal Studie\  ............................................ 200
  Clinical Studies of Possible Mechanism\  ............................ 30-l
Respiratory Infection\  ............................................. 303
  Smoking Cessation and Respiratory Infection  ........................ 107
Part II. Pulmonary Function Among Former Smoker\ ...................... 30X
Cross-Sectional Population Studies of FEVl .............  .............. 3)X
Pulmonary Function Studies After Smoking Ce\\ation  ................... 3 I h
  Changes in Spirometric Parameters After Ce\\ation  ................... 3 19
  Tests of Small Airways Function  .................................. 37.3
  Diffusing Capacity Among Former Smoher\  ......................... 327
  OtherMeasures  ................................................... X
Longitudinal Population-Bahed Studies ................................ 32X
Part 111. Airway Responsiveness, Cigarette Smohiig. and Smohing Ce\\ation 337
Mechanisms of Heightened Airway Responsivenc\\ in Smohcr\ and Fol-mer
  Smokers ....................................................... 33X
Cross-Sectional Studies  ............ , .............  ................. 33X
Longitudinal Studies  .............................................. 339
Clinical Studies .........................  ......................... i-40

Part IV. Effects of Smoking Cessation on COPD Mortality   311

Part V. Former Smokers With Eqablished Chronic Ob\tructi\e Pulmonar\
Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Effect of Smoking Cessation on FEVt Decline Among COPD Patlentx 345
Effect of Smoking Cessation on Mortality Among COPD Paticnt4 117
Conclusions . . . . ..~~................................................ 349

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...151


INTRODUCTION

Obstructive airways diseases constitute a heterogeneous - "roup of disorders that
include but are not limited to emph! wna. asthma. chronic bronchitis. md chronic
obstructive pulmonary disease (COPD). These tour clinical conditions are the most
prevalent of the obstructive airnays diseases and are responsible for substantial mor-
bidity and mortality. Over IX million Americans suffer from asthma. and about I?
million Americans have COPD. which is the fifth leading cause ofde;~th and the most
rapidI\, increasing cause ofdeath among adults older than 65 years (Feinleibet al. 19x9).
The 19x4 Report on the health consequences of \mohin g revieued information on
chronic obstructi\,e lung diseases (US DHHS 1YX-l). The Report concluded that
"cigarette smoking is the ma.jor cause of chronic obstructive lung disease in the Cnited
States for both men and u'omt`n. The contribution of cigarette smohiny to chronic
obstructive lung disease morbidity and mortality far outweighs all other factors" (US
DHHS I YX3. p. X 1. Approximately X5 percent of COPD mortalit\. among men and 7Y
percent among women is attributable to cigarette smohing (US DHHS IYXY). The
annual toll of smoking-attributable COPD in the United States is estimated to be 57.000
deaths (US DHHS 19x9). which are responsible for more than 500.000 years of
potential life lost before the average life expectancy (Davis and Novotny 19XY ).

The nosology of obstructive airways diseases has been eLol\Jing since the CIBA
Foundation Guest S>,mposium in 1959. one of the first attempts tocreate a standardi
classification. For the purposes of this Chapter. emphysema refers to pathologic
abnormal permanent enlargement of the airspace\ distal to the terminal bronchiole.
accompanied by destruction of airspace walls and uithout obvious fibrosis (American
Thoracic Society 1987). Chronic bronchitis refers to chronic cough and/or sputum
production for at least 3 months per year for 2 consecutive years. Asthma ha\ t-wn
defined as "a disease characterized by increased responsiveness of the airua!s to
various stimuli and manifested by slowing down of forced expiration. which changes
in severity either spontaneously or as a result of therapy" (American College of Chest
Physicians. American Thoracic Society Joint Statement I Y75). The term COPD is used
to describe persistent obstructive ventilatory impairment as determined b> ;I teht ot
pulmonary ventilatory function (O'Connor. Sparrow. Weiss 19X9).

Overlap of these conditions is extremely common. although discrete cases of each
can be identified (Figure I ). It is estimated that 60 to IO0 percent of COPD patients
also have airways hyperresponsiveness (Klein and Salvaggio 1966: Parker, Bilbo. Reed
1965: Ramsdell. Nachtwey. Moser 19X3: Ramsdale et al. IYX4: Bahous et al. 1YX-I).
Almost one-half of all asthmatics suffer from chronic bronchitis (Burrows et al. I YX7).
and asthma may be a risk factor for the development of chronic airtloh obstruction
(Fletcher et al. 1976: Schachter. Doyle. Beth lYX4: Buist and Vollmer 19X7: Peat.
Woolcock. Cullen 19X7). Although the extent of emphysema. as documented b!
postmortem examination of the lungs. correlates significantI>, with the degree of fixed
airflow obstruction. the correlation is modest. suggesting that emph! sema alone does
not full) explain the functional impairment in most persons u ith COPD tCosio et al.
1977).


CHRONIC BRONCHITIS         EMPHYSEMA

ASTHMA

AIRWAYS OBSTRUCTION

FIGURE I.--Nonproportional Venn Diagram of the interrelationship among
     chronic bronchitis, emphysema, asthma, and airways obstruction.
SOL RCE: Snider I IUXX).

Researchers in the United States and the United Kingdom tend to separate asthma
from the other obstructive airways diseases and to deemphasiLe the importance of
cigarette smoking in this particular clinical entity. However. the data suggest that
cigarette smoking may influence asthma and that allergy and airway hyperresponsive-
ness. strongly associated with asthma. may play a role in the development of fixed
airflow obstruction (O'Connor. Sparrou. Weiss lYX9).

The generally accepted model of the pathogenesis of COPD is based on the result\
of longitudinal investigations of lung function (Fletcher and Peto 1977: Becklahe and
Permutt 1979: Burrows I9X I: Speizer and Tager I97Y) (Figure 2). The model suggests
that disease development is preceded b\ a long latent period during which lung function
declines at an accelerated rate.


FEVl as%
ofvaiueal
aga M25

&      I       L   I       I             L       a       L      I
5    10    15    20    30   40    50   60    70   00

                AGE-yWt3

FIGURE 2.Theoretical curves depicting varying rates of decline of FEV 1
NOTE: Curves A and B represent never smokers and smokers. respectively. declining at normal
rates. Curve C shows increased decline without development of COPD. Rates of decline for former
smoker\ are represented hy curves D and E for those without and with clinical COPD. respectively.
Curve\ F and G show rates of decline with continued smoking after development of COPD.

SOURCE: Spewer and Tager (1979).

Several features of this conceptual model merit emphasis in relation to smoking.
First, disease development may occur as a result of factors that accelerate decline in
adult life. lead to less than maximal growth, or both. Second, because of the extremely
long latent period from the onset of smoking to disease development, factors important
in childhood and young adulthood cannot be addressed in longitudinal studies that begin
in adulthood. Third, longitudinal studies of children and adults have shown that
pulmonary function levels are very stable over time with tracking correlations ranging
from 0.70 to 0.90. This high degree of longitudinal correlation, consistent with both
environmental and genetic determinants of disease, demonstrates the importance of
previous level of function as a major determinant of future disease risk.

Research on risk factors for COPD was reviewed extensively in the 1984 Report of
the Surgeon General (US DHHS 1984). The review leads to several general findings


with regard to smoking. Cigarette smohing is associated with low levels of 1 -set forced
expiratory volume (FEVI) in cross-sectional investigations (Knudson. BUITOWS.
LebowitL 1976; Burrows et al. lY77; Beck. Doyle. Schachter 198 1; Dockery et al. 1988:
US DHHS lYX3). with accelerated decline of FEVI in longitudinal studies (Burrows et
al. lYX7: Beck. Doyle. Schachter 1982: Boss? et al. 1981: US DHHS 1984), and with
increased mortality from COPD (Best 1966; Doll and Peto lY76; Hammond 196.5:
Hammond and Horn 1958: US DHHS IYX4). The effect% of cigarette smoking on lung
function level or rate ofdecline and on mortality increase with the duration and amount
of smoking (US DHHS 1Y83).
Because the development of COPD in adults is associated with a long latent period.
the age at which cigarette smohin g might have a critical effect has not readily been
addressed.  Passive smoking impairs lung growth in children and thus, may limit
maximal lung growth (Tager et al. 1983: US DHHS lYX6). Smoking in adults may
shorten the phase when lung function tends to plateau between the ages of 20 and 10
and/or may accelerate the decline in lung function (Tuger et al. 1988). Cigarette
smoking is the predominant cause of lung function decline at a rate greater than the
annual volume loss of 20 to 30 mL associated with aging.
Although cigarette smoking has been clearly established as the major risk factor for
COPD. the interactions of the intensity of smoking with factors determining suscep-
tibility have not been fully characterized. For example. Burrows and coworkers ( 19X7)
suggested that two subsets of COPD patients can be differentiated by the presence or
absence of accompanying asthmatic features. According to thi:, hypothesis. subjects
with chronic asthmatic bronchitis have a better long-term prognosis. smaller cumulati\ e
exposure to tobacco smohe. and greater prevalence of allerg> and airway responsive-
ness. The second group of patients ha\ emphysema. poorer long-term prognosi\.
greater cumulative tobacco make exposure. and reduced prevalence of allerg!, and
airway hyperresponsiveness (Burrows el al. 1087). Available data do not discriminate
the relative contribution\ of cigarette smoking in these clinical subtypes of patients.
Studies of the mechanisms b\ which cigarette smoking cause> lung injur! \\ere
reviewed extensively in the 19X-l Report of the Surgeon General (US DHHS 1081).
That Report and other rtf\ itfb s (Thurlbeck 1976: Snider lYX9: Wright IYXY) also co\ t`r
the relationship between the structural changes associated with smoking and the
severity of airtlow obstruction. Cigarette smoking causes inflammation of both the
airways and parenchyma of the lun,. $7' the resulting structural damage has functional
consequences that can lead to the development of clinically diqnored COPD if there
is sustained making.  Franh parench\,mal damage is preceded by an increase in
intlammator> cells in lung parenchyma at the level of the hronchioli (Nieuoehner.
Kleinerman. Rice 197-I). Both neutrophil\ and alveolar macrophages are important in
the development of this inflammatory bronchiolitis. Although neutrophils store and
release greater quantities ofelastuse than alveolar macrophages (Janoffet al. 1979). the
macrophage may be an important cell in attracting neutrophils to the lung (Hunninphahe
and Cr) stal 1 YX3). Cigarette mohing-induced bronchiolitis is associated h ith func-
tional abnormalities detectable in the early stages onI!. with sensitive tests of small
airway function (Bui\t et al. I Y7Y: Casio et al. 1977: McCarthy. Craig. Chemiach 1976:
Ingram and Schilder 1967: Ingram and O'Cain 197 I ). E\en before Ggnificant t'n-


physema is present. destruction of peribronchiolar alveoli can be found in the lungs of
smokers (Saetta et al. 1985; Wright 1989); the loss of alveolar attachments may result
in loss of elastic recoil (Wright 1989).
The protease-antiprotease hypothesis proposes that the destruction of lung tissue
resulting in emphysema occurs as a consequence of genetic or acquired imbalance of
proteolytic and antiproteolytic enzymes in the lung. As noted in the 1984 Surgeon
General's Report (US DHHS 1984). this theory derives from two principal observa-
tions: ( 1) (Y- I -antitrypsin. a major anti-elastolytic enzyme of the lower respiratory tract.
is absent in persons genetically deficient in a- 1 -antitrypsin: these persons often develop
emphysema at an early age (Laurel] and Eriksson 1963), and (2) administration of
proteolytic enzymes in animal models produces emphysema (Gross et al. 1965).
Cigarette smoking is associated with increased numbers of neutrophils and activated
macrophages in the lungs of smokers, and neutrophil elastase can cause emphysema in
animal models (Harris et al. 1975: Galdston et al. 1983). In addition. the a-l-anti-
protease of cigarette smokers has reduced functional activity (Gadek. Fells. Crystal
1979: Gadek et al. 1981).
However, although damage to the airways and parenchyma of the lung by cigarette
smoke underlies excess lung function loss and COPD in smokers. the factor\ determin-
ing the development of disease in individual smokers have been only partially charac-
terized. A minority of cigarette smokers develop COPD. and cigarette smoking only
partially explains the variability in FEV t decline (Burrows et al. 1977: US DHHS 1984).
Data suggest that cigarette smoking may influence airway as well as parenchymal
inflammation. Thus. host factors determining the response of the airways and
parenchyma to cigarette smoking. as well as the intensity of smoking. are likely to
determine the development of disease.
Cigarette smoking has a variety of effects on the immune system: those effects may
be important in determining the risks of COPD and other respiratory diseases. Cigarette
smoking is associated with elevated total serum IgE. This total IgE does not exhibit
seasonal variability, as seen in atopic individuals. and the antigens responsible for this
increase have not been identitied. Cigarette smoking may influence the development
of an atopic diathesis via effects on T-cell helper and suppressor activity (Ginns et al.
1982: Milleret al. 1982). epithelial permeability (Joneset al. 1980; Simani, Inoue. Hogg
1974). or functional alterations of antigen-presenting cells (Warr and Martin 1977).
Cigarette smoking is associated with skin test positivity among children exposed to
maternal cigarette smoking (Weiss et al. 1985: Martinez et al. 1988); however. this
association is not seen in studies of active adult smokers (Burrows, Lebowitz. Barbee
1976). Jn adult subjects, skin test positivity is most prevalent among former smokers
(Taylor, Gross et al. 1985). These data are consistent with the hypothesis that atopic
individuals may not become or remain regular smokers because of airway inflammation
secondary to inflammatory effects of cigarette smoking. Thus, cigarette smoking may
interact with atopy in a complex manner, inducing atopy in less susceptible or initially
nonatopic subjects and discouraging highly atopic subjects from taking up smoking.
Eosinophils are primary effector cells for allergic inflammation (DeMonchy et al.
1985). Increases in eosinophils are associated with the severity and exacerbations of
asthma (Horn et al. 1975). Increased eosinophils are also associated with the occurrence


of respiratory symptoms and the level of pulmonary function (Burrows et al. 1980:
Kauffman et al. 1986). Cigarette smokers exhibit elevations of the peripheral blood
eosinophil count (Taylor. Gross et al. 1985). although it is unknown if allergen-induced
and cigarette smoking-induced eosinophilia occur by similar or different mechanisms.
Eosinophils in peripheral blood are also related to clinical correlates of emphysema
(Nagai. West, Thurlbeck 1985).

Cigarette smoking has also been associated with increased levels of airway respon-
siveness (Woolcock et al. 1987: Sparrow et al. 1987; Burney et al. 1987). Several
mechanisms could explain the relationship between cigarette smoking and increased
airway responsiveness. including smoking-associated reduction in prechallenge level
of lung function, chronic airway inflammation due to smoking. and smoking-induced
impairment of epithelial function. The potential central role of cigarette smoking in
parenchymal and aitways inflammation is depicted in Figure 3.

                 BRONCHIOLAR
AIRWAY --- ~~--   NARROWING
INFLAMMATION ,_ -.

               *                 -..
                                  `\ .
                             `\.       *
CX%Fl~;&E /'                         AIRWAY
                          HYPERRESPONSIVENESS
          `\

\\                                o
  ??
    ALVEOLAR
   INFLAMMATION

-. -w  EMPHYSEMA

FIGURE A-Hypothesized mechanisms by which airway hyperresponsiveness
      may be associated with developing or established COPD without
      necessarily being a preexisting risk factor
4OTE: COPD=chron~c oh\trucfi\ e pulmon~r) dieax..

When considered in this pathophysiologic framework. the potential consequences of
smohing cessation on the degree of impairment and future rish of COPD var) with the
extent of irreversible change\ at cessation and with host characteristics of the quitting
smoher. In adults. cigarette smoking cessation i, associated with a blowing of FEVt
decline to the rate of never smokers (Figure 2). To the extent that airway and alveolar
inflammation have cau\ed reversible epithclial and parenchymal inflammation. pul-
monary function could improve after cessation. particularly if heightened airway
responsiveness and bronchiolitis can resolve. To the extent that cigarette smoking has
caused permanent damage to lun g \tructure (e.g.. emphv\emu). those changes are

2X-1


unlikely to be reversible. Thus. the amount and duration of smoking. the relative extents
of parenchymal and airway inflammation. and the degree of permanent structural
damage are probably the key determinant\ of the ic\;el of function after smoking
cessation. Even in the settinp ofcytabli\hedCOPD. smohing cessation ma\ potentialI>
reduce the rate of functional los\.

Former smokers may differ from continuing smohers with regard to ho\t charac-
teristic> that potentially determine suxeptibility to ci garette smohe. Because presmoh-
ing levels of atopy and airs ay responsiveness modif) the short-term re\pon\e to smoke.
individual\ with atopy or heightened airway re\ponsivene\\ ma)' be les\ likely to tahe
up smoking. to reduce \mohing. or to quit smoking if respirator! symptom\ occur. Thi\
potential bias. termed the "healthy smoker effect" by O'Connor. Spurrou. and Wei
( lYX9). cannot be evaluated in cro\;+\ectional studies.

PART I. SMOKING CESSATION AND RESPIRATORl' MORHIDITY

Respiratory Symptoms

Since the 1950s. strong evidence has accumulated documenting increased respirator!
symptoms in smohers of all ages compared with nonsmokers (US PHS 1963: US
DHEW 197 I. 1979; US DHHS 1984). Further. the number of cigarette{ smoked per
day is the strongest risk factor for the principal chronic respiratory symptoms including
chronic cough. phlegm production. wheeze, and dyspnea (Lebowitzand Burroh s 1977:
Dean et al. 1978: Higgins. Keller. %tzner 1977: Huhti and Ikhala 19X0: Higenbottam
et al. 1980: Schenker. Samet. Speizer 19X?). The widespread effects of chronic
smoking on the lung, including decreased tracheal mucous velocity (Lourenqo. Klimeh.
Borowski 197 I : Goodman et al. 197X: Thomson and Pavia 1973). increased secretion
of mucus on the basis of mucous gland hypertrophy and hyperplaaia (Thurlbeck 1976).
chronic airway inflammation (Niewoehner. Kleinerman. Rice 197-I). increased
epithelial permeability (Jones et al. 1980; Minty. Jordon. Jones 1981: Mason et al.
1983). and emphysema (US DHHS 19X4), underlie the development of these
symptoms. Smoking cessation has been associated with a reduction in respiratory
morbidity, presumably through reversal of some of these pathophysiologic abnor-
malities. Relevant evidence can be found in clinical studies, which involve follow,up
of the symptoms of persons participating in smoking cessation clinics. and
epidemiologic studies.

Clinical Studies

Buist and coworkers (lY76) found that smohing cessation w'as associated with a
dramatic reduction in respiratory symptoms w)ithin I month of cessation. These
researcher7 assessed spirometry and respiratory symptoms for over I3 months in 75
cigarette smokers enrolled in a smoking cessation program. Subject\ were divided into
quitters (those who did not smoke during the entire I?-month period). modifier\
(individuals who reduced their cigarette consumption by 25 percent ). and nonmodifiers


(subjects who continued to smoke at the same level). The three groups were of
comparable ages (35 to 39 years) and had a cumulative cigarette consumption of 20 to
26 pack-years. A symptoms ratio was calculated at I. 3, 6. and I2 months by taking
the number of symptoms (e.g., cough, expectoration, shortness of breath, and wheezing)
observed and dividing by the total number of possible symptoms for that group. All
groups started with ratio values of approximately 0.55. The ratios for quitters declined
within I month of cessation and continued to decline over the course of the study from
0.52 to 0.08. In contrast, the ratios for modifiers decreased less than quitters, and
nonmodifiers had no change in their ratios over I2 months (Figure 4). Data on
individual symptoms were not presented, and smoking abstinence was not verified by
biologic markers. In a followup study of more than 30 months. Buist . Nagy. and Sexton
and colleagues (1979) again showed that among IS quitters, respiratory symptoms
disappeared by the third or fourth month of followup and did not return during the
remainder of the study. However. after a small initial decrease in symptoms among 45
continuing smokers. further decreases were not recorded. The small sample sizes and
a 4 1 -percent loss to followup must be considered in interpreting the latter findings.
Three studies reported different results for the effect of smoking cessation on
respiratory symptoms in asthmatics.  Higenbottam. Feyeraband. and Clark ( 1980)
conducted a cross-sectional study of I06 consecutive asthmatic clinic patients and
concluded that symptoms decreased after stopping smoking.  Age-standardized
prevalence rates for chronic cough. chronic cough and phlegm. and wheezing among
asthmatics were lower for the 27 former smokers than for the 27 current smokers and
the 52 never smokers. Only breathlessness was found more often in former smokers
than in the other smoking groups. possibly reflecting irreversible smoking-induced
changes. Quantification of smoking history and time since cessation among former
smokers was not reported. In contrast. Fennerty and colleagues (1987) as well as
Hillerdahl and Rylander ( 1984) reported increased respiratory symptoms in asthmatics
who stopped smoking. Fennerty and coworkers (1987) found that 7 of I4 asthmatics
( 13.3 percent) who stopped smoking for 23 hours complained that asthmatic symptoms
were worsening. Neither of the\e two subjects showsed a decrease in specific airway
conductance or peak flow. but one had an increase in airway responsiveness to
methacholine. However. four of seven asthmatics who abstained from smoking for 7
days recorded a reduction in symptoms. Hillerdahl and Rylander (1984) studied SC)
asthmatics who were recruited from an office practice and who had stopped smoking
"permanently or for short periods of time." Using questionnaires. these reseachers
found that symptoms worsened in IX asthmatics (30.5 percent) who had stopped
smoking. Three subjects claimed onset of neu asthmatic symptoms uithin months of
cessation. Asthmatics younger than 30 years of age were more likely to complain of
worsening of their asthma than those subjects older than -IO year\ of age. Hillerdahl
and Rylsnder (1984) concluded that among asthmatics v.ho smoke. psychological
reasons. improved secretion clearance. or both could explain the findings. The uncon-
trolled nature of these studies. the small numbers of subjects. the potential for selection
and information bias. and the noncomparability of treatment regimens among study
participants limit the usefulness of the\e findings.


0.8

0.7

0.6

  0.5





  0.4





  0.3,





  0.2
0
5
; 0.1.
!z
2 0

                19 NONMODIFIERS
3
3

il.... --..*.- .._,_. ., ,3 Q",rrERS       _ _.. . - . . . . .
                 . . ._ .* _._,..__... -....

TIME FROM

3           6           9          12
INITIAL (MO)

FIGURE k--Symptom ratio (number of observed symptoms to number of
     possible symptoms) in nonmodifiers, modifiers, and quitters at
     each test period; symptoms are cough. sputum production,
     wheezing, and shortness of breath
SOl'KCE: Bui\t e( al I 1976).

In summary. studies of participants of smoking cessation clinic\ have shown that
respiratory symptoms have disappeared rapidly on quitting, even after 20 path-\ear>
of exposure. Limited studies of asthmatics have provided conflicting rewlts.


Cross-Sectional Studies of Populations

The results of community-based studies have shown lower prevalence of respiratory
symptoms among former smokers compared with current smokers (Table I ). Twoearly
investigations evaluated symptoms ofchronic nonspecific lung disease among smoking
groups. Ferris and Anderson ( 1962) studied a random sample of subjects. aged 25 to
74. from an industrial town in New Hampshire. Using spirometry and interviewer-ad-
ministered questionnaires. these researchers recorded lung function and symptom\
associated with chronic nonspecific respiratory disease in 1.167 individuals. Chronic
nonspecific respiratory disease was considered present if ( 1) phlegm production was
reported six or more times per day for 3 day\ per week for 3 months per year for the
past 3 years (chronic bronchitis): (2) if a diagnosis of asthma had been made and was
still present: (3) if wheezing or whi\tling in the chest occurred most days or nights; (4)
if shortness of breath occurred while walking at subject's normal pace on level ground:
or (5) if an FEVI less than 60 percent of forced vital capacity (FVC) w'as noted (chronic
obstructive lung disease).  Age-standardized prevalence rates per 100 for chronic
nonspecific respiratory disease showed that both male and female ex-smokers had rates
of abnormality similar to those of never smokers and lower than those of current
smokers (for males. 18. I vs. X.4 vs. 50.3. and for females. 17.2 vs. 19.3 vs. 3 I.0 for
never smokers. ex-smokers. and current smokers. respectively). In 1967. a resurvey of
the population using a slightly different random sample was performed (Ferris et al.
1971). Again. the age-standardized rate\ were less for both male and female ex-
smokers than for current smokers.

Mueller and colleagues ( I97 I ) studied a random sample of one-fifth of the population
of Glenwood Springs. CO. S!,mptoms ofchronic nonspecific lung disease.comparable
with those defined by Ferris and colleagues ( I97 I ). wpere reported by 30 percent of 55
male former smokers and by Y percent of 22 female ex-smokers. These percentage5
were between those ofcurrent and never smokers. Age trend\ were not apparent amonp
males: the small sample Gre precluded analysi\ for females.

In the mid-1960s. two surveys assessed the effects of smohing on respirator)
symptoms in older men (Table I ). Wilhelmsen and Tibblin ( I Yhh) analyzed data from
334, men aged 50 jears. born in IYli and living in Giiteborf. an industrial town in
Sweden. Of 73 former mohers. the percentqes with morning cough for 3 month\ per
year. sputum for 3 month\ per >ear. and wheeling other than from colds were lower
than those for I X2 current mohers of le\s than or greater than I5 g of tobacco per da!
and similar to those of84 never smoher\. Dy\pnea n hen n,alhing fast or up a small hill
wa\ reported mo\t frequentI> b! current smohrr\ of more than I5 g of tobacco per da\,:
all other group\ \ho\\ed comparable percentage\ of \uhjects reporting this symptom.

Weis\ and coworkers ( IY63) \tudicd 350 consecutive men. aged 50 )car\ or older.
undergoing routine examination in the Philadelphia Pulmonary Neoplasm Re\carch
Pro.ject (N=h. 1.37). Fifty-three percent of former ciFaretts moher\ (N=6X) reported
one or more symptom\ of` cough. w bee/e. or dyspnea compared with 57 percent ot
current \rnoker\ tN=lX3) and 42 percent of never mohers (N=361. Furthermore.
former smoher\ complained of cough a\ frequentI! :I\ ne\er \moher\ (Y \ \. I I percent)
and complained of d) spnea ;I\ ot'tm :I\ current \mohcr\ (16 \`L 14 percent). Onl! 70

3XX


TABLE I.-Percentages of subjects in cross-sectional studies with respiratory
     symptoms, by cigarette smoking status and gender

S>mptom\"
ReferLWX

Cough 3 mo/yr

Wtlhelm\en    sot33Yl
and Tlbhltn
I IYhh)

Wei5\ et al.
I lY63,

XMY (7X7)

Fletcher and    4(bSY (i63)
TmhertIYhl)

Mueller et al.    20-69 (Xc)3
(lY71Jh

Manfreda. Nelwn.
Chemiach (lY78)
         25-54 (256)'
       25-94 (246)"

Schenker.     17-74 (5.670,
&met. Speiler
(19X')*

Phlegm 3 mo/yr

Wilhelmwn and
Tihblm (lY661

Fletcher and
Tinker(l96l)

Mueller et al.
(1971,h

Manfreda. Nelson,
Chemiack ( 1978)
        2S-S4 (256)'
       25-94 (246)"

Hawthorne
and Fry
(1978)

4sJ54

Miller et al.
( lY88jh

Male (mean):
42.0(1.169)
Female (mean)
42.9(1.1691

36.2

x.2

4 I .o

Y.0

lY.Y

13 (I

I3.0

7ll.O

s.0

25.4
31,s

70.3
31.7

0.1'
17s1'
3 1.x'

x.1
2.0

I I.5

I .4

17.6

16.9

I X.0

10.0

12.0

16.9     10.2       10.x
24.7    25.3        5.7

36.2    23.0       16.1

40.8

28.4

14.7

IO.0

IO.0


73

5.0

5.0

IO.9

6.9

4.x





I I .o



0.0



Y.0






x.3
4.0









I.2



7.5



4.0







0.0
4.0

IO. I





12.1

5.0








4.0


5.6









I .(I







0.0
4.0


6.7





0.4

2X9


Schenher. Samet.
Sprurrt lYX2jh

Lrbowlt,      ll-Y6t2.X57)
and Burrov. \
(1977,
Dvs~nea undy'

Wtlhelm\en and
Tihblin ( IYhhr

Fletcher et al.
(IMY)
Grde\ 2
or more      4-54


Fletcher and
TmhrrtlY61)
Gmde 3 or more

Mueller et rll.
(lY71th
Grade 2.
Grrrdr 3. or more

Manfreda.
Nrl\on.
Chemiach
(197X?
Grade 2
or more

Hav.thome ;md
Fr? t lY7X?

Vlller et 31.
(IYXX)"
Grade 7
GrJdr 3

Schrnhcr.
Samet.
Speller t I YX2 1"
Grade 3

I I.2







71.7



44.0







73.5





Xl





1Y.O
7.0









5.6
II.2


Ii.2

7.2'
16.7'
`1.X'


I I.0       3.Y

        2 I .Y



-        4h .o

72. I        5.1
17.5        5.X


I X.6        Y.Y

6.7





12.6









`3.1









-I I .o
I I .o









6. I
5.0


Xl.5

47     15.h        7.1     12.7
3 0     XY       3.3     II 5

5.6'
h.I'
17.6'

X.7

45.5







20.2



36.0







IO.0





2.5





L'S)
h.0









x.7
1.0


7.0

4.5





35.X









3 I .A









32.0
7.0









7.0
12.0


13.2

3.0     Y.5
0.4     2.h

5.Y


TABLE I.-Continued

Current smoker\

Fomw \moher\

Symptom\"
Reference

Age
(number of
wbiect\)

Wheeze

Wilhelmsen and
Tibhlm (lYh6#

17.6 -         t-J.9              1.x

Wei\\ et al. ( lY6iT

x.0 -         6.0              3.0

Fletcher et al I l9SY $

Mueller et al. I IO7 I lh '


Manfrrda.
Nelwn.
Chemiach t IY7X)"
        25-N (2Sh)

16.3     12.Y


I x.0     10.0







`6.X    23.4

II

25                    `1


2.1)     s 0       -I.0     I .(I







0.x     11.1        4.2     3.5

        2%.51(246 )`I   31.5    30.7       11.1     70.0       x.0     x.0


Hawthorne and             `I x     19.2        4.x     I0.h       hl     6.0
Fry ( 1978)'
Milleret al. ( 19XXjh '          30.X    2x.1       11.7     6.Y       12.2     1.4

Schenker. Samet.
Speizer ( 19X21h '

men reported wheeze. precluding meaningful analysis for this variable. The high
symptom rates seen in this study may reflect the older ages of the participants and the
selection factors contributing to enrollment in the Philadelphia Pulmonary Neoplasm
Research Project.

Three other early investigations confirmed a lower prevalence of specific respiratory
symptoms among former smokers (Table I ). Fletcher and coworkers (1959) reported
the respiratory symptoms of 244 British post office workers, aged 40 to 59. as part of
the study of the relationship between symptoms and tests of lung function. Former
smokers of both sexes reported wheezing on most days or nights less often than current
smokers, but former smokers also complained of grade 2 dyspnea (i.e.. stopping for
breath when walking at one's own pace on level ground) as often as current smokers.
Fletcher and Tinker ( I96 1) studied respiratory symptoms in 363 London male transport
workers. Former smokers had lower prevalence rates for cough. phlegm production.
and grade 3 dyspnea (i.e., stopping for breath after walking about 100 yards on level
ground) than current smokers of IS cigarettes or more per day. In a large community-


based study in Tecum\eh. MI. Payne and Kjelcberg (1963) reported age- and sex-
specific prevalence rates for cough and phlegm production that were comparable for
former and never smokers (Figure 5). In contrast. sex-specitic rates of dyspnea were
highest among former smokers and increased with age (Figure 6).

More recent studies have also found lower prevalence of respiratory symptoms
among former smokers and documented sex-specific differences among smoking
categories (Table I ). Mueller and colleagues ( I97 I ) showed that male former smokers
had fewer symptoms than current smokers. including cough for 3 months per year. grade
2 dyspnea. and wheezing. Only sputum production for 3 months per year was higher
among male former smokers than among never smokers. Female former smokers had
lower prevalence rates for cough and phlegm production but higher rates for dyspnea
and wheezing than current smokers. Rates for female former smokers were generally
higher than those for male former smokers. Manfreda. Nelson. and Cherniack ( 1978)
studied subjects from urban and rural communities in Canada. and found very similar
overall and sex-specific prevalence rates for these respiratory symptoms among former
smokers. In this study. however. female former smokers had prevalence rates between
those of current and never smokers for all symptoms.

In three separate surveys, Hawthorne and Fry ( 1978) evaluated the association among
smoking, respiratory symptoms, and cardiopulmonary mortality in I I.295 men and
7.491 women from southwest Scotland. Former smoher\ had prevalence rates for
phlegm production and wheezing intermediate to those of current and never smokers.
Male former smokers reported \hortnr\s of breath as often a\ male never smokers.
whereas female former smokers had an increased prevalence ofdyspnea compared u ith
current smoker\ of either \ex.

Miller and colleagues ( 1988) determined sex-specific prevalence rates for a wide
range of respiratory symptom\ in a stratified random sample from the general popula-
tion of Michigan. Mean age for the three smohing groups ma\ comparable. Male
current and former smohers had similar lifetime cigarette pack consumption (9.09 x IO'
vs. Y.93 x IO"). whereas female current smokers had almost twice the cigarette
consumption of former smokers (X.32 x IO' ~4. 1.50 x IO'). The prevalence rates of
persistent sputum and wheezing were Iovver among male former smokers compared
with current smoLer\. In contrast. the prevalence of dy\pnea uas similar for male
former and current amohers. and findings Mere Gmilar among females. Furthermore,
female former smoherj had higher rate\ for dyqtea than males but lower rate\ for all
other respiratory variables a\\es\ed.

Schenker. Samet. and Speirer (lYX7) ev,aluated the effect of smoking status on
respiratory symptoms of 5.686 women.  Age-aci.ju\trd prcv,alence rates for chronic
cough. chronic phlegm. and wheeze most day \ or night\ among fommcr mohers were
between those for current and never \mohers. Grade 3 dyspnea M as reported more often
by former smokers than current maker\ of I to 2-l cigarette\ per day or by never
smokers.

Several reports have addressed the occurrence of >ymptoms in an epidemiologic
study in Tucson. AZ (Lebouitz and Burrows lY77: Paoletti et al. 1985). Cro\s-
sectional analyses, ha\ed on the first survey of the population. indicated that former
smokers had a higher prevalence of chronic phlegm production than did never smoker\

292


                    MEN
50-T

50 -   7
40-                                                 I
                                                   I
                                            `..
                                          . .   `. I I
                                         
30-                           . . `. .                . .
                            :    .-.. ..y,.`.        `.t
                      .--      /'
                        . ..'        /      \      j..,/
                      . --        /        \
                  ._. A.7.        .I` ....
20 -                      / `.
                           /
                         /   ,.-`>f<
                        /                  \
                      /                    \ \ 1'
10 -                                         v

01               I                       1        I

0      10     20      30   40   5b     60     70

AGE

   Cigarette Smokers      . - Ex-Smokers
.s....... Pipe & Cigar Smokers    --- -- Never Smokers

FIGURE S.-Prevalence of cough and phlegm by smoking group
NOTE: Person with grade 2 cough and phlegm had both symptoms and at lea\! one symptom for
23 mdyr.

SOURCE: Payne and Kjelsberst 1964).


WOMEN

     10     20     30     40     50     50
AGE

70

50



40-



30-

     10     20     30     40     50     60     70
AGE

   Cigarette Smokers      -. Ex-Smokers

  Pipe & Cigar Smokers    - - - -- Never Smokers

FIGURE 5. (Continued)-Prevalence of cough and phlegm by smoking group
NOTE: Prrwn\ u ah grade 7 cough and phlegm had horh \gmptorn\ dnd ;II Iea\~ one \!mptom for
23 mo/~ r.

SOURCE: Payne and Kjcl\hty( 19641.


MEN

100 -

90 -

80 -

70 -

60 -

,:
10  ---~~ . ..-. ____-- --___a.
                      /-- ___I-

          I        I        1 I , I        I
       10     20     30 40 50 60     70
AGE

WOMEN

     10     20     30     40     50     60     70
AGE

- Cigarette Smokers     -.-.-.--- Ex-Sm&e~
......... Pipe 8 Cigar Smokers   ------------ Never Smokers

FIGURE 6.-Prevalence of dyspnea by smoking group
SOLIRCE: Payne and Kplhcrg (lY641.


but a lower prevalence compared with current smokers (Table 1). When examined
within age groups. the prevalence of chronic phlegm tended to be higher among older
male former smokers with substantial past consumption of cigarettes. suggesting that
symptoms may not revert quickly to those of never smokers.

To evaluate the effect of cumulative tar consumption on respiratory symptoms and
lung function in the Tucson population, Paoletti and coworkers (1985) studied the
predictive value of estimated tar exposure and pack-years on respiratory symptoms of
582 current smokers and 62 I former smokers. Tar exposure was calculated from the
Federal Trade Commission data on tar yield of each type of cigarette smoked and was
used to classify retrospectively the smokers' exposures into categories of low and high
tar pack-years as well as total tar (kilograms). Only current and former smokers with
consistent consumption behavior were analyzed. Ex-smokers had lower prevalence
rates of cough. chronic cough. phlegm. and chronic phlegm than did current smokers.
Multiple logistic regression analysis was used to determine risk factors for any cough.
any wheeze. and dyspnea. Statistical models for former smokers could not be derived
using total pack-years, total tar estimates. age. or deep inhalation that significantly
predicted respiratory symptoms among former smokers of either sex. The low
prevalence rates of symptoms among former smokers may have limited the modeling.

Ballal (1984) analyzed the effect of depth of inhalation on respiratory symptoms in
75 former smokers as part of a larger study of the smoking behavior of 753 Sudanese
medical practitioners. The proportion of former smokers complaining of any wheeze
increased with degree of inhalation (slightly. moderately, or deeply). but the trend was
not statistically significant. Small numbersand subject selection restrict the importance
of this finding.

In summary. cross-sectional population-based studies have generally shown that
former smokers have reduced prevalence rates for cough. phlegm production. and
vvheezing compared with current smokers. Dyspnea may not completely reverse after
cessation as shown by the compamble prevalence rate\ for current and ex-smokers in
several studies. However. dy\pnea may prompt cessation when sustained smoking has
caused significant physiologic impairment. Differences in symptom rates by gender
have been documented in former smokers: potential explanations include sex-specific
differences in reporting. differences in xmohing practices. or distinct underlying
physiologic responses to cessation by gender. Although the relevant data are limited.
rev,ersal of most symptoms reflecting mucous gland hypertrophy and hyperplasia and
airways inflammation appears to be rapid and not dependent on cumulative smoking at
the time of cessation. Measures of past cigarette consumption have not been associated
with current respiratory, symptoms among former smokers.

Occupational Groups

Studies of grain elevator uorhers. dairy farmers. cedar mill workers. and persons
exposed to dust. gas. fumes. and ashesto have addressed the influence of occupation
and smoking on respiratory symptoms (Table 2). Broder and coworkers ( 1979) and
Dopico and colleagues ( 1983) compared respiratory symptoms in grain handlers with
those of civic outside workers and of city worhers. respecti\ ely. In both studies. former


TABLE 2.-Percentages of subjects in cross-sectional occupational surveys with
     respiratory symptoms by smoking and occupational exposure status

S! mptomr"
Reference

         Cmxnt \molLer\       Former smokers      Never smokers

Mean age Occupationally      Occupationall)     Occupationall>
(TowI)    eXpO\ed   Control    eXpO\d   Control   expwed   Control

Coush 3 mo/\ r

Broder et al
(lY7YIh

Ghan-Yeun;
et al. I IYXI)

Kllbum.
Warshnw.
Thornton
t 1986)

Phlegm 3 mo/yr

Broder et al
( I979$

Dopico et al    Gram handlers 42.0
( 1984jd      41.0?1?.0(310)

Gram elevator 67.0
worLer\ (A)
39+13(18Y)

Gram elevator   SO.0
worker\ (B)
-II?13 (752,

Cwic out\ide -
H orkers I B I
41?lJ t IX01

Whne cedar    30.7
mill worhcr\
44.3+11.1 (51 I I

Nonuhne cedar 30.7
mill uorher\
39.hk9.I 1141)

White office
worker\
43.31 I.5 I3931

Nonwhite office
worker5
39.os.9 (46)

Shipyard
worker\
S8 (288,

55.0

Michigan men  5 1 .O
42 1.595)

45.0

City Norkerb -
41.M12.0 (239)

38.0





23.0

56.0

        17.3




        12.3





`I.8





`1.X

33.0

48.0      30.0

17.0

15.0

-        32.0

-      37.0

26.0             4.0             8.0

        `3.0





        15.0





IS.0             s.0





         X.5





        x.s





3.0        -     7.5





3.0             3.5





       33.0

13.0       IS.0     3.0

297


TABLE 2.--Continued

S>mptornr"
Keferencr

Babbott et al.
(19X0)' '

Dar? farmer\   7') 0
I IYX,

Indu\tr! norker\ ~

ISlh)

ChowYetme
et al. t IYXJ)

Ktlbum. War\han,
Thornton t I YXh)

Dy\pnea > grade 2
Brodrr et al. t lY7Y lh

Doptco et 31. t 19X-I)

Babbott et ill. I IYXO#

Ghan-Yeung et al. t IYXJ)

Ktlbum. War\haH,
Thornton t lc)Xh~

Wheerr

Broder et al. t lY7Y )"

Dop~co et al. ( 19X-1)'
Babhnt et al I IYXOI' '

Ghan-Yeuns et al. t IYX~I"'

Kllbum. Wur\hau,
Thornton ( IYXh)'

26. I



ss.0






27.0
IS.0


77.0


IS.0


31.1)


65.0






5.0
70


2' 0


-17.0


2.7 1


6X.0

31) 0



21 x



3.0






2 I .n



2.0


36.0

21.1


7.0






4.0



50.0


10

24.x

13.0

IY 0"








11.1



39.0






12.0
16.0


sx.0

s I A)'


26.1


54.0






x.0
7.0


I7 0

-ll.(?


12.3


43.0

Y.OF



8.2



15.0






I I .o



6.0

34.0~


IO.4


6.0






6.0



1 I.0

7Y.W


7.5


x.0

16.0








IO.0



3x.0






15.0
5.0


57.0


27.0


IX.1


s4.n






4 0
70


17.0


3 I .(I


0.2


32.0

IO.0



7.5



7.0






5 0



2.0


IY.O


6.4


2.0






x.0



30.0


77.0


7.5


I .o


smokers had intermediate prevalence rates for cough, sputum production. wheeze. and
shortness of breath compared with current and never smokers. Additionally. former
smokers who were grain handlers had more acute and chronic symptoms than ex-
smokers who were outside civil or city workers. For grain workers, length of employ-
ment had no effect on the prevalence of respiratory symptoms within each smoking
group. The results of these two studies differ in that the occupational effect u as minimal
and less than the smoking effect in the former investigation but significant and greater
in the latter. The choice of control subjects may explain this discrepancy.

Babbott and colleagues (1980) assessed the respiratory symptoms of I98 Vermont
dairy farmers and 5 I6 nonmineral industrial workers. Former smokers were matched
on age (mean 43 years) and years since cessation (mean 8 years). Chronic sputum
production, wheezing, and dyspnea were more common among current smokers than
among formeror never smokers. and more frequent among dairy farmers than industrial
workers. Similar results were found by Chan-Yeung and coworkers (19X-I) in a study
of 652 cedar mill workers and 440 control office vvorken. Korn and associates ( I YX7).
in a population sample of 8.515 white adults. showed that smoking and exposure to
dust. gases, or fumes were independently associated with an increased prevalence of
chronic cough, chronic phlegm. persistent wheeze. and breathlessness.  Former
smokers with gas or fume exposure were more likely to have respiratory symptoms.
particularly breathlessness. than exposed current or never smokers. A multiplicative
relationship between smoking and occupational exposure was found for breathlessness
but not for other symptoms.

Kilbum. Warshaw. and Thornton (1986) conducted an investigation of respiratory
symptoms. cardiopulmonary diseases. and asbestosis among 338 male and 8 I female
shipyard workers and their families. In general, the study group had more symptoms
than reported from a similarly stratified random sample of the Michigan population
(Miller et al. 1988). The authors suggested that environmental influences in the Los
Angeles area may explain the higher rates. Male shipyard workers who were former
smokers had more cough, sputum production. and wheezing than shipyard workers who
were current smokers, whereas the pattern was reversed for female shipyard workers.

In summary, results from selected occupational groups support the findings from the
community-based studies, although work exposures may interact with smoking in
determining the occurrence of symptoms among former smokers (US DHHS 1985).
The results of these investigations may be affected by misclassification of exposures
and by selection or recall bias. As in the community-based studies. limited descriptive
information is provided on former smokers.

Longitudinal Studies

Numerous longitudinal population-based studies have found rapid resolution of most
respiratory symptoms after smoking cessation (Table 3). A study by Woolf and Zamel
( 1980) indicated that 302 female former smokers with a mean cigarette consumption
of I5 pack-years had dramatic resolution of respiratory symptoms within 5 years. These
investigators defined former smokers as women who had not smoked for at least I year
before entry into the study. Persistent former and never smokers were comparable in


TABLE 3.--Change (%) in presence of respiratory symptoms, longitudinal studies, by cigarette smoking status

                         Continuing smoker\                Former \moka-\               Never smokers
Symptom\          Ape
Ketcrencc           ( mem )          LOX1    No change"     (klld       LU\I  No change"   Gained     Lwt   No change"   Guned

IX.0       hh.0         16.0        2.0     xs.0     13.0        5.0     X6.0       Y.0

h&!h1: 43.2+ I .7`
Mcrtcrclte: 2'). Ii I. I
t lea\) : 3X.h ti0.Y

Ptltelm 3 mo/yr

`T`a\hh~n et ill. ( I `JX4)

43 -5x

X.3       77.6         1.l.I        Id.?     x7.7      2.0

NCI change: I .O                 Net change:  -2 I .O

10.7       7x 0




7.6       x5.5
7.3       x5.2
53       x0.2
5.0       x0.7



x.x       77.4

II 3

lh.7     7x.5

h.Y
7.4
5.3
5.3

IO. I      XY.3
5.0     Y?.S
I.3     97 1
2.0     96.6

I3..?

7.7     X6.3

4.X

0.6
2.5
I.3
I.5

6.0

Nel change: 3.0

J.S     Y0.X       1.7

-



TABLE 3.--Continued

Cornstock et al.
( I Y70)

Net change: 4.0              Ner ch;qc: IS.0

Net ch;qc: 0.0

Sharp et al.
(1073)

IS.4       X6.2          6.4       IO.2      77.0     I1.X        x.0     x5.0       7.0

pJLq'"Llnea > rru
Woolf and Zamel
( IYXO)

`Ta\hkm et nl
(IYX3r'

C`om\tock t't 01.
(IY70)
Sharp et al.
t lY73)

Fwdm:cn et al. ( lY7.3)
  White male >I ppd
  Whate female >I ppd
Wh,a/.

Woollantl %amrl
(IYXO)'

Ta\hhin et al
c IYX4)'

17.0



4.h

II 0

IX.0



I I.2

x9.9

Ner change: 2.0

72.x

Net ct1arrp!: -X.Y
Net change: -I I .X

7 I .o

77.x

13.0



5.5

16.2

I I.0



I I .o

IX.0      75.0      x.0        7.0     Yl .I)



3.2       x0.x      0.0


  Net chance: I I .O              Net chance: 1.0



14.4      72.x     12.x        IO.1     70.x

0.0       %.I)      s.0        5.0     YI .o

13.7      x2.1      4.2

7.0


-

to.0

4.0


E    TABLE 3.-Continued

                              Continuing smokers                Former smokers              Never smokers
    Symptoms         Age
       Reference          (mean)          Lost    No change"    Gained       Lost  No change'   Gained     Lost   No change"   Gamed

Comstock et al.
(1970)`"

Net change: 5.0            Net change: -5.0

Net change: -2.0

Sharp et al.                       13.4       77.0          9.6       II.1       7x.7     10.2        7.3     xx.4      4.3
(1973jrn

"No change mdlcate\ that rqxratory symptom\ were ather conristently absent or conslstentty present.
hOnly females. cough and/or phlegm. S-yr wdy period.
`Llght=<70c1g./wk; moderate=?I-14Ocl~wk: hravy=more than 14Ocig/wk.
`Former rmokers defined ab those who atoppd between haselms and followup.
x4ales only. S-Cyr f~lltowup.
`Males only. former htudws defined as thox who stoppd between baseline and followup. 7.yr t~llowup
"Former studa defined as those who stopped between baaehne and followup. I.5yr followup.
hppd=packs/day.
`Grade 2 or 3 dyspnca.
`Dyspnea not defined.

`Dyspnea at ordinary pax.
`Wheeze not defined.
mEver wheeze.


age: former smohers had a shorter duration of smoking in years than current arnoher5
of I /? to I pack per day. but similar cumulative pack-years ( 1 1.5 vs. 15.0). More former
and never smokers reported consistent absence of cough or sputum. dyspnea. or u heerr
compared with current smokers. Thirteen percent of former smokers developed cough
or phlegm during the study period compared with 9 percent of never smoker\ and I6
percent of smokers. At enrollment. smokers had more respiratory symptoms and were
more likely to develop symptoms over the 5 years of the study.
Similarly, in a large population study in the Los Angeles area. respiratory symptom\
diminishedamongformersmokersafteronlySyearsofabstinence(Tashkinetal. 19X-l).
In this study, the following 4 smoking groups were defined: 27X persistent \moher\:
3 I4 never smokers; IO6 quitters. subjects who smoked regularly at baseline but were
nonsmokers at the conclusion of the study: and 294 former smokers. individual\ who
were regular smokers but had quit at least 2 years prior to baseline. The mean age for
female quitters (45.6 years) was comparable among the smoking categories: the mean
age for male quitters (43.4 years) was similar to the mean ages for current and never
smokers: however. it was 6.2 years less than that for former smokers. Quitters and
former smokers had smoked similar numbers of cigarettes per day (26.3 vs. 23.6 for
males: 19. I vs. 19.0 for females). but quitters had higher pack-years (3X.6 vs. 76.X for
males; 27.4 vs. 16.2 for females). In addition. quitters had pack-years comparable with
current smokers (38.6 vs. 40.5 for males: 27.4 vs. 30.9 for females). Over the 5 years
of the study. quitters recovered from the symptoms of cough. sputum. and wheeze more
frequently than continuing smokers. No difference in shortness of breath was found
between the two groups in the 5-year study period. Quitters and former smokers were
not compared to determine the relative importance of cumulative exposure versus time
since exposure on the observed reduction of symptoms among ex-smokers.
Comstock and coworkers (1970) reported comparable findings in a study of
respiratory symptoms in 670 male telephone company employees studied for 5 to 6
years. Symptoms of chronic cough, phlegm production, and wheeze decreased sig-
nificantly in quitters whose baseline prevalence for these symptoms was similar to
persistent smokers but whose followup values were comparable to never smokers.
Baseline and followup prevalence rates for breathlessness in quitters were equivalent
to those of persistent smokers.
Sharp and colleagues ( 1973) found similar trends in respiratory symptoms in 1,263
middle-aged males from an industrial population surveyed in 1961 and again in 196X.
Former smokers were defined as individuals who stopped smoking after entry into the
study; previous smoking histories were not provided. Over the 7 years of the study.
72.3 percent of former smokers with persistent cough and 64.4 percent with persistent
phlegm recovered from the symptoms. These rates of recovery were higher than for
the other smoking groups with similar symptoms. Additionally, former smokers who
originally complained of dyspnea and wheeze tended to lose these symptoms over the
study period, but less dramatically (49-percent and 45.5percent recovery, respective-
ly). New reports of cough and phlegm were made by less than IO percent of never and
former smokers and I6 percent of continuing smokers, whereas new wheeze was found
in 13.5 percent of former and 14. I percent of continuing smokers. In contrast. dyspnea
developed in 18. I percent of former smokers and 22.4 percent of continuing smokers.


In a study of shorter duration. Friedman and Siegelaub ( 1980) confirmed the findings
of Tashkin and coworkers (1983). Cornstock and associates ( 1970). and Sharp and
colleagues ( 1973). Over approximately I.5 years of observation, 3.815 recent quitters
more often reported decreased chronic cough but noexertional dyspnea when compared
with 9.391 persistent smokers.

Findings from two Finnish studies and one British study support the results of these
North American investigations (Huhti and Ikkala 1980; Poukkula. Huhti. MPknrBinen
I982 Leeder et al. 1977). In the I O-year study of Huhti and lkkala ( 1980). respiratory
symptoms increased in all groups of smoherr except male quitters. who had lower
prevalence of phlegm production and wheezing (Table 4). Similarly. in a IO-year
followupof male pulp mill workers. Poukkula. Huhti. and Makarainen ( 19X2) observed
a decrease in respiratory symptoms only for quitters and only for cough and phlegm
production. No explanation for the increase in symptoms over time for never smokers
was provided in either study. During a 6-year period. Leeder and colleagues ( 1977)
evaluated chronic cough and phlegm annually in 3.9 I6 young married adults. Men who
pave up smoking had a progressive decline in the reporting of cough and phlegm. Only,
a small number of female ex-smokers were included.

In summary. the findings from these longitudinal studies agree with those from the
cross-sectional surveys and suggest that cough. phlegm production. and vvheering
reverse after cessation. regardless of duration or quantity prev#iously smoked. Dyspnea.
however. may he less likely to resolve in subjects with longer smoking histories.
possibly indicating irreversible damage induced by smoking up to time of cessation.

Clinical Studies of Possible Mechanisms

Few studies have investigated the mechanisms by vv hich respiratory symptoms
improve after smohing cessation. Reversal of mucous gland hyperplasia and reduction
in airway inflammation have been considered likely mechanisms but have not been
documented. Recovery of epithelial integrity has been shown in two small clinical
studies of epithelial permeability (Minty. Jordan. Jones 1981: Mason et al. 19X.3).
Improvement in tracheal mucous v,elocity. another possible mechanism by, which
respiratory symptoms may' decrease after smokin, cr cessation. has also been examined.
Goodman and coworkers ( 197X) reported that five of nine y'oung former smohers had
tracheal mucous velocities that were comparable uith age-matched never smohers.
One subject had a minimally~ depressed velocity,. and three had markedly depressed
values. Only one subject was restudied 2 months after baseline and 9 months after
cessation. and at that time. tracheal mucous velocity was found still to be reduced.
Because subjects were not studied while smohin,. 0 the change after cessation could not
be determined. Camner. Philipson. and Arvidsson ( 1973) studied tracheal v,elocity in
subjects before and after smohinp cessation. They found that in I I of I7 male former
smokers. tracheal mucous v,elocity improved 3 months after cessation and that in the
remaining 6 former smohers. velocity was slower or similar when compared with
baseline values. Improved tracheal mucous velocity may lead to less mucus in the
airways and thereby reduce symptoms of cough and u heere among fomrer smohers.

303


TABLE A.-Percentage of subjects with respiratory symptoms b> smoking
     status, 1961 and 1971, in a cohort of middle-aged, rural Finns

      1
\e\er \moher\ IY61
se\er \nlohrn 197 I

           Mule\
S! mptom\     (X0)


Phleem all da\-* inter

  I')61         -I
  I')71         6

b'heetms! most daw

  1961
  1071         2

Weather affect\ chru

  1961         6
  1071        1')

Breaihle\we\\ grade< 34

  IY6l         1
  lY7l        IO

Chrome bronchitk

  IY61         Y
  IY7l        II

Mean ape (y)     so
in IYhl

Femab
1573)

    II
Evwwhw lY6l
       I Y7 I

Female\
1261

1

    III            IV

Smohrr\ IYhl     Smr)her\ I Y6 I
Ex-vnoher\ I Y7 I     Smohw I Y7 I


      Female\   Mdf\
       , I41    I?111

Female\
117,

I I      IX
     27

-I
Ii

             3
-l             I

IO
3

IO      I?      IS       I6     II       Y
I7      I7      I6      `I     21       6

I4
I5


so

I5
23

IS
I?


10

13
24

2')
Y


so

4
Y

I I     I3
I6     39

I6     36
5     11


47     4Y

2
II

6
IY

71
71


46

Respiratory Infections

Numerous clinical studies have shown alterations in immune and inflammatory
function among cigarette smokers compared with never smokers. Studies of peripheral
blood have shown that current smokers have as much as 30 percent higher leukocyte
counts than never smokers (Corre. Lellouch. Schwaart/ 1971: Friedman et al. 1973).
Increases have been reported in polymorphonuclear leukocytes (Bridges. Wy,att. Rehm
1985). which appear to have nonnal chemotactic. microbicidal. and secretory functions
(Nobel and Penny 1975: Abhoud et al. IY83). and monocytes (Nielsen IYXS). which
may partially lack the ability to kill intracellular C`rr~rtlitltr (Nielsen IYXS). Total

305


numbers of T lymphocytes are increased among \mohers (Kas7uhowki. Wysocki.
Machatski IYXI: Robertson et al. 1983: Burton et al. IYX?: Smart et al. 15%). Light
and moderate smokers have increa\ei in OKT3+ (total T cell\) and OKT3+ (T-helper
cells) (Hughes et at. 1985: Ginns et al. 1982). and heavy smoker\ have decreases in
OKT4+ and increases in OKTX+ (T-suppressor cells) (Ginns et al. IY81: Miller et at.
1982). Additionally. functional changes in T lymphocyte\ from smokers have been
observed (Whitehead et ai. 1974: Suciu-Foca et at. 1974: Onxi et al. I YXO). but these
findings remain controversial.
Changes in serum components have also been reported. Smokers have higher levels
of CS. CY. Cl inhibitor (Wyatt. Bridges. Halatek I%1 ). C-reactive protein. and
autoantibodies (antinuclear and rheumatoid factors) (Heiskett et al. 1962). but lower
levels of specific immunogtobutins (IgG. IgM. and IgA) (Ferson et al. 1979: Vos-Brat
and Rumke 1969: Kosmider. Fetus, Wycocki tY73: Dale\ et al. 107-l: Wingerd and
Sponzitti 1977: Guts\,ik and Fugerhot tY7Y: Gerrard. Heineret al. 1980: Leitch, Lumb.
Kay IYXI: Andersen et al. 19X1: Bartetik. Zioto. Bartetik 19X-l: McSharry. Banham.
Boyd 1985). As previously dewribed. IsE is elevated in smoker{ (Burrows et al. 198 I:
Zetterstriim et at. 19X1: Hittgren et al. 1982: Warren et al. 1987: Bonini IYX?: Stein et
at. 19X3). and this increase may result from suppression of regulatory T-lymphocyte
function (Hott 19X7).
Bronchoatveotar lavage has provided evidence on the noncellular and cellular com-
ponents of the peripheral airways and alveoli amon, 0 smokers and nonsmokers. Data
have indicated that smokers appear to have normal or \lightt!, elevated level? of IgA
and IgG (Reynotd\ and New ball 1973: Warr and Martin I Y77: Bell et al. I YX 1: Vetluti
et at. 19X3: Pre. Btudier. Batte\ti 19X0: Gotoh et at. 19X3). Similarly. value\ for
lysoqme (Harris et al. 1975). complement component\ (Rohertwn et al. 1976). and
fibronectin (Villiger et al. IYXI ) are elevated in tavage fluid from \mohers. The total
number of cells retrieved from tavage of smoher\ i\ increawd with marked elevation
in the percentage\ of activated mucrophages and neutrophils (Hunninghahe et al. IY79:
Harris. Swenson. Johnwn 1970). Ahwlute typhncyte number\ remain unchanged.
although T-cell function ma!' be altered (Danielc et at. IY77: DeShaLo et al. 19x3).
Recovered mucrophage\ have increaed chemotactic funcrwn (Warr and Martin 197-t:
Labed/ki et at. I%.?: Rwhartts et HI. 19X4) and increaed release of damaging product\
huch a\ wperoside anion\ (Hoidat ct at. 1970: Hoidat et at. 19X0: Jowph et al. 19X0:
Hoidat and NieHoehncr 19X2: Grecnin, cr and Loarie 19X3: Rwma et at. IYXI). hut
diminished microbicidal acti\ it? (iLlartin and Wxr tY77: Fisher et al. 14X2: Ando et
al. 19X1).
Smoker\ hake twn \houn to have reduced \peciiic immune reywnws to inhaled
antigen\ 111 4ever;lt occupation;lt \tudieh. Fxmer\ u ho Mere newr w-ioher\ had higher
levels ofwrum precipitin\ to .~~rc,/,o/lr~/\.\/~r~/.c~,f;/[,/r/ than furmer~ u ho ~rnohed (.\lorgan
et at. tY71: Morgan et at. I Y75: Gruchw ct al. 19X I: Cormier and B2tunser I YXY:
Kuuh et 111. I YXY). M herca\ pigeon breeder\ \j ho had ne\ er wohed had higher
precipitating antibodic\ to pigeon 7 globulin compared u ith their mohin? counterpurts
(McShurr> ct at. IYXI: Andcrsen and Chri\tcnwl IYX3: Bo>d et 4. 1977). Similar
result\ h3i.e been t'ound in pouttr) N orhcrs ( Anderwn and Schonheyder I YXI) and
proceaing uorher\ (McSharr! XICI Withinwn 19X6, in relation to I@.2 rr\ponses to hen


serum antigen and prawn antigen, respectively. Whether smokers have a lower in-
cidence of hypersensitivity pneumonitis has not been adequately studied.

Finally. smokers manifest a blunted immune response to influenza vaccination.
Although smokers and nonsmokers have similar postvaccination titers at 3 months
(Knowles. Taylor. Turner-Warwick I98 1). current smokers have reduced titers at 1 year
when compared with nonsmokers (Finklea et al. 197 1; Mackenzie. Mackenzie. Holt
1976). In a large clinical trial comparing responses to killed and live attenuated vaccine.
smokers had a decreased primary immune response to the killed vaccine (Mackenzie.
Mackenzie. Halt 1976).

Although effects of smoking on the immune system have been demonstrated. feM
studies have investigated the association between smoking and acute respirator)
illnesses of presumed infectious etiology. Aronson and coworkers ( 1982) found that
smoking was associated with an increased risk of acute respiratory tract illness. In
addition. these investigators found that smoking increased the likelihood of having a
lower respiratory tract illness and increased the duration of the symptom of cough.
These findingscorroborated the resultsofother investigations (Haynes. Krstulovic. Bell
1966: Peters and Ferris 1967: Parnell. Anderson. Kinnis 1966) that showed the came
trend for increased respiratory infections among smokers compared with nonsmokers.
In contrast, Pollard and associates (197.5) found no difference in the incidence of
respiratory illness observed among smokers compared with nonsmokers. Short fol-
low-up of 9 weeks and selection of Naval recruits who had a high prevalence of acute
respiratory disease as patients may explain the discrepancy in results.

Kark. Lebiush. and Rannon (1982) studied an outbreak of influenza among 3.76 men
serving in a military unit in Israel. They found that 68.5 percent of 168 current and
occasional smokers had clinically apparent influenza as compared with 47.2 percent of
never and former smokers. Smokers and nonsmokers with influenza had comparable
serologic response rates. Among smokers, the attributable risk percentage for severe
influenza, defined as illness resulting in bedrest or loss of workdays. was 40.6 percent
(95-percent confidence interval (CI), 2 1.6-54.8 percent). Similar results have also been
reported by several other researchers (Finklea, Sandifer. Smith 1969: MacKenzie.
Mackenzie, Halt 1976; Kark and Lebiush 198 I ).

Smoking Cessation and Respiratory Infection

The relationship between altered immune and inflammatory functions and the occur-
rence of respiratory infections among ex-smokers has not been extensively investigated.
This Section reviews available relevant studies.

Studies of animals have shown a return to normal immune and inflammatory function
after cessation of cigarette smoke exposure (Holt and Keast 1977). Investigations of
humans have yielded similar findings. Specifically. among former smokers, serum
concentrations of IgG, IgA, and IgM (Hersey, Prendergast. Edwards 1983) and
bronchoalveolar lavage cell numbers and percentages return to those of never smokers
(Holt 1987). Additionally, Miller and coworkers (1982) found that within 6 weeks of
smoking cessation. the number and function of T lymphocytes reverted to normal.
Finally, Raman. Swinburne. and Fedulla (19X3) found that 3 year\ after smoking

307


ce\hation. former \mokra had pneumococcal orophar> ngeal adherence value\ com-
parable uith those of nwer smoker\. The \ignific;mcc of thehe change< in specific
component\ of ho\t defense\ to the ri4. of \uhsequent respiratory infection\ amon?
f'ormer smokers ha\ not been chxrcterixed.

Mortality from int1uenc.a and pneumonia M ith wpect to ciyxette \mokin_c ha\ been
as\e\sed in several cohort \tudie\ (Table 5). Mortality from influenza and pneumonia
was increaed in ever smoher\ reluti\ e to never smohera in the American Cancer So&t)
Cancer Prevention Study I (ACS CPS-I) t'ollouup from I959 through I963 (Hammond
1965). In the British Phyhicilrns Study. current and former smokers had small excesses
of mortality from pneumonia. but annual mortalit) rate\ from pneumonia increaed with
the amount smoked (571 IOO.000 for I - I4 g tobacco/day. 61/iOO.O00 for 15-21 g
tobacco/day. 9l/lOO.tMK~ for 29.5 p/day) (Doll and Peto 1976). A similar exposure-
response relationship v. 3s found in the U.S. Veterans Stud! (Roget and Murray 1980).

Finding\ from ACS CPS-II WI afe-ad.justed mortality from influenza and pneumonia
have been examined for the effect\ of active smoking and smoking cessation (Table 5).
Male former smokers of t'eber than 21 cigarette\ per day have mortlrlit~ ratio\ after IO
years of abstinence that are approachin, ~7 unit\ Male former smohers of' more than 1 I
                                _
cigarettes per day have mortalit! ratio\ approaching unity after I5 years of abstinence.
hut much higher for shorter period\ ot` abstinence.  Female former smohers of an)
amount have mortalit> ratios that approach those of never smokers within 3 to 5 years
ofab\tincnce.

The a\\ociation het\+een cigarette \mohing status and mortality from intlurwa and
pneumonict ma)' partlall!, retlect the rft`ects of smohing on respirator> defense
mechanism\ including immune rwponws. The ~ulnerahilit\ of perxon~ M ith clgarztte-
related cardiopulmonar! di\c:r\e\ to resprratorl infection\ ma\ alo cwntribute to the
association. For ewiiple. Glexn. Decher. 2nd Perrotta ( 1987) studied underl!,ing
diagnow\ in patient\ hwpitalixd u lth xutr reyrator> disease during intluewu
epidemics in Houwn. TX. Chronic pulmonar! condition\ were the mwt co1~m~o11
underI> in? condition. and cardiac condition\ \\ere the ne\t most frequent.

PART II: PI~L1IONARY FI'NCTIOV AI\IO\v(; FORILlER S1ZOKERS

Cross-Sectional Population Studies of FEYI

`OX


TABLE K-Age-standardized mortality ratios for influenza and pneumonia for current and former smokers compared with
       never smokers

Doll and Pete      34.440 male
(1876)          Briri\h doctor\

20 vr


TABLE K-Continued

..J      I.4    2.1     I .x     t.x       I.1     I.1      7 0

.3     2.4          2.2     2 I       7.1     0.`)      I 2



.2       h                 -             -     2.7

.I)     --           I.4     0.6      0.3     I.2      3-t


`I'AHLE 6.-Association between cigarette smoking status and C'KVI levels in selected cross-sectional studies of'adult populations


`TABLE k--Continued

I `)0X

Finding\

     AliJU\td "XX, kVeh
             FEVl  FEV I/FVC ratlo
Nwrr \moher\       2.7       X6.7
Former \moher\      1.6       xs.0
Current \moher\      1.5       X4.6

    Mean value ol the FEVl/FVC ratio

Never \mohcr\       76.0
Former \moher\      74.3
Current \moher\      73.6

     Adfuwf FEV, (L)

Never vnoher\       3.3
Former \moher\      3.2
Current maker\      3.0

     Mean normnlwxl FEV 1 wow
               MtX    Women
Never \moher\       10.2       IO. f
Former wwher\       Y.0       IO.0
Current smoker\       9.6       Y.X


`TABLE 6.--Continued

Krtrrrlce


Anderwn ( I Y7Y)

Year of sludy

Location


Lufa. Papua
New Gutnea

       Popui;~lion

733 men and women aged 25 and older

H~penbottm et al.
( IYXO)

Huhti and Ikkalu (IYXO)    IY6l

BO\\t! et ill. ( IYXO)

I Y6.1

London. Englmd   I X.403 male civil wrvant5. aged 40-W

Bwton. MA

703 healthy male veteran\ lolloued
for IO yr


`I'AHLK h.--C'ontinued


TABLE 6.--Continued

Reference

Year of study

Location

Carnilli et al. (10X7)

Tucson. A%

Dockcry et al. (19Xx)

1974-77      6 US communities

h54 men nnd XY3 women agctl ?I) and
older, who had FEV, at hnwline and
fbllowup exams

Initial FEVl a percentage of predicted

              Men     Women
Nonsmoher\        0Y.X       97.x
Former \moher\      Y3.7      9.5.6
Current vnohw"      s1.x       YI .h

   Deficit ot FEVl (L) compared with expected

K. IO I men and women
aged 15-74

Nonvnoherh
Former \mohcr\
Current \moher\

Mf3l     Women
0.03     -o.oL?
-O.`h     -0.05
A).51     -0.23


reported that the level of FEVl had a highly significant quantitative relationship with
pack-years in a general population sample of 1.369 subjects in Tucson. AZ. and that
smokers and former smokers had comparable levels accounting for pack-years.

Higenbottam and coworkers ( 1980) assessed lung function in the I X.WO males in the
Whitehall Civil Servants Study. Mean FEVl values among former smokers. adjusted
for age and height. were lower than those for never smokers. but greater than those for
current smokers. FEVl among former smokers decreased with increasing total con-
sumption of cigarettes. but length of abstinence had little effect on FEV I among former
smokers, although the minimum period considered was less than 6 years. The authors
suggested that the depression of lung function associated with cigarette smoking has
two components-an irreversible component related to total consumption and a com-
ponent rapidly reversible on cessation.

Beck. Doyle. and Schachter ( I98 I ) analyzed FEVI data from 4.690 subjects. aged 7
years and older. in 3 separate U.S. communities. These investigators also found that
the deficit in FEVl compared with that expected for never smokers increased with
cumulative smoking as measured by pack-years and duration of smoking. After
adjusting for cumulative smoking. FEVl was I47 mL lower among male smokers and
78 mL lower among female smokers compared M ith former smokers.

Dockery and coworkers ( 198X) studied X.191 randomly selected adults in 6 U.S.
communities. These researchers found that the deficit of observed FEVl compared
u ith expected age-. height-. and sex-specific values increased linearly Lvith cumulative
pack-year\ among former smoher\ and current smoher\ (Figure 7) (Dockery et al.
198X). For the same pack-year\. FEV 1 M as I3 mL higher among male former makers
and I07 mL higher among female former smoher\ compared with current smoker\.

In a follow up study of 227 men. Tal lor. Joyx. and cob orher\ ( 1985) reported that
percent-predicted FEVl for former \mohers ( 107.X percent predicted, uas between that
of smokers ( 100.5) and neier smoker\ ( I 19. I ). Within each smoking catego?. men
with increased bronchial reactiliry to inhaled histamine had lower level\ of percent-
predicted FEVl than did nonreactor\. Thehe differences Mere srati\tically \ignificunt
among smoher\ (K-l.6 ~`4. 10X.5 percent predIcted for reactors and nonreacrorz. respec-
tivel! ) and former \moher\ (96.1 1'4. I I! I .S percent predicted for reactors and nonreac-
tor4. re\pccti\cl! 1.

Pulmonary Function Studies After Smoking Cessation

.Studie\ in v. hich the lung function ofmoherc M;L\ measured hefore and after smoking
ce\\ation are re\ ie\rctl in thi4 Src~iori: tt'4t\ ofpulnionar! function included \pirornetr)
nitrogen u;r\hout. and other technique\ potentialI! wn\iti\e to the effect\ ofce\\a1ion.
Inflammatory le\ionh of the small air\+ ;t! \ hai e been demonstrated to occur in 1 oung
adult wwher\ before the :lppcarance ot` clinicall! significant Artlo% ob\truction


MEN

8 -1000

   300


   200

b
5   100
8    0

   300


   200

c-r
5   100
8    0

PACK-YEARS
0   10  20  30  40  50  60  70  60  90 295

A

m

c5 10 20 30

PACK-YEARS

  fJ;;F?tT SMOKERS
L-
40  50  60  70  60  90  295

FIGCRE 7.-Sex-specific mean height-adjusted FEV 1 residuals versus
      pack-years for current and ex-smokers, and distributions of
      number of subjects by pack-Jears
NOTE: FE\`l=I -WC forced c\p~raror> \ ol~m~.
SO1 RCE: Do&r~ c`t al. I IYXX,

317


WOMEN

PACK-YEARS

0102030405060r65
                         I

2l
t;
2  -250
I5
8  -500
s
Ei
$  -750
5
ii -1000


   300

   200
g   100
8    0

EX-SMOKERS

CURRENT
SMOKERS

8
        <5  10  20  30  40  50  60  ~65

      PACK-YEARS

FIGURE 7. (Continued)--Sex-specific mean height-adjusted FEVl residuals
      versus pack-years for current and ex-smokers, and distributions
      of number of subjects by pack-years
NOTE:  FEV I =I -vx forced erpirxor~ 1 olume.

SOURCE: Docker> et al. (I%#).


(Niewoehner. Kleinerman. Rice lY73). Te5ts sensitive to abnormulitie\ of the small
airways (e.g.. helium-oxygen flop volume curves. the single breath nitrogen test or
other tests of closing volume, and frequency dependence of compliance) uould be
expected to be particularly sensitive for detecting changes in function after cessation.
In most of the studies reviewed in thi$ Section. participants were enrolled through
smoking cessation clinics and subsequentI), monitored for pulmonary function and
smoking status. The data from these studies can assess reversible effects of smoking
throqh documentation of functional change coincident with ceh\ation; irreversible
effects can be estimated by comparison of lung function le\,el M ith predicted value\ for
normal function.

Changes in Spirometric Parameters After Cessation

Studies ofspirometric measurements of pulmonq function before and after smoking
cessation are cummariLed in Table 7. Many of these studies suggested an improvement
in pulmonary function following cessation. although the magnitude of the improvement
was \mull in some of the studies.

Dirksen. Janzon. and Lindell ( lY73) studied a randomly selected sample of men born
in 19 14 in MalmB. Sweden. Fifty-eight heavy smoker\ were solicited to participate in
a smoking cessation program. with 31 abstaining for 2 months. Vital capacity (VC)
and FEV l/FVC improved 8 to 10 days after cessation.
Bode and coworkers ( 1975) studied IO healthy subjects who participated in a smoking
cessation program and remained abstinent for 6 to I4 weeks. Small and nonsignificant
improvements were found for VC (0.3 percent change) and FEVt (0.9 percent change).
Maximum expiratory flow rates with helium at SO and 25 percent of VC sifnificantlq
increased.
Martin and colleagues (1975) observed 1 2 successful subjects from a smoking
                                     .         .
cessation clinic for 1 to 3 months. Changes of V~XX) and Vrnak2c after smohins
cessation were variable and not statistically significant. Residual volume and total
pulmonary resistance w/ere also unchanged.

McCarthy, Craig. and Chemiack (1976) studied a group of smokers who volunteered
to participate in a smoking cessation program. At 25 to 4X weeks after cessation. only
IS participants were still not smoking. Among these subjects, FVC increased from 3.92
L to 4.04 L (3.1 percent change). but FEVI (Go.3 percent change) and mid-maximum
expiratory flow (MMEF) (-9.6 percent change) decreased. Fifty-nine subjects were
evaluated between 6 and 23 weeks following cessation. Significant improvements were
noted for FVC (2.3 percent of initial value) and the peak expiratory flow rate (6.7
percent of initial value). The FEVl. Vmax~. and \jmax25 did not change significant]}.

Bake and colleagues ( 1977) observed I7 subjects who were abstinent from cigarette\
for at least 5 months. During this int$rval. VC a;d FEVt improved by 4.3 and 4.X
percent predicted. respectively, while Vrnax~n and Vmax2 were reduced by 2.5 percent
predicted and 7.3 percent predicted, respectively.  At 3-vear followup. only nine
                                           ,
subjects were still smoking. No significant differences from baseline function were
found in this group.

3 I 0


TABLE 7.-Spirometric studies of participants in smoking cessation programs

l-1.(`     WC or vc


        I IO mL
        20 ml.

0.3'X

4.x

I.h

-40 ml.
-70 ml.
+30 ml.
+hO IllL

I.5
I.6
3.3

-V.h'/r

-2.5      -7 3


0.7     -I I.1

ho rnL/wc
t IO IllL/wc
+10 IllL/W
IMI lllL/W


TABLE 7.--Continued


Buikt and coworherh ( 1976) observed a group of \ix men and seven women who
stopped \mohing for at Ieat I year after a smoking cessation program. Small changes
were noted in \pirometric parameters. The author\ reported that MMEF distinguished
between smokers and quitters in that over a 1 -year period MMEF declined significantly
among smohers but not among quitters.

Buist. Nagy. and Sexton (1979) supplemented this sample with participants from
another smoking cessation program and extended followup to 30 months for both
groups. Significant improvement> were observed in VC. FEVl. and MMEF among the
quitters during the first 6 to 8 months (Figure 8). No further improvement was observed
up to 30 months.

FVC

FE'/1

7

4
-2                      *

0    .-mm"" ---
    * 10      20      30

MO AFTER CLINIC

Quitters     - - - - - - Smokers

FIGURE &--Mean values for FVC and FEL'l, expressed as a percentage of
      predicted values, in 15 quitters and 42 smokers during 30 months
      after 2 smoking cessation clinics
SOTE- .A\tt`rIAx t I know ;I \tfntttc.mt d~ltrrct~cc from thr IIIIILII \.IIw .II p41.05  F\`C=f~wrd
t it,il cnpacit!: FE\`, = I -a. ttvccd c`\plral,rr> i OILIIW

Zamel. Leroux. and Ramcharan ( 1979) studied X healthy hmoher\ for 2 month\ after
cessation. They reported Ggnificant increase\ in VC and FEVl of 3.0 and 3.0 percent
change. reqecti\,ely. In contra\t. Pride and coworkers ( 1980) in a -t-year study of eight
male smokers "who thought they would find it easy to give up smoking." reported no
improvement in apirometric tehts of MMEF.


Taken together, these studies suggest that smoking cessation quickly results in small
improvements in lung function. as assessed by spirometry. Although the changes were
not uniformly statistically significant in the investigations reviewed in this Section. the
number of subjects was small in most of the studies. Compared with baseline before
cessation, FVC or VC and FEVt may improve by about 4 or 5 percent at 3 to X months
after cessation.  In absolute value, this improvement is COtnpmbk with the ap-
proximately IOO-mL improvement reported by Beck, Doyle. and Schachter ( 19X I ) and
Dockery and coworkers ( 198X) based on cross-sectional comparison of former smoherc
to current smokers.

Tests of Small Airways Function

Several investigators have studied the effects of smoking cessation using measures
of small airways function as determined by the single breath nitrogen test (Table X) and
other tests. In the single breath nitrogen test, the subject breathe\ one breath of l(K)
percent oxygen from residual volume to total lung capacity (TLC). A concentration
gradient of nitrogen is thus established with the highest concentrations at the apex.
Subsequently, the subject exhales, and the nitrogen concentration of the exhaled air is
monitored. The indices of small airways function provided by this test include the
closing volume (CV) expressed as a percentage of the vita1 capacity (CV/VC percent).
the closing capacity (CC) expressed as a percentage of TLC (CC/rLC percent). and the
slope of the nitrogen concentration during the alveolar plateau (slope of phase III). Both
CV and CC are increased by abnormalities of the small airways, whereas the slope of
the nitrogen concentration reflects the evenness of the ventilation distribution.

Buist and colleagues (1976) studied a group of 25 cigarette smokers who attended a
smoking cessation clinic. Cessation resulted in significant improvements in CV. CC.
and the slope of alveolar plateau at 6 and I2 months after cessation. Participants in a
second smoking cessation clinic were added, and the followup continued to 30 month\
(Buist. Nagy, Sexton 1979). At the 6- to g-month followup, CV had improved by 33
percent predicted among those who quit. CC by 20 percent predicted, and the slope of
the alveolar plateau by 52 percent.  No further improvements were evident at the
30-month fo1lowup (Figure 9).

Similar improvements have been reported by several other investigators. Bode and
coworkers (I 975) found that CV improved by 20 percent 6 to I4 weeks after cessation
compared with initial values among 10 subjects. These investigators reported that the
slope of phase III was unchanged by cessation. McCarthy. Craig, and Cherniack ( 1976)
observed 131 smokers aged 17 to 66 years who volunteered to attend a smoking
cessation clinic. For I5 persons abstinent from 2.5 to 48 weeks, cessation resulted in a
significant 13-percent reduction in CC and a 27-percent reduction in the slope of phase
111.

Bake and coworkers (1977) showed a 33-percent reduction in the percent-predicted
slope of phase III among I7 subjects at 5 months after cessation. On the other hand.
only small changes in CV and CC were observed. Zamel. Leroux. and Ramcharan
( 1979) investigated 26 smokers for an average of 62 days after cessation. Similarly.

323


TABLE: K-Studies of closing volume (CV/VC% ), closing capacity (CC/TLC% 1, and slope of alveolar plateau (SBNrlL) among
     participants in smoking cessation programs

HAC Cl ;d.
I 1977)
Hui\t. Nag>.
SL~\ll)ll
I IO70)

(I.O'A

-o.X'k
+ I .h%
-5.7%
2.6%

t .x
0.3

-I .h
- 19.5
--15.4


TABLE 8.--Continued



           cwvc                 CCi-rLC
140 -

z
c
LYi
a  60 -
   MO AFTER CLINIC

200       A N2/L
f501p#e---------:
al00 5 I        1       6 I         i
2 0       10      20      30
s
2 50-
z
La
2       o ???
? ??
   MO AFTER CLINIC

- Quitter\ * - - -0 StlloLer5

FIGURE 9.--Mean \.alues for the ratio of CI'IVC. of CC/TLC, and slope for
     phase III of the single breath 32 test (XVI/L), expressed as a
     percentage of predicted values in 15 quitters and 42 smokers
     during 30 months after 2 smoking cessation clinics
NOTE: .A\trn\L\ I `I &note ;I ~~~n~l~~.mt dlttzrmcc tram the Initial \duz .H p<O.O5,
\olumc. V(`=\ttal cdp;lcll~. (`(`=clo\lll~ ~`+l~`ll~. 1 L(`=tor,ll lung c;,p:tc,t~.      C\`=clo,~ns

326


small improvement5 in CV and CC Nere observed. although slope of phase III improved
by IO percent.

Martin and coworkers ( 1975) stated that "CV did not improve \vith cessation" among
I? participants in a smoking cessation program tracked for I to 3 months. In a J-year
followup ofeight men who successfully save up smoking. Pride and colleague\ ( IWO)
reported no improvement in CV. but a significant decline in the slope of phase Ill within
the first feuo months of cessation. Further improvement did not occur over \uhsequent
years.

In summary. abnormalities in the mall airway\. as measured h\, CV. CC. and slope
of phase III. are substantially rever\ible among smoker\ who have not developed
significant airtlow obstruction. Recovery occurs rapidly and appear\ to be complete
for these measures between 6 months and I year after ces&on. although the implica-
tions of these changes for morbidity and mortality are uncertain.

Abnormal frequency dependence of lung compliance (an increased reduction of lung
compliance as respiratory frequency increases) also indicates abnormal function of the
small airways. Ingram and O'Cain (1971) examined six smokers with abnormal
frequency dependence of compliance who quit smoking. At I to 8 weeks after
cessation. values in all six had returned to normal. Martin and coworkers ( 1975) studied
12 participants in a smoking cessation program. At I to 3 months after cessation.
dynamic compliance was less frequency dependent among X ofthe 12 subject\. Zamel.
Leroux. and Ramcharan (1979~ also reported less frequency dependence of dynamic
compliance among 26 healthy smokers at 2 months after cessation.

Diffusing Capacity Among Former Smokers

Numerous studies. using a variety of methods. have shown that pulmonary diffusing
capacity is between 6 and 20 percent lower among smokers than among age-matched
nonsmokers (Teculescu and Stanescu 1970; Van Ganse. Ferris. Cotes 1972; KrumholI
and Hedrick 1973: Frans et al. 1975: Hyland et al. 1978: Enjeti et al. 1978: Bosisio et
al. 1980: Miller et al. 1983; Knudson et al. 1984). Only a few studies. however, have
assessed the effect of smoking cessation on diffusing capacity.

Marcq and Minette (1976) measured single breath carbon monoxide (CO) diffusing
capacity (DL&B) in male subjects with normal values of FEVI and FEVI divided b,
FVC. Diffusing capacity was below normal in 13 of 53 (24 percent) of the current
smokers compared with 1 of 17 (6 percent) of the former smokers of at least 6 months
abstinence.

Miller and colleagues ( 1983) examined DLcoSB in a survey of 5 I I randomly selected
subjects from a population in Michigan. Among never smokers. the mean DL&SB was
32.5 mL CO per mm Hg per minute for males and 23.0 mL CO per mm Hg per minute
for females. Compared with never smokers and adjusted for age and height. male
current smokers had 17 percent lower (5.4 mL CO/mm Hg per minute). and female
current smokers had 16 percent lower (3.4 mL CO/mm Hg per minute) DL&B Male
former smokers abstinent for at least 2 years were lower by 7 percent (2.3 mL CO/mm
Hg per minute) compared with never smokers, whereas no difference was found
between female current and former smokers.


Zamel. Leroux. and Ramcharan ( 1979) measured DLcoSB among 36 healthy smokers
before and 2 months after cessation. Although DL&B improved slightly following
cessation (0.8 mL CO/mm Hp per minute). the difference was not statistically sig-
nificant.

Knudson, Kaltenhorn. and Burrows ( 1989) measured DL,,SB in the seventh popula-
tion survey conducted in the longitudinal study of a population-based sample in Tucson.
AZ. Among current and former smokers. DLcoSB dropped as cumulative consumption
of cigarettes increased (Figure IO). Current smokers had significantly lower DL&SB
than either former smokers or never smokers: in persons with normal spirometry. former
and never smokers had comparable DL&B: former smokers in the group with
abnormal spirometry had signitlcantly lower DLcoSB. The DL&B quickly returned
to normal as the duration of abstinence increased. Within 2 years of quitting. DL,,,SB
had reached I00 percent of that predicted for women: after 3 years of abstinence. mean
DL&SB was 100 percent of that predicted for men.

These data suggest that the effects of cigarette smoking on pulmonary diffusing
capacity. as on other measures of lung function. include both irreversible and reversible
components. The extent of irreversible change i\ predicted by cumulative consump-
tion: the reversible component improves quickly after cessation.

Other Measures

Among I Y heavy smokers studied by Dirksen. Janron. and Lindell ( 1974). ventilation
distribution measured by open-circuit nitrogen clearance improved I week after smok-
ing cessation. Regional lung function measured with `""Xe showed improvement I to
3 months after cessation in the \tud\ by Martin and colleagues (1975). Zamel and
Webster ( IY83) performed detailed studies of five men and five women before and 60
days after cessation. Although Vma,ho perccnl TLC with helium and airand the maximum
tlow-static recoil curve did not change. static recoil pressure at 60 percent TLC did
decrease significantly 1 month\ after cessation in IX of 22 smokers. Michaels and
coworker\ ( 1979) al\o otxerved a decrease in static recoil pressure at an!' lung volume
after smoking cessation. There author\ concluded that a decrease in small sirwa!,
muscle tone might have accounted for these findings.

Longitudinal Population-Based Studies

The natural hi\tor> of COPD has been described in longitudinal studie\ of up to tL\ o
decades. Although a population ha\ not been studied from childhood to the develop-
ment of COPD during adulthood. the available data from existing separate investiga-
tions encompass the entire course of the disease and support the conceptual model
presented earlier (Figure 2).

Measure\ of pulmonar). function begin to decline after 25 to 30 year\ of aFe. For
FEVl. the annual rate of decline. as estimated from cro\s-sectional studies. i4 about 20
to 30 mL annually (US DHHS lY83). Fa\ter lash of function over a sufficient period
of time can lead to the development ofclinicall> significant airflow obstruction (Figure
1). The available longitudinal data indicate that cigarette mokinf i\ the primary ri\h


90

80

70

60

, cl0     lo-24

PACK-YEARS SMOKING

* ??????? O

Ex-Smokers

FIGURE IO.-Percent-predicted diffusing capacity (%pDL) by pack-years of
      smoking, current smokers and former smokers, in a study of
       adults in Tucson, AZ

NOTE. humben above bar\ rrprrwnt ample \ite\.
SOL'RCE: Knudwn. Kaltenbom. Burrow ( IYXY ).

factor for excessive loss of FEV) (US DHHS 1984). and smokers have much faster
rates of loss of FEVt than never smokers (Table 9). Table 9 describes rates of change
in lung function in selected major longitudinal studies. In each. former smokers or
quitters have less decline than current smokers during the followup period.

In many investigations. dose-response relationships have been found between the
amount smoked during the followup interval and the rate of the FEVt decline (US
DHHS 1984). For example, Fletcher and colleagues (1976) conducted a study of 792
employed men and performed pulmonary function measurements semiannually for 8
years. They reported that the annual loss of FEVl was 36 mL per year for never
smokers. The rate of decline among cigarette smokers increased with amount smoked
per day (44 ml/year for 54 cigarettes/day: 46 ml/year for 5 to IS cigarettes/day: 5-l
ml/year for I5 to 25 cigarettes/day; and 54 ml/year for >25 cigarettes/day). The rate


TABLE Y.-Population-based longitudinal studies of annual decline in pulmonary function

i:r:v, l'iiyl,
t.t:Vl/FV(' (%/yr)

3.3
27

0.3
I.3

52
6')

45
27

0.'
I .1

57
72

-0.1          0 T

30          3')
0.1          10

3x          50

JO

0.7
1.7

(72
73


TABLE 9.--Continued

Followup

Y-l3yr
4 exam\

7.5 )I
2 CX3"1\

Male and  FEVI (ml./yrb'         16.6           13.4                 24.5
Female   VC (mL/yr)'           13.7           13.2                 I5 7

M;1k

FEV I (mL/yr,"          Sh
FVC (mL/yrf'           60

57
h( )

h'          70
6X          64


:2
I-2


   TABLE 9.--Continued


of loss among former smokers (i.e.. smokers u ho stopped before the first examination)
was 3 I mL per year. not significantly different from that of never smokers. In addition,
smohers M ho stopped in the first 2 _ vears of the follow up had an annusl decline of 3X
mL per icar. The authors concluded that smokers M ho stopped before or early, in the
study had FEVt declines similar to nev'er smohers. In spite of FEVt lev,els having been
reduced by previous smohin_. (7 further damage to FEV t due to smohing ceases within
a few years of cessation. Hovvever. recovery of function vvas not documented in the
study, of Fletcher and colleagues ( I Y76). These results have been confirmed in multiple
population-based longitudinal studies of FEV) and other pulmonary function
parameters (Table Y ).
Camilli and associates ( lYX7) examined longitudinal decline of FEV) in a population
sample of I.705 adults in Tucson. AZ. Mean follow up uas Y.-t years uith an averqe
of 5.2 examinations. Fomler smohers were defined as having stopped before enroll-
ment and continuing to abstain at their last two follo\*up examinations.  Quitters
smoked on entry into the program but stopped before their last tuo follo\~ up c`\amina-
tions. Rates of loss for former smokers and quitters were comparable M ith those for
never smokers and less than those for smokers (Table Y ). The age-specific rates of loss
(Figure I I ) suggest that the benefits of cessation may be greatest among the youngest
smokers. that is those with the shortest smoking historv,.  FEVt increased in the
youngest group. a finding that the authors interpreted as indicating that the earliest
effects of smoking are relatively reversible and could represent. in part. a
bronchoconstrictive effect.
Among the males in the SO- to 69.year-old age proup (Figure I?). I Oof the 2-l subjects
who quit did so before their second followup examination. For these IO subjects. the
revised annual loss of FEV) from the time of cessation returned to that of never smokers.
and was much less than that among smokers. In several years, reduced lung function
due to previous smoking was not recovered. except possibly among former smokers
who had only been smoking a short time.
Taylor, Joyce. and coworkers ( 1985) examined the annual decline of height-corrected
FEV) (FEVt divided by height') over 7.5 years in 227 men who were free of a clinical
diagnosis of asthma and had not received bronchodilator treatment. Former smokers
had an annual decline of FEV) divided by height3 (X.0 i 0.8 ml/year/m') that Was not
statistically different from that of never smokers (6.6 31 0.6 ml/year/m') but was
significantly less than that of continuing smokers (10.9 + 0.7 mL/year/mj). The 7 I
former smokers included 50 smokers who had stopped during the followup period.
Smokers with bronchial reactivity to inhaled histamine had significantly accelerated
annual decline of FEVt. but an effect of bronchial reactivity was not found among
former smokers or never smokers. The reactive former smokers had a lower level
percent-predicted FEV) at the end of the followup (96.3 vs. I I I .3 percent predicted).
Because their annual rate of loss was not accelerated. the low level of former smokers
must be attributed toeither steeper decline while they were smoking. low level of FEVt
before they starred smoking. or both.
Townsend and colleagues (in press) have recently reported on FEV) decline in
participants in the Multiple Risk Factor Intervention Trial. The analysis was limited to
4.926 subjects who had not used P-blocking agents or smoked cigars. cigarillos. or pipes


  30





  20





  10






  0






-10





-20




c
3-30
.G
5-
I2
c -40

I-







-

MALES

L

<35

(75)     (53)   (39) (28) (15) (47)   (47) (82
hxx so        xx


      ss
           NN

NNL
  xx

35c50         5oc70

`1 6 !4) (72)

AGE GROUPS (YR)

FIGURE 1 I.--Mean AFEV 1 values in neber smokers (NN). consistent
      ex-smokers (XX), subjects who quit smoking during followup
      (SC)), and consistent smokers (SS) in several age groups
\Ol-E: .\utnher\ cd \uhlrct\ 11, each ci~t~~rg .trr hu I, 111 parcnthc\e\  EL',= I -WC Iorccxi r\plrmr~
\olumr.

during the trial and M ho uere ohser\ ed over 2 to 1 year\ during the latter half of the
study. Subjects who quit smoking during the first I? months of the study lo\t FEV 1 at
a significantly lower rate than those reporting \moLing throughout the trial. Crowsec-
tional analysis of data from the midpoint of the trial indicated the highest level ofFEV1
for never smokers and the loueht level\ for continuing \moher\ at all age\: FEVI level\
for former smokers at ttnrollment and [how quitting during the first year Mere inter-

333


  3c





  2c





  1C





  0






-1c





-2c




2
s-30
s
i
c -40

   (`6
d
(91

NN X>

14

FEMALES

     (64) (33) (9) (50)   (154) (72) (29) (96)   (156) (3d
iQ ss

ss -
    NN-
      xx

   -X:
5% NN

<35

35<50

50<70

?70

AGE GROUPS (YR)

FIGURE 11. (Continued)-Mean AFEV] values in never smokers (NK),
     consistent ex-smokers (XX), subjects who quit smoking during
     followup CSQ), and consistent smokers (SS) in several age groups
KOTE: Number\ of wbject\ in each catepory are shown in parenthrw\.
volume.                              FEV t= I -wc forcrd exptrutor)

SOURCE: Camilli et al. t 1987)

mediate. The findings in the group quitting smoking during the first 12 months may
underestimate the benefits of cessation because of subsequent relapse within this group:
16 percent of the quitters had an elevated serum thiocyanate level (>I00 pm/dL)
indicative of smoking at the first examination compared with 6 percent of never smokers
and 7 percent of former smokers.


  C






-l(





  -2(





-3(

c
P
$
- -4(
E
c

-5t

)-

I-

I-

l-

24

(72)

I-

3-   *Computing :_ starting from last smoking value

FI(iCHE: Il.-Effects of quitting smoking during follow up among men aged
        50-69

In the Copenhqen Cit! Heart Study. spiromrtr~ 44 AS pcrtormed on 2 occ;t\ion\
separated by !i years for I7.hYX adult resident\ of the tit! selected at rundom t Lange et
aI. I YXY). In fentzral. perwn\ v. ho stopped smohin, (7 during this Inter\ ;\I e\pcrienced
less decline of FEVl thnn those \i ho continued to srnohc tT;tble IO): the effect ot
cessation varied 1% ith whjtxt age and ;uwunt smohetl Bt the time of quitting.

In IYM. the Nxtional tIeart. Luns. xxi Blood ln\titute (NHLBI) initiated ;I multi-
center in\e\tifation, the Lung Health Stud!. to determine v hcther smohinf ce\\atwn
and bronchodilutor themp!, can influence the course of subjects u ithout clinical ilIne\\
M ho are at high rich i'or the de\.clopmcnt of COPD ( Anthoniwn I YXY I. Six thourand
smoker\. aFed 3.5 to 5Y year\. with evidence of airua\\ oh\trwtion v.ert' recruited.
They uerr randomi> a\\igned to one of three youp\:  a group that received no
intervention or usual care group: :I group that receivd 311 inten\i\e state-ot`-the-art

336


TABLE IO.- Decline of FEVI (mL/yr) in subjects in the Copenhagen City
      Heart Stud?

making cessation program and regular therapy with an inhaled hronchodilator
(ipratropium bromide): and a third group that received the smohinp cessation program
and a placebo bronchodilator. Placebo/bronchodilator therapy was administered in
double-blind fashion. All group\ were studied at yearly intervals for 5 years. with rate
of change of FEVl as the primary end point and respiratory morbidity as a secondary
end-point.

In this investigation. a large number of smoker\ with early airways obstruction were
characterized and will be studied clocely for 5 years. An extenGve data base will be
created to test numerous hypotheses regarding smoking cessation. The question of
airways reactivity as a risk factor for rapid lung function loss will be tested definitively
in that methacholine sensitivity will have been measured both at the beginning and at
the followup period.

The findings of the longitudinal studies on smoking cessation and decline of FEVI
have important implications. Persons losing FEVt at a greater rate are at risk of
developing COPD. After cessation. the return of the rate of decline of FEVt to that of
never smokers implies that the process leading to COPD can be arrested by cessation.

PART III. AIRWAY RESPONSIVENESS, CIGARETTE SMOKING. AND
               SMOKING CESSATION

Population-based studies support a role for smoking as a cause of heightened airway
responsiveness (Woolcock et al. 1987; Sparrow et al. 19X7: Burney et al. 1987). Most
cross-sectional studies that have evaluated this relationship have not adjusted for
baseline airway caliber. which may be reduced among smohers (Woolcoch et al. 19X7:
Bumey et al. 19X7: Welty et al. I983: Van der Lende et al. 1981: Pham et al. 1983:
Buczko et al. 1983). so that it is difficult to determine how much of the Increase in
airway responsiveness is accounted for by a direct smoking effect or by a reduction in

337


prechallenge pulmonar! function (I.,I~LI md Ingram I YX I ). Atop) ma) modif!, the
inlluence of wwhinp b! further increa\in, 0 nowpeci tic air\< a\, responG\ enes\.  ,A\
noted h> O'Connor. Spxrou. L ,uxi Wei\\ ( IYXC)). thi\ modification may be undercs-
timated in mo\t \tudic\ hecau~e thaw I+ ith an allergic prcdi\po\ition and heightened
nonspecific rrspon\i\ene\s ma> not begin smoLing+x ifthc>,tlo begin. they may won
quit. The importance of \mokin, `T-induced heightened ;tiruav responsiveness in the
puthogencsi\ ofa\thma i\ unhnwn. and airNay hyperre\ponsi\enes\ i\ ;I suspected rish
factor for COPD.

Mechanisms of Heightened Airway Responsil eness Among Smokers and
                Former Smokers

In both clinical and population-bawd htudie\. smohing ha been ;I\\ociated uith
increased airway epithelial permeability (Jones et al. IYXO: Mint),. Jordan. Jones IYXI:
Mason et al. lYX3). elevated levels of IgE t Burrow\ et ~11. IYX I: Warren et al. IYX?
Zetter\trcim et aI. IYXI: H%llpren et al. IYX2: Bonini et al. IYX2: Stetn et 4. lYX3). and
greater nutnbers of peripheral ro\inophil\ (Burro@\ et al. IYXO: Taylor. Gro\s et al.
IYXS: Tollerud et al. IYXY: Kaut't'mann et al. 19X6). Thtx physiologic and im-
munologic alterations may partI! explain the obwr\,ed relationship between cigarette
consumption and heightened uir\say respon\iveness and/or a\thma (Brown. McFadden.
Ingram lY77: Mulo. Filiatrnult. klxtin IYX2: Cochcroft Ed al. 197'): BucLhoet iti. IYXI:
Casale et al. I YX7: Van der Lende et al. I OX I : Gerrard. Cochcroft et al. I YXO: Kabir:!i
et al. lYX2: Phatn et al. IYXI: Enarwn ct al. IYX5: Talor. Jobcr et al. IYX5: Woolcoch
ct al. lYX7: Sparrw et al. IYX7: Rijchcn ct al. IYX7: Burnq et al. IYX7). Allerg to
environmental antigen\ i\ known to modit'! thi\ relution\hip (Burrw~~. L&on it/.
Barbee 1976: Welt) et al. 1YX-l: But/ho et al. 1YX-l: Schxhtzr. Dole. Beth 19X-l:
Kiviloog. Irnell. Ehiund lY7-1: Dodge and Burrow\ IYXO). The complexity of these
interrelationship\ i\ onI> partially explained h! published tindin+ and additional
clarif!,ing \tudie\ are needed. Thi\ Section rwieu\ \tudie\ that ha\e ;tddre\\ed the
above awciation\ hith rwpect to c\-wiohcr\ uhich III;I~ e\pluin uhy airua) wpon-
sivenas return\ to normal M ith ab\tincnce.

Smoking increase\ pultnonar> cpithelial permeabilit>. u hich rapidI> return\ to
normal among young wloher\ attcr ce\\ation. \lint>. Jordan. xd Jonr\ ( I YX I ) uwd ;I
radiolabeled aerosol technique to \tud\ IO boun g ;i\\ mptomatic male smoher\ M ho had
                                     _
stopped mohing tot- I. 3. 7. 11. and 2 I da! h. The! t`~wnd that rrcwer! ot`the epitheli:ll
integrity began M ithin 21 hour\ and reached m;1\imum at 7 da> \. blawn and c`ollt`a~ut`~
( IYXi) later confirmed these t`indiny\ in IO !oun, ~7 wiohcr\. The\c \tudirs included
wi;dl number\ of \ub.jcct\ ;md had +ort t'ollo~ up pcriodh after cc\\ation. rnahing
interpretation and genrrali/lttion of the finding\ dift`icult.

Cross-Sectional Studies

Cros\-wctwnul poptil~itiorl-b3\td data hu\,c \ho\r 11 that former wioherc ha\e It`\\
airMa> re\pon\ivene\\ than current wiohers. Burnr! and colleague\ t 19x7) \tudit'tl
5 I I r~indoml\ selected subject\ aged I X to 64 bear\ u\in, (7 inhaled histamine chalkngc.

33X


Ofthe population. 14 percent were histamine-responsive as defined by PD20 (the dose
of histamine resulting in a 20-percent decline in FEV]). Responsiveness was related
to atopy in younger subjects (aged ~40 years) and smoking in older participants (aged
>40 years). Former smokers (N= I 16) had bronchial reactivity similar to never smokers
but lower than current smokers across all age strata (I2 vs. IO vs. 24 percent.
respectively). The increase in threshold dose of histamine with age for former smokers
was 0.053 per year compared with 0.0X6 per year among current smokers and 0.027
per year among never smokers. However, for those aged 35 to 44 years. former smokers
were more responsive than the other smoking groups ( I4 vs. 13 and 7 percent for current
and never smokers. respectively). The criteria for classification of former smokers were
not provided.

Cerveri and colleagues ( 1989) found similar results in their study of 295 normal never
smokers. 70 normal current smokers, and SO former smokers randomly selected from
the general population of a small town in Lombardy. Italy. The daily amount smoked
was a stronger predictor of airway responsiveness than the duration of cigarette use.
Further. among ex-smokers. duration of abstinence did not significantly influence
airway responsiveness; however. former smokers with longer abstinence tended to have
less bronchial reactivity.

Longitudinal Studies

Longitudinal population-based studies have not been conducted specifically to
evaluate temporal changes in airway responsiveness among former smokers. Several
cohort studies designed to measure declines in spirometric function have included
single measurements of airway reactivity. These studies generally confirmed lower
responsiveness among former smokers than current smokers and suggested an associa-
tion between bronchial reactivity and a more rapid decline in ventilatory function.
Vollmer. Johnson. and Buist (1985) examined bronchodilator responsiveness among
subjects from 2 cohorts. 35 I members of the Portland Cohort. which included a random
sample of SO7 Multnomah County employees, and 444 adults from the Screening
Center Cohort, consisting of 1,024 subjects screened for emphysema. Individuals were
classified as responsive if they showed a 7.72-percent increase in FEV I after two puffs
of an isoproterenol metered-dose inhaler. Although no data were presented. former
smokers were reported to have a distribution of responsiveness similar to that of current
smokers and skewed toward higher values. In case<ontrol analysis conducted within
the cohort, responsiveness in both current and former smokers was associated with
lower baseline pulmonary function and more rapid ventilatory decline over 9 to II years.
Former smokers in both cohorts had rates of decline that approximated or exceeded
those for current smokers, especially among those subjects who were responsive.

In a 6-year study of 267 white male grain elevator workers, Tabona and coworhers
( 1984) found that the percentage of former smokers who were methacholine responsive.
defined as a PC20 18 mg/mL, was similar to that of never smoker\ ( 19.6 vs. 16.7 vs.
25.8 percent for former, never. and current smokers. respectively). In contrast to the
Vollmer, Johnson, and Buist study (1985). former smokers showed the lowest ven-
tilatory decline of all smoking groups across all age categories (Tabona et al. 1YX-I).


However. former \moher\ v.ho uere methacholine re\pon\ivc had greater FEVl loss
over the h year\ of the study than thwe \\ ho were not methachoiine re\pon\i\e. Atopy.
presence of ~>niptonik. and initial lung function \kere not predictive of decline in lung
function.

Finall. Taq lor. Joyce, and couorher\ ( 19X.5) conducted an imestipation over a
7.5year period of bronchial reacti\ it) and FEV I annual rate of decline among 137
London men, aged 3 to 6 I years. Theke investigators confirmed the result\ for current
smoker\ of Vollmer. Johnwn. and Bui\t (1985) and Tabona and coworkers ( 19X-l).
Similarly. former smoker\ had intermediate level\ of methacholine responsi\ene\s
compared with the other groups. and those former smokers u ho were responsive had
lower rate\, of baseline ventilatoy function. In contrast. how,ever. former smokers had
comparable rate\ of ventilatory decline. regardless ofmethacholine re\ponsivcne\s.

In all of thew longitudinal \tudie\. hronchodilator or methacholine responhivene\\
was measured near the end of the study period. Furthermore. precise definitions of
former smoherh u ith regard to amount smoked. duration of abstinence. and reasons for
quitting were not provided. A\ diwu\>ed previously. the prevalence of' airway wpon-
\ivenes\ may alw lead to ;1 decision to 5top smohing. Thehe limitations in \tud) design
muht be considered in interpretin, o the associations among \mohing cessation. non-
specific ;tirw;L> re\ponsivene\s. C xxi annual decline in FEVl.

Clinical Studies


In contrast. Bolin. Dahms. and Slavin (19X0) and Fennertl and co\+orhcrs ( 1YX7 J
found increases in airway responsiveness after cessation.  Bolin. Dahms. and Slavin
( 1980) evaluated the effect of discontinuing smohing on methacholine sensiti\ it!, in
seven asthmatic sub,jects. PC20 was measured before and I da> after stopping smohing
and was found to be 5.63 mg/mL and 1.56 m&L. respectivelv. This increase in air\+ a~
responsi\,eness ~iis 4een amon g four of the se\en subjects. Finall\. Fennerth and
colleques ( IYX7) recorded PD70 to histamine in l-1 asthmatic\ before and 11 hour\
after smoking cessation. PD20 did not increase significantI\. In se\en subjects ~4 ho
abstained for 7 da),\. honever. PD20 dose increased significantI> (0.67 + 0.43 mg/mL
vs. 7.X F 2.03 mg/,mL).

These studies are limited by short follow up. small numbers of sub.jects. and ;I lack of
ad.justment for baseline airway caliber or pulmonary function.  Additionally. the
analyses did not control for seasonal variation in te\tlng. and the latter three studies did
not include 3 control group.

In summq. former smohers appear to ha1.e bronchial reactivity comparable LI ith
that of never smokers.  The comparabilit>, of bronchial rexctivitb among formel
smokers and never smokers implies that smohing-induced changes in airway respon-
siveness may resolve with abstinence. Available data. hov.ever. are limited and not
definitive. More research is needed to determine the interaction of jmohing cessation
with nonspecific airway responsiveness in altering rates of decline in \,entilatq
function.

PART IV. EFFECTS OF SMOKING CESSATIOIV ON COPD MORTALITY

The Centers for Disease Control reported that 7 I .OYY persons in the United States
died in IYE-33 with COPD (ICD-9-CM 4Y I-2.496) as the under11 ing cause. and 161.04Y
prrsonsdiedwithCOPDas theunderllingcauseorasacontributingcause(CDC 1989).
It was estimated that 8 I .S percent ofCOPD mortality was attributable to mohing (Table
I I ).

Data from both prospective and retrospective studies have consistently indicated an
increased mortality from COPD in cigarette smokers compared ivith never smohers. In
addition. the degree of tobacco exposure. as measured by the number of cigarette\
smoked daily or duration of smoking. strongly. affects the risk of death from COPD.
This literature was reviewed in the 1983 Report of the Surgeon General (US DHHS
1984). in which cigarette smoking was identified as the major cause ofCOPD mortality
for men and women in the United States. The proceedings of a recent worhshop
sponsored by NHLBI address the rise in mortality from COPD (SpeiLer et al. IYXY ).

Several prospective studies have shown that cessation of smoking leads toadecreased
risk of mortality compared with that of continuing smokers (Table 13). In the British
Physicians Study, Doll and Peto ( 1976) reported on a X-year followup of 33.440 male
British doctors who completed a questionnaire about their smoking behavior in I95 I.
Compared with never smoker\. age-adjusted death rates for chronic bronchitis or
emphysema were elevated for current smokers and for former smohers (mortalit!
ratio= 16.7 and 13.7. respectively).


TABLE I I.--Mortality attributable to COPD, United States, 1986

Smohlng
   \tatu\



Current 5mohen


Male

Female


Former vnoker\


Male


Female


TOTAL

Kekmve
rirh






Y.6


10.5





x.7


7.0

A study of mortality among female British physicians has also been reported (Doll
et al. 1980). A cohort of 6.194 female doctors who had responded to the I95 I
questionnaire was studied for ?I? years. The ape-adjusted mortality ratio for chronic
bronchitis and emphysema among continuing smokers increased with reported cipa-
rettes smoked per day (Table 12). Former smokers had a mortality ratioofS.tlcompared
with never smokers. which represented a reduction in mortality ratios of 52 percent t I
to I3 cigarettes/day) when compared with light smokers and of 84 percent when
compared with heavy smokers (215 cigarettes/day).

Peto and coworkers (1983) reported COPD mortality based on a 20. to Z-year
followup of 2.7 IX British men N ho had been enrolled in 5 different respiratory studies
in the lY50s. There were no deaths attributed to COPD among never smokers. The
ratio of observed to expected COPD deaths M;LS I .20 and 0.65 for current and former
smokers. respectively. with expected deaths based on the entire cohort including
smokers and nonsmokers. Thus. the mortality ratio for former smokers was 46 percent
lower than that of continuing smokers (Pete et al. 1983).

Ebi-Kryston (19x9) recently reported on chronic bronchitis mortality in a l5-year
followup of 17.717 male British civil servants. Compared with nev{er smokers. former
smokers had a mortality ratio of 5.57 and continuing smokers had a ratio of X.2 I. Thus.
former smokers had a mortality ratio reduced by 32 percent compared with continuing
smokers. Although the data were not presented for COPD. the author reported that the
results were similar (Ebi-Kryston IYXY ).

In the United States. Roget and Murray ( 1980) reported data on emphysema and
bronchitis mortality. among 1Y3.YSX U.S. veterans studied for I6 years. Former
smokers were restricted to those v. ho stopped smohing cigarettes for reasons other than
a physician's orders. Current smokers had a mortality ratio of 17.07 compared with

342


t .I)     i h


TAHIX 12.~Continued

I3 yr

(`OPD

t 0634X       I.(H)      I .h        1.1
lObY-       I.ZI      I .o        7.5

20 yr

(`OPD               t Yf&6Y       I .tn1      7.0        \.Y
                  t Y7fL74       I.4      4.3        I .x
                  I Y7S-70       2.0       I .Y        2.7
                  I `)X%X4       1.7       I.1        5.7


never smokers. Former smokers had a mortality ratio of 5.20 compared with never
smokers.

The proceedings of the workshop sponsored by NHLBI on rising COPD mortality
included several reports from population-based cohort studies (Speizer et al. 1989).
Tockman and Comstock ( 1989) described mortality in more than 3S.000 white residents
of Washington County, MD, who were enrolled in 1963 and followed through 1975.
Based on the 1963 smoking information. former smokers generally had lower mortality
rates for COPD than did current smokers.  Marcus and colleagues ( 19X9) reported
similar analyses for subjects in the Honolulu Heart Program cohort. Coding of death
certificates for COPD differed substantially between the Honolulu Heart Program and
the State Health Department. Mortality rates based on the Honolulu Heart Program
coding showed a temporal pattern of declining mortality from COPD among former
smokers with increasing mortality among the current smokers during the followup
period 1965-l 983.

Recent data from ACS CPS-II provide new evidence on mortality from COPD (ACS.
unpublished tabulations). The age-adjusted death rates for COPD for men and women
were approximately tenfold higher among current smokers compared with never
smokers. The mortality ratios for male and female former smokers compared with
never smokers were 8.5 and 7.0. lower than for current smokers (ACS. unpublished
tabulations).

Several studies have reported on variation in COPD mortality by duration of
abstinence (Table 13). In these studies. COPD mortality for former smokers initially
increases after cessation above the rates for continuing smokers.  The maximum
mortality ratio for former smokers was found within the first 5 years of abstinence for
ACS CPS-II and between 5 and 9 years after cessation for the British Physicians Study
(Doll and Peto 1976). As discussed in Chapter 2. this initial increase in mortality
probably reflects cessation by persons with smoking-related illnesses or symptoms.
However, even in the U.S. Veterans Study (Roget and Murray 1980). in which only
former smokers who stopped for reasons other than a physician's orders were con-
sidered, death rates for emphysema and bronchitis among former smokers were higher
than for those of current smokers after 5 to 9 years of abstinence.

Following this initial rise in COPD mortality after cessation, the mortality ratios drop
with increasing duration of abstinence (Table 13). However, even after 20 years or
more of abstinence, the risk of COPD mortality among former smokers remains
elevated in comparison with never smokers.

PART V. FORMER SMOKERS WITH ESTABLISHED CHRONIC
       OBSTRUCTIVE PULMONARY DISEASE

Effect of Smoking Cessation on FEV I Decline Among COPD Patients

The beneficial effects of smoking cessation on reducing the annual loss of pulmonary
function are clearly shown in population studies and followup of smoking cessation
participants. These populations have been relatively young and largely free of


TABLE 13.~-Standardized mortality ratios for COPD among current and former smokers broken down by years of abstinence

11.1

Former w~ohcr\ by yr of ahqinrnce

S-9


Il.4

   IO-13      IS~20         21.5


   IO.'         5.7        7.6


Former vnohrr~ hy yr of ab>tmence


respiratory disease. The question arises whether the course of the disease can be
influenced by smoking cessation once clinically overt COPD becomes apparent.

Hughes and coworkers ( 1982) examined the annual change in lung function among
56 male patients with radiologic evidence of emphysema. Patients who had stopped
smoking prior to entry into the study and who did not smoke subsequently had a lower
initial level of FEVJ compared with patients who were smoking (45 vs. 55 percent
predicted). but the annual rate of loss of FEV I for the former smokers was less (I 6.4k8.8
ml/year vs. 53.5f5.4 ml/year). Similar results were reported for annual decline of VC
( 14.9+18.6mL/year vs. 53. If I I .3 ml/year). Diffusing capacity was lower at the initial
assessment among smokers. 57 percent predicted. compared with former smokers. 75
percent, but diffusing capacity did not change significantly during followup.

Postma and coworkers ( 1986) examined the change in lung function in a 2- to 2 I -year
followup of 81 patients with chronic airflow obstruction. Fifty-nine of the patients
smoked throughout the study, and 22 stopped at the start or some time during followup.
Initial level of FEVt was lower among former smokers. but the annual loss of FEVt
was smaller (49*7 mL/year) than for smokers (X5*5 ml/year).

In the National Institutes of Health Intermittent Positive Pressure Breathing Trial.
985 patients with COPD but without chronic hypoxemia were enrolled and studied for
almost 3 years (Anthonisen et al. 1986). Spirometry was performed at entry and
repeated every 3 months. The mean annual decline of FEVl was 44 mL per year: the
investigators reported that neither past nor present smoking behavior affected the
decline of FEVl although the data were not provided.

In summary, two of the three studies suggested that cessation of smoking is followed
by a reduction of the annual loss of pulmonary function, even among patients with
advanced COPD or emphysema. However, a beneficial effect of smoking cessation
was not found in the large Intermittent Positive Pressure Breathing Trial. Additional
investigation of the effect of continuing to smoke on lung function decline in patients
with COPD is warranted.

Effect of Smoking Cessation on Mortality Among COPD Patients

The evidence for an effect of smoking cessation on survival of patients with COPD
is limited. Traver, Cline. and Burrows (1979) found no association between the
smoking status and the survival of 2 patient groups, 200 COPD patients in Chicago. IL,
who were studied for 15 years and 100 patients in Tucson, AZ, evaluated for up to 7
years.

In a followup of up to I3 years, Kanner and coworkers ( 1983) examined the survival
of 100 patients with chronic airflow limitation, aged 32 to 55 at enrollment. Twelve-
year survival probabilities were 86. 79, and 64 percent for never, former, and current
smokers, respectively.

Postma and colleagues (1985) studied survival of 129 patients with severe chronic
aifflow obstruction (FEVt II ,000 mL) for up to I8 years. All nonrespiratory deaths
were censored. Patients were classified by the degree of reversibility of airflow
obstruction. For both smokers and former smokers. relative survival was highest among
those with the greatest reversibility of airflow obstruction. Smokers who quit smoking

347


before the start of followup had a higher survival rate than did continuing smokers
(Figure 13). Within each stratum of reversibility, former smokers had lower mortality
than current smokers.

In contrast. mortality in the 3-year followup period of the Intermittent Positive
Pressure Breathing Trial was not significantly related to smoking status. The followup
period was relatively brief. however. Patient age and the level of FEVt at enrollment
were the strongest predictors of mortality.

In those prospective studies, smoking was evaluated on entry into the study. Sub-
sequent changes in smoking status (i.e.. smokers ceasing to smoke or former smokers
reverting back to smoking) would reduce the estimated effects of smoking cessation
compared with continued smoking. Overall, the extent of the evidence is limited. and
a conclusion cannot yet be reached on the effect of smoking on mortality following
diagnosis of COPD.

348


CONCLUSIONS

I. Smoking cessation reduces rates of respiratory symptoms such a\ cough, sputum
production. and wheezing. and respiratory infections such as bronchitis and
pneumonia, compared with continued smoking.

2. For persons without overt chronic obstructive pulmonary disease (COPD). smoking
cessation improves pulmonary function about 5 percent within a few months after
  cessation.

3. Cigarette smoking accelerates the age-related decline in lung function that occurs
among never smokers. With sustained abstinence from smoking, the rate of decline
in pulmonary function among former smokers returns to that of never smokers.

4. With sustained abstinence, the COPD mortality rates among former smokers decline
in comparison with continuing smokers.



References

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362


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366


     CHAPTER 8
SMOKING CESSATION AND
   REPRODUCTION

367


CONTENTS

PartI. Female  ................................................... ..37 I
PregnancyandPregnancyOutcome  ................................ ..37 I
  Introduction ................................................. ..37 1
  Pathophysiologic Framework  ..................................... 37 I
  Nonexperimental Studies ......................................... 374
   Fertility and Infertility ......................................... 374
   Ectopic Pregnancy and Spontaneous Abortion ...................... 375
   Fetal, Neonatal, and Perinatal Mortality ........................... 376
   Birthweight and Gestational Duration  ............................ 379
    Introduction  ................................................ 379
   Continued Smoking .............. .`. .......................... 381
   Cessation Before Conception  .................................. 381
   Cessation After Conception  ................................... 383
     Birthweight ............................................. 3X3
     Preterm Delivery  ........................................ 386
   Complications of Pregnancy  ................................... 387
Randomized Trials of Smoking Cessation During Pregnancy  ............ 387
Prevalence of Smoking and Smoking Cessation During Pregnancy and Time
   Trends in Prevalence and Cessation  ............................... 390
    Introduction ............................................... ..39 0
  Prevalence of Smoking and Smoking Cessation ..................... 390
  Time Trends in Smoking and Smoking Cessation  ................... 393
  Estimates of Attributable Risk Percent  .............................. 393
AgeatNaturalMenopause..........................................39 6
  Introduction  ................................................... 396
Pathophysiologic Framework  ..................................... 396
  Studies of Former Smokers  ....................................... 39X

PartII. Male ___..~ ~ ~.
          ...................................
Introduction  .................................
Pathophysiologic Framework ....................
Sexual Activity and Performance  ................
Sperm Density and Quality  .....................

Conclusions  ............... ..j .................

Referencer  ....................................

.

. . .

.

. .

. .








PART I. FEMALE

Pregnancy and Pregnancy Outcome

Introduction

Since the late 1940s. cigarette smoking during pregnancy has been linked with poor
pregnancy outcome (Bernhard 1949; Athayde 1948). Adverse effects of smoking on
pregnancy began to receive considerable attention after publication of the results of a
study of 7,499 pregnant women in San Bernardino County, CA. in which the rate of
prematurity, defined as birthwjeight less than 2.500 g. was found to be about twice as
high among smokers as among nonsmokers during pregnancy (Simpson 1957).

Early reports of the Surgeon General (US DHEW I97 I. 1973. 1978) concluded that
maternal smoking during pregnancy retards fetal growth and is a probable cause of late
fetal and infant mortality (US DHEW 1973). The 1977 Report of the Surgeon General
(US DHEW 1978) concluded that smoking during pregnancy has dose-response
relationships with abruptio placentae. placenta previa. bleeding during pregnancy.
premature and prolonged rupture of the membranes. and preterm delivery. The 1979
and 1980 Reports of the Surgeon General (US DHEW 1979; US DHHS 1980)
comprehensively reviewed information on the association of maternal smoking with
pregnancy outcome and further concluded that the risk of spontaneous abortion in-
creases with the amount of smoking and that the risk of sudden infant death syndrome
(SIDS) is increased by maternal smoking during pregnancy. The 1980 Report (US
DHHS 1980) also indicated the possibility of a link between cigarette smoking and
impaired fertility.

Two earlier reports of the Surgeon General (US DHEW 1979; US DHHS 1980)
concluded that mean gestational duration is not affected by maternal smoking and that
data are not sufficient to support a conclusion that maternal smoking increases,
decreases, or has no association with risk of congenital malformations.

This Section reviews observational studies of smoking cessation and the following
reproductive outcomes: fertility and infertility; ectopic pregnancy and spontaneous
abortion; fetal, neonatal, and perinatal mortality; birthweight and gestational duration:
and complications of pregnancy. Three randomized trials of smoking cessation and
pregnancy outcome are described and discussed in detail. Information on the
prevalence of smoking during pregnancy and time trends in prevalence is presented,
along with estimates of the attributable risk of several pregnancy outcomes. SIDS and
congenital malformations are not considered because of the limited information on
smoking cessation.

Pathophysiologic Framework

The effects of smoking that might mediate adverse effects on the developing fetus
and on fertility, fetal loss, and pregnancy complications have been reviewed in other
publications (Long0 1982; Mattison 1982: US DHHS 1980). These reviews are
summarized with attention to the temporal course of the relation between exposure to

371


cigarette smoking and pregnancy outcome as well as the distinction between reversible
and irreversible effects of smoking. Reversible effects would be espected to result in
similar risks for never smokers and former smokers. whereas irreversible effects would
be expected to lead to different risks in both current and former smokers compared with
never smokers.

Several pathways have been postulated by which tobacco smoke might adversely
affect fertility (Mattison 1982) (Table I ). These include disturbance of hypothalamic-
pituitary function, interference with motility in the female reproductive tract (Chow et
al. 1988). and impairment of implantation, all of which are thought to be reversible
consequences of exposure to absorbed chemicals in tobacco smoke (principally
nicotine). It has also been suggested that smoking results in oocyte depletion through
direct toxicity (Mattison 1980), which would have irreversible consequences for
fertility. Chow and colleagues (1988) postulated that altered immune function (Hersey.
Prendergast, Edwards 1983) may predispose smokers to pelvic inflammatory disease.
which in turn can result in permanent scarring and occlusion of the fallopian tubes.
Alterations in the neuroendocrine control of ovulation have been suggested to account
for increased amenorrhea reported among smokers (Pettersson. Fries, Nillius 1973):
this mechanism, as an effect of smoking on fertility. would be reversible.

TABLE I.-Possible mechanisms for the effect of smoking on pregnancy
      and pregnancy outcome

OUtCWlle                            Po\ublr mechant\m

Hormonal effwth
Impaired tubal motilir)
lmpalrrd implantatton
Ooq te drpkrion
Altered lmmunit> Ieadmg to peI\ ic
intlammator) di\ea\e

spwltaneou\ ahntlon
Reduced birth\rsight

Mechanisms for an effect of cigarette smoking on apontaneou\ abortion have not been
clearly defined. partly because so little i5 known about the pathophysiologic basis for
spontaneou\ abortion. The cause\ of spontaneous abortion are broadly divided into
genetic and nongenetic causes (Kline 19X-1). Because smoking seems to have its
primary impact on chromo\omally normal spontaneous abortions (Kline 1984: Alber-
man et al. 1976). nongenetic pathways are implicated for hmokinp (Table I ).

372


Most attention has been focused on the mechanisms mediating a reduction of fetal
growth among smokers (Table 1). An indirect, nutritionally based mechanism in which
smokers are postulated to eat less and gain less weight during pregnancy. thus delivering
smaller infants, has been prominent in discussions of fetal growth retardation in smokers
(Papoz et al. 1982: Rush 1974; Meyer 1978; Davies and Abernethy 1976). This subject
has been reviewed in depth in previous reports of the Surgeon General (US DHEW
1979; US DHHS 1980) and more recently by other researchers (Werler. Pober. Holmes
198.5). Differences in weight gain do not entirely explain fetal growth retardation in
smokers because differences in weight gain during pregnancy between smokers and
nonsmokers are very small and have not been observed consistently and because a
relationship between growth retardation and smoking persists after adjusting for mater-
nal weight gain.

In this context. however, the studies of weight gain in women who quit smoking
during pregnancy are of interest.  Pulkkinen (1985) found that women who quit
smoking during the first trimester gained more weight than nonsmokers or continuing
smokers (I .O vs. 1.3 kg average difference. respectively). Kuzma and Kissinger ( I98 I )
also found that women who quit smoking during pregnancy gained more weight
compared with women who did not smoke during pregnancy (average difference of 4.7
kg) and women who smoked throughout pregnancy (average difference of 5.6 kg).
Also, women who quit smoking before the onset of pregnancy were reported to gain
more weight during pregnancy than nonsmokers or smokers ( I .3 kg and 0.9 kg average
difference, respectively) (Anderson et al. 1984). Rush (1974) reported a reduction in
weight gain of 0.12 pounds per week among continuing smokers compared with those
who quit. This pattern may reflect the well-established tendency to gain weight
following smoking cessation (Manley and Boland 1983: Rabkin 1984). as discussed
further in Chapter 1 I.

There are several hypotheses that attempt to explain the mechanism by which fetal
growth is affected by cigarette smoking (Table I), but cigarette smoking is believed to
impact on fetal growth through intrauterine hypoxia (Long0 1977).  Carbon monoxide.
a component of cigarette smoke, has the ability to cross the placenta and bind with the
hemoglobin in both the mother and the fetus producing carboxyhemoglobin. Car-
boxyhemoglobin reduces the ability of the blood to carry adequate levels of oxygen to
the fetus. Smoking is also believed to cause vasoconstriction of the umbilical arteries.
and therefore. impact on placental blood flow (Lehtovirta and Forss 1978; Naeye and
Tafari 1983; Longo 1982). Cigarette smoking during pregnancy decreases the
availability of oxygen to the fetus by both mechanisms.

These mechanisms imply a reversible effect of cigarette smoking for fetal growth
because normal function would resume shortly after nicotine or CO is cleared from the
system. Support for the suggestion that these effects are reversible is derived from
several sources. Davies and coworkers ( 1979) found that 48 hours of smoking cessation
late in pregnancy increased oxygen availability to the fetus. ViSnjevac and Mikov
(1986) found similarly low levels of carboxyhemoglobin (COHb) in mothers and
newborns when the mother was a former smoker or never smoker; mothers who smoked
during pregnancy and their newborns had high levels of COHb.

373


Mechanisms for the effects of smoking on neonatal. perinatal. and infant mortality
are poorly understood. although the reduction in birthweight is often considered to be
the mediating process. However. smoking appears to cause a shift in the distribution
of birthweight without having much effect on mean gestational age (US DHEW 1979;
US DHHS 1980), and shifts in birthweight distribution across different populations do
not always produce corresponding shifts in mortality (Wilcox 1983: Wilcox and Russell
1983a.b).

That gestational age is little affected by smoking, whereas birthweight is reduced at
every gestational age. explains why small infants of smokers have a better prognosis
than small infants of nonsmokers (Yerushalmy I97 I; MacMahon. Alpert. Salber 1966).
Increases in perinatal mortality among smokers may result not from the reduction in
birthweight, but rather from the modest increases in preterm delivery, very low
birthweight, and specific pathologic conditions such as placenta previa and abruptio
placentae. However, this has not been addressed explicitly in any study. Because the
smaller smoking-related increases in less frequent, more severe outcomes parallel the
pronounced smoking-related reduction in birthweight. birthweight serves as a useful
empirical marker of smoking's harmful consequences. even if it is not the direct
mediator of those effects.

Nonexperimental Studies

Fertility and Infertility

Consistent evidence indicates that smokers have lower fertility than nonsmokers
(Dal@ et al. 1987: Howe et al. 1985: Baird and Wilcox 1985; Hartz et al. 1987). as
noted in the 1989 Report of the Surgeon General (US DHHS 1989). The studies that
have assessed indicators of fertility in former smokers are summarized in Table 2.

Pettersson. Fries. and Nillius ( 1973) studied secondary amenorrhea. one mechanism
for reduced fertility, and found an increased prevalence among smokers. However.
prevalence among former smokers was even higher than among continuing smokers.
Hammond ( 196 I ) found that irregular menstrual cycles were more common among
smokers than never smokers and that former smokers were at slightly lower risk than
never smokers.

Howe and colleagues (19X5) analyzed data on more than 4.000 women in a British
cohort study. which assessed the safety of oral contraceptives. Compared with never
smokers, women who smoked 20 cigarettes or more at entry into the study were twice
as likely to be undelivered 5 years after ceasing contraceptive use with the intention of
becoming pregnant. whereas former smokers had the same likelihood of being un-
delivered as never smokers. Baird and Wilcox ( 1985) reported that the time period until
pregnancy was the same for 3 I women who quit smoking in the year prior to attempting
to conceive as it was for never smokers.

Daling and coworkers (1987) conducted a large case-control study in Washington
State and found that. compared with never smokers. the relative risk of primary tubal
infertility was 1.7 among current smokers and 1. I among former smokers. Information

374


TABLE 2.-Summary of studies of fertility among smokers and former smokers

                            Relatme mh of meawrr of fertlllt!"

Reference

Location

Meaure ol
fertilit!

SlllddX\

Prttrrwm. Frm.
NllliU\ t IY73)

Sweden    Secondary amenorrhea

I.3           I .6

Hov.e et al.
(10X5)

Bad and Wilco\
(19X.5)

England


Minnewto

2.11h          I (I



3.4          I .(I

Ihlltlf er 31.
t 19x71

Seartle

Prtmq tuhd infertilit>

`7
-.           I .o

Dalq! er 31.
(lYX.5)

Se;rttlr

Secondary tubal infertilit)

I .6           I.3

on secondary tubal infertility from the same study (Daling et al. 1985) revealed a smaller
difference between current and former smokers. Although the study focused on prior
induced abortion, data are presented that allow computation of crude odds ratios for
current and former cigarette smokers. Current smokers had a I .6-fold increase in the
risk of secondary tubal infertility. and former smokers had a I .3-fold increase in risk.
It is difficult to assess the causal effect of smoking on tubal infertility independent of
the effects of sexually transmitted diseases (STDs) known to co-v'ary with smoking in
many populations.

In summary, the data suggest that impairment of fertility measured as delay in time
to conception is related to smoking near the time of attempting to conceive and that
smoking cessation prior to conception returns fertility to that of never smokers.
Conclusions about smoking and the risk of tubal infertility cannot be drawn because of
concern about uncontrolled confounding.

Ectopic Pregnancy and Spontaneous Abortion

Tubal (ectopic) pregnancy occurs at about the same time in the reproductive process
as fetal loss. However, the mechanisms are thought to be similar to those operating in
tuba1 infertility and largely concern tubal motility and patency. Several reports indicate
an increased risk of ectopic pregnancy in smokers (Campbell and Gray 1987: Mat-
sunaga and Shiota 1980), but only Chow and associates ( 198X) examined the associa-
tion with prior smoking in detail. In a case<ontrol study in western Washington State.
IS5 cases of tubal pregnancy were compared with 456 controls vvho had given birth.
Current smokers had an estimated 2.2-fold increased risk of ectopic pregnancy com-



pared with never smokers. All former smokers had a I .6-fold increase. but this increase
was limited to those who had quit within the preceding X years. Longer durations of
abstinence yielded an odds ratio of I .O.

Concerns about the possibility of differences in sexual activity between smokers and
nonsmokers and the occurrence of STDs limit the ability to draw firm conclusions about
the association of smoking with ectopic pregnancy. There is little information about
former smokers, and consequently, no conclusion can be drawn.

Some data suggest an association between smoking and increased risk of spontaneous
abortion (US DHHS 1989). Data on smoking cessation are very sparse. Kline (I 9X4)
noted that the adverse effect of smoking observed in a case-control study of smoking
and spontaneous abortion (Kline et al. 1977) was limited to current, not former.
smokers. Alberman and colleagues (1976) found that the proportion of spontaneous
abortions with abnormal karyotypes decreased with increased smoking but was identi-
cal for never smokers and women who stopped smoking prior to pregnancy (Alberman
et al. 1976). The interpretation of this finding is uncertain.

Fetal. Neonatal, and Perinatal Mortality

Information linking cigarette smoking with an increased risk of the various measures
of mortality used to assess pregnancy outcome has been reviewed in previous reports
of the Surgeon General and other publications (US DHEW 1979: US DHHS 1980: US
DHHS 1986). Table 3 provides data on perinatal and neonatal mortality from the earlier
reports of the Surgeon General (US DHEW 1979; US DHHS 1980) and adds informa-
tion from a more recent publication on the topic (Rush and Cassano 1983). The studies
are consistent in indicating higher mortality in children born to women who smoke.
The high risk of mortality is independent of various factors. such as education and social
class. that are also associated with mortality.

Kleinman and colleagues (19X8) assessed the effect of smoking on fetal and infant
mortality in 363.621 births in Missouri during 1979-1983. Using multivariate statisti-
cal techniques, these investigators estimated the effects of smoking on fetal and infant
mortality among black and white primiparous and multiparous women. After adjust-
ment for marital status. education. and age. fetal plus infant mortality rates were 25 to
56 percent higher in smokers for all categories of maternal race and parity. The
elevations in the estimated risks of fetal plus infant mortality were statistically sig-
nificant in all categories. In further analyses ofdata from the Missouri births and deaths.
Malloy and coworkers (19Xx) showed that the relative risk of fetal plus infant mortality~
among whites was significantI> elevated for the infants of women who smoked in all
categories of low birthweight. even after adjustment for marital status. education. age.
and parity (Table 1). This data set is unique in its sile. consisting of more than 3SO.OfW)
births. The data indicate that even in the nomtal birthweight infants of smokers-those
that wjeiahed 7.500 g or more-mortalitv was significantly elev#ated for infants of
      c
mothers who smoked.

Information on fetal. neonatal. and perinatal mortality in former smokers is sparse
(Table 5). Butler. Goldstein. and Ross (1973) analy,red data from the British Perinatal
Mortality Survey and estimated that perinatal mortality was the same for women who

376


TABLE 3.-Summary of studies of perinatal and neonatal mortality in smokers
     and nonsmokers during pregnancy

Reference

Number of
birth\

       Perinatal mortality"     Uronalal morlalIl~"
Carepq   Smnher\    Non\mohrr\    Smoher\   Non\mohsr\

Com\toch and   12.37
Lundin
t 1967,

Meyer and     5 I .lYO
Tona\cia
llY77,

Rantahalllo    12.06X
(lY7XI

Ru\h and
ca\\ano
lI9X.3)

Butler.       2 I .7X8
Goldstein. Rev
1972)

Whltr\
Blach\

Amount mohrd

<I wd        2X.0      23.0
>I ppd        33.3

Social cl9s.
~.. .______~.
I+11
III+IV
Farmer\
Lnhnown

XI"    22.4"
25.1      14.6
753 <I    3s .I?
29.4"    36.X"

Amount \mohed

4 q/day
S-11 cig/day
>I5 cigda)

IS.0      IX.7
26. I
2x.3

Andrews and
McGarry
t 1972)

IS.63 I

Nihwander    37,912
and Gordon
(1972)

  I4 cig/day
  S-9 c&/day
IObl9cigiday
  t70 ctg/day

  Race and
Amount smoked

White
I-IOciddq
2 I I cig/da)

Black
IplOcigjdq
21 I c&iq

11.1      32.0

2s
20
32
36

25

       31.1
31.5
3x.2

       3x.5
41.5
57.1

17.6     13.7

377


TABLE X-Continued

TABLE L-Estimated relative risk of fetal plus infant mortality for maternal
     smoking in several birthweight groups, adjusting for maternal
      marital status, education, age. and parity

Y.i'i Cl


Perinatal mortality among those who smoked before pregnancy but quit during preg-
nancy (lS.O/l,OOO) was lower than for either nonsmokers during pregnancy ( I8.7/
I .OOO) or smokers of 5 cigarettes or more per day throughout pregnancy (26.9/1.0(K)).

TABLE 5. --Summary of studies of perinatal mortalit? in smokers throughout
      pregnancy, smokers who quit in the early months of pregnancy, and
      nonsmokers during pregnancy

Reference

Fetal, neonatal, and perinatal mortality are rare events. This limits the study of their
association with smoking cessation. Lack of data makes it impossible to draw a firm
conclusion about the association of smoking cessation with the risk of fetal, neonatal.
or perinatal mortality. However, the limited available data are consistent with the
conclusion that perinatal and neonatal mortality are lower among infants of women who
quit smoking than among those women who smoke throughout pregnancy. The
possibility must be considered that differences between women who quit smoking and
those who continue to smoke account for the lower rate of perinatal and neonatal
mortality in the studies in which this has been observed.

Birthweight and Gestational Duration

Fetal. neonatal. and perinatal mortality are the most direct measures of pregnancy
outcome. Mortality is relatively uncommon, and very large samples are needed for
study. This has led to the widespread study of birthweight and the percentage of births
that are low birthweight (<2.500 p) as surrogates for the study of mortality. This
strategy has been justified by the extremely strong association between birthweight and
the percent of low birthweipht and each of the measures ofmortality (Figure I 1. Equally
important is weight at birth as a determinant of infant health (McCormick 1985 J.


W Perinatal mortality =
      fetal deaths and neonatal
      deaths/total births

x-.. .. .,x Neonatal mortality =
     death through 28 days in
      liveborn infants/live births

0 - -0 Fetal mortality =
       stillbirths/total births

500-    lOOO-    1500-    2000-   2500-   3000-   3500-   4000-
749    1249    1749    2249    2749    3249    3749    4249
BIRTHWEIGHT (g)
FIGURE I.-Perinatal, neonatal, and fetal mortality rates by birthweight
      in singleton white males, 1980

SOURCE: Williams and Chen (1982).


Birthueight is. ho&ever. :I result ofgestational age at birth and the rate of fetal yrou th.
Recognition ot the complex relationship5 amon, 0 ft3tationul duration. rate of fetal
growth. birth\\teight. and mortalitv has led to attempt\ to classif\ infant\ according to
cre\tational duration or joint distribution of hirthueight and ~~c\tatioii;il duration.
Eenerallj. births are catefori/ed ;I!, preterm (~37 ueehs gr\tatiotyl and/or 34 \mal I for
gestational age (SGA) (<lOth percentile of weight for ;I gi\,en ge\tational age ). Joint
cla\4fication is thought to pro\ ide a more discriminating hasi\ for the \tucl! ofetiologic
agents.

Preterm dcli\,ery i\ strongly a\>oci;ltcd V, ith incrc;Lht`\ in the risk of fetal. neonatal.
and perinatal mortalit\ and \j ith significant childhood morbidit!.  Both preterm
delivery and SGA increase the rish of cerebral pal\!. although the ri4 i\ much greater
for prcterm delivery (Ellenberg and Nelson Ic)7Y). SC;+. I\ as\ociatcd M ith increased
ri\k of neonatal and perinatal mortalit) at e\`er! c catation;d qe (Koop\. hlorgan.
Battaglia 19X2: Lubchenco. Searl$. Bralie 1071): Lsith SIDS tBuch et al. IWSJ: and
with neurocognitive deficits. 4ort \taturc. :md small head circumference in childhood
(Fitzhardinge and Steven IY72: Hill et al. IYX4: We\thood et al. lYX3; Ounted and
Taylor 197 I; Harvey et al. 19X7: Ounsted. Moar. Scott IYXI. I YXX: Fancourt et al.
1076).

A\ reviewed in previous Surgeon General'\ report\ (US DHEW lY7Y: US DHHS
IYXO) and in other literature (Landesman-Dv. yer and Emanuel 1979: Longo 19X2:
Werler. Pober. Holme\ 19X5: Kramer 1987). cmokin2 during pregnancy decreases
mean birthweight and increase\ the proportion of IOU' birthweight births. Ei;timates
vary among studies. but birthweight is reduced by an average of approximately 100 g.
and the proportion of 1ow birthweight is approximately doubled by cigarette smoking
(Meyer. Jonas. Tonascia 1976: US DHHS 19X0: L'S DHEW 1979: Mclnto\h 19X-I:
Committee to Study the Prevention of Low Birthweight IYXS: Kramer 19X7). Mean
birthweight decrea5e.s and the percent low birthbeight increases with increasing num-
ber of cigarettes smoked daily. The relationship between cigarette smoking and
decreased birthweight is considered to be causal (US DHEW 1979: US DHHS 1980.
I9XY).

Smoking affects birthweight and the percentage of babies who are born of ION
birthweight by retarding fetal growth. A measure of fetal growth retardation is the
probability ofdeliverinp an infant who is in the lee than 10th percentile for gestational
age. The relative risk of SGA is about 3.5. to l.O-fold higher among the infants ot
\mokerc than for the infant4 of nonsmokers (Ounsted. Mnar. Scott IYX5 1. Preterm birth
is also associated with maternal smoking. although not as strongly. Estimates of the
relative risk of delivering before 37 weeks of yestation are typically about I.5 for
smoking during pregnancy (Committee to Study the Pre\zntion of Low Birthueight
19X5: Kramer 19X7: Shiono. Klebanoff. Rhoads 19X6). Mean Fe\tntional duration
among makers i\ not significantly shorter than it i\ among nonsmoher\ (C`S DHEW
1979: US DHHS 19x0). This finding is consistent with the observation that the ri\h ot
delivering early ik greater amon? smokers than nonsmoher\. but the percentay of


preterm deliveries is so small that the mean would not be affected unless the shift were
very large (US DHEW 1979; US DHHS 1980).

Most studies of cigarette smoking and birthweight have failed to separate never
smokers from women who quit smoking prior to conception. MacMahon. Alpert, and
Salber (1966) first examined the association of pre-pregnancy smoking with
birthweipht and found no significant difference in the mean birthweight of infants
whose mothers smoked before but not during pregnancy compared with never smokers.
Subsequent research has confirmed the absence of an association between smoking
prior to conception and reduced birthweight (Table 6). In all of these studies. smokers
who quit before conception had mean birthweight values that were equivalent or higher
than those of never smokers. Other studies in which information on mean birthweight
could not be derived (Kline, Stein. Hutzler 1987: Anderson et al. 1983: Wainright
1983). with the exception of Zabriskie (1963). have also consistently shown no
association between birthweight and smoking that ceased prior to conception. Zabris-
kie (1963) failed, however. to adjust for smoking during pregnancy. and these results
are not directly pertinent in a comparison of birthweight in never smokers and smokers
who quit before conception.

TABLE 6.-Summary of studies of mean birthweight, by smoking status

In interpreting these data. misclaa\itication of exposure needs to be considered.
MacArthur and Knox ( 198X) reported that women who quit smoking during pregnancy.
and possibly those who quit before pregnancy. were more often living with a partner
who smoked. Passive smoke exposure may adversely affect the fetus (Martin and


Bracken 1986). Furthermore. for whatever reason, some women ma) misrepresent
their smoking status, denying that they have continued amohing. thus leading to an
underestimation of the benefit of smoking cessation prior to conception.

More important. women who quit smoking prior to conception differ in other respects
from women who continue to smohe. Women who quit may have smohcd feuer
cigarettes per day prior to quitting. Studies of smoking cessation prior to conception
have not accounted fully for other difference\ between women who quit and those who
continue to smoke.

Birthweight

Table 7 summarires nonexperimental studies in u hich information on mean
birthweight in nonsmokers. smohers throughout pregnancy. and smoker\ u ho quit after
conception could be derived. The data from each of these studies are con\i\tcnt in t\j o
important ways. First. women who smohed throughout pregnancy delivered infant\
who weighed less than the infants of nonsmokers. Second. women who quit smoking
delivered infants who weighed more than the infants of smokers throughout pregnancy.
In most of these studies. mean birthweight values among infants whose mother\ \toppcd
smoking were the same or higher than those of infant\ of nonsmokers.
Table 8 summarizes nonexperimental studie< estimating the relative rish of IOM
birthweight for continuing smokers and quitters some time during pregnancy compared
with nonsmokers during pregnancy. These studies are consistent with those examining
mean birthweight. Compared with nonsmokers. the risk of low birthweight is elevated
among smokers throughout pregnancy. and the risk is about I .O for women M ho quit.
In addition. Kleinman and Madans (1985) reported no association between the rish ot
low birthweight for women who quit smoking during pregnancy compared with those
who had not smoked in the I2 months prior to conception among participants in the
1980 National Natality Survey (NNS ).

An important aspect of smoking cessation and pregnancy outcome is the timing of
cessation during pregnancy and its relation to birthweight. How early in pregancl
cessation must occur to avoid the adverse effects of smoking on birthweight is a ke\
issue with important implications for counseling pregnant smokers.

In most of the studies examining this question, only information on cessation in the
early months of pregnancy is presented. However. Rush and Cassano ( 1983) found that
mean birthweight among women who quit as late as the seventh to eighth month of
pregnancy was higher than for women who smoked throughout pregnant)`. but lower
than for nonsmokers and for women who quit earlier in gestation. MacArthur and Knox
(1988) concluded that quitting any time before the 30th week of gestation increase\
birthweight when compared with continuing to smoke. Cooper (19X9) assessed
patterns of cigarette smoking by trimester of pregnancy. Women who reponed
smoking during the "first trimester of pregnancy only" had a X)-percent increased ri\h
of having a low birthweight baby. while women who reported smohinp during the "first
and second trimester of pregnancy only" had a 7%percent higher rt\h ot. ;I lo\{


TABLE 7.-Summary of nonexperimental studies of smoking cessation after
     conception, mean increase (+I or decrease (-) in birthweight (g)
     according to timing of cessation

Month of ce\\ation

Smohed

Reference

I 2 3 4 5 6 7 x Y      L'tlktlOWl   throughout

Lowe
(IYSY)

Underwood et al.
t 1967)

Butler. Gold\tein.
Ro\\
(1972)

Andrew and
McGarry t I472 1
Pap07 et 31.
(19X?)

+9X

Rush and
Cnssano ( 19x3 1

Pulhkinen
(IYXS)

Councilman and
MacKay t 19x5)

Kline. Stein.
Hutrler
(19X7)

MacArthur     +`17
and Knox
(IYXXI

       +I3                             -IX'



-IOX       -152                         -730



    +Jh                                -160





-x0                                    -170



          + IO                           -70



          +-I.?     c.76 -90                -155



41                                    -22s



10                                   -3s



                            +I?        -202




    -sx                                 -2-t:

birthweight baby.  Women M ho reported mokin, 17 throughout their pregnancy had a
90.percent increased risk. of having a low birthweifht babl in contrat to nonjmohers.

Most fetal gwwth occurs late in pregnancy. and the primary smoke comtituents
considered as candidate\ in mediating the effect of wloking on fetal grow. th (i.e.. CO
and nicotine leading to intrauterine hypoxia) have short-term reversible effects. The
data in Table\ 6 and 7 wpport the conclusion that the adverse effect of making on
birthweight occur5 in the latter part of Fe\tation. primarily during the third trimester.
and that cessation at any time during gestation i4 lihely to mltlzL
                                 `vte the adverse effect
of smoking on fetal growth.

Because it is difficult to perwade ull pregnant \moher\ to quit vnohing entirely. the
benefit of reducing the number of cigarette\ smoked per day becomes a public health
issue. The obhervstion that cigarette mohing retard\ fetal gro\hth in ;I do\e-rehpon\e

3x3


TABLE 8.-Summary of nonexperimental studies of relative risk of low
     birthweight for smoking cessation after conception

Fruier et al. ( IYhl I
Van den Berg (lY771~
Petltti and Coleman on prr\\I

   Vv'hlte\    <I mo
          I-? mo
          2-3 mo
   Blach\    <I mo
         I-2 mo
          7-1 m.

Andrew and
McGarr? ( iY77)

0.S                `7
                -.
I .(I
(1.6
I A               3X
I .o
I.1

1.3               1.0

fashion supports the benefit of reducing the number of cigarettes smoked per day.
Hebel. Fox. and Sexton (19%) used data from their randomized trial of smoking
cessation to examine this question.  These researchers found that the benefit of
decreased smoking for birthweight during pregnancy w'as almost entirely, restricted to
those who achieved total cessation. perhaps because women who reduce the number of
cigarettes smoked compensate by inhaling more deeply. by puffing more frequently.
or by smoking the cigarette to a shorter butt length. Findings from another randomized
trial support the conclusion that abstinence. not reduction. should be the goal in
pregnancy (MacArthur. Newton. Knox 1987). In this latter study, the intervention led
to a considerable reduction in the reported mean number of cigarettes smoked per day
but almost no difference in the percentage of women who quit entirely: there was no
difference in birthweight between the treatment and control groups (MacArthur.
Newton, Knox 1987). Because of the social stigma associated with smoking during
pregnancy, it is possible that some women in this intervention trial falsely reported a
reduction in smoking; if so. this underreporting would lead to an underestimation of
possible benefits of reducing cigarette consumption.

Whether quitting only during the first half of pregnancy will prev'ent a reduction in
birthweight is another important consideration. Most fetal growth takes place in the
last trimester: early quitting virtually eliminates the effect of smoking on birthweight.
Thus. smoking late in pregnancy may have an adverse effect on birthvveight even if
there is abstinence in the first trimester. Lowe (1959) found that the mean birthweight
of infants of smokers who quit early in pregnancy but resumed smoking was between
that of smokers throughout pregnancy and that of never smokers. Infants of women
whogave upcigarettes by the fifth month ofpregnancy and whodid not resume smohin_g


had a mean birthweight identical to that of never smokers. MacArthur and Knox ( 198X)
also found that infants born to women who quit smokin? early in their pregnancy but
started again before delivery had a mean birthweight value between that of smokers
throughout pregnancy and those of both early quitters and never smokers. These data
indicate that abstinence throughout the third trimester of pregnancy is necessary to
realize the full benefit of smoking cessation for birthweight.

Preterm Delivery

The effect of smoking on birthweight is principally due to a reduction in size for a
given gestational ape rather than to a large decrease in gestational duration (US DHEW
1979: US DHHS 1980). Thus. it would be expected that pregnancy outcome in women
who quit would reflect a predominant effect on size for gestational age.

Andrews and McGarry ( lY72) considered preterm delivery as a distinct endpoint in
continuing smokers and quitters: the latter group included a mixture of women who
quit prior to conception and women who quit during their pregnancy. The rate ot
preterm delivery among nonsmokers was 6.7 per 100 compared with 7.5 per 100 for
ex-smokers and 9.1 per 100 for women who continued to smoke throughout pregnancy
(Andrewc and McGun-y 1971).

Berkowitz. Holford. and Berkowitz ( 1981) examined the association between smok-
ing during each trimesterof pregnancy and the risk of preterm delivery in acase-control
study of 175 mothers of singleton. preterm infants and 3 I3 mothers of singleton. term
infants. The risk of preterm delivery was increased among women vvho smoked in the
third trimester of pregnancy. especially if they smoked heavily (>I0 cigarettes per day ).

Using data from a longitudinal study of pregnant women. Van den Berg and Oechsli
( 1984) reported rates of preterm delivery (137 weeks) among never smokers. smokers
who stopped at the beginning of pregnancy. and continuing smokers for 10,937 white
women whose singleton pregnancies progressed beyond 22 weehs. The rate of preterm
delivery was 5.3 percent in nev'er smokers. 6.X percent in quitters. and 7.6 percent in
continuing smokers. The difference in the rate of pretemr delivery between never
smokers and quitters was not statistically significant (pN.05): however. the difference
between never smokers and continuinp smokers was significant.

In a population-based case<ontrol study of white and black women delivering
singleton infants without congenital anomalies in a large urban county. Petitti and
Coleman (in press) reported that the estimated relative risk of very low birthweight
(<I.500 g) or of other preterm births among blach and white women who quit smohing
prior to the fourth month of gestation was not increased in comparison with those of
nonsmokers. The estimated relative risk of very low birthweight (< I.500 g) in continu-
ing smokers M as 2.5 for u hites and 3. I for blacks and that of other preterm births u as
2.0 for wshites and 3.7 for blacks.

MacArthur and Knox (1988) examined gestational duration according to smoking
during pregnancy. Mean gestational length was 1.7 days shorter among continuing
smokers than nonsmohers. Compared with nonsmohers. gestational periods were 0.4
days shorter for women who quit smoking by the 6th week of pregnancy, I.5 days longer


for women who quit between the 6th and 16th weeks of pregnancy. and 0.3 days longer
for women who quit after the 16th week of pregnancy.

Because of the limited data on the risk of preterm delivery among women who quit
smoking after conception. a firm conclusion about benefit. or lack of benefit. at-
tributable to smoking cessation for this pregnancy outcome cannot be drawn.

Women who smoke during pregnancy are at increased ri>k of bleeding during
pregnancy and of placenta previa and abruptio placentae (US DHEW 1979: US DHHS
1980: Naeye 1978: Naeye 1980). These women are probably at decreased risk of
preeclampsia (US DHEW 1979: US DHHS 1980: Marcoux, Bribson. Fabia 1989). Few
data on these pregnancy complications among former smokers are available.

In Naeye's ( 1980) analysis of data from the Collaborative Perinatal Project, smoking
for more than 6 years (but not short-term smoking) was found to be associated with a
relative risk of I.6 to 1.9 for abruptio placentae and a relative risk of 2.4 to 2.8 for
placenta previa. Women who had stopped smoking by their first prenatal visit were not
at increased risk of abruptio placentae, but were still at twofold increased risk of
placenta previa if they were long-term smokers. However, the latter result was based
on only 18 exposed cases.

Marcoux, Brisson, and Fabia (1989) found that. compared with women who had
never smoked, those who smoked at the time of conception were protected from
preeclampsia (estimated relative risk (RR)=OS 1). whereas women who smoked but
quit prior to conception had the same risk of preeclampsia as never smokers (RR=O.97).
Women who smoked at conception but quit prior to 20 weeks' gestation were not as
protected from development of preeclampsia as were continuing smokers. Because of
the otherwise serious adverse effects of smoking on the fetus, this minor "benefit" of
smoking during pregnancy probably has no public health consequence.

Randomized Trials of Smoking Cessation During Pregnancy

Three randomized trials have been conducted on pregnancy outcome in relation to
advice to stop smoking (Donovan 1977; Sexton and Hebel 1984: MacArthur, Newton,
Knox 1987). Table 9 summarizes the studies and birthweight results. Two other
randomized trials have also been conducted on the effect of various programs on
smoking cessation rates among pregnant women (Ershoff, Mullen, Quinn 1989:
Windsor et al. 1985). and other trials are in progress. Information on pregnancy
outcome is not available, and these studies are not reviewed.

Donovan (1977) studied smokers in three maternity units in England. Women aged
35 years or younger at the start of pregnancy. who smoked more than 5 cigarettes per
day, who had less than 30 weeks of gestation at the first prenatal visit. and who had no
prior perinatal deaths, were randomly assigned to a control group that received usual
prenatal care or to a test group that was given intense individual antismoking advice by
a physician at each prenatal care unit. There were 263 women in the test group and 289
in the control group. Mean daily cigarette consumption decreased from 17.1 cigarettes
per day early in pregnancy to 9.2 cigarettes per day late in pregnancy in the intervention


for women who quit between the 6th and 16th weeks of pregnancy, and 0.3 days longer
for women who quit after the 16th week of pregnancy.

Because of the limited data on the risk of preterm delivery among women who quit
smoking after conception. a firm conclusion about benefit. or lack of benefit. at-
tributable to smoking cessation for this pregnancy outcome cannot be drawn.

Women who smoke during pregnancy are at increased risk of bleeding during
pregnancy and of placenta previa and abruptio placentae (US DHEW 1979; US DHHS
1980: Naeye 1978: Naeye 1980). These women are probably at decreased ri\k of
preeclampsia (US DHEW 1979: US DHHS 1980: Marcoux. Brisson. Fabia 1989). Few
data on these pregnancy complications among former smokers are available.

In Naeye's (1980) analysis of data from the Coltabordtive Perinatal Project. smoking
for more than 6 years (but not short-term smoking) was found to be associated with a
relative risk of I .6 to I .9 for abruptio placentae and a relativ*e risk of 2.4 to 2.8 for
placenta previa. Women who had stopped smoking by their first prenatal visit were not
at increased risk of abruptio placentae, but were still at twofold increased risk of
placenta previa if they were long-term smokers. However, the latter result wa$ ba$ed
on only I8 exposed cases.

Marcoux, Brisson. and Fabia (1989) found that, compared with women who had
never smoked, those who smoked at the time of conception were protected from
preeclampsia (estimated relative risk (RR)=O.Sl). whereas women who smoked but
quit prior toconception had the same risk of preeclampsia as never smokers (RR=O.97 ).
Women who smoked at conception but quit prior to 20 weeks' gestation were not as
protected from development of preeclampsia as were continuing smokers. Because of
the otherwise serious adverse effects of smoking on the fetus, this minor "benefit" of
smoking during pregnancy probably has no public health consequence.

Randomized Trials of Smoking Cessation During Pregnancy

Three randomized trials have been conducted on pregnancy outcome in relation to
advice to stop smoking (Donovan 1977: Sexton and Hebel 1984; MacArthur. Newton.
Knox 1987). Table 9 summarizes the studies and birthweight results. Two other
randomized trials have also been conducted on the effect of various programs on
smoking cessation rates among pregnant women (Ershoff. Mullen, Quinn 1989:
Windsor et al. 1985). and other trials are in progress. Information on pregnancy
outcome is not available, and these studies are not reviewed.

Donovan (1977) studied smokers in three maternity units in England. Women aged
3.5 years or younger at the start of pregnancy, who smoked more than 5 cigarettes per
day, who had less than 30 weeks of gestation at the first prenatal visit. and who had no
prior perinatal deaths. were randomly assigned to a control group that received usual
prenatal care or to a test group that was given intense individual antismoking advice by
a physician at each prenatal care unit. There were 263 women in the test group and 289
in the control group. Mean daily cigarette consumption decreased from 17. I cigarettes
per day early in pregnancy to 9.2 cigarettes per day late in pregnancy in the intervention

ix7


TABLE 9.-Summary of birthweight outcome in randomized trials of
      smoking cessation in pregnancy

Reference

Number of     Smohmg aI end
\uhjecr\      of prq"""c)

I       c      I         c

   Binhueiyht rp)

1     c    Difference (g I'

Donovan I lY77)    x?

Sexton and Hebel   463
liYX4

MacArthur. Newton. 4Yi
Knox (IYX7)

group. but increased slightly from 13.7 to 16.4 in the control group. Mean birthweight
was 3. I72 g in the test group and 3. I83 g in the control group. In the test group IO
percent of the infants had low birthweight (4.500 g) compared with 9 percent in the
control group. There were four perinatal deaths in the test group and one in the control
group. None of the differences in birth outcome betueen the test and control groups
were statistically 4gnificant.

Although this trial might be regarded as evidence against a benefit of smoking
cessation during pregnancy. a number of limitations of the study must be considered.
First. no data are presented concerning the percentage of pregnant smohers who quit
smoking entirely. Reducing cigarette consumption almost certainly has a smaller
     c
benefit for pregnancy outcome than complete cessation. Second. the time at uhich
smoking behavior changed during pregnancy is unclear: data on cigarette consumption
for three periods during pregnancy uere obtained postnatally. and may have been
affected by recall bias. Data from ohser\ational studies discu\\ed in the pre\ ious
section strongly suggest that mohing during the last trimester of pregnancy i\ a critical
mediator of reduction in fttal growth among smokers.

Information from another British randomized trial (MacArthur. Neti ton. Knox 19x7)
alsoquestions the benefit ofmohing ce\\ation during pregnancy. In this \tud!. ~\omen
who \mohed at the time thei were scheduled for ;I prenatal 1 isit ;II a large hospital v.crc
assigned randomI> to a control group that received routine care or to an intervention
group that received supplementary health education about mohing during pregnant!
The planned intervention consisted of ad\ ice to 4top \mohin= 11 and information about
the effects of smoking on the fetus. pre\cnted I isuall> h! a bnohlet or \erball! by the
obstetrician. There were 4X9 \tomen in the control group and 193 in the inter\rntion
group. Mean birthweight for infant\ in the control group v.34 3. I30 g compared with
3.163 g for the intervention group. The pcrccntage\ of 1~ birthueight and perinatal
mortality in the tv.o groups \\erc not reported. The difference in mean hirth\\eight was


not statistically significant as determined by the conventional 0.05 probability value
and a two-sided test.
In this trial, only Y percent of the women in the intervention group quit smoking
entirely. compared with 6 percent of the women in the control group. The failure of
the intervention to cause smoking cessation makes this trial essentially uninformative
concerning the benefit. or lack of benefit. of smohing cessation during pregnancy. In
the intervention group. 28 percent of the women reduced the number of cigarettes
smoked per day, compared with IY percent of the women in the control group. The
greater reduction in cigarette consumption in the inter\,ention group. in the absence of
a difference in mean birthweight between the intervention and control groups. suggests
that reducing smoking does not entirely prevent the adverse effects of smohing on
birthweight.
The third randomized trial (Sexton and Hebel IY8-t) recruited women in a large
metropolitan area from various sources. Smokers of at least locigarettes per day at the
beginning of pregnancy, who had not passed the 18th week of gestation. were randomly
assigned to a control group that received routine advice or to a treatment group that
received intensive. ongoing advice throughout pregnancy from specially trained profes-
sional staff. There were 472 women in the control group and 363 women in the
treatment group. The mean birthweight of infants born to women in the control group
was 3.186 g compared with 3,278 g for infants of women in the treatment group. The
percentage of low birthweight infants was 8.9 in the control group and 6.X in the
treatment group. There were I I stillbirths in the control group and Y in the treatment
group. The difference in mean birthweight was statistically significant (~~0.05. two-
tailed test); the differences in the percentages of low birthweight and in fetal mortality
were not statistically significant.
In this trial, 43 percent of the women in the treatment group had ceased smoking
entirely by the eighth month of pregnancy. compared with 20 percent of the women in
the control group. The intervention was, therefore. highly successful in causing
substantial changes in smoking that exceeded changes in the comparison group. The
investigators ruled out concomitant changes in consumption of alcohol and coffee as
explanations for the increase in birthweight. Weight gain was 1 .O kg greater among the
treatment group than the control group. but at least part of the difference in weight gain
was a result of the higher birthweight of the infant (Sexton and Hebel 1984).
Review of these three randomized trials leads to two conclusions. First, to prevent
entirely the adverse consequences of smoking on birthweight, it is necessary for women
to cease smoking completely. Second. intensive interventions spanning the entire
period of gestation may be necessary to effect large changes among the percentage of
women who abstain from smoking entirely.


Prevalence of Smoking and Smoking Cessation During Pregnancy and Time
Trends in Prevalence and Cessation

Introduction

Ideally, conclusions about the prevalence of smoking during pregnancy and trends
in prevalence would be based on representative samples of pregnant women performed
at regular intervals using the same methodology. Assessment of smoking cessation
during pregnancy and time trends in smoking cessation should be based on repre-
sentative samples of women who start pregnancy as smokers and who are monitored
for smoking behavior throughout gestation. Available data fall short of these ideals.

Furthermore, available information on smoking and smoking cessation in pregnancy
is based almost exclusively on self-reported behavior. Few data on the quality of
self-reported smoking specifically in relation to pregnancy have been collected. and it
is possible that the societal pressures against smoking during pregnancy would make
underreporting more problematic than for other populations (Chapter 2). Similarly,
pregnant smokers who admit to smoking might underreport their daily cigarette
consumption. perhaps to a greater extent than nonpregnant smokers. The effect of
underreporting of smoking and overreporting of cessation would make the data from
former smokers more similar to that of continuing smokers with respect to their
reproductive health outcomes. Also. smokers who reduce the amount of nicotine in
their cigarettes by changing brands or those M ho reduce the number of cigarettes they
smoke per day without quittin, ~7 may compensate to maintain the \ame nicotine do\e
(US DHHS lY88).

Prevalence of Smoking and Smoking Cessation

Pertinent data on smoking during pregnancy from the 1985 National Health Interview
Survey (NHIS) (NCHS IYXX) are presented in Table IO. The IYXS survey focused on
health promotion and disease prevention.  The survey involved nearly 35.000
households and more than YO.Ot)O persons. and the response rate was 95.7 percent.
Information concerning smoking during pregnancy' vvas obtained from all female
household members aged IX to 4-I kears ti ho had had a live birth in the 5 years prior to
the survey. The proportion of vvomen u ho had smohed at any time during the year
preceding pregnancy ~`a\ 32 percent overall. Of Momen uith less than I? years of
education. 46 percent smohed in the year preceding pregnancy. compared with I.3
percent of women with I6 or more years ofeducation. Thirty percent of married women
had smoked. compared u ith 10 percent of formerly married u'omen.

Patterns of smohing cessation or reduction uere reported in detail for some
demographic subgroup\. Overall. 2 I percent of women who smoked prior to pregnancy
quit upon learning of their pregnancy. and an addittonal 36 percent reduced the number
of cigarette\ they smohed. Cessation (but not reduction) *as strongly related to
education and family income. Among uomen with less than 12 years of education. I2
years of education. and more than 12 years of education. 15. 10. and 32 percent quit.


TABLE IO.-Smoking and smoking cessation during pregnancy. summary of
      results of two surveys of national probability samples

respectively. The proportions for reduction in smoking were 34. 3X. and 36 percent.
respectively. Younger mothers were slightly more likely to quit than older mothers.
and white mothers quit slightly more often than black mothers (2 I vs. IX percent ). More
married mothers (23 percent) than never married (19 percent) or formerly married ( I3
percent) mothers quit. although the proportions reducing their smoking levels were
similar (36. 37. and 35 percent. respectively).

Fingerhut. Kleinman. and Kendrick (1990) also reported data on smoking in whites
before and during pregnancy based on the Linked Telephone Survey. which reinter-
viewed I.550 women aged 20 to 44 years who were respondents to the 1985 NHIS.
This analysis confirmed the previous findings that smoking prior to pregnancy and
quitting during pregnancy were strongly related to age and educational attainment.
Information on amount smoked prior to pregnancy was obtained in this survey.
Fifty-nine percent of women who smoked less than I pack per day prior to pregnancy
quit smoking. compared with 25 percent of those who smoked I pack or more per day.
Of the white women who smoked prior to pregnancy, 3Y percent quit during pregnancy
(27 percent when they found out they were pregnant and I2 percent later in pregnancy).
This estimate of quitting during pregnancy is higher than the previous estimate of
quitting from whites in this survey because it includes as quitters both women who quit
upon learning that they were pregnant and those who quit later in pregnancy.

Smoking during pregnancy was also assessed in the 1980 NNS (Prager et al. 1983)
(Table IO). Questionnaires were distributed to a national probability sample of married
women who had had live births in 19X0; the response rate was 56 percent. The
restriction to married women severely compromises the generalizability of results.
especially for subgroups such as blacks and youth because smoking during pregnancy~


is consistently more common among unmarried mothers (Schramm 1980; Rush and
Cassano 19x3) and nearly one-half of black infants are born to unmarried mothers
(NCHS IYXZ). The low response rate might have also affected the validity of the study,
Prayer and associates ( 19X4) asked women how many cigarettes they smoked per day
before and after they found out they were pregnant. Among all married respondents.
3 I percent smoked before pregnancy. Whites were more likely to smoke than blacks
(32 vs. 25 percent). These investigators reported a strong association of smoking with
age. with younger mothers more likely to smoke than older mothers. There were even
more pronounced gradients with education. Among women with less than a high school
education. 50 percent smoked before pregnancy, and this percentage diminished
monotonically to IS percent among women with 16 or more years of education.
Amonp the women in the study (PraLger et al. 19x3) who smoked prior to pregnancy.
IX percent quit after realizing they were pregnant. White women were somewhat more
likely to quit than black women ( IX vs. I3 percent). Mothers older than 35 years of age
were markedly less likely to quit: only 7 percent did. Again. education had a strong
association with quitting: IO percent of mothers with less than I2 years of education
quit. and the percentage increased monotonically to 33 percent among mothers with I6
or more years of education. The patterns of cessation by amount of smoking are also
of interest. Women who were smoking I to IO cigarettes per day at the time of
pregnancy recognition were far more likely to quit than women smoking I1 or more
cigarettes per dav (3 I v's. I2 percent). Among the heavier smokers. 27 percent reduced
their consumption to IO or fewer cigarettes per day even though they did not quit.
Williamson and associates ( 19x9) used data from the Behavioral Risk Factor Surveil-
lance System in 1985 and I986 to compare smoking patterns among pregnant and
nonpregnant women. Data were collected through 19.12-t telephone interviews of a
population-based sample of women in 26 States. with ascertainment of current preg-
nancy status. smohing history. and current smoking practices. Women pregnant at the
time of interview were less likely to be current smokers than nonpregnant women (3 I
vs. 30 percent). but had a similar likelihood of ever having smoked (43 vs. 35 percent).
The proportion of former smokers was thus greater among pregnant women (?1 v's;. I5
percent). largely accounting for the difference in current smoking patterns. This study,
(Williamson et al. I 0x4,) suggests that if 30 percent of women pregnant at the time of
the sutvey smoked prior to pregnancy. then 30 percent of smokers would have had to
quit after becoming pregnant to account for the reported smoking rate of 1 I percent.
Among pregnant women w.ho smoked. the mean number of cigarettes consumed per
day was I?. compared M ith 20 cigarettes per day among nonpregnant w otnen who
smohed. These data suggest that smokers who do not quit upon becoming pregnant
tend to reduce their cigarette consumption (Williamson et al. IYXYI.
Patterns ot`smohing were generally similar across demogaphic subgroups. with one
important exception. Among unmarried women. smohin, ~7 was slightly more common
in pregnant than nonpregnant women (36 vs. 3-t percent,. implying no change in
smoking among unmarried pregnant women. The absence ofpregnancy-related reduc-
tion in smoking for unmarried women was due exclusively to a markedly higher
smoking prevalence for white unmarried pregnant women. The results suggest that
data on married mothers cannot be generalized to unmarried mothers.


A number of investigators reported smohing patterns in selected populations. such as
women delivering in a particular hospital or geographic region or those receiving
prenatal care at a specific clinic.  Table I I summarizes se\,eral of these studies.
Although none are true probability samples. these studies provide an indication of the
diversity of smoking and smoking cessation among different populations. The propor-
tion quitting during pregnancy ranges from 6 to 3Y percent.

Time Trends in Smoking and Smoking Cessation

Kleinman and Kopstein ( 19X7) compared the pattern of smohing cessation during
pregnancy from the similarly designed IY67 and 1980 NNS. Although there were some
changes in the proportion of mothers vv ho were married at the time of each of the 1~ o
surveys and the characteristics of nonrespondents might have varied. the surveys
provide a unique opportunity to assess temporal trends in smoking and smohing
cessation during pregnancy. The percentage of mothers u ho smohed prior to pregnancy
decreased markedly during that period. from 55 to 30 percent for white mothers and 40
to 3 percent for black mothers. The percentage of v.hite mothers who quit after
pregnancy rose from I I to I7 percent between the two surveys. whereas the percentage
of black mothers who quit decreased from I7 to I I percent over that interval. During
the interval between the surveys. the diminution of smoking during pregnancy was more
pronounced for highly educated women. increasing the differential exposure to tobacco
by educational status (Kleinman and Kopstein 1587).

Estimates of Attributable Risk Percent

Although several measures of attributable risk are commonly used to describe the
burden of disease associated with an exposure, the most recent report of the Surgeon
General (US DHHS 1989) has focused on attributable risk percent. frequently termed
etiologic fraction, as the most relevant measure of the likely public health impact of
smoking cessation. Calculation of the attributable risk percent uses the formula as
follows:

where p is the proportion of persons with the exposure and RR is an estimate of the
relative risk of the outcome in those who are exposed compared with those unexposed.

At least three different studies (Meyer. Jonas. Tonascia 1976: McIntosh 1983:
Kramer 19X7) estimated the relative risk of several pregnancy outcomes after reviewing
the research literature. Table I2 summarizes these studies and provides estimates of
attributable risk for prevalences of smoking of 20. 30.40. and SO percent based on the
relative risk estimates from the three studies. As noted earlier. demographic subgroups
of women differ markedly in smoking prevalence. Of those women with less than a
high school education, 50 percent smoked during pregnancy: of those women with some
college education, 20 percent smoked during pregnancy (NCHS 19X8). Approximate-
ly 30 percent of married women and 30 percent of unmarried women smoked prior to


`I'AIILE 1 I.--Patterns of smoking cessation during pregnancy among selected populations



K~lclcllc~             I.~~c;lll,lll                 SOlILY             YW\     `4 Snrohing iilltially

I'jSX            43             3)            NK


I `M1 (30          I7             II            IO


I'j5X            3X             IX            YK

NK             so             NK           1-I


I97h- 70          37            4')            NK


I'JXO            22            3x            NK


I'JXO            NK            2X            NK


I'MI  x1          20            22            NK


I')X I -x2          1')             h            I `1

NK             32             I7            NK


TABLE 12.-Summary of studies that estimated relative risk of various
      pregnancy outcomes for smoking based on a "q nthesis" of
      the literature, and attributable risk percent based on several
      estimates of the pre\,alence of smoking during pregnanq

P"

Prcwrm lklI\~r!

RR         .AR'r

Ile>cr. Joru\.   031   I 2ib       1
TOn;i\LLl      0 Xl              h
l19?hl       0.10              X
          0.w             IO

Llclnlo\tl      0.3)    I.25
I IYX1l       o.io
          I).10
          0.50

Kwn1er       0.21)    NK
/19X7)       0.20
          0.10
          0.50

i        I.81

Y
I I

        2 12

I,YY"

pregnancy (NCHS 198X). The most recent estimates suggest that about 25 percent of
U.S. women smoke throughout pregnancy (NCHS 1988).

The relative risk estimates forperinatal mortality and preterm delivery are remarkably
consistent. especially considering that these authors conducted independent syntheses
of the literature. Estimates of the relative risk of low birthweight ranged from 1.81
(McIntosh 1984) to 2.42 (Kramer 1987). probably because ofdifferences in the number
of studies used to derive the estimate. For this reason. attributable risk percent for a
given prevalence of smoking is more variable for low birthweight than for perinatal
mortality and preterm delivery.

Based on data that indicate that about 25 percent of U.S. women smoke throughout
pregnancy. it can be estimated that 5 to 6 percent of perinatal deaths. 17 to 26 percent
of low birthweight births. and 7 to 10 percent of preterm deliveries could be prevented
by elimination of smoking during pregnancy. In groups with a SO-percent prevalence
of smoking. such as women with less than a high school education. approximately IO
to 1 1 percent of perinatal deaths . 29 to 42 percent of low birthweight births. and 13 to
18 percent of preterm deliveries might be prevented by elimination of smoking during
pregnancy. These contributions to adverse pregnancy outcome are sizable. and smoh-
inp is probably the most important modifiable cause of poor pregnancy outcome among
women in the United States (Kramer 1987).


Age at Natural Menopause

Introduction

The significance of menopause extends beyond marking the end of female reproduc-
tive potential. The age at which menopause occurs also may have implications for the
risks ofosteoporotic fractures. irchemic heart disease. and cancers of the reproductive
system. Thus. the effect of smoking on the age of menopause could have potentially
broad health implications.

In fact. an early natural menopause has been observed consistently among women
who smoke cigarette\. As summarized in Table 13. the major studies addressing this
topic have indicated that currently smoking women cease menstruating from I to 2
years earlier than otherwise similar nonsmokers. Expressed as relativje risk. women
ased 43 to 54 years who \mohe become menopausal at about twice the rate of never
smokers (Willett et al. IYX3: Bailey. Robinson. Ves\ey 1977: Hartz et al. 1987:
Andersen. Transbol. Christiansen 1983: Baron 1990).

Several features of the data suggest that [hi\ is a causal relationship. By using both
cohort and cross-sectional methodology with a variety of subject populations. the
results have been replicated repeatedly in studies in several areas of the United States
and Europe. Dose-response effects have generally been found. with heavy smokers
experiencing an even earlier menopause on average than light smokers. HowevJer. these
trends have not a1uay.s been assessed with formal test\ of statistical significance in the
reports describing the data. Several studie\ demonstrating thi4 association have con-
trolled for potential covlariates. That premenopausal smokers may be more lihely than
nonsmokers to have a hysterectomy does not appear to explain the relationship (Krailo
and Pike 1983).

Pathophgsiologic Framework

There are at lea\t three way\ in which cigarette smoking could lead to an early natural
menopuu\e. Experiments M ith laboratory rodents indicate that the polycyclic aromatic
hydrocarbons found in cigarette smoke may be directly, toxic to ovarian follicles
(Mattison IYXO). Mattison and colleagues found that intraperitoncal injection of
benzo(a)pyrene. .i-meth~lcholanthrene. or 7.12.dimethylbenz(a)anthtracene led to
ovarian folliculur atresia (Matti~nl and Thorgcirsson lY7X. lY7Y: Gulyas and Mattison
lY7Y). Earlier uncontrolled studic`s of prolonged exposure of mice to cigarette smohe
led to similar findings (Es\enbcrg. Fa~an. 5lalerstein IYC I ). which were also seen in a
later controlled study of rut\ rsubbarao IYKX). However. other investigator\ failed to
find ovarian atrophy in rodent\ chronically rxposcd to cigarette mohe (Haag. Larson.
Weatherby 1960: Dontenuill ct al. IY73a). and in most studies. parentersl nicotine or
tobacco extract has had minimal effect on the ovaries of experimental animals (Es\en-
berg. Fagan. Maler\tein I Y5 I : Thienes I Y60: Lar\on. Haag. Silv ette I Y6 I ; Larson and
Silvette 196X).

The other two postulated mechanims for premature menopause do not involve direct
ovarian toxicity. Cigarette smoking may interfere with IuteiniLing hormone release at


TABLE 1X-Summary of studies reporting relationship of cigarette smoking
      and age at natural menopause

Dantell t IY7X1

Lindqui\t and
Rell!It\\on t IY7Y)

Kaufmm et 21
t I YXO,

Adenu and
Gtlla~hrr t I `)X2)

Willert et al. t IYXi)

I O.YYS health
\creenrrs

McKinlay. Bifano.
McKinla) (19X.5)

E\er\on et 31. (19X6)

Hiatt and Fireman
(10X6)

Stanford et al. t 19x7 )

Brambilla and
McKinlny (19X9)

s.350 generul
populatton subject\

261 population wbjcct\

5.316 HMO health
scrrenees

I.7




I .3"





?.(I'

I P



1i.X'


1.2"



1.7'





I .o



I .4







I .7



1.I

NYS'



0.3



I .s


least in rodents exposed to parenteral nicotine or cigarette smoke (Andersson et al. 1980:
Andersson et al. 1984; Andersson et al. 1988: Eneroth et al. 1977a.b; Kanematsu and
Sawyer 1973: Blake. Norman. Sawyer 1974: Blake 1974: Blake et al. 1971a.b: McLean.
Rubel. Nikitovitch-Winer 1977). This effect appears to be due to a nicotinic effect on
neurotransmitter release. A return to a more normal function after the end of exposure
to smoke or nicotine has not been documented. but it seems likely that such a nicotinic
effect on the brain would not be permanent. Therefore. it is possible that in humans.
smoking could cause a reversible interference in the pituitary-ovarian axis, which could
lead to a cessation of menses. Several investigators found that smoking has been
associated with menstrual it-regularity earlier in reproductive life (Wood 1978; Pet-
tersson. Fries, Nillius 1973: Brown. Vessey. Stratton 19X8: Hammond 1961).

Smoking has also been associated with disturbances of estradiol metabolism. Mich-
novicz and colleagues (1986) found that premenopausal smokers tend to metabolize
estradiol through pathways producing more catechol-estrogen metabolites than non-
smokers. This change would be expected to result in a relative antiestrogenic influence
because of the lack ofestrogenic potency of the catechol-estrogens compared with the
estrogenic metabolites. such as estriol. which are produced in larger amounts in
nonsmokers. There is also evidence that nicotine may inhibit aromatase. an enzyme
important in the synthesis of estrogen\ (Barbieri. McShane. Ryan 1986: Barbieri.
Gochberg. Ryan 1986). Again. the recovery of normal enzymatic function after
cessation of smoking has not been studied. However. it is postulated that these or
similar disturbances could result in enough antagonism of estrogen effect to cause an
early cessation of menstrual cycling in women already in the perimenopausal years
(Baron. LaVecchia. Levi 1990)

Studies of Former Smokers

Former smoker\ experience menopause only slightly earlier than never smokers
(Table 13). In a study of hospitalized women. Jick. Porter. and Morrison ( 1977) found
that former smokers had a median age at menopause between that of never smokers
and that of women currently smoking half a pack of cigarettes per day. Kaufman and
coworkers ( 19X0) reported on hospitalized women aged 60 to 69 years. Data from 10
women who stopped smoking before age 35 indicated that the mean age at menopause
was 0.2 year\ earlier than in never makers. after adjustment for parity and body habitu\
(Kaufman et al. 1980). In a cross-sectional study ofwomen attending a screening clinic.
Adena and Gallagher (19X2) found ex-smokers to have a median age of natural
menopause 0.3 year\ earlier than never makers. Finally. Hiatt and Fireman (1986)
found among a group of enrollees in a prepaid health plan attending a screening clinic
that es-\moken reached menopause about 0.5 years earlier than never smokers. Thu\.
natural menopause appears to occur. at most. 6 month\ earlier in ex-smokers than in
never smokers.

Limited findings on relative risk of early menopause in former smokers are av,ailable
(Willett et al. 1983; Baron. LuVecchia. Levi 1990). From data presented hy, Lindquist
and Bengtsson ( 1979) regarding %-year-old women. it can be calculated that compared
with never smokers. former smokers had a relative ri& of early menopause of I.8


TABLE Id.-Summary of studies of age at natural menopause among former
        smokers

              Vumtxr of         COViiKiI~~
Reference          ei-rmoker\         considered            Fmdllw\

Lmdqw\t and Bengtwn
f 1071))

Kaufman et al.
I IYXO)

Adena and Gallagher
IIYX?~

Willett et al.
(10X3)

30







I 0







NR

I6.034

Age. welght.
nulliparity

Sib           None

Pan). reyon.
Quetelst'\ Index

None

Htatt and Fireman
(19861

Mean age at menopauw
wit\ 0.2 \`rarllrr among
e\-moher\ than amcmy
never vnohw

Odd\ ratto of herng
menopausal for current
\moher\ v,. never
smoker\ ua\ I. IO

Mean aFe at menopause
u3k 0.5 y earlier among
ex-\mohrr\ than among
never vnoher\

(95percent confidence interval, (CI), 1.14.7). In a prospective study of American
nurses, Willett and coworkers ( 1983) found ex-smokers to have a relative risk of early
menopause of I.1 (95percent CI, 0.98-1.23) compared with never smokers after
adjustment for age, weight, and nulliparity. In this study, those who stopped smoking
in the 2 years previously retained a modest increase in risk of early menopause
(RR=1.4); after a longer period of abstinence, there was no effect associated with
previous smoking (Willett et al. 1983).

All the investigations of smoking and menopause have relied on self-report of
menstrual status and smoking history. It is unlikely that misclassification with regard
to these features would seriously distort the findings regarding current smoking, but the
results for former smoking may be more susceptible to artifact. In particular. some of
the study participants who claimed to be former smokers might actually have continued
to smoke, or they might have quit for health reasons related to an early natural

399


menopause. Like current smokers. former smoher\ may be more likely to be passively
exposed to passive 3mohing than ne\er smokers. thus po\cihly affecting menopaui;al
age. These factors would tend to lead to an exaggeration of the apparent impact of
former smoking on menopausal age (Chapter 2). Therefore. the results summarized
above may overstate the degree to which former smoking is associated with any
disturbance in menopausal age.

It appears that age at menopause in former smokers is closer to that of never smokers
than to current smokers. and the data are consistent with a decline in the risk of early
menopause with the cessation of smoking. The effect of smoking on menopausal age
may be partly or wholly rever\ible with cessation of smoking during the premenopausal
years. However. some pertinent data are lacking. Most of the studies did not consider
how long it takes after cessation of smoking for the ri\k of early natural menopause to
decrease. Ko studies have verified that the women bho stopped smoking had a lifetime
smoking exposure similar to that of women who continued smoking.

PART IL MALE

Introduction

Cigarette smoking has been considered to be associated with impairment of male
sexual functioning. and tobacco abstinence has been recommended for men attempting
to maximize sexual performance (Larson. Haag. Silvette 1961: Sterling and Kobayajhi
1975: Ochsner I97 1a.b). An association between mokin2 and impaired sexual per-
formance among men ha\ been publicized in the lay pre\\ (Reuben 19X8). Althouph
some data pro\ ide e\ idcnce for this association. the> are inconclusix e.

Pathophysiologic Framework

Three general type\ of mechanisms habe been proposed to explain the harmful effect
of cigarette 9ilohing on wxtial performance. impotence. and sperm qualit),. First.
smoking ma! expose the te\te\ to compounds that are directI! toxic to the 5pern-
producing germinal epithelium. to earl! sperm form\. or to the hormone-producing
Leydig cell\. The effect\ on sperm rna\~ be ;I manifestation of ;I genotoxic effect of
cigarette <make constituents (Ohe and Herha 197X: DcSlarini 19x3 ).

Second. smoking C;IIIW\ atherosclerotic peripheral \ a\cular disease (Chapter 6): thi\
may translate into adiminished va\cuIar \uppl> to the genital\. a\ reflected b! the penile
brachial index (PBI) and other 1 atcular mt`a\urement\. A diminished va\cuIar \uppl>
to the genitals would compromi\c w~ual performance and spermatogenesis and hor-
mone production. Although athero\clero\i5 i\ often considered a fixed lesion. several
studie\ ha\,c \ugcsted that :ithcro\clerotic plaque\ ma! regre\\ v, ith approprlatr
lifestyle change\ (Barndt et aI. 1077: Nihhil;l 19X0: Kram~h et al. 19X I: Chapter 6).
However. no studies ha\e been conducted on the effect of \mohing cessation on
regression of atherosclerotic lesion\.



Nonatherosclerotic vascular changes may also mediate the effect of smoking on
genital function. The vasoconstrictive effects of nicotine in cigarette smohe may impair
the complicated vascular processes involved in erection (Benowitz 198X). This may
be due in part to disturbances of prostaglandin production in the vascular endothelium
or to an enhancement of platelet aggregation noted by several investigators (Nadler.
Velasco. Horton 1983; Alster et al. 1986: Taylor et al. 19X7: Lassila et al. 198X: Jeremy
et al. 1986: FitzGerald. Oates, Nowak 1 Y8X: Chapter 6).

Finally. hormonal effects of cigarette smoking could alter sexual responsiveness and
spermatogenesis. Alterations in the secretion of luteiniring hormone releahing hor-
mone (Moss, Riskind. Dudley 1979) or catecholamine\ (Patra. Sanyo]. Biswas IY79:
Klaiber and Broverman 1988) are two such possibilities. but disturbances in sex
hormones. particularly low testosterone or high estradiol. have been suggested more
often. In general. men who smoke cigarettes have similar or higher testosterone level\
than nonsmokers: thus. it is difficult to associate low testosterone with sexual dysfunc-
tion among men who smoke (Briggs 1973: Shaarawy and Mahmoud 1982: Andersen.
Semczuk. Tabor 1984; Handelsman et al. 1984: Deslypere and Vermeulen 1984;
Vermeulen and Deslypere 1985: Vogt, Heller. Borelli 1986: Barrett-Connor and Khaw
1987; Dai et al. 1988: Lichtenstein et al. 1987; Meikle et al. 19x7: Klaiber and
Broverman   1988).     The   adrenal  androgens   (i.e..   androstenedione.
dehydroepiandrosterone. and dehydroepiandrosterone sulfate) are elevated in male
smokers (Barrett-Connor. Khaw. Yen 1986; Barrett-Connor and Khaw 1987; Dai et al.
1988). Aromatization of these hormones may explain the elevated levels of estradiol
among males who currently smoke (Entrican. Mackie. Douglas 1978: Lindholm et al.
1982; Klaiber, Broverman, Dalen 1984: Barrett-Connor and Khan 1987; Lichtenstein
et al. 1987: Dai et al. 1988; Klaiber and Broverman lYX8). Elevations in circulating
estrogens may interfere with spermatogenesis and sexual behavior (Klaiber and Brover-
man 1988); such an explanation remains speculative.

Several studies have suggested that the estradiol and testosterone levels of former
smokers are comparable with those of never smokers (Deslypere and Vermeulen 1984:
Vogt, Heller, Borelli 1986; Barrett-Connor and Khaw 1987; Lichtenstein et al. 1987).
This observation implies that smoking cessation is likely to reverse any effect mediated
by disturbances of these hormones. Alternatively, former smokers may have had a
lower total dose. Androstenedione and dehydroepiandrosterone sulfate levels may be
modestly higher in former smokers compared with those of never smokers (Barrett-
Connor. Khaw, Yen 1986; Barrett-Connor and Khaw 1987: Lichtenstein et al. 1987).
However, the relevance of these findings to sexual capabilities is unlikely to be
significant. These hormones appear to have little intrinsic potency, and are important
because of their capacity for conversion to more active hormones such as testosterone
and estradiol (Baxter and Tyrrell 1987).

Sexual Activity and Performance

Surveys of the relationship between smokin p and frequency of sexual episodes
(intercourse or masturbation) have generally found smokers to be as sexually active as
nonsmokers. In two studies of elderly men. sexual activity in smokers was comparable /


with that of nonsmokers (Tjitouras. Martin, Harman IYX?: Diokno. Brown. Herzog
1990): in a cross-sectional study of younger men. no difference\ were indicated (Vogt.
Heller. Borelli lY86). Adolescent smohers are more sexually active than nonsmokers
(Russell I97 I: Malcolm and Shephard 197X ). In contrast. Cendron and Vallery-Mas-
son (IY71 ). in study,ing 70 men older than age 45. found that those who reported
smoking between ages 25 to 40 al\o reported being less sexually active at those ages
than those who denied smoking. Ovrerall. it appean that the relation between current
cigarette smoking and the level of male sexual activity is not very strong. Among
younger males. personality differences between smokers and nonsmokers may
dominate any adverse physiologic effects (Russell 197 I ).
If. as the aforementioned studies suggest, current smokers (or ever smokers) are
similar in sexual habits to never smokers, then no differences would be expected for
former smokers. Vogt, Heller. and Borelli (19X6) evaluated 239 healthy male volun-
teers aged 19 to 30 without genital abnormalities or diseases and taking no medications.
The study results indicated that the 36 former smokers among them were comparable
with both never smokers and current smokers in sexual activity (Vogt. Heller. Borelli
1986).
Impotence. the inability to maintain an erection sufficient for intercourse. has been
more extensively investigated in relation to smoking. Among treated hypertensives
aged 40 to 64. cigarette smoker3 were more likely to report impotence. although the
differences were modest and not statistically significant (Biihler et al. IYXX). A
statistically significant association was reported among men undergoing radiation
therapy for prostatic cancer (Goldstein et al. 1983). However. in both studies. poten-
tially important covariates. such as alcohol intake and age. M#ere not considered. Two
other studies of men undergoing impotence evaluation indicated a high prev*alence ot
smoking and suggested an association between smoking with impotence (Virag.
Bouilly. Frydman 1985: Condra et al. IYXh). Unfortunately. neither study included a
sexually functional control group. and both studie\ based their conclusions on ques-
tionable comparisons ot`the smohing rate in their clinic patients with that of the general
population. Vopt. Heller. and Borelli (1986) studied a group of young volunteers
vvithout selecting for impotence. These investigators found that smokers reported more
difficulties with decrea& libido and erection than nonsmokers (Vogt. Heller. Borelli
19X6). This analysis did not consider former smokers separately.
An acute effect ofsmohing on sexual performance is suggested by a study of smokers
monitored while viewing erotic films (Gilbert. Hagen. D'.Agostino IYX6). The succes-
sive smoking of 2 cigarette\ high in nicotine content significantly impaired the rate of
penile diameter change compared with that observed after smoking I cigarette or eating
candy. Hovvever. the clinical relevance ofthese oh\enation\ is unhnoan hecauke franh
impotence has not studied.
An important clinical measurement in the evaluation of impotence is the PBI. v.hich
indicates the \y stolic blood pressure in the penis div,ided by systolic blood pres\urc in
the arm. A low \,alue i\ considered to be ev idcnce of compromise of the penile blood
apply. a factor v+ hich may interfere v+ ith erection. Several \tudie\ of men undergoing
evaluation of impotence reported an association between smohing and Ioh PBI (Jacobs
et al. IYX3: Condra et al. 1986: Bornman and Du Ples\i\ lYX6: DePulma et al. IYX7).


Among impotent diabetics, evidence of nocturnal erections wJas found less in smokers
compared with nonsmokers. thus suggesting an increased risk of vascular compromise
in smokers (Takahashi and Hirata 1988). However. other studies of impotent men have
not reported differences between smokers and nonsmokers in vascular measurements
(Wabrek et al. 1983; Virag, Bouilly. Frydman 1985: Kaiser et al. 1988). Most of these
investigations did not consider covariates such as alcohol use, although one study
suggested that smoking in isolation had little effect and that an association of smoking
with an abnormal PBI may be due to the association of smohing with other arterial rish
factors (Virag. Bouilly, Frydman 1985).

In many of the studies relating smoking and impotence. the investigators did not
distinquish nonsmokers as ex-smokers or never smokers. However. two investigations
considered former smokers separately (Table 15). Wabrek and associates (1983)
studied I20 men who were referred to a hospital-based erectile dysfunction program.
The percentage of former smokers vvas approximately the same among men with
impaired, borderline. and normal PBI. Condra and colleagues ( 1986) reported on I78
patients also referred for impotence. Former smokers were not separated for analysis.
but this study suggests that the PBI for ex-smokers is more normal than in current
smokers (Condraet al. lY86). However. neither study considered important covariates.
such as age and alcohol use (Wabrek et al. 1983: Condra et al. 1986).

Two recent investigations considered the effect of smoking cessation on impotence.
Forsberg and colleagues (1979) noted that two smoking men who were impotent
improved their functioning after smoking cessation at the same time that measures of
penile blood flow improved. However. it is not clear how these two men were selected
for this study. and control subjects were lacking. Elist. Jarman. and Edson (1984)
reported on the treatment of 60 impotent men. Twenty nonsmoker\ were treated with
the vasodilator isoxsuprine. and 40 smokers were either advised to stop smoking or
advised to stop smoking and also given isoxsuprine. There was no mention of
randomization. and there was no untreated control group. Similar proportions im-
proved whether given isoxsuprine. convinced to stop smoking. or both (Elist. Jarman.
Edson 1984).

Animal data have not elucidated the relation between smoking and either sexual
activity or impotence. Soulairac and Soulairac (1972) studied the sexual activity of
male rats given either a 0.6 mg/kg or a 1.2 mg/kg dose of nicotine subcutaneously. The
sexual activity of the rats after the nicotine administration was compared with that
before treatment. Sexual activity was markedly increased with the 0.6 mg/kg dose. and
at 1.2 mg/kg there was trembling and twitching and no sexual behavior for 2 to 3 hours.
In contrast, exposure to smoke from 1 cigarette has been shown to interfere with the
physiology of erection in male dogs (Juenemann et al. 1987).

In summary, the level of sexual activity does not appear to be affected by cigarette
smoking. Cigarette smoking may be associated with impaired male sexual perfor-
mance. Among impotent men, smokers are more likely to have an underlying vascular
problem. These associations have been more commonly noted in groups already at high
risk of impotence. such as hypertensives and diabetics. However. these associations
have not been consistently observed, and the positive findings may be due to the
association of smoking with other factors such as alcohol use. Moreover. because the

303


TABLE IS.-Sexual performance among male former smokers

studies of PBI are generated entirel) in referral populations. it i\ unclear if these finding\
can be generalired. Because of limited and uncontrolled data. no conclusion\ can be
drawn regarding WYLI~I performance or PBI among former makers.

Sperm Densit- and Qualit>

Measul-ements of sperm den\it!. mr)rpholog . and motilif arc commonI>, uxd
assessmcntk of sperm qualit! (Roger\ and Ru\\ell IYX7 I. O\er 20 \tudie\ hare dealt
with the relation of cigarette \mohing to sperm den\it!,. motility. and morpholog>
(Vicxian lY6Xa: Schirren and Gt'! 1960: Cm~phcll md Harrison lY7Y: Vogel. Braver-
man. Klaiber lY7Y: Stehhun IYXO: Nebe and Schirrcn IYXO: EVXII\ t't al. I98 I: Godfre!
19X1: Roclrisuc/-Rigau. Smith. Steinherger IYXI: Shaaraw! and hlahmoud IYX2:
Buiatti et al. I YX4: Andervx. Semc/uh. Tabor I YX4: Norden\on. Xbrams\on. Ducheh
19X3: Handcl\man et al. IYX-I: Hoda\ et al. IYX5: Kulihausk. Bluustein. Ahlin IYXS:
Ablin IYXh: Rantala and Ko\himie\ lYX7: Vast. Heller. Borelli lYX6: Klaiber et al.
lYX7: Dihshit. Buch. Jlansuri lYX7: Sxrrunen et al. IYX7: Klaiberand Bro\erman IYXX:
Svaranen et al. I9XY: Rui. Oldereid. Purvi\ IYXY: klar\hburn. Sloan. Hammond IYXY:
Oldereid et al. I YXY). Table I6 `rummari/es the finding\ of those studie\ that reported
mean values for maker\ and nonsmohcrx In mo\t \tudie\. men smohing cigarette\
had lower sperm Jen\it>. although many ofthe\e \tudie\ indicated differences that \+ere
not \tati\tically riynificant. The \moher\' a\`erage sperm density uxs at lea\t X0 percent
that of the nonsmohers. In ~\cral studies sperm morphology or motility L\;LS impaired


in smokers compared with nonsmokers. but this was a less consistent findincg. Few
studies have considered the spermatic chromosomal characteristics of smokers com-
pared with nonsmokers. Nordenson. Abramsson. and Ducheh ( 1983) found smokers
to have more chromosome breaks than nonsmokers. but Oldereid and couorkers ( I YXY)
reported no difference5 in DNA condensation as assessed by flow cytometr\`.
Although differences in mean values of any of these measurements suggest an effect
of smoking. the most relevant parameter may be the percentage of smokers and
nonsmokers who exhibit deficiencies in sperm densit). morpholog\,. or motility.
Several researchers have investigated the relative risk ofa/oospermia (no sperm in the
ejaculate) or oligospermia (reduced number of sperm) in smokers versus nonsmokers
or never smokers (Table 17). Although the ranpe of relative rishs is uide. there is a
clear pattern of increased risk among smokers. However. the clinical significance ot
oligospermia is uncertain. Most studies have used one cjvculate per man. although the
within-man coefficient of variation can be a\ much a\ 60 percent (Schenker et al. 1 YXX ).
The available information suggests that current smohins is related to IOU sperm
density. However. these data are limited. Many studies investigated men visiting
infertility clinics. limiting generalization. Moreover. if male makers with poor sperm
quality are most likely to attend these clinics. selection biases may distort the results.
Also. many of these studies were relatively informal. Few of the studies accounted for
potentially confounding factors such as alcohol use and age. Less than half of the
studies documented that a period of sexual abstinence was required for subjects before
giving the sperm sample, and few of the studies anstyLed multiple semen specimens as
some authorities recommend (Zaneveld and Jeyendran 1988). Most studies have a
small number of subjects. and their statistical pouer is limited for this reason. In come
of the studies. it is not clear whether former smokers u'ere included in the smoker or
nonsmoker group.
A few studies investigated ex-smokers (Table IX). One M;IS a case-control stud!, of
male infertility in Italy (Buiatti et al. 1984). The cases were a/.oospermic or oiigosper-
mic men being treated for infertility at the University of Florence. Controls were
University outpatients who had normal sperm counts.  There were no significant
differences between smoking categories in the percentage of men with Iov. sperm
counts.  Vogt. Heller. and Borelli (1986) e\,aluated 139 male volunteers. Among
former smokers (those who had smoked for at least I year and those who had stopped
smoking for at least 1 year). percent normal spermatozoa. percent young forms. percent
old forms. and percent degenerate forms were comparable with those of never smokers.
Stekhun ( 1980) reported that 42 percent of former smokers had oligospermia compared
with I8 percent of never smokers. Schirren and Gel ( 1969) reported that three men
with low sperm density and motility showed substantial increases in these parameters
3 to 6 months after smoking cessation. However. there w'erc no control\ defined in this
analysis. Because of the limitations of the four studies. no conclusions are possible
regarding the effects of smoking cessation on sperm quality in humans.
Animal studies have not been particularly informative. In some studies. rodent\ that
were heavily exposed to nicotine or cigarette smoke demonstrated testicular atroph!,.
but this has not been a general finding (Larson. Haag. Silvette I96 I ; Larson and Silycttc
IY6X: Dontenuill et al. lY73b: Essenbq. Fagan. Maler\tein lY.5 I: Thienes IYhO:


TABLE 16.-Sperm quality among smokers and nonsmokers

Vtcfian
I IYhXa,

Vogel. Broverman.
Klather
I IY7YI

Nebe and Schlrren
I 19x0)

Evatx er al
(1981)

Spira et 31.
(I')XI)

Rodrtguw-Rteau.
Smith. Stetnkryzr
(19x7)

Andrr\ett. Semcuh
Tahor ( I 0X-l I

Handel\man
et 31. (IYXI)

Kulihaukt\.
Blaustem.
Ahlin i 1985)

Rantala and
Kokimie\
(10X7)

Vogt. Heller. Borellt

lnlerttltt! clmtc
(71175 1

Volttntwr~
1 `O/2 I

Inferttltt\ cltmc (Xhili7,

Semen donor\ (7 I12 3 /

Frrttltt) clmic (1351107,

Volunteer\

0.x7







O.ho"




I .Ol









(1.75"



0.X6



O.Y5





O.Y3



O.YY





0 67



0.43"





(I.40




0.x IJ

1).40








lS







O.Y7"







0.Y-t





O.YJ



0.') I"



I (WI




0 h4"



I .07





0 YX



I .ot)





0.0x





I .Ol

I) 77







0.x7"

O.Y.7~'



O.Y)i



I .(Hl




O.h7"



LOX




0.03"



0.7x"





O.Y5





0,YY

Smohrr\ and
non\moLrr~
marched on qxm
den\tl)

OItgoqwrmtc* men
omttted
(<I x IOh/mLI

Ol~foqxrtt~~c~ men
umttted (<I x
I Oh/"lL 1

(1986)         152/l%))

406


TABLE 16.-Continued

Reference

Study population      Ratto of mea\ure among

   (number of     \moker\ to that among non\moher\

non\moker4numhrrof   Sperm   "4 Normal  `4 Motile
    smoker\ I      denwy    sperm    sperm      Comment\

Saaranrn
et al. (IYX7)

Klaiher et al
t lYX7)

Dth\hit. Buch.    lnfertllltj clinic
Man\urI ( I YX7,    t2XXi7lY)

Klaiber and
Broverman ( IYXX)

Saarllnen Cl al.
i 1 YXY)

Volunteers
I'll",
- --


Semen donor\
and fertile men (32/2X I

Mar\hhum. Sloan.
Hammond ( IYXY)

Infenilityclintc
12Y41152,

Rul. Oldereid.
Pur\l\(lYXY)

Infertilq clm~c
( 2031 I47 1

infertillt? clime
(61131 I

InfertIlity clmx
( I I O/.54)

Patd volunteer\ iYO/hOb

Male\ from mterttle
couple\ t4W I,

0.x I



0.77"



0.5?



O.Yh



l1.U



0.x.3



O.YZ



1.17



I.13

I .oU



O.YX



0 Y-I



O.Y4



I 02



0 4



O.YY



I .os



I Oh

0.97



O.XY"

o.xo'l

I 01

0 Y?

I .Ol

0.Y-l

O.Y)h

I.12

Thompson et al. lY73: Patra. Sanyal. Bi\uah 1979: Bi\L\a and Patra 19x1 ). Some
5tudk have noted a disturbance of spermatogrnr~is. ;I decrea\t` in the interstitium. or
a dectruction of the seminiferous epithelium (Lar~n. Haag. Silvette 1961: Larson and
Silvette 1%X: Es\enberg. Fagan. Malerstein lY.5 I : VicAan IY6Xb: Wyrobrch and
Bruce 1975: Bihwas and Patra 19x1: Alwuchi et al. lYX6: El-Salad t`t al. 19x7). The
result> may depend on the duration and dose ofexpo~re. a\ well :I\ on the age\ at u hich
exposure take\ place. Morco\,er. the relevance to humal> of the large don\ yi\cn to
the animals k uncc`rtain. None ofthehe investigation\ considcrcd \pt'rmatogenc\is at'ter
exposure ended: thu4. feu conclusion\ may he draun rt,`
                         ~vrding the t'i'fcct of ct's\ation
ofcspo~re even within the limitation\ of lhe animal \Iuclie\.


TABLE 17.~-Estimated relative risk of azoospermia or oligospermia among
       smokers versus nonsmokers or never smokers

Reference

Study population
  tnumher of
  non\moher\,
number of \moher\)

Contra\t

Estimated
relattve rthk tn
\moher\

Comments

Schirren and Ge)  Andrology clmlc
(IYhYl        lsxo/ll77l

Campbell and    Fertility clmic
Harrlwn t I Y7Y I   (I 19/13-i,


Stehhun       Uot stated (?3/1051
I IYXII)

Rodrtg~r/-Rtyu. Frrtilitk cllnlc
Smith. Stetnherger t 101/5X1

I lYX21

Buwtl et 31.     Fertillt\ cltmc
(14X-I)     ,xo;l.G~

Andrr\en.
Srmc/uh.
T`lhor~ IYX1,

,Ahiln 1 IQXh)

l'og. Heller.
B~Wlll (14X6)

FenlIlt> clonic
lX61l-l7)

uot \tatwi
1 I .7S/`2iX,


Volunteer\
1.53150,

A/oo\permta:
\moher\ v\. nonhmohrrs

Oligoywmia: \mohen
\ `1. non\mohers

Ollgo\permta: current
\mohrr\ ~5. nexer
\mokrr\

OItgo\permta:
I<20 x IOh/mLI:
current smokers VI.
non\mohrr\

Oligoyxrmta
(<?O x IOh/mL):
\mohrr\ ~5.
non\moker\

.A/oo\permta: current
\moher\ x \. nonvnokerx

ollgo\permla
(<JO x IO'/mL):
\moher\ v\ non\mohrr\

Ollao\permiu (<I x
IO'jmLj: current
\moher\ \ 5. nr\cr
rmoher\

.A~ooqxrni~a:
current \mohcr\ \ \.
nt3zr \mohrr\

I .17

I.'


I .h'l

Oligoywmia not
defined
Aroospermic men
omitted

3.2"

Oligoyxrmia not
defined

0.`)






I .o






co,'




2.Yd

I.?






77


TABLE 17.-Continued

Reference

Study population
  tnumber of
non\moLer\l
number of smoker\)

Contra5r

Ewmated
rrlatlvr rt\k in
smohers

Klaiber et al.
lIYX7)
(continued)

Fertility clime    Oligo\permia I<20 x       I .5
without varicocele  10h/mL): current
(35/30)          \moher\ v\. neber
             \moher5

Dthshit. Buch.   Fertility clinic    Olleo\pernlla (GO *       I.2
Manwrt (1987)   (2lY/?XX)     IO5mL,: current
                         \moker\ v\. never
                         smoher\
                  .A/oo\pertnia: current       I I
                         moherh Y\. neker
                         hmohrr\

TABLE l&-Sperm quality among former smokers

Reference     Study population

Findings

Comment\

Schtrren and Gey  Andrology      Smoking cessation improved sperm      No control
(1069)       patients       density and motility in 3 smokers
Stekhun (1980)    Not stated       Former smokers had RR of 2.3 for     Oligo\permia not
                   oligospermia                  defined

Buiatti et al.     Male partners of    No difference between current, former.
( 1984)       infertile couples    and never smoker\ in prevalence of
                    azoo-/oligospermia
Vogt. Heller.    Healthy volunteers   No difference between current. former.    No consrderation
Borelli ( 1986)              and never smokers In rperm          of covariate\
                    morphology

NOTE: RR=relatwe ri\h


CONCLUSIONS

I. Women who stop smoking before becoming pregnant have infants of the same
birthweight as those born to never smokers.

2. Pregnant smokers who stop smoking at any time up to the 30th week of gestation
have infants with higher birthweight than do women who smoke throughout
pregnancy. Quitting in the first .? to 3 months of pregnancy and abstaining
throughout the remainder of pregnancy protect the fetus from the adverse effects of
smoking on birthweight.

3. Evidence from two intervention trials suggests that reducing daily cigarette con-
sumption without quitting has little or no benefit for birthweight.
4. Recent estimates of the prevalence of smoking during pregnancy. combined with an
estimate ofthe relative risk of low birthweight outcome in smokers, suggest that I7
to 26 percent of low birthweight births could be prevented by eliminating smoking
during pregnancy: in groups with a high prevalence of smoking (e.g.. women with
less than a high school education) ,29 to 31 percent of low birthweight births might
be prevjented by elimination of cigarette smoking during pregnancy.
5. Approximately 30 percent of women who are cigarette smokers quit after recogni-
tion of pregnancy. with greater proportions quitting among married women and
especially among women with higher levels of educational attainment.
6. Smoking causes women to have natural menopause I to 7 years early. Former
smokers have an age at natural menopause similar to that of nev'er smokers.

II0


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        CHAPTER 9
SMOKING, SMOKING CESSATION, AND
OTHER NONMALIGNANT DISEASES



CONTENTS

Part 1. Peptic Ulcer Disease. .............................. .I
Introduction  ............................................
Impact of Smoking and Smoking Cessation on Ulcer Occurrence . .
  Smoking and Gastrointestinal Physiology ...................
  Trends in Peptic Ulcer Disease  ...........................
  Morbidity From Peptic Ulcers  ...........................
  Mortality From Peptic Ulcers  ............................
Effects of Smoking on Ulcer Healing and Recurrence  ...........
  Healing of Duodenal Ulcers  .............................
  RecurrenceofDuodenalUlcers ...........................
  Healing of Gastric Ulcers  ...............................
  Recurrence of Gastric Ulcers .............................
Summary ...............................................
Part II. Osteoporosis and Skin Wrinkling .................... .~I.
Osteoporosis.. ..........................................
  Introduction  ..........................................
  Pathophysiologic Framework  ............................
  Bone Mineral Content in Smokers Compared With Nonsmokers
  Smoking as a Risk Factor for Osteoporotic Fractures ..........
  Smoking Cessation and Osteoporosis and Fracture  ...........
  Summary  ............................................
SkinWrinkling.. ........................................
  Introduction  ..........................................
  Pathophysiologic Framework  ............................
  Smoking and Skin Wrinkling  ............................
  Smoking Cessation and Skin Wrinkling  ....................
  Summary  ............................................

Conclusions  ..............................................

References  ...............................................

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327


PART I. PEPTIC ULCER DISEASE

Introduction

Numerous studies have demonstrated the association between smoking and the
occurrence of peptic ulcer disease. This association was noted in the 1964. 197 I. and
1972 Surgeon General's Reports (US PHS 1964: US DHEW I97 I. 1972). The 1979
Report stated that the evidence of an association between cigarette smoking and peptic
ulcer was strong enough to suggest a causal relationship (US DHEW 1979). That
Report concluded that cigarette smoking was associated with the incidence of peptic
ulcer disease and with increased risk of dying from peptic ulcer disease: the evidence
that smoking retards healing of peptic ulcers was regarded as highly suggestive. The
1989 Report (US DHHS 1989) stated that smoking cessation may reduce peptic ulcer
incidence and is an important component of peptic ulcer treatment. even with the
effective drug therapy presently available. This Section focuses on smoking cessation
and the occurrence and course of peptic ulcer disease.

Impact of Smoking and Smoking Cessation on Ulcer Occurrence

Smoking and Gastrointestinal Physiology

Kikendall. Evaul, and Johnson (1984) reviewed the effect of cigarette smoking on
aspects of gastrointestinal physiology relevant to peptic ulcer disease. The literature
available at the time of their review supported the following concepts. Chronic cigarette
smokers have higher maximal acid output than nonsmokers. Smoking I cigarette or
more has no consistent immediate effect on acid secretion.  Smoking 1 cigarette
immediately decreases alkaline pancreatic secretion and immediately results in a
pronounced fall in duodenal bulb pH, especially in subjects with gastric acid hyper-
secretion. Smoking has a variable effect on gastric emptying, depending on experimen-
tal design. Smoking increases duodenogastric reflux.  Smoking decreases gastric
mucosal blood flow. Smoking during waking hours inhibits the antisecretory effects
of a nocturnal dose of cimetidine, ranitidine. or poldine.

Subsequent to this review, the two latter concepts have been seriously challenged.
Robert, Leung. and Guth ( 1986) found that neither nicotine nor smoking inhibited basal
gastric mucosal blood flow in rats.  Several investigators could not confirm that
smoking antagonized the antisecretory effect of cimetidine or ranitidine (Deakin.
Ramage, Williams 1988: Bianchi Porro et al. 1983: Bauerfeind et al. 1987).

However, several of the findings from this earlier review (Kikendall, Evaul, Johnson
1984) have been confirmed by more recent reports.  Parente and associates (1985)
confirmed higher pentagastrin-stimulated acid secretion among chronic heavy smokers
than among nonsmokers. Smokers also had higher basal serum pepsinogen-I levels.
These differences were statistically significant and large enough to be of clinical
importance. Higher maximal gastric acid secretory rates among smokers compared


v. ith non\mohers were al\o demonstrated by Whitfield and Hobsley ( 19X5) in a study
of 201 patient\ M ith duodenal ulcer.

Additionall). Mueller-Lissner ( 1986) noted that chronic smokers M.ho abstained from
smohing for I2 hours had more duodenopastric bile retlux than nonsmoher\ and
confirmed that smoking cigarettes acutely augments the already elevated rate of bile
reflux. Quimby and coworkers (1986) reported that active smoking transiently
decreased gastric mucosal prostaglandin synthesis.

In summary. the known effects of smoking on gastroduodenal physiology provide
multiple potential mechanisms for enhancement of an ulcerdiathesis by active smoking.
Several of the effects of smoking, most notably the inhibition of alkaline pancreatic
secretion. the reduction of duodenal bulb pH, and the reduction of prostaglandin
synthesis. are transient effects that could be reversed quickly by abstinence from
smoking.

Trends in Peptic Ulcer Disease

During the past several decades. the rates of hospitalization for and mortality from
peptic ulcer disease in the United States have declined dramatically (Kurataet al. 19X3).
Although changes in coding practices and/ordiagnostic procedures could explain some
of the decline, the trends in mortality from peptic ulcer have paralleled the decreasing
prevalence of smoking. Kurata and coworkers (1986) studied trends in ulcer mortality
and smoking in the United States between 1920 and 1980 and estimated that the portion
of duodenal-ulcer-related mortality attributable to smoking was between 33 and 63
percent for men and 25 and 50 percent for women. In contrast, Sonnenberg ( 1986)
concluded that smoking was not the main determinant of the birth cohort phenomenon
of declining peptic ulcer mortality in the United Kingdom. This study descriptively
compared the death rates for duodenal and gastric ulcer with the annual cigarette
consumption in the United Kingdom according to birth cohorts and found a lack of
correlation between ulcer mortality and cigarette consumption (Sonnenberg 1986).
Thu\, factors in addition to cigarette smoking may also underlie the recent trends in
these indicators of peptic ulcer disease.

Two factors that have receivedconsiderable attention in recent years are Hc~lic~ohtrc~tcr~
py/orV gastritis (Graham 1989) and the use of nonsteroidal anti-inflammatory drugs
(Griffin. Ray. Schaffner 1988). Martin and associates ( 1989). in an endoscopic stud).
found that smoking was a risk factor for peptic ulcer disease among patient\ who had
Hc~lic~ohut~er plori gastritis. Willoughby and colleagues ( 1986) found that smoking
Was associated wnith peptic ulcer disease among subjects with rheumatoid arthritis. most
of whom were taking nonsteroidal anti-inflammatory drugs. Ehsanullah and colleagues
( 1988) and Yeomans and associates ( 1988) also showed an association of smoking with
the acute gastric erosions and submucosal hemorrhages induced by these drugs. The\e
studies demonstrated that smoking is associated with ulcer disease related to both
Helic~ohut~fer./~~/or.i and nonsteroidal anti-inflammatory drugs.

430


Morbidity From Peptic Ulcers

In an analysis of prospective cohort data on ulcer incidence in women from the
National Health and Nutrition Examination Survey 1 Epidemiologic Follouup Study.
the relative risk for developing peptic ulcer was I.3 amon? former smoherc (Y5-percent
confidence interval (Cl). 0.7-3.`)) and I.9 among current smoher\ (c)5-percent Cl.
1.2-2.6) compared with lifetime nonsmokers (Anda et al. 1990). In this study. former
smokers were defined as persons who had smoked at least IO0 cigarettes in their lifetime
but who were not smohing at the time of the baseline interview. The mean length of
followup in this cohort was Y years. This analysis used the Cox proportional haLards
model to adjust for the potential confoundin effects of age. sex. socioeconomic status.
regular aspirin use. alcohol intake. and coffee consumption.

Ainley and associates (19X6) surveyed the smoking behavior of I.217 patients
undergoing endoscopy. This study did not include "normal" or community controls as
all patients had indications for endoscopy. Of the smokers. I I.Y percent had gastric
ulcers. a diagnosis shared by 7.7 percent of ex-smohers (p<O.O25) and 4.6 percent of
never smokers (p<O.(X) I ). Of the smokers. 12.X percent had duodenal ulcer compared
with 6.X percent of ex-smoker\ (p<O.Ol ) and 6. I percent of never smohers (p<O.OOI ).

In a study of nearly 6.000 Japanese men living in Hawaii (Stemmermann et al. IYXY).
243 developed gastric ulcers and 99 developed duodenal ulcers in 20 years of followup.
Gastric ulcer developed amon g 6.7 percent of current smoker\ compared with 3.X
percent of former smokers and 3.2 percent of lifetime nonsmokers (p<O.OOOl).
Duodenal ulcer developed more often (p<O.OOOl ) among current smokers than among
former smokers or never smokers (2.7 vs. 1.4 vs. 0.9 percent. respectively).

These three studies show that smokers are more likely than never smokers and former
smokers to develop peptic ulcer disease. Two of the studies show higher frequencies
among smokers for both duodenal and gastric ulcer. All three studies demonstrate that
the risk of peptic ulcer for former smokers is between that for current smokers and for
never smokers. The tendency of symptomatic smokers to stop smoking would bias the
results of such studies toward reducing the apparent benefit of cessation (Chapter 2).
These studies strongly suggest that the smoker's risk of developing either gastric or
duodenal ulcer is diminished after smoking cessation.

In an early analysis of cross-sectional survey data among men aged 20 to 79 in
Tecumseh. MI (Higgins and Kjelsberg 1967). the age-adjusted prevalences of self-
reported peptic ulcer among nonsmokers (presumably never smokers), ex-smokers. and
current smokers were 5.2, X.0, and 7. I percent. respectively. The definitions of smoking
status were not presented, and the differences were not statistically significant. In this
study. the prevalences of peptic ulcer among women who were nonsmokers. ex-
smokers. or current smokers were I .4. I .5. and 2.X percent. respectively: these differen-
ces were reported as statistically significant between smokers and nonsmokers (Higgins
and Kjelsberg 1967). Earlier studies such as this. which were conducted before the
advent of endoscopy. had relatively poor diagnostic accuracy and may consequently
have been biased toward underestimating the effects of smoking.

Additional reports linked smoking to some of the complications of peptic ulcer
disease. For example. X6 percent of 12X patients pre\enting with perforated duodenal


ulcer were cigarette smokers compared with 5 I percent (p<O.Ol ) of retrospectively
matched controls (Smedley et al. 1988). Other reports noted that smokers comprised
87 percent (Heuman. Larsson, Norrby 1983) and 86 percent (Hodnett et al. 1989) of
patients with perforated duodenal ulcers and X3 percent of males undergoing surgery
for peptic ulcer (Ross et al. 1982). These latter studies were uncontrolled, and the high
percentages of smokers have not been confirmed in some other surgical series. Never-
theless, these latter studies support the findings of Smedley and associates (1988) and
suggest that smokers with peptic ulcer who continue to smoke may be at greater risk
for ulcer complications than nonsmokers.

Mortality From Peptic Ulcers

The American Cancer Society Cancer Prevention Study I (ACS CPS-I) found that
the relative risk of mortality for peptic ulcer among men was 3. I for current smokers
(95-percent Cl. 2.2-4.2) and 1.5 for former smokers (95-percent CI, I .O-2.3)compared
with lifetime nonsmokers (US DHHS 1989).

In the U.S. Veterans Study, the duodenal ulcer morfality ratios for current and
ex-smokers compared with never smokers were 3.2 and 1.8, respectively (Kahn 1966).
Ex-smokers in this report were persons who stopped smoking for reasons other than
physician's orders but were otherwise not clearly defined. The mortality ratios for
gastric ulcer among current and ex-smokers were 4. I and 3.4. respectively. Although
these differences in mortality were not statistically significant. the trends were similar
to those in ACS CPS-I and supported the results of that study.

Effects of Smoking on Ulcer Healing and Recurrence

Healing of Duodenal Ulcers

Numerous trials evaluating ulcer therapy have suggested that smoking adversely
affects ulcer healing. Kikendall, Evaul, and Johnson ( 1984) reviewed the results of IX
studies that assessed the impact of smoking on healing of duodenal ulcers. In most of
these studies. the percentage of healed ulcers was lower among current smokers than
among nonsmokers (Table I ). These studies were not explicitly designed to study
smoking. and the nonsmoking category presumably included never as well as former
smokers. When the data from these studies were subjected to meta-analysis, the
percentage of healed ulcers was lower among smokers than among nonsmokers in
patients treated with Hz-blockers (p<O.OOOl) and in patients given placebo (p<O.OOOl)
(Table 2). The median difference in percentage of subjects completely healed was 22
percentage points in favor of nonsmokers in groups treated with Hz-blockers, 21.5
percentage points in groups receiving other active therapy, and 22 percentage points in
groups receiving placebo. The data for groups receiving active therapy other than
Hz-blockers were not subjected to statistical analysis because the data were not
homogeneous, but the data in Table I show that nonsmokers in most of these other
treatment groups fared better than their smoking peers. Most trials published since this

432


1984 review show similar trends toward greater likelihood of healing of duodenal ulcers
in nonsmokers.

Recently, several reports have suggested that sucralfate (Lam et al. 1987) and
misoprostol (Lam et al. 1986) may have particular value in treating duodenal ulcers
among patients who smoke. Lam (1989) has compiled a list of six studies showing
comparable duodenal ulcer healing rates for smokers and nonsmokers treated with
sucralfate. Although a few studies offer contrary data (Van Deventer. Schneidman,
Walsh 1985; Martin 1989). much of the evidence suggests that sucralfate heals
duodenal ulcers in smokers and nonsmokers at comparable rates.

The claim that the efficacy of prostaglandins for duodenal ulcer healing is unaffected
by smoking is based on the results of a single study (Lam et al. 1986). The design of
this study is unusual because patients who smoked were encouraged to abstain from
smoking during the study; therefore. healing efficacy in smokers may have been due to
the combined effects of misoprostol and smoking cessation. Other duodenal ulcer
treatment trials (Bianchi Porro and Parente 1988: Brand et al. 1985; Nicholson 1985)
showed improved healing among nonsmokers. Nicholson ( 1985) treated duodenal
ulcer patients with 200 1-18 misoprostol4 times daily and documented healing in 73 of
138 smokers (53 percent) and 66 of 93 nonsmokers (71 percent, p<O.Ol). Thus, the
evidence is tenuous at best that oral prostaglandins can overcome the adverse effects
of smoking on the healing of duodenal ulcers.

Other recently reported clinical trials are not systematically reviewed in this Chapter.
Most of the recent trials that have analyzed the effects of smoking on duodenal ulcer
healing show lower healing rates among smokers than among nonsmokers.

In contrast to the numerous comparisons of duodenal ulcer healing rates among
smokers and nonsmokers, only one study has examined specifically the effect of
smoking cessation on duodenal ulcer healing (Hull and Beale 1985). In this study, 70
male smokers with duodenal ulcers were advised to stop smoking and were treated with
cimetidine for 3 months. Those who stopped were no more likely than those who
continued smoking to have healed their ulcers on endoscopic exam at 3 months (75 vs.
8 I percent, respectively, not significant).  Cimetidine treatment was then stopped.
Three months later. 72 percent of those who quit smoking and 39 percent of smokers
were ulcer-free at repeat endoscopy (p<O.OS) (Hull and Beale 1985). Although these
results require confirmation, the findings suggest either that some of the adverse effects
of smoking on duodenal ulcer disease may persist for a few weeks after cessation of
smoking or that cimetidine therapy may mitigate these effects.

Recurrence of Duodenal Ulcers

A number of prospective clinical trials of maintenance therapy for duodenal ulcer
have assessed the impact of smoking on ulcer recurrence. In one of the larger trials
(Sontag et al. 1984). 370 subjects with previously documented duodenal ulcer. who had
no active ulcer at enrollment endoscopy. were randomized to placebo or cimetidine.
Endoscopy was repeated at 6 and I2 months or whenever dyspepsia occurred during
the I2 months of follow up. In the placebo group. smokers were more likely than
nonsmokers to experience recurrence (72 vs. 21 percent. p<O.OOI ). In addition.


TABLE l.-Percentage of healed duodenal ulcers among smoking and nonsmoking patients

Patient5 with henled ulcers

Reference               Drug

Duration of Rx
  (Wh)

Exclu\ivrly Hdkcker therapy

Bianchi Porro et al. ( IYX I )
Korman et al. ( IYX3)
Korman. Hanky et al. ( 19X'-)
Hrtxl et id. ( lY7X)
Korman et al. ( 19X I )
Marks et al. ( IYXO)
Bardhan ct al. ( 1Y7Y)
Guglcret A. (19X2)
Gugler et al. ( IYX?)
Korman, Hetlel et aI. (IYX2)
Korman, llrt/el ct al. ( IYXZ)

H:-hIocher\
H:-hlochcr\
R:untdmt2

CmvAline

Cimetdine

Cimetdine
Cimetidine

Cimetidine

Oxmctidine

Oxmettdine

Ctmrtidme

4

4-b

4

h

h

6

4

X

X

4

4

76      66

71      62

13     h3,

43      Xh

IO      50

I Y      7x

94      h.5

33      b4

35      71

27      70

2x      6X

3h      X6

h4      YS

12     IO0

43      x0

I.5     loo

IO      ho

30      hS

lb      94

14      Y3

IS      x7

I3      Y2

40.5

4.0 I

4.05

NS

<o.os

NS

NS

<o.os

NS

NS

<o.os


TABLE I.-Continued

Patients with healed ulcers

Reference               Drug

Duration of Rx
  (W

  Smokers         Nonsmokers                Difference in
N"    sh       N"    P/rh      p-value     % healed

Active therapy other than Hz-blockers

Bianchi Porro et al. (19X0)
Sonnenherg et al. ( IYX I)


Barbara et al. ( lY79)
Vantrappen et al. (lYX2)
Peterwn et ill. (1977)
Korman et al. ( I YX I )
Marks et al. (1980)
Nagy (lY7X)
Young and St. John (IYXZ)
Lametal.(lY70)
Lam et al. (lY7Y)

Mu\wrrut and Eisrnmann

(IYUI)

Cimetidine or pirenzepine
Cimetidine, pirenzepine. ot
placebo
Pirenzepine
Arbaprostil
Antacid

Antacid

Sucralfate

Carbenoxolone

Carbenoxolone
Antacid + sulpiride
Placebo or sulpiride
Antacid

4

4

63      71         27      XI

66      54        68      73

I6      69        28     43

68     65         I4      79

28      7s         x      xx

I3      39        I2      67

20      90         Y      67

II      55         10      x0

I4      so         6      x3

I7      59        s4      YI

I5      27        3s      51

56      4x        24      7.5

NS         IO

<o.os         I9

NS        -26

NS        I4

NS        I3

<o.os        2x

NS        -23

NS        25

NS        33

`co.05        32

NS        24

<o.os        27


TABLE L-Continued

Krference


Placebo therapy

Drug

Duration of Rx
  (wk)

     Patients with healed ulcer\

  Smokers          Nonsmoker5                Diftct-encc in
N"    c/rh       N"    Qh      p-value      % healed

Bianchi Porro ct al. (10X0)
Nqy (lY7X)
Young and St. John t 19x7)
Ha/cl et al. (11)7X)
Peterson et al. (1977)
Vantrapprn et al. (IYX2)
Barham et al. ( lY7Y)
Korman. Han&y c't nl. ( IYX2)
Bianchi Porro et al. ( IYX I)
Bardhan ct al. ( IY7Y)

Plawbo

Placrho

Pl;&w

Pl;UTbo

PIXLAX~

Placeho

Placebo

Placebo

Placebo

PlLIcebo

5s      31

II      2.7

IS      20

42      37

2s      32

6S      2x

2.5      2x

I4       0

62      24

33      24

IS      53

I I      30

5      40

42      42

I3      6Y

26      65

I 0      so

II      36

20      so

I3      3x

NS

NS

NS

NS

<o.os

<o.os

NS

4.05

4.0 I

NS

27

5

`0

5

37

37

22

Xl

76

II


TABLE 2.-Results of statistical analysis of pooled data from Table 1

Percentage healed

Smokers          Nonsmoker\

N"    Qb       N"    ?ch

Test
\tatlitic
Z    p-value

All patient groups
Hz-blockers
Placebo

Subset of large patient groups
H?-blockers
Placebo

449      70        27x      90     7. I     <o.oao I
341      2x         I66      JY     4.6     <o.ooo I



284      70        IX3      XY     5,s     <O.orwl
I49      29         8X      51      3.4     <o.oo I 2

"N=tml followed m \mokmg categor)
h%=percenrage of total who experienced healed ulcer\ -1thm qeclfwd t!mr
SOLRCE:  Kikendall. Evaul. Johnwn llYX11

smokers receiving cimetidine were as likely to experience recurrence as nonsmokers
receiving placebo, leading the authors to conclude that for smokers, quitting smoking
may be more important in the prevention of ulcer recurrence than receiving cimetidine
treatment (Sontag et al. 1984). Table 3 displays the results of similar prospective,
controlled trials of the recurrence of duodenal ulcer identified in a literature search
performed in March 1990. Trials or treatment groups with fewer than 12 smokers or
I2 nonsmokers and reports that did not provide the raw data relative to smoking were
omitted. Smokers had more recurrences than nonsmokers in every trial or every
treatment group, regardless of the treatment (even surgery) and prophylactic therapy
used to achieve healing. The difference was statistically significant in about half of the
studies.

The only study of larger size that failed to show even a nonsignificant advantage for
nonsmokers was an Australian community-based study, not included in Table 3 because
the requisite raw data were not published (Nasiry et al. 1987). This study differed from
most of those listed in Table 3 in several ways, including larger numbers of exclusions.
4l-percent withdrawals, primary reliance on symptoms rather than endoscopy to
document recurrences, and lack of systematic effort to control the use of medications
that may affect ulcer recurrence. Factors such as these may explain the disparate results.

One trial listed in Table 3 found that incremental increases of cigarette consumption
were significantly associated with greater risk of duodenal ulcer recurrence (Korman
et al. 1983). Massarrat. Mtiller, and Schmitz-Moormann (1988) and Piper, McIntosh
and Hudson (1985) also found that the number of cigarettes smoked per day was a
significant predictor for ulcer recurrence. Although these studies were designed to
assess risk factors for recurrence of duodenal ulcer. the latter two studies are not listed
in Table 3 because one did not present the necessary raw data (Massarrat. Miiller.
Schmitz-Moormann 1988) and the other (Piper. McIntosh. Hudson 1985) had a study,
design that differed from that of the studies listed in Table 3.


TABLE 3.-Recurrences of duodenal ulcer in smokers and nonsmokers in clinical trials

Reference                Prophylaxlh

Followup
(ml

Smokers               Nonsmoker\

N'     sh         N"     Qh        p-~"IUC

Sontag et al. ( 19X4)
Bianchi Porro et al. (19X2)
Lauritsen et al. (10x7)
Gihinski et al. (19X4)
Cerulli et al. (IYX7)
Brunner ( I YXX)
Lauritsrn et al. (19x7)
Sonnenherg et al. ( 19X I )
Battaglia et al. (19X4)
Paakkonen et al. (IYXY)
Bynum and Koch (19x9)
Cla\\en et al. ( I YX3)
Graffner and Lindell ( IYXX)
Rydninp et al. ( IYXZ)
Sontng et al. (19x4)
Balm et al. (lYX7)
Marks et al. ( I YX9)
Paahkonrn el al. (IYXY)
Bynum and Koch (IYXY)
Classen et al. (IYX3)
Cerulli et al. (IYX7)

Cimetidine

Cimetidine

Ranitidine

Ranitidine

Nwatidine

Roxatidine acetate
Enprostil
Various

Various

Sucralfate

Sucralfate

Sucralfate
Parietal cell vagotomy
Diet

Placeho

Placebo

Placebo

Placebo

Placebo

Placebo

Plncebo

I2

I2

I2

I2

6

I2

12

I2

I2

4

6

60-16X

6

I2

I2

I2

I2

6

IX6

6h

4x

62

I.39

4x

.s2

33

46

I3

5X

27

I YO

5s

3Y

13

21

I6

so

30

I46

34

s9

33

4.5

I7

4x

6.5

52

30

69

45

2s

24

69

72

X.5

95

XX

XI

62

37

I I4      IX           <o.o I

40      42           NS'

21      19            NS

I23      II          <o.oos

11x      4           0.00 I

41      20           <o.o I

I4      so            NS

33      33            NS

24      ?I             NS

IO      47            NS

64      3Y             NS

51      IX             NS

I I6       7           <o.o I

IX      39           40s

31      21           4l.00 I

I3      77            NS

I2      67           <o.os

24      67            NS

67      so           40 I

4.5      41             NS

I IO      2s            0.05


TABLE 3.--Continued

Recurrences

Reference               Prophylaxi\

tl;dlcrhoch et al. (IYX7t"           None
Kornlan et al. ( I OX.?)             None
I~alll Cl al. ( 10x7 I               None
I.cc. Samloll. Hardman ( IYXS)        None

KocI/ and Hallct ( IYXY)           None

Followup
(mu)


  I2

  I1

  24

  4

  I2

Smohcr5              Nonsmoker\

N'l     `/h         N"     vh       p-value


III       x0          I47      5x          4.00I

4s       X-l           60      53           <o.o I

h(l      IW          17x     14'          <o.os

5x      hY           4Y      4s           <o.os

25       64          2X      so            NS


Healing of Gastric Ulcers

Doll, Jones. and Pygott ( 1958) studied 80 smokers hospitalized with gastric ulcer.
Of these, 40 randomly chosen patients were advised to stop smoking; the remaining 40
did not receive advice regarding smoking. As assessed by barium examination, the
average reduction in ulcer crater size at 28 days was 78.1 percent among those advised
to stop smoking and 56.6 percent among those not advised to stop (~~0.05). The
reduction in crater size was 83.2 percent among smokers who stopped smoking
completely versus 71.8 percent among those advised to stop but who did not do so.
Most of the latter group substantially reduced their tobacco consumption during the
trial. This study indicates that gastric ulcer patients who stopped or reduced smoking
after receiving medical advice responded much better to treatment than smokers who
were not advised to stop (Doll, Jones, Pygott 1958). This study, performed in the era
before the availability of potent antisecretory agents, suggests that smoking cessation
alters the natural history of gastric ulcer among smokers.

These findings have been confirmed by Tatsuta, Iishi, and Okuda (1987). Sixty-four
Japanese outpatients with endoscopically proven gastric ulcer were treated with ant-
acids and dicyclomine hydrochloric acid. Additionally, half of the 40 smokers were
advised to stop smoking or to reduce smoking by at least one-half. Advice regarding
smoking was not given to the remaining smokers. Endoscopy was repeated in I2 weeks
by an endoscopist who was unaware of the patients' symptoms or smoking status.
Ulcers had healed in I I of I? smokers (92 percent) who stopped or reduced smoking
and in 7 of 28 smokers (25 percent) who continued to smoke at their pretreatment level
(p<O.OOl). Ulcers also healed in 60 percent of nonsmokers (Tatsuta, Iishi, Okuda
1987).

A retrospective study (Herrmann and Piper 1973) that employed air contrast radiog-
raphy to assess ulcer presence and size in 101 gastric ulcer patients found mean
decreases in ulcer size at 3 weeks of 69,73, and 84 percent, for smokers who continued
to smoke. smokers who stopped smoking, and nonsmokers, respectively. Although
seeming to support the findings of Doll, Jones, and Pygott (1958) and Tatsuta. Iishi.
and Okuda (1987). these differences were not statistically significant (Hermann and
Piper 1973). The ulcer size at entry into this study was three times as great among
smokers as among nonsmokers, rendering inappropriate a comparison of the time
required for complete healing among groups.

Only these three clinical studies have assessed the benefits of smoking cessation on
the healing of gastric ulcer: all three demonstrate or suggest a benefit. In contrast, recent
randomized therapeutic clinical trials have generally shown no advantage in gastric
ulcer healing for nonsmokers compared with smokers (Wright et al. 1982; Kellow et
al. 1983: Farley et al. 1985: Euler et al. 1989; McCullough et al. 1989).

Recurrence of Gastric Ulcers

Tatsuta, Iishi, and Okuda (1987) evaluated the effect of smoking cessation on the
recurrence of gastric ulcers for 47 participants who had an endoscopically proven
gastric ulcer within the previous 6 months but who were ulcer-free at entry into the trial.

440


All were treated as outpatients with antacids and dicyclomine hydrochloric acid. Half
of the smokers were advised to stop smoking or to reduce cigarette consumption by at
least one-half. The remainder were not given this advice. Endoscopy was repeated at
3 and 6 months or whenever symptoms recurred. Data for seven patients who failed to
complete the trial were not presented or analyzed. Ulcers recurred among 9 of 12
patients who continued to smoke at their previous level and in 3 of 13 patients who quit
or substantially reduced their smoking (75 vs. 23 percent, ~~0.05). An ulcer recurred
in I of 15 (7 percent) nonsmokers (Tatsuta. Iishi. Okuda 1987).

This is the only prospective, controlled study that has evaluated the effect of smoking
cessation on gastric ulcer recurrence. However, the reports of several clinical trials of
maintenance therapy for gastric ulcer have provided data on the impact of smoking on
the trial results. All such prospective, controlled clinical trials are displayed in Table
4. Although several of these trials or treatment groups are small, every treatment group
shows an advantage for nonsmokers. In two trials, the difference was statistically
significant. The median percentage difference in recurrences for smokers compared
with nonsmokers is 20 percentage points.

Summary

The known effects of smoking on gastroduodenal physiology include several
mechanisms that might enhance an ulcer diathesis. Most of these mechanisms are
rapidly reversible upon cessation of smoking. The association of smoking with in-
creased maxima1 gastric acid secretory capacity has not been assessed for reversibility.

Epidemiologic studies consistently demonstrate that current smokers compared with
nonsmokers are at increased risk for occurrence of and death from duodenal and gastric
ulcer. The risks for former smokers are generally found to be between those of current
smokers and nonsmokers.

Duodenal ulcers are less likely to heal within specific time intervals among smokers
than among nonsmokers, regardless of whether patients are treated with placebo or most
active therapies. Both gastric and duodenal ulcers are more likely to recur within
specified periods of observation among smokers compared with nonsmokers.

A limited number of clinical trials have been performed to assess the effect of
smoking cessation on the course of peptic ulcer disease. These show that smoking
cessation, or in some trials, substantial reduction of daily cigarette consumption. is
associated with fewer duodenal ulcers at 6 months but not at 3 months, with improved
short-term healing of gastric ulcers. and with reduced recurrence of gastric ulcers.


TABLE A.-Recurrences of gastric ulcer in smokers and nonsmokers in clinical trials


PART II. OSTEOPOROSIS AND SKIN WRINKLING

Osteoporosis

Introduction

Osteoporosis is a condition of reduced bone mass that increases the risk of fractures.
especially of the hip, distal forearm, and vertebrae, after minimal trauma (Consensus
Conference 1984). The most devastating outcome of osteoporosis is hip fracture,
occurring in over 200.000 persons each year in the United States (Haupt and Graves
1982: Lewinnek et al. 1980). Mortality in the first years after hip fracture is increased
IS to 20 percent (Cummings and Black 1986: Gallagher et al. 1980; Jensen and
Tsndevold 1979: Lewinnek et al. 1980: Miller 1978). Results from three studies
indicate that approximately IS to 25 percent of previously functionally independent
persons who sustained a hip fracture remained in a long-term facility after I year, and
25 to 35 percent of those who returned home after a hip fracture required help in
performing daily activities (Campbell 1976; Jensen and Bagger 1982: Thomas and
Stevens 1974).

Osteoporotic forearm and vertebral fractures also have been found common among
the elderly. Most cases do not require hospitalization or result in long-term disability
(Ga  cay et al. 1979: Owen et al. 1982): however. the cost of caring for these fractures
has been estimated to be $ I40 million per year (Melton and Riggs 19X3).

Established risk factors for osteoporotic fractures include advanced age. white race.
female sex, number of years since natural or surgical menopause. slender body build.
prolonged immobilization, alcohol use. and use of certain medications (Cummings et
al. 198.5). Postmenopausal estrogen replacement therapy decreases the risk of os-
teoporotic fractures: this risk reduction is greater with longer duration of treatment
(Weiss et al. 1980).

Pathophysiologic Framework

Smoking may alter risk of osteoporosis and fracture through several mechanisms.
First. bone loss accelerates at menopause (Lindquist and Bengtsson 1979: Lindquist et
al. I98 1: Paganini-Hill et al. 198 I; Richelson et al. 1984: Mazess 1982). and smokers
undergo menopause I to 2 years earlier than never smokers (Chapter 8). Second. a thin
body build increases risk of osteoporotic fracture (Daniel] 1976: Hutchinson, Polansky.
Feinstein 1979; Kiel et al. 1987; Paganini-Hill et al. I98 I : Williams et al. 1982; Wyshak
l981), and smokers generally weigh less than nonsmokers (Chapter IO). Third,
smoking has been reported to reduce the endogenous production of estrogen (Mac-
Mahon et al. 1982) and increase its metabolism (Jensen. Christiansen. Rodbro 198.5:
Michnovicz et al. 1986).

Smoking also may decrease the effectiveness of exogenous estrogens (Daniel] 1987).
Endogenous estrogen metabolism is widely believed to affect the risk of osteoporosis
and fracture. and exogenous estrogen use is firmly linked with lower rates of
postmenopausal bone loss and lower risk of hip, forearm. and vertebral fracture among


women (Ettinger, Genant. Cann 1985; Hutchinson, Polansky, Feinstein 1979: Kreiger
et al. 1982; Paganini-Hill et al. I98 I ; Weiss et al. 1980: Riis. Thomsen. Christiansen
1987: Kiel et al. 1987). However, a I - to 2-year shift in age at menopause probably
does not alter the risk of osteoporotic fracture substantially. Not all researchers have
found differences in endogenous estrogen levels between smokers and nonsmokers
(Crawford et al. 1981; Friedman, Ravnikar, Barbieri 1987). Although therapy with
exogenous estrogen reduces the risk of osteoporotic fractures among women (Ettinger.
Genant, Cann 198.5; Hutchinson, Polansky, Feinstein 1979; Kreiger et al. 1982:
Paganini-Hill et al. I98 I; Weiss et al. 1980: Riis, Thomsen, Christiansen 1987; Kiel et
al. 1987), it is not certain whether levels of endogenous estrogen are lower in women
with osteoporosis than in women without osteoporosis (Cauley et al. 1986: Davidson
et al. 1983). The likely effects on osteoporosis and fracture risk of smoking-related
changes in circulating levels of male sex hormones, if such changes occur (Chapter 8.
Part 1). are impossible to predict.

Bone Mineral Content in Smokers Compared With Nonsmokers

Susceptibility to fractures is increased by a reduction in bone mass. Smoking has
been studied extensively in relation to various measurements of bone mass.

Using radiographs of the hand, Daniel] (1976) measured percent cortical area (PCA)
of the second metacarpal midpoint in I03 women aged 40 to 49 years and in 208 women
aged 60 to 69 years.  Smoking was associated with lower PCA among older women,
but there was no difference in PCA between smokers and nonsmokers among younger
women. PCA loss was estimated in 80 of the women aged 60 to 69 by comparison
with averages for the younger women. Smokers had significantly greater PCA loss
per year after menopause compared with nonsmokers (1.02 vs. 0.69 percent/ year.
respectively, p<O.OOl). Nonobese smokers had greater PCA loss per year compared
with nonobese nonsmokers, but obese smokers and obese nonsmokers did not differ
in PCA loss. In both smokers and nonsmokers, nonobese women lost more PCA per
year after menopause than obese women. None of these comparisons controlled for
age or years since menopause.

Since this first report describing "osteoporosis of the slender smokers," at least 21
other studies comparing bone mass in smokers and nonsmokers have been published
(Table 5). Nine of the nineteen studies found lower bone mass in smokers compared
with nonsmokers (Aloia et al. 19X8: Hello, Gergely. Boross 1979: Jensen, Christiansen.
Rodbro 1985: McNair et al. 19X0: Mellstrom et al. 1982; Rundgren and Mellstrom
1984: Sparrow et al. 19X2: Suominen et al. 1984: Slemenda et al. 1989). and the
difference was statistically significant in all but one of these nine studies (Suominen et
al. 1984). The populationba5ed studies by Mellstrom and associates (1982) and
Rundgren and Mellstrom ( 19X-I) are noteworthy because they controlled for potentially
confounding variable\. In both studie\. bone mass was measured by dual photon
densitomrtry of the heel. Mell\triim and colleagues (19X3) reported that bone mass of
the heel was significantly lower in smokers than in nonsmokers. Rundgren and
Mellstrom ( 19X-I) reported IO to 70 percent lower bone mass in male smokers and IS
to 30 percent lower bone ma\s in female smoker\.


TABLE S.--Summary of studies of smoking and bone mass

Reference

Ho116. Ccrfrlj
BorOh\ ( I Y7Y)

McNar et al.
(IYXO)

Population

Bone measurement            Fmding\

l.mtlqui\t et aI.    I.30 women in it
(IYXI)       populatw-had ady in
           SWL?dt?fl

Llndcl-pSrd     I26 healthy voIuntwr\
(IYXI)       uged 20-h')

PCA trom x my of the right 2nd
metacarpal

Women aped 404Y yr: no aeociution
of wwhing 210 ciglday for 25 yr nnd
PCA: women aged 60-6Y yr: vnohers
had lower PCA than nonsmoker\"

BM by DPA at 3rd
lumbar vrrtehrur

BM by SPA of mid\haft
of forearm


TABLE S.--Continued

Referencr

Popul;ttion

Mellstrtim et al.
(IYX?)

Lindquial
(IYXZ)

Sparrow et ill.
(19X?)

Rundgren and
Mellstrixn
(IYX4)

Suominrn et 31.
(IYX4)

Johnell and
Nilaon
(1984)

ZS7 men in a popul:ltion-hahed
study in Sweden

I .JhZ women in a
populnlloll-baaed \lUdY I"
Sweden

33 I men aged 40 x0 ti,llowcd
for 3-S yr

409 men and SSY women horn
m I YO IH)? or I YOh~)7 from 3
populntlon-hnwd study I"
SWdUl

142 me,, aged 3 I -7s

3YS 49.yr-old white women
randomly selected from
participants in a
population-based study in
SWttdNl

Bone meawrement

RM hy DPA a heel

HM hy DPA at 31-d lumbar
vertebrae

PCA x ray ot right ?nd metacarpal
performed at hawline and 3-S yr
later

BM hy DPA at heel

BM hy yray attenuatwn in the
calcaneums

BM hy yabwrptiometry at the
mdiu\ I cm and 6 cm proximal to
the ulnar \tyloid

Findings

BM Iowcr in smokers v\.
non\mokeri'

Stratifying hy age and menopausal
status. no difference in BM between
smoker\ and non~mohen

At baaelme. no dtffrrrnce between
PCA in smokers and nonsmoker\:
wer the 3%S-yr perwd. smokers lost
more PCA than nonsmokers"
(B=-O. 14X. p=O.O3)

BM in wnmen was IS-30% lowrr m
smokers vs. nonsmoker\" and in men
1%Xl'% lower in smokers vs.
nonwlokera": no difference between
ex-cmokerb and smokers

BM in smokers luwrr than that m
nonsmokers. but not \tatihtically
Ggnificant

No association of smoking and BM in
univariate or multivariate analysis

Controlled for age. rxc. \c\.
menopausal *It;uu\: d;tt;l lx,)
include that reported 111
Lmdqul\t t IYX I )

Controlled only tor age

Controlled for age. raw. \c'x,
weight, hut not for menopaual
status or estrogen use

Multiple te\t\ performed
controlled for apt only

Control led for age, race (white).
sex. height. weight. age ;It
menarche. menopauwl QBIU\.
numbwot chtldren hreaht
feeding. oral contracepttvr we.
phy\icul activity. and calcium
intake


TAHLE S.--Continued

P0pulat10n

I Zh po~tmenopnu~l women
volunteers ftom Sweden
randomly ;r\\ipnrd to different
estrogen dew\ and followed for
I br

X6 \homen volunttxr\ from
1 rural communities in Iowa

7X bbhitt' po\tnicnopausal
wombat not on estrogen thernpg

Bone measurement

BM by SPA at distal rudws
performed at baselme and after
I yr of estrogen treatment

BM hy SPA at distal radius

BM CT am ot the dominant
radiw at 30'~ ofdiance from
v.rist tu elbow

BM SPA at mldshaft and tltstal
radiu\

BM SPA ofm~dradiu~

Findmgs

At baseline. no difference in BM
between smokers (smoked in prior
6 mo) and non$moherr (no wokmg in
prior 6 mo): m 2X smohcr\ treated
with high dews ewogen. the mean %
increase in BM wa\ les\ than the mean
% increaw in 1X treated nonw~okrra"

No a\wciation of mokmg nnd BM

No a\wci;ltinn of wlohing and RM in
Imivarlate analy\ia

No ;IMKI~IIO~ of wohing and BM
over311 in pert- and postmenopausal
group,

No aw)ciut ion of wlohmg d BM

Comment\

No control for confounders

Small study with poor power:
hubJectb were young. limiting
generalibility: no control for
confounders

Small wdy with poor power:
no control of confounder\

Small study with poor power;
no control of confounder\

Author\ aat` that power to
detect 3 5% difference between
group, iit a= 0.05 wa5 >XO% in
buth mef~ mtl women:
confounding controlled hy
marching

c"
.J


TABLE S.--Continued

Kt?tNHICC

Ahl Kl ill.
(IYXX)

Picard ct al.
(IYXX)

Bilhrry. Wcix.
Kaplan ( I YXX 1

Slcnlelllh t'l ill.
(IYXY)

HM hq DPA of ternoral nech,
Ward\ trtanglc. trochanterlc regwn
;md 7nd4th lumbar vcrtehrur

HM hy SPA ut'did and
mdratliu\. DPA of lumbar \pine

Fintlmg\

Smoking wa a\soci;tted with Iowcr
BM in the rxiiu\ tp<O.Ol ) and of the
\pine (p4.03)

No awwiatmn ofhmohmg with etthrr
BM of the lumbar vertebrae or disral
radtu5


Eleven other published studies reported no association between smoking and bone
mineral content (Bilbrey, Weix, Kaplan 1988: Cauley et al. 1986: Johnell and Nilsson
1984; Linderglrd 1981; Lindquist 1982; Lindquist et al. 1981: McDermott and Witte
1988; Picard et al. 1988; Slemenda et al. 1987: Sowers. Wallace, Lemke 1985;
Stevenson et al. 1989). In addition. one study that found differences in bone mass
between heavy smokers and nonsmokers reported no differences in longitudinally
measured rates of bone loss (Slemenda et al. 1989). Some of these studies were small.
and the findings of no association may be due to type II statistical errors. that i<. the
failure to find a true association (Cauley et al. 1986: Slemenda et al. 1987: Sowers.
Wallace. Lemke 1985); other studies were large and had excellent statistical power
(Bilbrey. Weix, Kaplan 1988: Johnell and Nilsson 1983: Lindquist 1983: McDermott
and Witte 1988).

One study evaluated the effect of smoking on bone mass among women taking
estrogen (Jensen. Christiansen. Rodbro 1985). Among 56 postmenopausal women who
underwent replacement therapy with high doses of estrogen for I year. the mean
percentage increase in bone mass of the distal radius was I .0 I in 28 smokers compared
with 2.58 in nonsmokers. This difference was statistically significant.

Smoking as a Risk Factor for Osteoporotic Fractures

Daniel1 (1976) reported that 76 percent of women with osteoporotic vertebral
fractures smoked IO cigarettes or more per day for 5 years or more, compared with 43
percent of controls with no vertebral fracture. Smoking is strongly associated with age.
alcohol use, and, among some populations, use of exogenous estrogens. These are
potentially strong confounders of the relationship between smoking and vertebral
fracture, but Daniell's comparison between cases and controls did not consider them.

Since Daniell's 1976 study, seven other case-control studies have examined the
association between smoking and fracture of the hip or vertebrae (Table 6). Five of the
seven case<ontrol studies reported an increased risk of these osteoporotic fractures
among smokers (Aloia et al. 1985; Cooper, Barker. Wickham 1988; Paganini-Hill et
al. 1981: Seeman et al. 1983: Williamset al. 1982). and this association was statistically
significant in three of the studies (Aloia et al. 1985; Cooper, Barker, Wickham 1988:
Williams et al. 1982). In the study by Williams and coworkers (1982). smokers vvere
compared with obese nonsmokers, making it difficult to assess the independent associa-
tion of smoking with the risk of osteoporotic fractures. A second analysis of smoking
and the risk of hip or forearm fracture among the same subjects who were studied by
Williams andcolleagues (I 982) showed no overall association of smoking and fractures
(Alderman et al. 1986). In only two case<ontrol studies were statistical adjustments
made for age and exogenous estrogen use, which are potentially strong confounding
variables: in both of these studies. there was no statistically significant association of
smoking and fracture risk (Paganini-Hill et al. I98 I : Kreiger et al. 1982: Kreiger and
Hilditch 1986).

In five cohort studies (Table 7). there was no increase in the risk of fracture among
smokers (Farmer et al. 1989: Felson et al. 1988: Hemenway et al. 1988: Holbrook.
Barrett-Connor. Wingard 1988; Jensen 1986). Three of these reports were based on


TABLE 6.-Summary of case-control studies of smoking and fractures

Krferrnce


Daniel1
(iY76)

Srenian ct 31
(IYXR)

Aloia et al.
(IYX.5)

Vertebral fracture\

Population

Comparison

Estimated relattvr risk           (`omments

C&W\: 3X women aged 40 69 with
acute \ymptom:ttlc vertchrd fractures
after mm~mol trauma
Controls: 572 women outpatlcnt volunteers
aged soxw

>I0 tip/day for 3 yr vs. leaz,

4.2" h

No control for conlountlerx
no \tati\ticsl anslyv\

Caw\: 105 men aged J-l-X3 with
vertebral fracture\
Controls: I OS men aged I-LX3 with
Paget'\ diebe matched for ape and
length of ti~llowup

Nonohee. nondrinking. nonsmokers
vs. non&x. nondrinking smokers with
no underlying chv.3~:
aged <ho
aged M)MY
a&y,1 270

0.x
I .h
3.1

medid condition as\ociatcd
with hone lo\\; control\ \* ith
Paget`s disrahe may not he
representative of men unhout
vert&ral frxturex deign
controls for age. ohrslty. and
alcohol u\e

Cases: 5X white women (mca~ age 645)
volunteers with vertebral fixture
Controls 5X white women volunteerc
matched for ape

Smokers vs. nonsmokers

3.7" h

Controlled for up2 only:
multiple other ri4 factors
examined ubinf univariate tea5



TABLE 6.--Continued

Hip and/or forearm fractures

Reference

Population

Compartx,n

Estimated rebtive risk          Comments

Paganint-Hill   (`ae4: YI pohtmenopau\al women
elal.(lYXIl    aged 20 with hip fractures
       Controls: I X2 age. race-matched
         postmenopausal women

Krelgcret al.   Car\: OX po.\tmenopausal women aged
t IYX1): Krelger  45-74 yr ho\pitalired with hip fracture
and Htldnch   Trauma Controls: X3 postmenopausd
( IYXh)      women hospitali/.ed for trauma
       Nontrauma Controls: XX4 po\tmenopaussl
        women hospitalixd for medical illness

Williiml\et id.   Cnseh: 344 (3%) white women aged
(19x2):      S(b-74 with hip or forearm fracture
Aldc`rman ct al. Controls Sh7 (562) white women from a
( IYXh)      hou.xhold atrvey

I-lOcig/day vs. none
21 I cig/day Y\. none

I .os
I .Yh

Adjusted for age, age at
menopause. Quelelet'\ Index,
physical activity, alcohol
conxumprion. and exogenous
estrogen use

Ever vs. never smoker\
Trauma controls
Nontram~acornrol\

Among c\tropen nonusers
Hip fractures
Average weight ever smoker vs
  obese never smoker
Thm ever maker v\. obese
  never \moher
Forearm fracture
Thin ever maker v\. obese
  never moher
51 ppd v\. never
> I ppd v\. never

I.27
I.?`)

6.Sh

13.Sh

S.4h


I .o
I.2

Adjusted for ape. Quetelet's
Index, months breast feeding.
ovariectomy, and estrogen use

Smokers and nonsmokers were
not directly compared; the
comparison group for all
analyses was obese nonsmokers
who had used estrogen for
2 I yr; controlled for hex and
race only


TABLE 6.--Continued

Hip and/or fwxrm frnctutw

Kcfcrence        Population

(`ompariwn

E\tlmated relative rl\i\

Smohcr\ v\. nonmoher\

I.3


large samples from the Framingham Heart Study, the Nurses Health Study, and the first
National Health and Nutrition Examination Survey. In the largest study by Hemenway
and colleagues (1988) 96,508 nurses reported 975 hip or forearm fractures during an
average 4 years of observation. The relative risk of fracture was 1 .O in each smoking
category (former smokers, smokers of I-14 cigarettes/day, 15-25 cigarettes/day. and
>25 cigarettes/day) compared with never smokers.

Smoking Cessation and Osteoporosis and Fracture

No studies have evaluated the effect of smoking cessation on osteoporosis and
fracture, nor are there studies of the risk of osteoporosis or fracture in former smokers
compared with continuing smokers.

Summary

There is insufficient evidence to conclude that smoking decreases bone mineral
content and the risk of osteoporotic fractures. Some studies have found lower bone
mineral content in smokers compared with nonsmokers, but others have not. Some.
but not all, case-control studies have found a higher risk of osteoporotic fracture among
smokers. Most negative studies were limited by small sample size, and most positive
studies were not designed to control for potentially strong confounding variables.
Analysis of data in five cohort studies has found no association of smoking with
increased risk of fracture.

Skin Wrinkling

Introduction

Although wrinkling of the facial skin is nearly universal among elderly persons, it is
rarely mentioned in textbooks of dermatology or medicine, and little research has been
published concerning its etiology or risk factors. Skin wrinkling is associated with sun
exposure (Kligman 1969; Allen, Johnson, Diamond 1973; Daniel1 197 1; Knox.
Cockerell, Freeman 1962; Rook, Wilkinson, Ebling 1979). Wrinkling occurs with
increasing age (Daniel1 1971; Knox, Cockerell, Freeman 1962: Rook, Wilkinson.
Ebling 1979), but even among the elderly, wrinkling usually is confined to sun-exposed
areas (Kligman 1969; Allen, Johnson, Diamond 1973; Knox, Cockerell. Freeman
1962). There is limited evidence that dramatic weight loss is associated with skin
wrinkling (Daniel1 1971).

Pathophysiologic Framework

It is not clear how cigarette smoking may promote skin wrinkling. Some investigators
have concluded that a localized finding such as wrinkling of the face and hands could
not be caused by a systemic factor such as the absorbed components of cigarette smoke.


TABLE 7.--Summary of cohort studies of smoking and fractures

Keference


JeflV31
(14X6)

  Populatlon/out~on~~

Population-bawd study of 70-year-old
women in Copenhrigen. Denmarh: 77
smohed daily for 220 yr: 103 never \mohed
0utc0111r: all fractures

Hemenway
et al. (IYXX)

0630X nurwb aged 35-50 31 hahellnc
( IYXO) followed fur 4 yr.
Outcome: self-report of Y7S fracture\ of hip
or fwxrm

Felson et al
(IYXX)

Holbrook.
Barrett-Connor.
Wingard
(IYXX)

Farmer et al.
(19X0)

52OY men and women m the Framingham
Heart Study followed retrr)qxxtively for
about 30 yr.
Outcome. ? I7 documented hip fracture5

Y7S men and women aped S(b7Y at haaeline
followed for I4 yr,
Outcome: 33 documented hip fractures

3,595 white women in NHANES-I aped
4&77 at baseline ( lY71-75) followed fur
an uvernge of IO yr,
Outcome: X4 documcntrd hip fractuw

Comparison

`% smoker\ with fracture vs.
% nonsmokrr~ with fracture:
All po\tmenopauwl fractures
O~troporot~c frscturesh

Age-adjusted fracture rate compared to:
never smoher\
Ex-smokrrx
Smokers
I I4 tip/day
IS-24 c@day
23 cig/d/dny

Bawd on ciglday

Smohrrs vs. nonsmoker\                 I.1

Bawd on number of yr smoked at
huwlinr exam

Relative risk

Comments

All wbject\ were 70.yr-old
women: no control for other
confounders

I .o

  I .o
  I .o
  I .o

No incrrase

No mcreasr

A very large cohort study
producing narrow Cl3 (upper hmn
I .2.5). hut most women were
mlddlr-aged or younger;
controlled for age only

Cox re@re%ion model. adJusted for
age. wx. body ma\\ Index, dietary
calcium. and alwhol conwmptwn

No data given. hut reported no
significant 35wiation: ilnaly~a
adJusted for age. body muss Index.
menopausal Qtuh. citlcium
conwmption. and activity


However. facial skin, and to a lesser extent, the skin of the hands contain an intradermal
elastic tissue mesh that is denser and more complex than in other areas (Shelley and
Wood 1974). Thus. the toxic effect of both sunlight and smoking may be most
damaging in these more susceptible areas. Alternatively. damage from sunlight and
smoking may simply be additive. and the threshold for clinically apparent changes from
smoking may not be reached in sun-protected areas of the skin. Histopathologic
examination of sun-exposed skin commonly shows abnormalities of collagen in the
dermis that decrease the elastic properties of the skin. a condition known as elastosis
(Marks 1976: Shelley and Wood 1974). However. the mechanism by which sunlight
might cause these changes is uncertain, and there is no evidence that smoking is
associated with elastosis. Cigarette smoking has been shown to decrease capillary and
arteriolar blood flow in the skin acutely (Klemp. Staberg. Thomsen 1982: Reus et al.
1984: Richardson 1987). and hence. may cause tissue hypoxia. However. there is no
evidence that this causes changes in skin transparency and turgor or produces wrinkles.

Smoking and Skin Wrinkling

Several studies have reported that smoking is associated with prominent skin wrin-
kling, particularly in the periorbital or "crow's foot" area of the face.

lppen and Ippen (1965) defined "cigarette skin" as appearing pale. grayish. and
wrinkled. especially on the cheeks. with thick skin between the wrinkles. In an
examination of women aged 35 to 84.66 of the 84 .;mokers had cigarette skin compared
with 27 of the 140 nonsmokers (relative risk=4. I. p<O.Ol ). This study did not adjust
for differences in age or sun exposure between the smokers and nonsmokers (lppen and
lppen 1965 ).

Daniel1 ( 197 1) examined facial wrinkles and smoking status among I. 104 subjects.
most of whom were patients or visitors to his medical practice in Redding, CA. Skin
wrinkling was assessed in the crow's foot area and the adjacent areas of the forehead
and cheeks and graded as one of six categories of severity. Potential confounders such
as age, race (98 percent of the subjects were white). sex. sun exposure. and body weight
were also measured. Smokers were more often prominently wrinkled (wrinkle score
4-6) than nonsmokers. Prominent skin wrinkling was also more common in relation
to increasing age and sun exposure. The association between smoking and prominent
wrinkling was found in each age. sex. and sun exposure subgroup and was statistically
significant in most of the subgroups. The most heavily wrinkled class in each age-sex
group was composed entirely of smokers.  Wrinkling increased with duration of
smoking and number of cigarettes smoked daily. Prominent skin wrinkling was more
common among smokers aged 30 to 49 than among nonsmokers aged 60 to 69 years.
This study provided strong evidence that smoking is associated with skin wrinkling
(Daniel1 1971). However. the measurements of wrinkling are not very precise. and
although an attempt was made to blind the wrinkle assessment. the subjects were
patients and friends of the investigator. who may have known their smoking status.

Allen, Johnson. and Diamond (1973). reported on a ctudy that they claimed refuted
the above findings,, but the data presented actually supported an association between
smoking and skin wrinkling in whites (Boston 1973: Daniel1 1973: Weiss 1973). U'cing


Daniell's 6 categories of wrinkling sevserity. Allen. Johnson, and Diamond (1973)
examined 650 persons and obtained information on age, race, sex. smoking status, and
sun exposure. Biopsies of the crow's foot area also were performed on some subjects,
As evidence that there is no association between smoking and skin wrinkling, the
researchers reported that among 137 black subjects, only 2 had prominent wrinkling,
regardless of sun exposure or smoking status. Although only fragmentary data are
presented, wrinkle scores among white smokers who were exposed to the sun less than
2 hours daily were significantly higher than wrinkle scores for white nonsmokers with
limited sun exposure.

In a survey of 122 new patients attending a general medical practice in England. all
but I of whom was white, wrinkling and other skin changes were found to be much
more common among smokers than nonsmokers (Model 1985). "Smoker's face" was
defined as exhibiting one or more of the following: lines or wrinkles on the face.
typically radiating from the corners of the lips or eyes; gaunt facial features: grayish
skin; and a plethoric complexion. Smoker's face was found among 46 percent of
smokers, and none of the nonsmokers were classified as having smoker's face. The
association of smoking and smoker's face was statistically significant (p<O.OOl) and
remained so after controlling for age. social class. sun exposure, and recent weight
change. Although this study shows a striking difference between smokers and non-
smokers. it is not clear that prominent skin wrinkling is the major or most common
criterion for the diagnosis of smoker's face. Thus. the association reported may not be
specific for wrinkling.

Smoking Cessation and Skin Wrinkling

No studies have assessed the effect of smoking cessation on skin wrinkling.  Daniel1
( I97 I ) noted that prominent wrinkling was common in former smokers, but supporting
data were not presented. Model ( 1985) reported that 8 percent of former smokers had
smoker's face compared with 46 percent of smokers.

Summary

There is limited but consistent evidence that smoking is associated with prominent
facial skin wrinkling among whites (Allen. Johnson, Diamond 1973: Daniel1 1971:
Ippen and Ippen 1965: Model 1985) but not among blacks (Allen. Johnson, Diamond
1973). It is not clear whether former smokers are less wrinkled than smokers (Daniel1
1971: Model 1985).

CONCLUSIONS

I. Smokers have an increased risk of development of both duodenal and gastric ulcer,
and this increased risk is reduced by smoking cessation.

2. Ulcer disease is more severe among smokers than among nonsmokers. Smokers are
less likely to experience healing of duodenal ulcers and are more likely to have

456


recurrences of both duodenal and gastric ulcers within specified timeframes. Most
ulcer medications fail to alter these tendencies.

3. Smokers with gastric or duodenal ulcers who stop smoking improve their clinical
course relative to smokers who continue to smoke.

4. The evidence that smoking increases the risk of osteoporotic fractures or decreases
bone mass is inconclusive, with many conflicting findings. Data on smoking
cessation are extremely limited at present.

5. There is evidence that smoking is associated with prominent facial skin wrinkling
in whites, particularly in the periorbital ("crow's foot") and perioral areas of the
face. The effect of cessation on skin wrinkling is unstudied.


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X2( I ): 163. January 1982.

468


          CHAPTER 10
SMOKING CESSATION AND BODY WEIGHT
           CHANGE


CONTENTS

Introduction  ..................................................... ..47 3
Amount of Weight Gain After Smoking Cessation and-Likelihood of Gaining
Weight ....................................................... ..47 3

Causes of Postcessation Weight Gain  ................................... 483
Food Intake ...................................................   4x4
Physical Activity  ..............................................   486
Energy Expenditure  ............................................... 487

Relationship Between Overweight and Adverse Medical and Psychosocial
Outcomes  ....................................................
Change in Weight-Related Health Risks After Smoking Cessation  .........

Strategies to Control Postcessation Weight Gain  .......................
Behavioral Methods for Reducing Postcessation Weight Gain  ..........
Pharmacologic Methods for Reducing Postcessation Weight Gain  .......

Conclusions  ....................................................
                           ...
References ..................... ................................

490

497

-500

500
502

SOS

so7


INTRODUCTION

Cigarette smoking is associated with decreased body weight. and many smokers
report that a major reason they smoke is to reduce body weight (Grunberg 1986: Klespes
et al. 1989; US DHHS 19gXa). However. as documented in this Chapter. the weight
gain associated with smoking cessation is generally small and poses a minimal health
risk.

This Chapter is organized into six sections. Drawing from prospective investigations
meeting specific criteria. the first section of this Chapter determines average weight
gain following smoking cessation compared with continued smoking. assesses the
percentage of continuing smokers and quitters gaining weight. and calculates the risk
of gaining weight after smoking cessation versus continued smoking. The next section
of this Chapter discusses the mechanisms responsible for weight gain after mohing
cessation. The available literature is reviewed on dietary,. activity. and metabolic
changes after smoking cessation The third section reviews the relationship between
body weight and adverse medical and psychosocial outcomes. The fourth section
examines whether weight-related health effects accompany weight gain in ex-smokers.
The fifth section presents potential treatments for reducing postcessation weight gain.
including pharmacologic (e.g.. nicotine polacrilex gum. phenylpropanolamine. and
d-fenfluramine) and nonpharmacologic approaches. The sixth section presents con-
clusions regarding smoking cessation and body weight change.

AMOUNT OF WEIGHT GAIN AFTER SMOKING CESSATION AND
        LIKELIHOOD OF GAINING WEIGHT

To evaluate postcessation weight gain and to determine the likelihood or relativ,e risk
of gaining weight after smoking cessation, longitudinal investigations after 1970 of
postcessation weight gain were examined. Only studies that included a control group
of continuing smokers were evaluated. Requirements for studies in this review included
a minimum followup period of 1 month and at least IO smokers who quit. Studies were
excluded if a weight loss component or severe caloric restriction was part of the
intervention or if an agent known to affect body weight (e.g., nicotine polacrilex gum)
was used; however, placebo conditions within drug trials were considered. A few
studies were excluded for methodologic or interpretive reasons, such as relapsed
subjects included in data analysis along with quit subjects or whenever a weight change
could not be calculated. Table I summarizes the IS studies that fulfilled the\e
inclusionary and exclusionary criteria.

The following information is included for each study listed in Table 1: the study
reference, the followup or period of abstinence. the mean weight gain among in
dividuals whoquit smoking, the mean weight gain of subjects whodid not quit smoking.
the percentage of subjects quitting smoking who gained weight from baseline to the
followup period, the percentage of nonabstinent subjects who gained weight during the
same period, and the relative risk of gaining any weight after smoking cessation versus
continued smoking. Adjusted averages of weight gain are provided to summarize
across all studies. These adjusted averages control for differing sample sizes and assign

173


TAHIX I.--Summary of prospective studies on smoking and body weight

5 yr

! yr

I qr

I Yr

h yr

6.3.5



7.5



5.15



I I.1



3.1X



(1. I



I .h








(1.94



7.7

2.01          -




2.2



0.04          76.9          JO.3         I.66



7.3           x7.0           60.7         I .a3



0.r)                                  -




0.3



0.9                       -



-           7x.0          Sh.0         I ..I9



0.44          -                       -




2.4           X0.6          61.7         1.31


TABLE I.--Continued

Krference

Sample     Number of
\i7c     quitters

Quit
period

     Mean weight               % continuing     Relative ri\h
      gain (lb)         `2 quitter\
                 who gain     \moher\ who     of gaining
Qumer\    Continuing \moher5   weight     gain weight      weight

Puddry et al.
(IYXS)

zx

Kabhin
( lYX4h)

107

Kotlin                42
(lYX7)

Scltfrr
(l'J73)

31X

Tuomilehto et al.
( IYX6)

3Yh

I..( mn



3 mo



I .5 mo



5 yr


s yr

2.Y7



4.4



3.1x



7.`)



6.02

Median l'ollowup
period=7 yr

Avcragc
~elght gain
among
quitter\=l.h:
N=J.h47

0.44

0.7



0.70          5X.3          33.3         I .75



33

I .57

Avcragc
wclght gain
among
continumg
w~oker\=O.X:
N= 15.046

Averq!e       Average      Average
`I$ of quitter\     % ot cclntirlulng   relntive rlah
uho gain        \mcrher\ who    olgaming
wcighk7Y";:    gain \cright=Wk:  weight= I.451
Numhcr ot        Numhcrot      Numher ot
\tudie\ reportlng=5: dud~c\        \tudie\
N=714       reporting=5:    rcpwmg=S:
            N=l,l I3       N= I.77



more weight to large versus small samples. Table 2 provides more detailed information
(e.9.. Y-percent confidence intervals for weight gain and relative risk) regarding each
of these investigation<.
As indicated in Tables I and 2. the average sample sire of these investigations was
I .34X (range=ZX-9.539). The followup period ranged from I month to 5 years. with a
median followup period of 7 years. Consistent w'ith previous reviews of the smoking
and body weight literature (Klesges et al. 19X9: US DHHS I9XXa). the adjusted average
weight gain among smokers u ho quit was approximately 5 pounds (mean=4.6:
range= I .&I I .2 pounds). The weight gain among smokers who quit was considerably
greater than the adjusted average gain of 0.X pounds observed among subjects who
continued to smoke (range=0 to +3.S pounds). Thus. although variability of wseight
gain is quite marked (Tables I and 2). smoking cessation produces approximately a
l-pound greater weight gain thail that associated with continued smoking.
A commonly reported, but erroneous. estimate regarding postcessation weight gain
is that one-third of smokers gain weight after smoking cessation. one-third maintain
body weight. and one-third lose weight after cessation (US DHEW 1977). In the five
investigations providing detailed information regarding changes in body weight. the
actual percentage of quitters gaining weight appears to be much greater than previously
estimated. Considering the results of all five studies and adjusting for sample size, 79
percent of those who quit smohing experienced a weight gain (range=%-87 percent).
Over the same followup period, an adjusted average of 56 percent of continuing smokers
experienced an increase in body weight (range=33-62 percent) and. as presented above.
the average amount of weight gain was less among continuing smokers.
Data allowing computation of a relative rish estimate of weight gain after smohing
cessation w'ere available from five investigations. This relative risk estimate compares
the likelihood of weight gain in quitters versus continuing smokers. That is. a higher
relative risk ratio indicates that the percentage ofquitters who ssined wright was higher
compared with that of corresponding continuing smokers. Overall. the risk of n,eight
gain after cessation was 45 percent greater for quitters (mean=l.35. ranFe=I .3 l-l .7S)
than for continuing smokers. This increased rish of weight gain was consistent across
differing follow up periods. appearin,      _
                    (7 as earlv as 6 weeks (Rodin 19X7: relative rish
(RR)=I.75) and lasting up to 6 bears after smohinf cessation (hoppa and Bengtsson
19x0: RR=I 3 I ). Additionall) _ one investigation found the relative risk ofgaining more
than 1 pounds after smohin, (7 cessation to he I .3X (Bosst!. Carve!. Costa 19X0). In
another investigation. the rish of gaining more than IO pounds was XX percent higher
for quitters than for continuin g smohers (RR= I .XX) (Friedman and Sieselaub 19X0).
Although the rish of yining more than IO pounds appears to be almost 90 percent
greater among quitter\ than con1lnuin, `7 smohcrs (Friedman and Siegelaub IYXO). actual
occurrence of I ()-pound L\ eight fains uas reluti\el\ Iou (20.3 ~4. 10.X percent amonp
quitters and conlinuin, `7 smohers. respccti\el\ 1. Frkman and Siegelaub (19x0). with
a large sample of quitters (`1:=7.7.3X) xid continuin g smohers (N=6.X() I ). presented the
percentage\ of those gaining 20 pounds or mow o\ t`r ;I median I X-month follow up.
Among males. 3.7 percent of those i\ ho quit smohin, 17 gained more than 20 pounds
compared 14 ith 0.9 percent of those u ho continued to smohe. Amon females, 3. I



`I'AHLE: 2.--Continued

Kclallvc IWh ol ~;IIIlIn~ >I0 Ih=I.XX
`)5'/; (`I ( t .70-1.0X)


TABLE 2.--Continued



TABLE 2.--Continued

Quit
period

Average gain
+SD (lb)

Re\ult\

Rwl~n t tYX7)

Sctl/er t lY7-t)

Quitters: 3.1+3.Y     (?.I-S.7)
Males: S.Y+4. I     (3.X-X. I )
Fcmalrs: 3.2f3.0   (2.04.h)

Continuing
>mohera: 0.753.7    (60.2-1.5)
M&x 7 `+3 1
      A.___.     (O.Y-3.5)
Femalw 4.4k3.0 t-1.34).4)

Quitters: 3. IX

(`ontinumg
smohrrs: 0.30

Quitters: 7.Y

No chance or Io\t
41.7'/;(10)
66.7% ( I?)

ucight=l.75


TABLE 2.-Continued


percent of those who quit smoking gained more than 20 pounds compared with 1.6
percent of those who continued to smoke.

In summary. while approximately four-fifths of smokers who quit will gain weight
after cessation. average weight gain is approximately 4 pounds greater than that
expected among continuing smokers. The risk of weight gain after cessation is 45
percent greater than the risk associated with continued smoking. although individual
weight gains of 20 pounds or more are rare.

Although weight gain is common after cessation. little is known concerning the types
of individuals at risk for substantial increases in body weight. Researchers have
concluded that women. moderate smokers. and older smokers have the greatest weight
control effect from smoking (US DHHS 1988a). although the tremendous variability
in body weight changes after cessation has yet to be explained. That is. while the
average weight gain after smoking cessation is approximately 5 pounds. individual
responses range from weight loss to a weight gain exceeding 20 pounds. Studies are
needed that focus carefully on individuals at risk of excessive weight gain after smoking
cessation and the differences between these individuals and those who do not gain
weight.

Additionally. investigators hypothesize that the relationship between smoking and
body weight is attenuated by other health behaviors (Marti et al. 1989). Although the
effects of smoking to reduce body weight are acknowledged, individuals who smoke
are more likely than nonsmokers to have unhealthy lifestyles associated with increased
body weight (e.g.. lower levelsof physical activity and higher dietary intakes)(Klesges.
Eck et al. 1990: Chapter I I ).

CAUSES OF POSTCESSATION WEIGHT GAIN

Cross-sectional and longitudinal studies clearly indicate the inverse relationship
between smoking and body weight in humans and between nicotine and body weight
in animals (Grunberg 1986: Klesges et al. 1989: US DHHS 1988a: Winders and
Grunberg 1989). However, no study has included a simultaneous evaluation of the
long-term changes in all of the variables that may account for this relationship. including
food intake. physical activity. and energy expenditure. Of the currently published
investigations, the longest followup period evaluating all three aspects of the energy
balance equation has been 8 weeks (Stamford et al. 1986). A recent study evaluated
food intake and physical activity changes over a 26-week followup but did not include
metabolic measures (Hall et al. 1989). Short-term evaluations do not allow for an
adequate determination of predictors of weight gain. This review focuses on those
studies that have directly evaluated either food intake, physical activity, and/or meta-
bolic rate as a function of smoking cessation. nicotine administration. or nicotine
deprivation. The available data on changes in the energy balance equation that result
from smoking cessation are summarized below.


Food Intake

Most short-term evaluations (e.g.. 3 days or less) found that food intake, particularly
the consumption of sweet foods and simple carbohydrates, increases after smoking
cessation. For example in a I -day experiment. Grunberg ( 1982a) reported that smokers
who were allowed to smoke ate fewer sweet foods, but consumed similar amounts of
non-sweet foods. compared with nonsmokers and smokers not allowed to smoke. This
between-subjects laboratory study was short term and did not measure body weight
changes. In another short-term study. Hatsukami and colleagues (1984) hospitalized
27 smokers for 7 days. After a 3-day baseline, 20 of the subjects were deprived of
smoking for 4 days while the remaining 7 served as a control group. During this 4-day
abstinence. caloric intake increased significantly in the abstinence group and was
accompanied by a I .76-pound increase in weight compared with baseline. Recently,
Duffy and Hall ( 1988) assessed smokers who differed in degree of eating disinhibition.
defined as eating that occurs in situations in which self-control behaviors are disrupted
(e.g.. binge eating). Smokers who were allowed to smoke before eating ice cream did
not show food consumption differences as a function of level of disinhibition. How-
ever, results for smokers who had abstained from smoking for 24 hours showed a
different pattern. Abstaining smokers who scored high on eating disinhibition ate more
than three times (273.6 g) as much ice cream as those who scored low (86.4 g) on eating
disinhibition. The results from this investigation indicate that dietary changes follow-
ing smoking cessation may vary as a function of dieting history. use of cigarettes to
curb appetite. and other wei_pht history variables.

Some prospective investigations have qualitatively ashed participants who quit
smoking if they believed that their dietary intake had changed. These studies also
reported that food intake increases after cessation. For example. Manley and Boland
(19X3) examined the side effects experienced by 94 subjects quitting smoking and
whether these side effects varied as a function of relapse. On a withdrawal rating
system. those whoquit smoking rated themselvesas furthest from"optimal"at followup
on general appetite and overeating. On a separate rating scale. abstainers also ga1.e
higher ratings than relapsers at followupon "eating more." In astudy of 53 self-quitters.
Black and coworker\ ( IYXX) found that of those reporting that they ate more. average
weight gain uas 6.9 pounds. In contrast. of those reporting that they ate the same or
less. average Mcifht gain ua'r I .-I pounds.

Unfortunately. there are few prospective human investigations that have attempted
to quantify carefully food intahe changes over time among subjects after quitting
smohing. The\e 5tudies penerally indicate that food intahe increases after cessation;
however, result\ v'ary greatly across investigation\. Of eight studies to date. t&o
reported clear increases in food consumption after cessation (Leischow and Stitzer
IYXY: Stamford et al. 19X6). four provided qualified support for increased food
consumption after cessation (Hall et al. 1989: Kles,_ges et al.. in press: Perkins. Epstein.
Pastor I YYO: Rodin 19x7). and tv+ o reported no changes in food intake after cessation
(Dallosso and James 19x3: DiLorenTo et al. 1988).

In what may be the most comprehensive evaluation to date of change in energry
balance. Stamford and colleagues ( 1986) analy.zed changes in food intake. physical


activity, and resting metabolic rate in 13 sedentary females who quit smoking for 48
days. Mean daily food intake increased by 177 kcal and explained 69 percent of the
variance in changes in weight (3.85 pounds). No changes in physical activ,ity or resting
metabolic rate were observed.
To evaluate dietary changes after cessation. Leischow and Stitzer ( 1989) assigned
subjects, in an inpatient setting, to either smoke-ad-libidum (N=6) or quit-smoking
(N=9) conditions for at least I4 days after a 4-day baseline period. Results revealed a
significant difference in weight gain (p<O.OS) between smokers and those who quit
smoking (2.0 vs. 4.7 pounds. respectively). The weight gain in those who quit smoking
was associated with a significant increase in food intahe over time compared with
continuing smokers.
Four investigations have provided qualified support for dietary changes after cessa-
tion. Perkins, Epstein, and Pastor (1990) evaluated caloric intahe, resting energy
expenditure (REE). and physical activity in seven female smokers for 3 weeks. vvhich
included normal smoking (week I ). smoking cessation (week 3). and resumption of
smoking (week 3). Total caloric intake did not increase during the week of cessation.
However, once smokers resumed smoking during week 3. caloric intake decreased
significantly. Caloric intake from alcohol. however. rose from 3 I9 kcal per day in the
first week to 432 kcal per day during the week of abstinence. When subjects resumed
smoking during the third week, alcohol intake dropped to I19 kcal per day. During the
cessation week, REE did not decrease compared with baseline. However. a significant
increase in REE was observed when subjects resumed smoking compared with the week
of abstinence (p<O.OOl ). No changes in physical activity were observed.
Rodin (1987) evaluated changes in food intake and physical activity in 24 subjects
who quit smoking and I8 smokers who failed to quit smoking. Subjects w'ho quit
smoking gained an average of 3.2 pounds over the R-week study. Consistent with the
literature concerning animals as subjects and some studies using humans (Grunberg
1986; Winders and Grunberg 1989). smokers who gained weight after stopping smok-
ing increased their carbohydrate consumption. particularly sugar. This increase was
accompanied by decreased protein consumption.  However. these subjects did not
increase their total food intake nor did they decrease their levels of physical activity.
Levels of physical activity generally increased.
Hall and coworkers (1989) assessed changes in food intake and physical activity
among 9.5 subjects who enrolled in a stop-smoking program. In contrast to all other
investigations reviewed in this Section, Hall and coworkers ( 1989) evaluated long-term
changes in food intake and physical activity (for a 6-month followup). Caloric intake
increased significantly in one group and marginally in another group during the first 8
weeks of abstinence. Both sugar and total fat increases were noted in the group that
significantly increased energy intake. Total dietary intake increased approximately 200
kcal per day over the 8-week period. In assessing 6-month changes, Hall and coworkers
(1989) reported a gender difference in caloric intake with time. Among men who quit.
mean daily caloric intake decreased by almost 1,000 kcal from a mean of 3.014 kcal
during week I to 2,035 kcal at week 26. Among women. caloric intake remained stable
(mean= I .84 I kcal at week I: mean=1 .X67 kcal at week 16). However. vveight con-
tinued to increase for both groups. From the 13.week to the 6month followup. men


increased their weight 3.56 pounds (X.65 pounds total). and women increased their
weight by 4.53 pounds ( 10.34 pounds total). NO changes in physical activity were
observed. Weight continued to increase despite no changes from baseline in dietary
intake and physical activity in female ex-smokers and despite decreases in dietary intake
and no physical activity changes in male ex-smokers.

Klesges and coworkers (in press) reported gender differences in response to smoking
cessation. In this study, the food intake and physical activity of 68 smokers and
nonsmokers were evaluated during a 2- week period. At the end of the first week, the
smokers were paid to quit smoking, and 36 percent were successful at remaining
abstinent for the entire week (confirmed by carbon monoxide (CO) readings). Non-
smokers continued to monitor their food intake and physical activity. At the end of the
second week, subjects were allowed to return to smoking. In this investigation, female
smokers who quit smoking increased their body weight in comparison with non-
smokers. Smokers who quit increased their consumption of mono- and polyunsaturated
fats and decreased their intake of fiber. In contrast, males who quit smoking did not
change either their weight or dietary intake compared with males in the other groups.
No changes in physical activity were detected in any of the groups.

Dallosso and James (1984) reported on IO subjects who quit smoking and were
observed for 6 weeks after they participated in a stop-smoking clinic. Resting metabolic
rate dropped by 4 percent in smokers who quit, a drop which was significant only when
the data were expressed as per kilogram of body weight. The average food intake
increased by 6.5 percent, but this difference was not statistically significant.

DiLorenzo and colleagues (1988) evaluated changes in body weight and caloric
consumption in I6 subjects who quit smoking for 5 weeks compared with I I subjects
who continued to smoke and I6 nonsmokers studied over the same time period.
Subjects who quit smoking gained an average of 5 pounds over the 5 weeks; the smoking
and nonsmoking control groups did not change body weight significantly (p<O.OOOl ).
This weight gain was not associated with changes in dietary intake.

Physical Activity

In contrast to the findings on dietary intake and smoking cessation. the available data
indicate that change in physical activity does not play a role in either differences in
body weight between smokers and nonsmokers or the weight gain associated with
smoking cessation. The small number of prospective investigations has generally
reported unchanged physical activity after smoking cessation (Hall et al. 1989; Hat-
sukami et al. 19X-l: Klesges et al.. in press: Perkins. Epstein. Pastor 1990; Stamford et
al. 1986). and those that found a change in activity reported an increase in physical
activity after smoking cessation (Leischou and Stitzer 1989: Rodin 1987). The
literature consistently indicates that reduced physical activity after cessation cannot
account for postcessation weight gain.


Energy Expenditure

An important and often overlooked variable in energy imbalance leading to weight
gain is REE. Approximately 75 percent of total energy expenditure is in the form of
metabolism (Ravussin et al. 19X2). Ample indirect evidence supports the hypothesis
of increased energy expenditure in smohers. That is. given that smohers do not have
higher levels of physical activity compared with nonsmohers. the only known
mechanism remaining to explain the energy imbalance is \orne aspect of metabolism
(Blair. Jacobs. Powell 19X5): smokers' dietary intahes may be the same or higher than
those of nonsmokers (Picone et al. 19X2; Stamford. Matter. Fell. Sady. Cresanta et al.
19X4: Stamford. Matter. Fell. Sady. Papanek et al. I9X-4): mohers maintain lower body
weights than do nonsmokers (Klesges et al. 19X9: US DHHS I9XXa): and weight gain
has been reported in individuals quitting smokin g without any dietary and physical
activity changes (DiLorenro et al. 1988: Hall et al. 19X9). Additionally. several reports
document nicotine-induced reductions in body weight in laboratory animals without a
concomitant reduction in food intake (Grunber g. Bouen. Morse 19X1: Schechter and
Cook 1976; Wellman et al. 19X6). However. those few studies that have evaluated
metabolic changes in response to smoking cessation among humans have produced
inconclusive and equivocal results.

Eight studies have reported either acute changes in REE following smoking or
nicotine administration or have reported decreases in REE after smoking cessation. An
early study (Glauser et al. 1970) reported decreases in oxygen consumption for seven
male subjects who quit smoking for I month. Food intake and physical activity were
not monitored. Reanalysis of these data (Klesges et al. 19X9) revealed that the changes
in metabolic rate reported by Glauser and cowtorkers ( 1970) waere significant only with
improper methods of statistical analysis. In the only study that utilized an indirect
calorimetry respiration chamber. Hofstetter and coworkers ( 1986) reported a I O-percent
difference in total energy expenditure during a 24-hour period of smoking compared
with a 24-hour period of abstinence among eight smokers. However. this difference in
energy expenditure disappeared after 24 hours. No changes were observed in mean
basal (sleeping) metabolic rate. Diet was held constant.

Perkins and colleagues have conducted a series of studies evaluating the effects of
nicotine, in the form of nicotine nasal spray, on changes in REE. In a study of nicotine
administration in I8 male smokers, Perkins and colleagues (Perkins. Epstein, Stiller.
Marks et al. 1989) reported REE changes that were 6 percent above baseline after
nicotine administration, which was significantly greater than the 3-percent increase
after placebo administration. Another investigation (Perkins et al. 1989a) sought to
determine if nicotine-induced increases in metabolic rate observed at rest were also
present during physical activity. Ten male smokers were administered nicotine and
were then compared with IO male smokers who were administered placebo. Metabolic
rates increased both at rest and during light exercise. Although the percent change in
REE due to nicotine was equivalent both at rest and during activity. the excess energy
expenditure (in kilocalories) attributable to nicotine was more than twice as great during
exercise. A third study using nicotine nasal spray assessed the combined effects of
nicotine and consumption of a meal on REE (Perkins. Epstein. Stiller. Sexton et al.

4x7


1989). Eight male smokers were assessed using a repeated measures design. These
individuals were given a caloric load (vs. water) and nicotine (vs. placebo). Both the
caloric load and nicotine increased REE significantly. However, no interaction be-
tween these factors emerged, and the effects were slightly less than additive when
combined. Nicotine alone increased REE by 4.95 kcal per hour. food alone increased
metabolic rate by 14.30 kcal per hour, but nicotine plus food increased metabolic rate
by 17.00 kcal per hour. Finally. in a study of the effects of changes in energy balance
as a function of smoking cessation, Perkins, Epstein, and Pastor (1990) evaluated REE
in seven female smokers across 3 weeks: normal smoking (week I), smoking cessation
(week 2), and resumption of smoking (week 3). REE did not drop during the week of
abstinence compared with baseline. However. a significant increase in REE was
observed when subjects resumed smoking compared with the week that they were
abstinent.
The effects of smoking and coffee consumption on REE were recently evaluated by
Klesges. Brown. and colleagues (1990). Of 45 regular cigarette smokers and coffee
drinkers, IS were randomly assigned to smoke 2 cigarettes, I5 were assigned to drink
two standardized cups of coffee, and I5 were assigned to smoke cigarettes and drink
coffee. All three groups had acute increases in REE with a similar pattern of response
in each group.
In the largest study to date of all-day changes in metabolic rate, Klesges, Coday, and
coworkers (1990) evaluated changes in REE among 39 individuals over a IO-hour
period using multiple assessments of REE. Of the 30 smokers. 20 were assigned
randomly to continuous, regular smoking and IO were assigned to a no-smoking group.
A nonsmoking control group of nine subjects was also evaluated over the same time
period. The increase in REE among nonsmokers was not significant. In marked
contrast, smokers who did not smoke decreased REE over the course of the day.
Additionally, there were two distinct patterns of results among smokers who smoked
over time. Of the 20 smokers. I3 (70 percent) markedly increased their REE over time,
but 6 smokers (30 percent) decreased REE over time (similar to the pattern of smokers
who did not smoke). Closer inspection of the minute-by-minute metabolic changes of
those subjects who increased metabolic rate indicated an acute metabolic increase
followed by a return to baseline early in the day. or an acute metabolic increase followed
by a reduction. but to a level higher than baseline later in the day. In contrast, subjects
who had a mean decrease in REE also had an acute metabolic increase followed by a
drop below baseline early in the day, or an acute metabolic increase followed by a return
to baseline later in the day. Subjects who responded with decreases in REE smoked
more (as measured by expired CO) than those who responded with a cumulative
increase in energy expenditure. These results are consistent with recent observations
of a U-shaped relationship between daily cigarette consumption and body weight. with
moderate smokers weighing less than nonsmokers but heavy smokers approximating
the body weights of nonsmohcr\ (Albanes et al. 1987).
Four studies found no relationship between smoking and metabolic rate. Burse and
coworhers ( 1982) did not observe chronic changes in resting metabolism in a sample
of three makers who quit for 3 vveeks.  However, the small sample size in this
investigation limits interpretation of the results. Although Robinson and York (1986)


reported an elevated metabolic response to food intake (i.e.. thermic effect of food).
chronic REE did not change as a function of smoking and total energy expenditure after
a meal during the cessation period. Stamford and colleagues (1986) did not find
changes in oxygen consumption in 13 subjects who quit smoking for 38 days. These
investigators did find marked food intake changes that accounted for 69 percent of the
variance of postcessation weight gain. In a study of the chronic effects of smoking
status on REE, Perkins and coworkers ( 1989b) assessed 20 male smoker, and IO male
nonsmokers after overnight abstinence from food and caffeine in both groups and after
overnight abstinence from smoking in the smohing group. No differences in REE were
observed.
Two recent studies evaluating the acute effects of cigarette smoking on REE have
provided equivocal findings. In a sample of five occasional and five regular smoker4
(Warwick. Chapple. Thomson 1987). REE did not increase after smoking. even during
the first IS to 30 minutes after smoking. Additionally. the thermic effect of food was
slightly, but not significantly. lower with smoking than without smoking. Dallosso and
James ( 1984) evaluated short- and long-term metabolic changes associated with smok-
ing. The thermogenic (metabolic) response for I hour after smoking 1 cigarette wa\
not significant, although an acute increase w/as observed during the first 30 minutes.
However, variability of responses was marked, ranging from a 4.5percent decrease in
metabolic rate to a 9.0-percent increase. No consistent long-term changes in metabolic
rate were observed. Rather, the metabolic rate of four smokers clearly decreased after
cessation; the rate stayed the same in two smokers and increased in two others.
The literature generally indicates that both dietary and metabolic changes are respon-
sible for weight gain after smoking cessation, but these changes probably occur through
complex mechanisms. Physical activity does not appear to be related to postcessation
weight gain. Although the pattern generally indicates that both dietary and metabolic
factors are involved. there is inconsistency both within and between studies indicating
tremendous individual differences in subjects' dietary and metabolic changes after
smoking cessation.
Investigators need to try to determine carefully the potential moderator variables of
dietary and metabolic changes after smoking cessation. Factors such as gender, age,
race, weight history, and concerns about postcessation weight gain may all play a role
in predicting dietary changes after cessation. Some individuals, for example, may
respond to smoking cessation by dramatically increasing their dietary intake (Duffy and
Hall l988), whereas others may impose dietary restrictions in an attempt to avoid
postcessation weight gain (Klesges et al.. in press).
There also appears to be tremendous individual variation in the metabolic response
to smoking and smoking cessation. Overall, evaluations of short-term, acute responses
to smoking generally report increases in metabolic rate as a function of nicotine
administration and smoking (Hofstetter et al. 1986; Perkins et al. 1989a; Klesges.
Brown et al. 1990), although long-term (overnight or longer) studies generally do not
indicate changes in metabolic rate as a function of smoking cessation (Stamford et al.
1986). However, some investigators have reported that the acute effects of smoking
have not produced a change in REE (Warwick, Chapple. Thomson 1987).


Research needs to focus on a number of potential moderators of smoking and
metabolic rate. Levels of plasma nicotine vary greatly even for the same level of
cigarette consumption and for the same nicotine content of cigarettes (US DHHS
I98Xa). The relationship between nicotine, as well as other constituents of tobacco
smoke. and metabolic rate needs to be evaluated carefully. It is also possible that
heavier, chronic smokers may habituate to the effects of nicotine over time (US DHHS
1988a) and their metabolic responses may become blunted (Klesges, Coday et al. 1990).
Other important moderators. such as years smoked. gender. and relative weight. should
also be carefully evaluated in future investigations.

RELATIONSHIP BETWEEN OVERWEIGHT AND ADVERSE MEDICAL
           AND PSYCHOSOCIAL OUTCOMES

Obesity refers to excess body fat. whereas overweight refers to excess body weight
relative to height compared with gender-specific norms (Powers 1980). Obesity and
overweight are highly correlated across the population. although some individuals are
overweight but not obese (e.g., bodybuilders). and others are obese but not overweight
(e.g., a normal weight "couch potato") (Grunberg 1982b). In the context of this
Chapter. the relevant data are those that are related to health risks. The most commonly
used methods to measure or estimate body fat in studies of health consequences of body
size are measures of height and weight in comparison with gender-specific norms
(which actually determine overweight) and measurement of subcutaneous fat by
skinfold thickness at one or more sites (which determines obesity). Therefore. the data
cited in this Chapter are sometimes based on estimates of obesity and sometimes based
on estimates of overweight; both terms appear in the text. Normative values for these
anthropometric measures have generally been derived in one of two ways: either by
averaging the values found in populations of healthy persons or by tabulating values
reported to be associated with greatest longevity in population-based studies. Inclusion
of data based on these various standard measures provides the most complete informa-
tion available. Although the volume of research related to obesity and health risk
precludes comprehensive review here. a summary of this literature is a useful starting
point for examining the health risks of weight gain following smoking cessation.

Large amount\ of epidemiologic and clinical data clearly indicate a positive associa-
tion between excess body weight and medical ri5k. Cross-sectional. longitudinal.
ecologic. and case<ontrol studies indicate that there is a graded relationship between
weight and various diseases and disease risk factors. Positive associations have been
reported between body weight and glucose intolerance and type II diabetes (Kannell.
Gordon. Castelli 1979: Rimm et al. 1972: West and Kalblleisch I Y7 I: Negri et al. 1988:
Hadden and Harris 1987): elevated blood pressure and hypertension (MacMahon et al.
1987: Chiang. Perlman. Epstein lY6Y: MacMahon et al. lY83: Blackburn and Prineas
1983: Pan et al. 1986): elevated total blood cholesterol and lowered high-density
lipoprotein cholesterol (HDL-C) (Jooste et al. 1988: Garrison et al. 1980: Nanas et al.
IYX7): gout (Larsson. Bjorntorp. Tibblin IYXI ): kidney stones (Larc\on. Bjorntorp.
Tibblin 1981 ): gall bladder disease (Rimm et al. 1972): cardiovascular disease (CVD)
(Rabkin. Mathewson. Hsu 1977: Noppa et al. 1980: Garrison and Castelli 1985):

490


cancers of the endometrium and colon (Garfinkel 1985: Graham et al. 1988: Verreault
et al. 1989): arthritis (Anderson and Felson 1988: Felson 1988): and varicose veins.
Obese women are more likely than lean women to experience menstrual abnormalities
(Hartz et al. 1979) and complications in pregnancy (Abrams and Parker 1988). Obese
individuals require more medical care (Tsai. Lucas, Bernacki 1988). experience more
complications during and following surgical procedures (Schwartz 1955). and report
greater limitations in performing tasks ofeveryday living (Stewart. Brook. Kane 1980).

The strength and consistency of the data and the understanding of causal mechanisms
underlying obesitydisease associations vary from end-point to end-point. Neverthe-
less, there is little doubt that obesity represents an important health risk that may reduce
both the quality and duration of life. The overall evidence linking overweight todisease
has led to recommendations from numerous health organizations for individuals in the
general population to control their weight as a means of preventing future illness
(National Institutes of Health Consensus Development Conference Statement lY8S;
Subcommittee on Nonpharmacological Therapy of the I984 Joint National Committee
on Detection. Evaluation. and Treatment of High Blood Pressure 1986: US DHHS
1988b).

Despite convincing data linking obesity to ill health. several issues in the area remain
controversial. A key issue that is particularly germane to smoking cessation-induced
weight gain is the extent to which modest degrees of overweight represent a health
hazard. The most commonly recognized standards for acceptable body weights are
those developed by the life insurance industry based on followup studies of policy
holders conducted in 1959 and 1979 (Metropolitan Life Insurance Company 1960:
Society of Actuaries and Association of Life Insurance Medical Directors of America
1980).

Each of these studies evaluated the mortality of approximately 4,000,000 life in-
surance policy holders. "Ideal" weight standards that were developed from these
studies and widely used in subsequent research represent the gender- and height-
specific weights associated with lowest mortality. Overall. a J-shaped relationship is
observed between weight and mortality. Lowest premature mortality is associated with
body weights that are about IO percent below the population average. Excess premature
mortality is associated with extremely low weights (i.e., body weights more than IO
percent below the standards), and premature mortality increases incrementally for
increasing weights above the standard. In the range of weights that encompasses the
vast majority of the population (i.e., relative weights of I.0 to 1.3). the relationship
between weight and mortality was approximately linear with each l-percent increase
in weight associated with about a l-percent increase in premature mortality. Above
relative weights of about 1.3, the curve rises even more steeply so that premature
mortality may double at relative weights of I .5 or more (Manson et al. 1987).

The overall relationship between weight and mortality has been confirmed in several
other large scale prospective studies.  For example. the American Cancer Society
followup study of 750,000 men and women from the general U.S. population provides
confirmatory data with specific detail on various causes of death (Lew and Garfinkel
1979). Table 3 presents mortality ratios for this study group by weight status for
selected causes. Table 4 presents mortality ratios by weight and smoking status. Most

491


of the deaths associated with leanness occur among smokers, and although the shape
of the weight-mortality curve\ are similar among smokers and never smokers. smokers
have nearly twice the mortality rate compared with never smokers over much of the
weight distribution. A recent IO-year followup study of 1.700.000 Norwegians con-
firms these findings in a non-U.S. population with regard to the shape of the weight
mortality association and the causes of death at both ends of the distribution (Waaler
1988).

The reported relationship with age further complicates the relationship between body
weight and health (Andres et al. 1985). For example. the strongest relationship between
body weight and premature mortality holds for younger age groups (i.e.. under 40 years
of age). In older adults. the relationship between weight and mortality is weak over
much of the weight distribution. and in the oldest groups studied (i.e.. over 60 years of
age), mortality appears inversely related to weight. Indeed. many prospective studies
of middle-aged adults have observed little or no prognostic significance of body weight
for either total premature mortality or major disease endpoints except at the extremes
of the body weight distribution. These findings have led some researchers to argue that
concerns about weight and overall health for most individuals have been exaggerated
(Keys 1981; Barrett-Connor 1985). In contrast, other investigators have noted that
cigarette smoking has not been statistically controlled in many of these analyses, and
in addition, pathophysiologic effects of obesity. such as hypertension and hyper-
glycemia. have been inappropriately adjusted (Manson et al. 1987). Therefore. the
health risks of obesity may have been underestimated.

Another issue to consider in the relationship between body weight and health is that
all forms of overweight may not pose the same health risks. In particular. health risk
may depend on weight status at different times in an individual's life. A study by
Abraham, Collins, and Nordsieck ( I97 I ). for example. studied 1.087 white males for
whom height and weight data were available at ages 9 to I3 and after a period of
approximately 30 years. By cross-classifying respondents by childhood and adult
weight status, these researchers found that individuals who were at the low end of the
weight distribution as children. but who gained weight to reach the high end of the
weight distribution as adults, were at significantly higher risk of hypertensive vascular
disease and cardiovascular renal disease than were individuals who had high weights
both as children and as adults. Similarly, in a report based on the Normative Aging
Study. Borkan and colleagues ( IYXh) found age by weight gain interactions. relating
weight gain to health risk. Weight gain had a stronger positive association with change
in fasting glucose levels for older men compared with younger men: however. weight
gain was more strongly related to change in uric acid (positive) and forced vital capacity
(negative) in younger men (Borkan et al. 1986).

The importance oftiming issue\ in the relationship between body weight and disease
is also apparent in weight cycling. Weight cycling refers to gaining and losing weight
repeatedly over time. Such weight fluctuations might occur in individuals who
repeatedly diet but are unable to maintain weight losses. Weight cycling might be
caused by recurrent illnesses or major fluctuations in lifestyle. Such fluctuations might
conceivably also occur among smokers who quit but relapse to smoking on multiple
occasions. Several recent reports suggest that weight cycling may be associated with

497


TABLE 3.-Mortality ratios for all ages combined in relation to the death rate of those 90-109% of average weight


                                          Weight index"
CXM uf        7th rev
  death         ICD       Gendrr        <x0        X&X9      YO- IO')       I IO-I I')      120-12')     I.%-ii')     >I40

Total dtxiths                MA          I .2s        I .os        I .oo         I.15         I 27        I .4b       I .x7
                       F~lll~k        1.1')       0.Yc-J        I .oo         1.17         I .2Y        I .Jh       I .XY

CIiD          420         Male         o.xx       O.YO        I .oo         I .73         1.32        I .ss       I .YS
                       Femalr        I .o I       0.x9        I .oo         I .2i         LAY        I.54       1.07

CXKW.         I4tk20.5      Mdr         I .33        I.13        I .oo         I .07         I .OY        I.13       I ..11
011 \ite\                    Frm:ilr        0.96       0.02        I .oo         I.10         I I 0        I .23       I.55


Diabetes        260         Male         o.xx       0.x4        I .oo         I .hS         2.X-l        3,s I       S.IY
                       Female        O.hS       O.hl        I .oo         I .Y2         3.3-l        2.7x       7.00
Dlgative        S4ObS42      Male          I.3Y        1.2x        I .oo         I .-Is         .XX        7.X')       3.w
tliw~w~         570-57x


             5X4-5X6      Femalr        1.5X       O.Y2        I .lK)         I .hh          h I        7.1s       7.3

C`errhrovawulnr    330-3.34      Mb          I.21        I .OY        I .oo         I.15         .I7        I .SJ       1.17
diwaw                  F~lll~k        1.33       O.YX        I .oo         I .OY         I.10        1.40       I.52


Nol`E. (`llD=co~ w.q he;w d,\~il\~!
"C`;il~ul.~trd hy ~hvdin~ a t"r\,m`\ .~ctuid wc,gt,t hy the ~orrc\,,w,d,n~ ;,vcr.,g' welghl t,,r Ihc .~,,,mqm.w wx-IIICII 01 thaghl-5.!r ;I~C ~"`L,,`. n~d~,t~t,cd II> 11Kl
SOI XC'E: 1.w id (;artinkl ( lY7Y I.


TABLE 4.-Mortality ratios for all ages combined according to smoking status in relation to those 90-1099'~ of average age

Weight index"

Never vwkd       o.xx
20 cig/dny        I .6X
Other            I.77
Ncvcr \n~kxi       1.10
x0 q/day        I .YH
Other            I..53

0.75
I .40
1.01
o.xx
1.5')
I.13

0.75
I.34
O.Y3
O.Y3
1.64
I.12

0.98
I .76
1.1s
I .20
2.22
I .42

1.16       I .6Y
2.00      2.21
I.29       I .66
1.37       I .74
2.30       2.73
I .62       2.04

Coronq
artery dwax
(ICD 420)

Never wwked
t20 clg/day
Other
Never smohed
X0 cig/duy
Other

0.72
I .Oh
0.`) t
O.Y3
t 3 I
1.54

0.66        0.76
I.13        1.33
0.90       0.93
ox        0.92
I .70        2.12
I.14        I.IX

0.96
t .66
1.12
I.10
2.20
I .xx

I .04
I.81
1.1')
I .2Y
3.4x
I .44

1.24
2.1 I
t 37
t .3Y
3.79
2.01

1.73
2.1 I
1.x4
I.86
4.74
2 .3 3

Cancer,
at1 slteh
( ICD I-K-205)

Malt'




Fcmule

Never mohrd
220 cydday
Other
Never welled
220 cigiday
Other

0.60
2.07
I.20
0.x.5
t .4Y
I.1 I

0.60
I.71
I .03
0.x5
t .x1
O.YX

0.66
I .43
I .YO
O.Yh
I.34
I .03

0.69
I .46
0.89
t .Oh
t .x1
I .Oh

0.7Y
t 5s
t .05
I.th
I.34
I.16

0.90
I.71
0.87
1.1')
I .70
I.1 I

0.76
2.00
I .22
t .so
I .4Y
I.60


elevated premature mortality compared with maintaining a more stable weight ov'er
time. In a study by Hamm. Shekelle. and Stamler ( IYXY). for example. CVD and cancer
mortality and total mortality were compared among individuals who reported either
having gained significant weight (N=l33). having remained at the same weight
(N=l7X), or both having gained and lost significant weight (N=YX). Both gainers and
cyclers had significantly elevated total mortality experience. relative risks of 1 .S and
I .4. respectively. compared with individuals whose weights remained constant. Three
recently published abstracts (Lissner et al. l9XY: Lissner. Collins et al. IYXX: Lissner.
Odell et al. 19X8) have reported even Freater health risks of weight cycling. Using
prospective data from the Multiple Risk Factor Intervention Trial (MRFIT) (Lissner.
Collins et al. IYXX). two prospective studies from Goteborg. Sw,eden (Lissner et al.
1987). and the Framingham Study (Lissner. Odell et al. 19Xx). weight cycling vvas
defined as the variability of vveights recorded at repeat examinations. Controlling for
a variety of possible confounding variables, weight cycling was independently predic-
tive of total premature mortality and CVD mortality. In the analyses based on MRFIT.
premature mortality among men with the most variable weights was 36 to X9 percent
higher than among men with the most stable weights.
An additional issue to consider in the relationship between body weight and health
is the distribution of body fat. Individuals differ in the location of stored adipose tissue.
Research data show that individuals who store greater amounts of body fnt in the
abdominal region rather than in the hips or limbs have elevated cardiovascular risk
factors (Gillum 19X7; Selby. Friedman. Quesenberry l9XY ). CVD. and diabetes rates
(Freedman and Rimm 19X9: Lapidus and Bengtsson 198X) as well as reproductive
system cancers among women (Bjomtorp 198X ).
Usually measured by the ratio of abdominal circumference to hip circumference or
the ratio of trunk versus peripheral skinfolds. a central body fat distribution is positively
correlated with absolute body weight. However. in several studies, the centrality of fat
distribution has proven to be a much stronger predictor of disease than body weight. A
landmark study in this area was conducted by Larsson and colleagues (1984) who
reported on I3 years of followup for 792 Swedish men aged 54 years at the time of first
observation. Outcome measures were stroke. ischemic heart disease. and all-cause
mortality. None of these health outcomes was significantly related to measures of
adiposity (body mass index weight/height', the sum of several skinfold measurements.
and body circumferences). However. the ratio of waist to hip circumference (WHR)
was significantly and positively related to all three measures of illness and death. The
relevance of this finding for ex-smokers, as discussed below, is that smoking is
positively related to WHR and that smoking cessation is associated with a reduced
WHR (Shimokata. Muller. Andres 1989).
Compared with pathophysiologic health risks, social and psychological pathologies
associated with overweight are not as well established. This situation may reflect the
relative absence of research in this area, but it may also indicate the absence of a strong
relationship. Obesity is strongly disapproved of and discriminated against in this
society (Allon 1973: Grunberg 19X2b; Wadden and Stunkard 19X5). Overweight
individuals are falsely stereotyped as having a variety of undesirable characteristics.
including self-indulgence, laziness. lack of self-control, and lack of intelligence.


The perception in this culture of obesity as unattractive has been documented in
various populations. For example Richardson (1971). in a study of IO- and I l-year-
olds' perception of the likableness of children with a variety of handicaps. found that
obese children were judged less attractive than were children with amputations and
facial disfigurement or children confined to wheelchairs. Similar biased impressions
have been documented among adults and among physicians and medical students
(Allon 1973; Maddox and Liederman 1969). Canning and Mayer ( 1966) found that the
prevalence of obese students in college was less than the prevalence of obese students
in high school despite no difference in academic performance in high school or in
college application rates. A survey of employers indicates that many profess not to hire
obese individuals (Roe and Eickwort 1976). and at least one survey of business
executives suggests an inverse association between obesity and salary (Indrrst~:\ We&
1974). In a survey of college students, Kallen and Doughty ( 19X4) found lower rates
of reported dating in overweight subjects. although no less satisfaction with intimate
relationships.
Although it is obvious that many overweight individuals are dissatisfied with their
personal appearance. desire to lose weight. and frequently make efforts to lose weight
(Wadden et al. 19X9: Polivy, Gamer. Garfinkel 1986: Adams 19X0: Guggenheim.
Poznanski. Kaufmann 1973: Dwyer. Feldman, Mayer 1975: Dwyer and Mayer 1970:
Stewart and Brook 1983; Jeffery et al. 19X4), evidence for severe psychological or
social impairment in all but the most severe cases of obesity is generally lacking.
Moore. Stunkard. and Srole ( 1962), reporting data from the Midtown Manhattan Study.
found higher scores on three measures of psychological disability in the obese compared
with the nonobese.
Data from the Rand Health Study and a Dutch population-based study indicated that
obese individuals report that their weight imposes some restrictions on their everyday
activities and causes them more pain and worry compared with the nonobese (Stew*art.
Brook, Kane 19X0: Stewart and Brook 19X.1: Seidell et al. 19X6). However. Stewart
and Brook ( 19X3) also reported that obese persons are less depressed than normal-
woeight persons. a finding corroborated in a study of British citizens by Crisp and
McGuiness ( 1976). These mixed and inconsistent findings from studies of obese adults
also have characterized studies of obese children (Wadden et al. 1989: Wadden et al.
19X4). In extremely obese individuals presenting themselves for treatment (i.e.. those
75 percent or more overweight). higher levels of psychological disturbance have been
reported (Halmi et al. 1980: Atkinson and Ringuette 1967). Even here. it has been
questioned whether such pathology is greater than that oh\erved in normal-weight
individuals pre\enting for medical or surgical procedures (Wise and Fernandez 1979:
Swenson. Pearson. Osborne 1973). It has been su,,
                           CToested that unwarranted concerns
about vveight gain mav contribute to eating disorders such as anorexia and bulimia
(Wooley and Wooley 19X-l). Data supportin, (7 this idea. however. are largely anecdotal
(Wadden and Stunkard 19X5 ).
Prospective studies on the effects of weight gain on psychosocial functioning have
not yet been reported. Studies of psychological changes accompanying weight loss
generally show positive effects. even when weight loss is modest and not well main-
tained (Wing et al. 19X-t). Therefore. consistent with intuition. many people feel better


about themselves when they lose weight. However. the extrapolation of these findings
to weight gain lacks empirical support.

In summary. although adverse psychological and social consequences of overweight
have been much discussed in both lay and professional circles. \uch effect\ have not
been well documented. Moreover. to the extent that associations have been reported.
the direction of causation is unclear. More research in this area is warranted. particu-
larly because the available research is not extensive and much of it is methodologically
weak. At this time. data suggest that only the most extreme forms of obesity, the upper
I or 2 percent of the weight distribution in this domain. pose significant hazards.
However. it is important to emphasize that these conclusions reflect the lack of evidence
for serious psychosocial problems resulting from modest weight pains. Nevertheless.
many persons want to lose weight. many persons seek ways to lose height. and many
persons feel better about themselves when they lose weight.

CHANGE IIV WEIGHT-RELATED HEALTH RISKS
     AFTER SMOKING CESSATION

As documented earlier in this Chapter. smoking cessation is associated with weight
gain. An important question is the extent to which this weight gain might lead to
elevations in blood pressure. cholesterol. glucose intolerance, or other factors that
would offset the benefits of smoking cessation discussed in detail throughout this
Report.

Relatively few studies have specifically examined the effect of smoking cessation on
weight-related health risks. Seven studies were reviewed for this Report. Gordon and
coworkers ( 1975) reported changes over an I S-year period in weight and related risk
characteristics among individuals in the Framingham Study. At entry into the study,
61 percent of men and 40 percent of women smoked cigarettes; at the I S-year followup.
37 percent of men and 3 I percent of women continued to smoke. Analyses of changes
were restricted to men because of the small numbers of women who quit smoking in
this sample. Male quitters were similar to those who continued to smoke in baseline
characteristics except that the former group contained more diabetics. The authors
interpret this finding as suggesting that ill health is an incentive to stop smoking.

Short-term effects of smoking cessation, defined as the change between the last
examination at which smoking was reported and the first examination at which
nonsmoking was reported (I-year intervals). included a weight gain of 3.8 pounds. an
increase in systolic blood pressure of I .6 mm Hg. and an increase in serum cholesterol
of0.2 mg/dL. Continuing smokers had an average weight gain of 0.3 pound. increased
systolic blood pressure of 0.7 mm Hp. and decreased serum cholesterol of 0.2 mgjdl.
For the same time period, nonsmokers had an average weight gain of 0.5 pound.
increased systolic blood pressure of 0.7 mm Hg, and increased serum cholesterol of 0.3
mg/dL. Differences among groups in blood pressure and cholesterol changes were not
statistically significant. Long-term changes associated with smohing cessation were
evaluated by comparing changes between the fourth and the tenth examination. a period
of 11 years. among continuing smokers. nonsmokers. and individuals smoking at entry
but not smoking from the fourth to the tenth examination. Trends in weight. blood


pressure, serum cholesterol. and blood glucose did not differ significantly among these
three groups.
Schoenenberger (19x2) reported the relationship between smoking cessation and
changes in body weight. blood pressure, and serum cholesterol over 3 years among men
in the special intervention group in MRFIT. All men in the study were at high risk for
heart disease and were being counseled throughout the study in smoking cessation and
dietary changes to effect cholesterol reduction. When necessary. the men were also
treated pharmacologically for elevated blood pressure. Results indicated significantly
less weight loss in quitters (-0.6 pounds. i.e.. a gain of 0.6 pounds) compared with
nonsmokers and continuing smokers (5.7 and 3.6 pounds, respectively), no differences
in blood pressure change (-9.6, -8.7. and -9.4 mm Hg, respectively, for systolic blood
pressure among men not on medication). and greater reductions in serum cholesterol
among quitters (-I 3.4 mg/dL) than in the other two groups (-10.0 and -8. I mg/dL).
The latter effect was interpreted as possibly reflecting a higher level of generalized
motivation to reduce risk in the quitting group.
In a S-year followup study of 2.383 persons with mild hypertension in eastern Finland,
Tuomilehto and colleagues (1986) found that 26 percent of men and 35 percent of
women who smoked at the time of the initial examination had quit. Among men,
smoking cessation was associated with a 7.9-pound weight gain compared with 0.2-
pound and 2.2~pound weight gains among nonsmokers and continuing smokers. respec-
tively. Among women. weight loss after smoking cessation averaged 0.7 pound
compared with gains of 0. I pound and 2.2 pounds among nonsmokers and continuing
smokers, respectively. Smoking cessation was not associated with a significant in-
crease in blood pressure or serum cholesterol compared with continuing smokers or
nonsmokers. Mean arterial pressure fell by 5.0 and 13.1 mm Hg in male and female
quitters. respectively. compared with decreases of 6.9 and 8.7 mm Hg among non-
smokers and of 7.0 and 9.6 mm Hg among continuing smokers. Serum cholesterol fell
between 0.63 and 0.66 mmol/L across the various subgroups.
Two papers relating smoking cessation to weight-related risks have been published
based on data from the Normative Aging Study. The first report examined change over
5 years among 2 14 continuing smokers and 103 quitters (Garvey. Bosse, Seltzer 1973).
An average weight gain of 4.2 pounds. which was accompanied by a 3.6 mm Hg
increase in diastolic blood pressure. was observed among quitters compared with
continuing smokers. The second report examined the relationship between smoking
and body fat distribution. both cross-sectionally and longitudinally between examina-
tion visits scheduled 7 years apart (Shimokata, Muller. Andres 1989). Central body fat
distribution. which poses increased health risks. as assessed by WHR was positively
associated u ith making. Moreover. among smokers. daily cigarette consumption was
positively associated with central adiposity. Smoking cessation was associated with
increased body weight. However. despite the weight gain. the change in WHR among
ex-smohers was small and. in hct, decreased slightly because hip circumference
increased. Therefore. based on WHR data only. smoking rather than smoking cessation
may pose a wjeight-related health risk.
Stamford and coworkers ( 19X6) studied the short-tern1 effects of smoking cessation
on lipoprotein fractions. Amon I3 women who successfully quit smoking for a period


of 48 days, these investigators observed a weight increase of 4.9 pounds. This weight
change was accompanied by a nonsignificant increase in total cholesterol of 9 mg/dL
and a significant increase in HDL-C of 7 mg/dL. Over the subsequent year. these
favorable HDL-C changes were maintained in three individuals continuing to abstain
from smoking, but were lost in nine individuals who returned to smoking.
One randomized trial of smoking cessation and weight-related health risks was
located for this review. Rabkin (1984a) randomized I07 smokers to smoking cessation
and 33 to continued smoking in a comparative study of smoking cessation strategies.
A battery of physiologic measures was obtained at baseline and repeated 2 to 3 months
following randomization. No differences were found in cessation rates among the
different quitting strategies. Physiologic changes observed in the smoking cessation
group as a whole (i.e., all those randomized) included a significant increase in weight
(I .8 pounds) and skinfold thickness (6.6 mm) compared with the control group (0.4
pound and -7.0 mm). but no significant change in lipid profiles, fasting glucose, or
blood pressure. Only 35 subjects in the cessation groups were successful in quitting
smoking. Successful quitters gained significant amounts of weight compared with
individuals who did not quit (4.4 vs. 0.7 pounds, respectively). Successful quitters also
experienced significant increases in HDL-C compared with nonquitters (4.2 vs. 0.1
mg/dL). Changes in other weight-related risk factors did not differ among groups.
The studies reviewed above are consistent in their findings. Individuals who quit
smoking andgain weight appearto experience relatively small changes in health-related
risk factors such as blood pressure. serum cholesterol, and blood glucose. Moreover.
some of the potentially adverse effects of weight gain on health risks are mitigated by
changes in lipid profiles and in body fat distribution in a direction predictive of
improved health outcomes. It seems likely that only those smokers who have large
weight gains after smoking cessation would experience important changes in weight-
related risk factors.
The characteristics of individuals most likely to gain harmfully large amounts of
weight after smoking cessation merit additional investigation. Bosse, Garvey. and
Costa (1980) have reported relevant findings from the Normative Aging Study. Over
a S-year period these investigators found that factors most predictive of weight gain
among recent quitters were younger age, leanness of body build. and greater amounts
of smoking. The latter finding is confirmed by other studies (Blitzer. Rimm. Giefer
1977; Gordon et al. 1975). There are no data available on specific predictors of
excessive weight gain among ex-smokers.  Research on predictors of weight gain
suggest that those persons most likely to gain weight after smoking cessation may be
those who can best afford it because they are relatively lean. They also may be those
who need smoking cessation most because they smoke the most.
Quantitatively estimating the extent of health risk associated with weight gain after
smoking cessation is a complex process. The health risks of obesity vary with age, the
temporal patterning of weight changes. type of obesity, and other risk factors.
Moreover, smoking cessation itself appears to have independent effects on some
weight-related risk factors that may actually be beneficial.
It has been estimated that the health risks posed by regular smoking double overall
mortality rates compared with never smoking (US DHHS 1989). Moreover. as detailed


elsewhere in this Report. there are clear health benefits associated with smoking
cessation. The amount of excess body weight that would have to occur to offset the
benefits of smoking cessation would have to be considerable. Yet. average weight gains
after smoking cessation are only about 5 pounds. bringing most individuals to a weight
level similar to that of their nonsmoking peers. As discussed in this Chapter. the
proportion of ex-smokers who are likely to gain large amounts of weight (e.g.. more
than 20 pounds) is small. Therefore. although some individuals may experience these
large weight gains. the number of individuals likely to gain enough weight to offset the
benefits of smoking cessation is negligible. Also, the likelihood of adverse psychoso-
cial consequences because of small weight gain seems remote for most people.
Although further research in this area is w)arranted. there is little reason to expect weight
gain to pose a substantive medical or psychosocial hazard to the vast majority of
smokers who are quitting. For those persons wsho do pain excessive amounts of weight
after smoking cessation. the health benefits of cessation still exist. and weight control
programs rather than smoking relapse should be implemented. In conclusion, the clear
reduction in health risks that results from smoking cessation overshadows any health
risks that may result from smoking cessation-induced body weight gain.

STRATEGIES TO CONTROL POSTCESSATION WEIGHT CAIN

Because weight gain after smoking cessation commonly occurs and because many
people, particularly young women, report smoking to control weight gain (Klesges and
Klesges I9XX: US DHHS 1990). strategies that successfully moderate postcessation
weight gain ma) encourage weight-conscious smohers to attempt cessation and ma)
facilitate the efforts of successful quitters to remain abstinent. Only a few controlled
investigations have examined interventions for reducing wjeight gain after smoking
cessation. Currcntl! existing behavioral and pharmacologic intervention\ are sum
marized belo\

Behavioral Methods for Reducing Postcessation Weight Gain

Smoking cessation programs that include a M eight control component have not
successfull! increased \mohing cessation. In one study. 79 women Here randomly
assigned to a 7-h eek smohing cc\sation program either u ith or u ithout @eight control
information (Mermrlsrein 19x7 ). At po\ttreatmt'nt and at thllowup. there Mere no
significant differences in \mohing ct`\\ation rate\ bet\rren the tuo groups. Participant\
in both groups gained Meight during treatment: ho\\tc\,er. the weight increase for the
smohing-ce\~;ltic,n-plLi~-~\ei~ht-colitr~)l - c'roup ~3s \ignit'icantl) le\s than the increase
for the \rnokin~-cc~~ati(~~i-~)~ll~ group ( I .f \ s. 2.4 pound\).

Several \reight control \tratcgie\. as adjunct\ to smohing cessation. were evaluated
b> Grinstead ( 19X I ). Fort>-fi\,e \ub.jects were randomly a\\ifned to ;I I-weeh smohing
a\,er\ion pr+ram LI ith one of three height control intt'r\,cntions. No difference\ in
smohing cc\sation rate\ wcrc observed. and there were no \\cight change differences
among the group\. Suh,ject\ in all groups gained iheight during treatment.

500



In another smoking cessation stud). Bowen. Spring. and Fox (submitted for publica-
tion) randomly a\\iged 3 I participant\ to either a high- or low -carbohydrate diet.
Sub.jects in the high-carbohydrate group uere given specific dietary ad\,& encouraging
the use of carbohydrates: they v,ere also given tQ,ptophan a\ a dietar! supplement. In
the low-carhohydrutc proup. dietary advice focused on consumption of food\ IW in
carbohydrate\. Each group attended four Z-hour meeting\ per Mech. Scs\ions for both
group\ $tres\ed information about the effect\ of tobacco. self-m~tnalreni~lit \trategit'\.
rapid smoking. and relapse prevention techniques.
The rationale for this treatment approach i\ haed on a IYXZ report that smohing
ce\\ation is accompanied by an increase in preference for \ueet-ta\ting high car-
bohydrate food\ (Grunberg 1YXZa). Grunberg ( IYX6) suppe\ted that carbohydrate\ act
through \erotonergic mechanism\ to attenuate L\ ithdraual. Tqtophan is thou@t to
increase the production of \erotonin in the brain.  At the end of treatment. I3 of 16
subjects (XI percent) in the high-carbohydrate group were abstinent (confirmed by CO
assessments) compared with Y of 15 subject\ (60 percent) in the low-carb(~h~,dr~lte
group. Thi\ difference M';I\ in the hypo;he\iLed direction but was not \tatisticall>
sifniticant.  Also consistent uith the hypothesis. nonab\tainers in the high-car-
bohydrate group were smoking significantly fen,er cigarettes than nonabhtainers in the
low-carbohydrate group. In both group\ sub.ject\ gined ueight after quitting smohing.
No significant differences were observed between experimental group\ in the number
of subject\ who gained weight or in the average amount of weight gain per subject.
Ofthe three investigations that have evaluated the impact of a weight-control program
on weight gain and cessation (Bowen. Spring. Fox. submitted for publication: Crin\tead
I YX I : Mermelstein I YX7). none were successful in preventing weight gain and only one
(Mermelstein IYX7) reported a significant between-groups difference in the amount of
weight gain. None of the smoking-plus-weight-control programs were clearly succe\\-
ful in significantly enhancing cessation rates.
At least three investigations have indicated that individualscan stop smoking without
significant w(eipht gain. However, these studies have been limited to subjects typicalI\
at h&h risk of CVD who participated in multicomponent CVD rich factor reduction
trials. In ;1 study involving MRFIT participants at the upper 10 to IS percent on a
measure of CVD risk. Schoenenberger (IY81) reported that continuing smokers had
lost an average of4.6 pounds at a J-year followup. but that those who quit \mohin$ had
gained less than 1 pound. All subjects participated in several treatmentc that focused
on stopping smoking and improving diet. III a h-vex followup of these participants.
quitters had gained4.7 pounds compared with a I .3-pound weight lo\4 among nonquit-
ters overall (Gerace et al.. in press). However. weight gained after cessation varied as
a function of baseline daily ciparette consumption. For those H ho had smohed 1 to IY
cigarette\ per day. quitters averaged a O.S-pound weight gain compared uith ;I 2.1.
pound weight loss among continuing smokers For those who had smoked 20 to 3Y
cigarettes per day. quitters avetqed ;I -If-pound weight gain compared with ;I I .I-
pound weight loss among continuing 5mohers. For those who had smohed more than
40 cigarettes per day. quitters averaged ;i 7.2.pound weight gain compared \rith a
I .()-pound weight toss amoncg continuing smokers. Thus, weight gain after cmohiny


cessation was positively related to daily cigarette consumption before quitting (Gerace
et al.. in press).

Hickey and Mulcahy (1973) reported on 124 male smokers who survived a myocar-
dial infarction and participated in a lifestyle modification program. At I-year followup.
these investigators found an average weight gain of I .6 pounds (change not significant)
among the 60 individuals (4X percent) who quit smoking. Those individuals who
continued to smoke averaged a small. but nonsignificant weight loss (0.8 pound). In a
study of CVD risk factor assessment in Paris. Ducimetiere and colleagues (197X)
randomly assigned 271 smokers to either a cessation-plus-diet advice group or a
smoking cessation-only group. The two groups did not differ in weight at pretest, but
at Z-year followup. subjects in the cessation-plus-diet group had significantly lower
weights than subjects in the cessation-only group. However, the two groups did not
differ in smoking cessation. and the large degree of attrition in the cessation-plus-diet
group must be noted when evaluating treatment outcome.

Thus, it appears that for individuals at high risk for CVD participating in intensive,
multicomponent risk factor trials, smoking cessation can occur without significant
increases in body weight. Future research needs to focus on whether similar results can
be obtained with the typical smoker in a more cost-effective intervention.

Pharmacologic Methods for Reducing Postcessation Weight Gain

Three pharmacologic approaches have been evaluated as potential treatments for
reducing postcessation weight gain:  nicotine polacrilex gum. d-fenfluramine. and
phenylpropanolamine (PPA). The available information on pharmacologic interven-
tions for reducing postcessation weight gain is summarized below.

There is substantial evidence that nicotine is the agent in tobacco that causes changes
in body weight (US DHHS I9XXa)  Therefore. the most obvious pharmacologic
approach that may prove useful in reducing postcessation weight gain is nicotine
replacement. The least hazardous vehicle currently available to deliver nicotine is
nicotine polacrilex gum. As literature documenting the use of the gum to aid in quitting
smoking has grown (Schwartz 19x7; US DHHS 1988a). several correlational studies
have reported that use of the Furn reduces postcessation weight gain (Emont and
Cummings 1987: Fagerstrom 19X7: Hajek. Jackson. Belcher 198X). although this effect
is not observed uniformly (Hjalmarson IYX4: Tonnesen et al. IYXX). In one study.
Fagerstrom (19X7) conducted a followup of 2X patients who were still abstinent at
b-month posttreatment after attending a smoking cessation clinic. These subjects
received 7 mg of nicotine gum. Subjects were divided at the median (263) number of
pieces of gum chewed. Six months after treatment. less frequent gum users had gained
an average of 6.X pound\. whereas the body weight of more frequent gum user\ had
increased by 3.0 pounds. Fagerstrom (1987) hypothesized that higher nicotine pola-
crilex gum use was necessary' to produce blood nicotine levels approaching the effective
dosages achieved by smoking.

Emont and Cummings ( 1087) also found that nicotine polacrilex gum use reduced
postcessation weight gain and that this effect was related to the amount of gum chewed.
These investigators studied 103 participants of a 2.5week stop-smoking clinic. Of the


subjects who were either abstinent at 1 month or had smoked fewer than 5 cigarettes in
the month since treatment. 20 had used nicotine polacrilex gum in their attempts to quit.
Use of nicotine polacrilex gum in general was not significantly related to weight gain.
However. when number of pieces of gum chewed per day was considered. there wa\ a
significant inverse correlation (r=O.37) between nicotine polacrilex gum use and
increase in body weight. When broken down by initial daily cigarette consumption.
the relationship between nicotine polacrilex gum use and weight pain held only for
individuals who had smoked more than 26 cigarettes per day. Neither the Fager\trom
( 1987) nor the Emont and Cummings ( 1987) studies biochemically verified smoking
status or measured blood nicotine levels.
In the only controlled investigation ofthi\ hind. Gro\s. Stitzer. and Maldonado ( 1989 1
examined the relationship between nicotine polacrilex gum u\e and body weight.
Subjects were randomly assigned in a double-blind study either to a nicotine polacrilex
gum or a placebo condition. Smohing and nicotine polacrilex gum use were verified
with CO. thiocyanate, and cotinine measurements. Of the original 117 subjects. 40
completed the IO-week abstinence trial. In this period. abstinent subjects in the placebo
group gained an average of 7.X pounds. 4.0 pounds more than the abstinent nicotine
polacrilex gum users. There was also evidence for a nicotine dose effect on weight
gain. Users of fewer than 6.5 pieces of gum per day gained 5.0 pounds over the IO
weeks. whereas more frequent nicotine polacrilex gum users gained I .S pounds. Gro\s.
Stitzer, and Maldonado (198Y) present strong support for nicotine polacrilex gum's
suppression of postcessation weight gain in this rigorous study. Once nicotine
polacrilex gum use was discontinued. weight gain in both active gum and placebo
conditions was comparable (6.8 vs. X.7 pounds at 6-month followup). Thus. in this
study. nicotine replacement delayed rather than prevented postcessation weight gain.
A recent controlled study (Spring et al.. in press) evaluated the effects of d-
fenfluramine on postcessation changes in food intake and weight gain. D-fenfluramine.
which releases and blocks re-uptake of serotonin. is a prescription drug that has
anorectic qualities without stimulating the central nervous system (CNS). For this
study. 31 overweight female smokers were placed either on placebo or 30 mg d-
fenfluramine per day in a double-blind assignment. Subjects then quit smoking and
were observed for4 weeks. Although the numbers of subjects remaining abstinent were
small (five in the placebo group and eight in the d-fenfluramine group), significant
differences in food intake between the two groups were observed over time. By 4X
hours after discontinuing smoking, placebo-treated subjects consumed approximately
300 cal more per day than during the baseline measurement period. This increase
resulted largely from increased consumption of carbohydrate-rich meal and snack
foods. The difference in weight gain between the two groups was significant. with the
placebo-treated subjects gaining an average of 3.5 pounds and the d-fentTurdmine-
treated subjects losing an average of I .X pounds. No significant differences in smoking
cessation were observed, although statistical power to detect a difference was low.
A recently completed. placebo-controlled investigation evaluated the effects of
phenylpropanolamine (PPA). which is an over-the-counter sympathomimetic agent that
has weak CNS effects and more pronounced peripheral effects. on weight gain a\-
sociated with smoking cessation (Klesges. Klesges et al. I990). It is used both LS an


anorectic agent and as adeconge\tant. Subjects vvere S7 adult female cigarette smokers
who were randomly assigned, in a double-blind procedure. to either gum with PPA. (7-S
mg tid). placebo gum. or no gum. After a baseline assessment, subjects were paid to
quit smoking for 2 weeks. Smoking cessation was verified by weekly as well as by
random (spot), CO assessments. Of the 57 subjectsenrolled in the study. 4 1 (72 percent)
were successful in quitting smoking. Of subjects receiving PPA, 94 percent quit
smoking. whereas 63 percent of the two control groups quit smoking. Of those subjects
remaining continuously abstinent over the 2 weeks. dietary intake decreased 630 kcal
on average in the PPA group, whereas intake in the other two groups remained
unchanged. Decreases in intake of all major nutrients (carbohydrate. fat. and protein)
were observed in the PPA group. Abstinent subjects receiving PPA gained significantly
less weight (mean change=0.09 pounds) compared with either the placebo gum group
(mean change=l.S9 pounds) or the no gum group (mean change=I.W pounds).

To summarize this Section, additional minor weight control modifications to smoking
cessation programs do not generally yield beneficial effects in terms of reducing
postcessation weight gain or increasing cessation rates. However, aggressive weight
control programs, perhaps offered after individuals have quit smoking (Wittsten 1988).
may be able to produce smoking cessation without unwanted weight gain. Nicotine
polacrilex gum, d-fenfluramine. and PPA all have promise as adjuncts for reducing
postcessation weight gain, but research to date is extremely preliminary.

Focus needs to be on more effective behavioral methods for reducing unwanted
postcessation weight gain and on combination therapies that include behavioral and
pharmacologic strategies. High priority must be given to the development and evalua-
tion of effective programs that can be offered in a cost-effective manner. Given the
probable role of metabolic rate on postcessation weight gain, weight programs may
need to focus on reduction of dietary intake rather than dietary maintenance. Addition-
ally. aggressive weight management programs may not be necessary, or even wanted.
for many subjects who quit smoking (Gritz. Klesges. Meyers 1989). Future inve5tiga-
tions need to determine. of those who quit smoking. the individuals best suited for
weight management programs without compromising smoking cessation.

Studies on the effects of nicotine polacrilex gum. d-fenllurdmine, and PPA on
postcessation weight gain yield some cautious optimism. However. longer followup
periods and larger. more heterogeneous sample\ must be utilized in future investiga-
tions. It al\o appears. at lea\t with nicotine polacrilex gum (Gross. Stitzer. Maldonado
19X9). that weight gain can occur rapidly after gum use is discontinued. This delayed
weight gain . and it\ possible role on post-drug relapse .needs to be investigated. Future
research also needs to focus on specifying the influence of moderator variables. such
as initial daily cigarette consumption. age. gender. and level of drug use on the
effectiveness of the\c pharmacologic agents in preventing weight gain. Finally. the
relative efficacy of these agents needs to be evaluated. and comparisons between
pharmacologic and behavioral approache\ to postcessation weight gain should be
considered.

50-l


CONCLUSIONS

I. Average weight gain after smoking cessation is only about 5 pounds (2.3 kg). This
weight gain poses a minimal health risk.

2. Approximately 80 percent of smokers who quit gain weight after cessation. but only
about 3.5 percent of those who quit smoking gain more than 20 pounds.

3. Increases in food intake and decreases in resting energy expenditure are largely
responsible for postcessation weight gain.


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SIS


         CHAPTER 11
PSYCHOLOGICAL AND BEHAVIORAL
CONSEQUENCES AND CORRELATES OF
     SMOKING CESSATION

517


CONTENTS

Introduction ..................................................... ..52 1

Short-Term Effects of Smoking Cessation: Nicotine Withdravval ............. 511
Brief Review of Previous Worh ...................................... 57 1
Craving as a Withdrawal Symptom  ................................... 523
Changes in Alcohol and Caffeine Use ................................. 51-I
Withdrawal Relief Versus Enhancement Models of the Effects of Smohinp on
  Performance  ................................................... 53
Variability in Withdrawal  .......................................... 526
Timecourse of Withdrawal .......................................... 529
Withdrawal as a Cause of Relapse .................................... 530
Summary ........................................................ 531

Long-Term Psychological and Behavioral Consequences and Correlates of
Smoking Cessation ...........................................     532
Introduction  ................................................     5.32
Mood. Anxiety. Perceived Stress. and Psychological Well-Being  ......     533
  Research Results  ..........................................     s3-l
Self-Efficacy and Locus of Control  ..............................     541
  Self-Efficacy  .............................................     S-11
   LocusofControl  ..........................................     541
Coping and Self-Management Skills  .............................     513
Social Support and Interpersonal Interactions ......................     s-is
Summary ...................................................     5-w

Health Practices of Former Smokers .................................... 516

Introduction  ........................................
Physical Activity  ....................................
Dietary Practices. ....................................
Use of Other Substances  ..............................
  Other Tobacco Products .............................
   Alcohol ..........................................
Studies of Multiple Health Habits  .......................
Summary ...........................................

Participation of Former Smokers in Health-Screening Programs
Summary  ............................................

Conclusions  ..........................................

References ................... ..~ .....................

.





.





.





.

.


INTRODUCTION

Former smokers often describe quitting smoking as a tuminy point in their lives. For
many individuals, cessation leads to an improved sense of well-being and often $erve\
as a catalyst for other positive health-related lifestyle changes (Finnegan and Suler
1985: Knudsen et al. 1984: Suedfeld and Best 1977). These improv,ement\ in psycho-
social functioning and health-related lifestyle behaviors may contribute to and reinforce
continued abstinence. However, some smokers may hesitate to try to quit because they
fear negative changes in mood and vvell-being (Gritz IYXO: Hall IYX1: Tamerin lY77).
In addition. relapsers often attribute their return to smohing to unwanted changes in
mood or to a strong desire for a cigarette (Baer 1985: Chapman. Smith. Lay den 197 I:
Marlatt and Gordon 1980; Russell 1970: Shiffman 1982).

This Chapter reviews findings on short-term withdrawal effect\ and the longer term
psychological and behavioral effects related to abstinence from smoking. Short-term
withdrawal effects are described in the 1988 Report of the Surgeon General on nicotine
addiction (US DHHS 1988). The first Section of this Chapter updates this review by
examining recent studies in six areas: cravin_p as a withdrawal symptom. changes in
alcohol and caffeine use. withdrawal relief versus enhancement models of the effects
of abstinence on performance. variability in withdrawal. timecourse of withdrawal. and
nicotine withdrawal as a cause of relapse. The second Section reviews lonser term
changes. such as changes in the use of alcohol. illicit drugs. and other tobacco products
as well as increases in other health-related practices and preventive health behaviors.
including participation in cardiovascular and cancer screening. A major portion of this
Section reviews the relationship of long-term abstinence to psychological factors such
as mood, coping with stress, self-efficacy, and locus of control. Because the long-term
psychological and behavioral effects of smoking abstinence have never been sum-
marized, this Section will include a more indepth review of studies than will be provided
in the Section on short-term effects.

Providing smokers with information on transient adverse withdravval effects and the
distinction between these and the longer term psychological and behavioral benefits of
abstinence may allay fears and help remove barriers to quitting or to maintaining
abstinence. This information may also help to develop more effective programs that
help the smoker plan and cope with the effects of cigarette abstinence. For example.
education about the signs and symptoms of withdrawal from tranquilizers appears to
help long-term users stop using tranquilizers (Lader and Higgitt 1986).

SHORT-TERM EFFECTS OF SMOKING CESSATION:
        NICOTINE WITHDRAWAL

Brief Review of Previous Work

Over the last decade, several reviews have been published on nicotine withdrawal
(Hatsukami, Hughes, Pickens 1985: Henningfield 1983; Hughes. Higgins, Hatsukami
1990; Murray and Lawrence 1984; Shiffman 1979: US DHHS 1988: West 1984).
Perhaps the most widely-accepted description of nicotine withdrawal i\ that which


appears in the Dia,~/ros/ic~ ulrtl Stotistiol Mutl~rul (!f` Mcutul Di.sodo~.s (DSM-III-R.
American Psychiatric Association 1987) (Table I ). In addition to the signs and
symptoms listed in DSM-III-R. depression. disrupted sleep. impatience. and perhaps
increased pleasantness of sweets are common and valid indicators of nicotine
withdrawal (Hughes. Higgins. Hatsukami 1990). However, an especially important
effect not included in DSM-III-R is impaired performance. particularly on vigilance
and rapid information processing tasks (Snyder. Davis. Henningfield 1989: Wesnes and
Warburton 1983). Other consequences of withdrawal. which may not be clinically
evident. include slowin_g ofthe electroencephalogram. changes in rapid eye movement
during sleep. decreased levels of catecholamines. decreased thyroid function. increased
levels of medications. decreased orthostatis. and increased skin temperature (American
Psychiatric Association 1987: Hughes. Higgim. Hatsukami 1990).

TABLE I.-Diagnostic categorization and criteria for nicotine withdrawal-
      nicotine-induced organic mental disorder

  The e\wntial feature ofthi\ d~wrder I\ a characterl\ttc withdrawal syndrome due to the
abrupt ce\\ation of or reduction in the we of nicotine-contatninf wbamces (e.g.. ciparette\.
ctfarx. ptprr. cheuing tobacco. or nlcotlne sum) and that has been at lest moderate in
duratton and amount.

  Among many heavy ciyrette smoker\. change\ in mood and performance that are
related to \slthdraual can be detected withm 7 hr after the kt tobacco we. The `ewe of
cravmg appear\ to reach ;L peah u ithm the first 23 hr after ce\\atlon of tobacco u\e and
pradually decline\ thereafter ovrr a few day\ to several week\. In an) eiven caw it i\
dtfftcult to di\tinyut\h a withdrawal effect from the emergence of p~ychologicsl twit\ that
are wppre\\ed. controlled. or altered h) the effects of nicotine or from a behaworal reaction
(e.g.. fru\trstton) to the In\\ of a remforcer.

  Mtld symptom\ of H ithdraual ma) occur after \H ttchtnp to low-tar (ntcorine)
cigarette\ and after \toppmg the we of \mohelr\\ (chewing) tobacco or nicotme polacrilex
ym.

Dqno\ttc criteria for nicotine H ithdrawnl:
A. Dally we of nlcotinr for at lea\1 several wreh\
6. Abrupt cesttion ot nwtms u\e or reduction in the amount of mcotine wed
folIoned wtthin 24 hr b> at least four of the following \ipn\:
( II crav~np for nicotine

(2) irrnability. frustration. or anger
(31 anale

(41 dtfficult) concentrattng
(5) restle\we\\

161 decreased heart rate

(7) increased appetite or weight gain

The signs and symptoms of nicotine withdrawal are observable: they are often of
clinically significant magnitude and occur in self-quitters as well as those who attend
smoking cessation clinics (Hughes. Higgins, Hatsukami 1990). Most withdrawal


symptoms are opposite to those produced by administration of nicotine. occur for a
specified period of time, and with continued abstinence. return to levels similar to those
experienced by a smoker. Relief of withdrawal by use of nicotine polacrilex gum.
occurrence of withdrawal upon cessation of nicotine polacrilex gum. and occurrence
of withdrawal upon switching to Low-nicotine cigarettes indicate that a lack of nicotine
is responsible for most withdrawal effects (Hughes, Higgins Hatsukami 1990: We\t
1984).

Craving as a Withdrawal Symptom

Recent articles have attempted to clarify the role of craving in cigarette smoking
(Kozlowski and Wilkinson 1987a: West and Kranzler 1990: West and Schneider 19X7).
The term "craving" has been used loosely and interchangeably by both smokers and
investigators to indicate a strong desire or urge to smoke. The problems associated with
this terminology and the advantages to using the term "strong desire" have been outlined
(Hughes 1986a; Kozlowski and Wilkinson 1987a; Kozlowski and Wilkinson 1987b:
Marlatt 1987; Rankin 1987; Shiffman 1987; Stockwell 1987: West 1987: We\t and
Schneider 1987: Kozlowski, Mann et al. 1989). Although an increased desire for a
cigarette is a common consequence of abstinence, part of the craving may result from
the desire to relieve other withdrawal symptoms by having a cigarette. For example. a
review by West and Schneider (1987) demonstrated that withdrawal effect\. such as
irritability and restlessness, are positively associated with craving. They noted that
drugs such as clonidine may alleviate craving because these agents reduce the other
symptoms. Thus, craving might be alleviated by reducing other withdrawal symptoms
(Kozlowski and Wilkinson 1987a).

An urge to smoke may be due to several factors, such as response to environmental
stimuli associated with cigarette smoking or deprivation, onset of withdrawal
symptoms, and protracted withdrawal.  That such effects are physiologically. be-
haviorally, orcognitively mediated has been debated widely (Kozlowski and Wilkinson
1987a. b; West and Kranzler 1990; West and Schneider 1987).

The desire to smoke as indicative of nicotine withdrawal has been a subject of some
controversy for five reasons. First, the referent for the terms craving and desire is
unclear. In 1955, the World Health Organization (WHO) stated. "a term such as
`craving' with its everyday connotations should not be used in the scientific literature

. . . if confusion is to be avoided" (WHO 1955, p. 63). On the other hand, craving for
a cigarette is the most commonly reported postcessation symptom (Hughes. Higgins,
Hatsukami 1990); and therefore, it is difficult to ignore these self-reports.

Second, craving readily occurs even when smokers are not trying to abstain (Hughes,
Higgins, Hatsukami 1990; Hughes and Hatsukami 1986). However, many other
withdrawal symptoms, such as irritability. are also experienced by smokers (Hughes,
Higgins, Hatsukami 1990).

Third, several factors other than abstinence. such as sensory cues associated with
smoking (Rose 1988). the "behavior" of smoking (Hajek et al. 19X9). and expectancy
(Hughes et al. 1989; Gottlieb et al. 1987). can intluence craving. However. these factors
can also affect other withdrawal symptoms (Francis and Nelson 19x4). In addition.


demonstrating that a symptom is influenced by a nonabstinence variable does not mean
that the symptom cannot be induced by abstinence: it simply suggests nonspecificity;
that is, abstinence is only one of many causes.

Fourth, nicotine polacrilex gum does not predictably reduce the desire for a cigarette
(Hughes 1986b; West 1984; West and Schneider 1987). However, one possibility is
that more cigarette-like (i.e., more bolus-like) routes of administration of nicotine, such
as aerosols. nasal sprays, and vapors, would decrease desire to smoke (Pomerleau et al.
1988).

Fifth. managing craving may be critical to cessation of smoking. Recent prospective
studies have indicated that postcessation self-reports of craving are predictive of later
relapse (Gritz, Carr, Marcus 1990; West, Hajek, Belcher 1989; Killen et al. 1990). Also,
the ubiquity of smoking cues and the availability of cigarettes may make craving
especially prevalent and difficult to resist.

Recent research contradicts the commonly held notion that the desire for cigarettes
is less than that for prototypic drugs of abuse (Kozlowski, Wilkinson et al. 1989).
Persons presenting for treatment of alcohol and drug problems compared the strongest
urge they had for cigarettes with their strongest urge for the alcohol or drug for which
they were seeking treatment. Among alcohol-dependent persons, 50 percent reported
that their strongest urges for cigarettes were greater than their strongest alcohol urges.
32 percent reported that the strongest urges were about the same for both cigarettes and
alcohol, and I8 percent reported that their strongest urges for alcohol were greater than
for cigarettes. Among drug-dependent persons, 25 percent said their strongest urges
were for cigarettes. 27 percent said their strongest urges were about the same, and 48
percent said their strongest urges were for their drug of choice.

In the treatment of drug dependencies. such as alcohol, use of the term craving has
been historically associated with theories of loss of control (Ludwig and Wikler 1974).
Typically, tobacco researchers are not implying loss of control over smoking when they
use the term craving (Kozlowski and Wilkinson 1987a). Smokers may or may not be
implying loss of control when they use the term.

In summary. although the desire to smoke may have a more complex origin than other
withdrawal symptoms, it is a predictable and important withdrawal effect. The occur-
rence of craving after cessation has several implications. It suggests that nicotine
delivered in a cigarette-like system may be the best method to relieve the desire to smoke
because the delivery would mimic some of the sensory cues associated with smoking
(Rose 1988: Hajek et al. 1989). Also. it suggests that for smokers who wish to avoid
medication, behavioral strategies could be used to combat even pharmacologically
mediated desires to smoke.

Changes in Alcohol and Caffeine Use

Initial short-term changes in alcohol and caffeine intake upon smoking abstinence
are of increasing interest. It is unclear that smoking cessation impedes abstinence or
prompts relapse back to drinking among those with alcohol dependence (Kozlowski,
Ferrence, Corbit 1990). Such changes in alcohol and caffeine use were not reviewed
extensively in the 1988 Surgeon General's Report on nicotine addiction (US DHHS

524


1988). Long-term effects of abstinence on alcohol intake are reviewed later in this
Chapter.

Two prospective studies found that among smokers trying to stop smoking per-
manently. alcohol use significantly decreased, by about 75 percent per drink per day in
one study, during the first week after abstinence (Hughes and Hat\ukami 1986: Puddey
et al. 1985). A third study reported that subjects who had a larger decrease in the number
of cigarettes smoked postcessation had a larger decrease in alcohol use (Olbrisch and
Oades-Souther 1986). However. a recent study suggested the opposite: that is. alcohol
use increased among females who stopped smoking temporarily for I week for the
duration of an experiment (Perkins. Epstein. Pastor 1990). This discrepancy across
experiments may be due to gender or motivational differences in the populations. In
the latter case. an increase in alcohol consumption may occur when smokers in an
experiment do not try to control their alcohol intake during temporary smoking
abstinence; however, when smokers are trying to stop permanently they may decrease
alcohol use voluntarily as an aid to smoking cessation.

Abstinence does not appear to change short-term caffeine intake (Benowitz, Hall.
Modin 1989: Hughes and Hatsukami 1986; Hughes 1990: Hughes et al. 1990: Koz-
lowski 1976; Puddey et al. 1985: Rodin 1987). Smoking increases the elimination of
caffeine, probably through non-nicotine-related mechanisms (Benowitz 1988): thus,
when smokers stop, their rates of elimination of caffeine decrease (Benowitz, Hall.
Modin 1989: Brown et al. 1988). With no change in caffeine intake, blood levels of
caffeine increase 2.5-fold (Brown et al. 1988). Because several of the symptoms of
caffeine intoxication are similar to those of nicotine withdrawal (e.g.. anxiety, restless-
ness. and irritability), it has been suggested that these increased levels of caffeine may
mimic or potentiate symptoms attributed to tobacco withdrawal (Sachs and Benowitz
1990).

Withdrawal Relief Versus Enhancement Models of the
    Effects of Smoking on Performance

The effects of abstinence on performance were reviewed in the Surgeon General's
Report on nicotine addiction (US DHHS 1988). This review and others (Hughes.
Higgins. Hatsukami 1990) have concluded that abstinence impairs performance on
attention tasks, especially those labeled as rapid information processing, selective
attention. sustained attention, or vigilance tasks. This impairment may persist for at
least 7 to 10 days (Snyder, Davis, Henningfield 1989) and is reversed by nicotine
replacement (Snyder and Henningfield 1989). However. it is not clear that abstinence
impairs learning, memory, performance on more complex tasks, problem solving, or
reaction time.

In the prototypic procedure for studying the effects of smoking on performance,
smokers abstain overnight; performance is then measured before and after smoking a
cigarette. A possible result would be that performance on a vigilance task was better
after smoking than before smoking, Some researchers might interpret this difference
as an indication that smoking enhances performance (Wesnes. Warburton. Matz 1983).
However, another interpretation is that the presmoking performance level was poor

525



because of tobacco withdrawal and that the improvement in performance occurred
because smoking relieves tobacco withdrawal (Schachter 1979; Silverstein 1982). This
latter interpretation assumes that overnight deprivation induces withdrawal; although
this assumption has not been tested directly, withdrawal effects can occur after only 12
hours of deprivation (Hughes, Higgins, Hatsukami 1990).

Ideally, studying smokers before initiation would allow comparison of this baseline
with before and after a smoking episode. As this is impractical, one solution has been
to add a control group of nonsmokers (Hughes, Higgins, Hatsukami 1990). For
example, smokers performed better after smoking and the same as nonsmokers in
several studies of errors on a vigilance task (Taylor and Blezard 1979; Hughes, Keenan,
Yellin 1989; Lyon et al. 1975; Heimstra et al. 1980; Tong et al. 1977; Tarriere and
Hartmann 1983; Keenan, Hatsukami, Anton 1989) and a tracking task (Lyon et al. 1975)
(Figure 1, upper panel). The effect was attributed to relief of withdrawal.

One study provided evidence for enhancement of performance from smoking inde-
pendent of reversing withdrawal. Wesnes and Warburton (1978) reported a pattern
consistent with enhancement when errors on vigilance tasks were studied (Figure I,
lower panel).

Other indirect evidence can be used to test the withdrawal relief versus enhancement
models. Two studies reported enhancement of tracking or motor skills when smokers
were not deprived (Parrott and Winder 1989; Hindmarch. Kerr, Sherwood 1990;
Larson, Finnegan, Haag 1950; Pomerleau and Pomerleau 1986). Several studies have
examined the effect of cigarette smoking or nicotine administration on the performance
of nonsmokers (Dunne, MacDonald, Hartley 1986; Hindmarch, Kerr, Sherwood 1990;
Wesnes, Warburton. Matz 1983; Wesnes and Revel1 1984; West and Jarvis 1986:
Wesnes and Warburton 1984). In two studies, the improvement in nonsmokers was
similar to that of deprived smokers (Wesnes, Warburton, Matz 1983; Wesnes and
Revel1 1984). One study reported performance to be similar between deprived smokers
and nonsmokers (Warburton 1990). Finally, nicotine appears to improve the perfor-
mance of animals not previously exposed to nicotine (Clarke 1987; Emley and Hutchin-
son 1984).

In summary, the results of studies to assess if smoking increases performance through
withdrawal relief or by direct enhancement appear contradictory. One possible ex-
planation of this discrepancy is that smoking may increase performance through both
withdrawal relief and direct enhancement. The specific mechanism that is operative
may vary not only among smokers but also within smokers across situations.

Variability in Withdrawal

Whereas the necessary and sufficient condition to establish dependence is repeated
exposure to the drug, other factors may exacerbate nicotine withdrawal symptoms.
Although several investigators have commented on the variability of postcessation
symptoms, it is unclear that this variability is greater than with other drug withdrawal
syndromes (Hughes, Higgins, Hatsukami 1990: US DHHS 1988). The results of
retrospective and postcessation studies on self-reported withdrawal symptoms (e.g.,
hunger, restlessness, or inability to concentrate) among smokers who have a greater

526


60

  50  -

2                         NONSMOKERS
2
$j  40  -

c-
5
3
e 30     I           I           I           I           I         I

       1         2         3         4         5         6

    HOURS

0.9 r

NONSMOKERS

2                                 DEPRIVED SMOKERS
F:
VJ 0.6     1        1        I        I        I        I        I I

      10     20     30     40     50     60     70 80

MINUTES

FIGURE I.-Uppc~ pu~wl: Performance on a meter (i.e., visual) vigilance task
SOURCE: Heinhm CI al. IW).
     f,o~~~r~puwI: Performance on the continuous clock task, a visual
      vigilance task


nicotine intake are inconclusive (Goldstein, Ward, Niaura 1988; Hughes, Higgins,
Hatsukami 1990: Shiffman 1979: US DHHS 1988; Williams 1979). Withdrawal
effects. including weight gain, have not been found to differ consistently by gender or
age (Hughes, Higgins, Hatsukami 1990).

Several studies have suggested that expectancy influences the effects of abstinence;
that is, some individuals may amplify. deny, or misattribute their withdrawal symptoms
(Barefoot and Girodo 1972; Gottlieb et al. 1987: Hughes and Krahn 1985; Hughes et
al. 1989). According to the misattribution model, at times the individual can "mistake"
withdrawal symptoms for other possible events. For example, in one study a labeling
mistake was made when individuals were told that a placebo they were taking was
alleged to have side effects similar to the effects of cigarette withdrawal (Barefoot and
Girodo 1972).

Three direct tests of expectancy have been published (Gottlieb et al. 1987; Hughes
and Krahn 1985; Hughes et al. 1989). In one study, subjects in a double-blind trial of
nicotine polacrilex gum were asked if they thought they had received nicotine or
placebo gum. Those who believed they had received placebo gum had more abstinence
discomfort than those who could not differentiate what they had received; this latter
group had more discomfort than those who thought they had received the nicotine
polacrilex gum (Hughes and Krahn 198.5). Because this study used post hoc ratings, it
is unclear that the belief in which gum had been received modified the level of
abstinence effects, or that the level of abstinence effects modified the belief of which
gum had been received.

Two experimental trials have manipulated instructions and thereby directly tested if
expectancy influences abstinence effects. The first study randomly assigned smokers
to a 2x2 design of contrasting instructions; subjects were told that they received either
nicotine polacrilex gum or placebo gum, and actually received either nicotine polacrilex
gum or placebo gum (Gottlieb et al. 1987). Most of the measures of abstinence effects
were unchanged by instructions or by actual drugs. The physical symptoms and
stimulation scores on the Shiffman-Jarvik Withdrawal Scale were less only on some
days in the group told they were receiving nicotine than in the group told they were
receiving placebo. A second study used a similar design and found that abstinence
symptoms were fewer among those who received nicotine polacrilex gum than among
those who received placebo gum. but found no effect of instructions (Hughes et al.
1989). In summary, the seemingly valid proposition that abstinence effects are in-
fluenced by expectancy has not been completely supported by empirical tests.

Abstinence effects have been hypothesized to be greater in more dependent smokers.
However, the scales for dependence used to test this hypothesis vary according to
whether they are quantifying physical dependence (withdrawal), behavioral depen-
dence (desire for tobacco or tendency to relapse), or dependence on tobacco or on the
nicotine in tobacco (Hughes 1984). The Fagerstrom Tolerance Scale (TQ) is the most
widely used dependence scale (Fagerstrom 1978). TQ consists mostly of items that
refer to behavioral dependence on tobacco.  The total TQ score predicted total
abstinence discomfort in one study (Fagerstrom 1980) and weight gain in another study
(Tonnesen et al. 1988). However, two detailed studies failed to indicate that TQ

528


predicted weight gain (Emont and Cummings 1987) or self-reported withdrawal
symptoms.

The Reasons for Smoking Scale has two scales relevant to the dependence con-
struct-the addiction scale and the negative affect scale (Ikard, Green. Horn 1969).
Neither of these has been shown to predict weight gain (Boss& Garvey. Costa 1980).
self-reported withdrawal (Hughes and Hatsukami 1986). or relief by nicotine polacrilex
gum (Hughes and Hatsukami 1986).

Russell's Smoking Motivation Questionnaire has a subscale for dependence (Russell,
Peto. Pate1 1974). In one study, the scale predicted total abstinence discomfort and
irritability but did not predict restlessness, depression. hunger. or inability to con-
centrate (West and Russell 1985).

Another measure somewhat related to dependence includes the sevoerity of abstinence
discomfort in the past, which appears to predict self-reported abstinence (Hughes and
Hatsukami 1986). Other generic scales, such as the MacAndrews Scale for Addiction
(MacAndrew 1979) and Eysenk Personality Questionnaire (Eysenk and Eysenk 1975).
do not predict abstinence discomfort and weight gain (Bosse. Garvey. Costa 1980).
Although one study found that self-reported smoking for stimulation predicted
abstinence effects (Niaura et al. 1989), an earlier study had found no such relationship
(West and Russell 1985).

In summary, the evidence that any dependence scale predicts abstinence effects is
quite limited. Further tests that use scales that more specifically determine physical
versus behavioral dependence and dependence on nicotine versus tobacco may provide
more informative data.

Timecourse of Withdrawal

Several recent studies produced concordant results on the timecourse of nicotine
withdrawal. Most signs and symptoms of nicotine withdrawal are readily detected
within 24 hours (Hughes, Higgins, Hatsukami 1990). Previous studies have suggested
that abstinence effects can occur even sooner. for example, within 2 hours (US DHHS
1988). These studies have measured effects during smoking and 2 to 6 hours post-
smoking: it was noted that 2 to 6 hours after smoking. self-ratings of performance were
worse than during smoking. Several investigators have interpreted the scores during
smoking as representing baseline and the postsmoking scores as representing
withdrawal. However. as discussed earlier. an alternate interpretation is possible: the
scores 2 to 6 hours po\tsmoking represent baseline scores and the scores during smohing
represent the acute effects of smoking (Hughes et al. 1990).

The results of several prospective studies indicate that the \ignj and symptoms of
nicotine withdrawal peak in the first I to 2 days following cessation (Gumming\ et al.
1985: Hughes and Hatsukami 1986: West et al. 1983: Shil`fmun and Jarvik 1976:
Schneider. Jarvik. Forsythe 19X3) and la\t about I month (Grit/. Carr. Marcus 1990:
Cummings et al. 1985: Gross and Stitrer 1989: Hughe\ 1990: Hughes t`t al. 1990:
Lawrence. Amoedi. Murray 19x2: West. Hajek. Belcher 19X7). For each of IO weehs.
Gross and Stitzer ( 1989) recorded symptoms of quitters and found a peak during the
first week and a return to bu\eline 3 to 4 ueeh\ po\tcessation. Snyder. Davi\. and


Henningfield ( I YXY) trached perfomiance on several ta\h\ over IO day\. Impairment
in performance peahed at I to 2 da) \. and performance on mo\t ta\h\ I-eturned to
baseline during the IO day\: however. performance on mne task\ &;I\ still impaired
after IO days. A study by Gumming\ and colleague\ ( IYXS) included 33 subject\ uho
hept a daily record oCX withdrawal symptoms. AI 21 days. few subjects were reporting
withdrawal symptoms. with the exception of a11 occasional desire for a cigarette. A
fourth study (Hughes IYYO) provided a less-detailed timecour\e but included group\ of
never smokers. ex-smokers. and continuing smokers.  The withdrawal scores ot
abstinent smokers at I month were equivalent to their baseline score4 and to those of
never smokers and continuin g smokers (Hughes IYYO). Although the average
withdrawal symptom score returned to baseline at I month, 45 percent of \ub,jectr
reported symptoms still above precessation levels at I -month followup (Hughe\ IYYO).
Further followup of these subjects indicated that their withdrawal score\ had returned
to baseline or below baseline by 6 month\ postcessation. Craving. hunger. and ueight
gain are exceptions to the I -month duration: they may continue at least through the first
h-months after cessation (Gritz. Carr. Marcus 1990: Hughe\ 1990; Hughes et al. IYYO:
West. Hajek. Belcher 1987).

With cessation of other drugs. a prolonged withdrawal syndrome has been postulated
(Martin and Jasinski IY69). There is no evidence of a prolonged nicotine withdrawal
syndrome. In fact, scores on withdrawal scales appear to decrease below prece\\ation
levels at followup (Figure 2): that is. positive mood changes occur after Ions-term
abstinence from smoking (Chapter I I. see section on long-term psychological and
behavioral consequences and correlates of smoking cessation) (Grit/. Carr. Marcus
1990: Gross and Stitzer 1989: Hughes IYYO: Hughes et al. IYYO).

Withdrawal as a Cause of Relapse

Seven recent studies have examined nicotine withdrawal as a predictor of rclap\e.
that is. whether smokers with severe withdraual are more likely to relapse. Five studies
found that some withdrawal symptoms predicted relapse at some points in time (Gritz.
Carr. Marcus IYYO; West. Hajek. Belcher IYYO: Hughes IYYO: Killen et al. IYYO: Swan
et al. IYXX). The two studies that did not indicate such a relationship examined the
ability of withdrawal to predict abstinence at very earl!, followup (Hughes and Hut-
sukami 19X6) or very late followup (Hughes et al. IYYO). In the five positive studie\.
mood changes. such as depression and anxiety. were the more common predictors.
However, both across and within the studies. there \va\ no con\i\tent or clear grouping
of symptoms predicting wlithdrawal at specific points in time. One common findin?
wa\ that the number of symptoms appeared to be a predictor (Gritz. Carr. Marcus I YYO:
Hughes 19YO). For subgroups of smokers. such ;I> more dependent mohers.
withdrawal may be an especially important factor in relapse. hut this relationship ha\
not been demonstrated.

Postcessation weight gain ha$ often been hypothesized to be a major cause of relapse.
especially among women (Hall. Ginsberg. Jones 1986). Contrary to several (I /~/`ior.i
hypotheses. three prospective studies have found that more weight gain predicted les\
relapse (Duffy and Hall I Y90: Hall. Ginsberg. Jones I YX6: Hughes et al. 1990). There


8

6

I    I    I   I   I    I   I    I   I    I   I

BL 1 2 3 4 5 6 7 8 9 10

0 l-

      24

WEEKS

FIGURE 2.-Self-reported withdrawal discomfort among abstinent smokers
SOURCE: Groa and St~trer I YXL): Hughe\ I IWO).

was no gender difference in this prediction in any of the three studies. This finding is
further supported by a study in which women who reported eating more in the first 4
days ofcessation were more likely to be abstinent at 6-month followup (Guilford 1966).
One explanation for the weight gain-relapse finding is that food deprivation increases
the reinforcing effects of drugs (Carroll and Meisch 1984). Cessation of smoking may
decrease metabolic rate (Perkins, Epstein, Pastor 1990); if this is true, to avoid weight
gain, smokers may deprive themselves of food and thereby increase the reinforcing
effects of cigarettes smoked during periods of relapse.

In summary, this recent evidence shows that smokers with more severe withdrawal
symptoms are more likely to relapse.  However, these results should not be
misinterpreted. First, prediction is not equivalent to causality: withdrawal symptoms
may predict relapse, not because they cause relapse, but because they are associated
with some other variable, such as degree of dependence. Second, those symptoms that
predict the occurrence of relapse and the timing of relapse-very early (<2 days), early
(2-10 days), or later (IO-30 days)-vary across studies. Third. although studies have
shown that withdrawal is an early predictor of relapse, these studies have not shown
that withdrawal predicts eventual outcome (i.e., long-term abstinence).

Summary

Strong evidence indicates that smokers who stop smoking experience a nicotine
withdrawal syndrome that includes the short-term consequences of anxiety, irritability.


frustration, anger. difficulty concentrating, and restlessness. These symptoms general-
ly occur within 24 hours and subside after about 1 month. Smokers also report strong
cravings or urges to smoke when they are not smoking; this symptom will persist among
some former smokers. Hunger and weight gain may also persist longer than I month.
Abstinence does not appear to affect short-term caffeine intake. However, it does
increase caffeine metabolism, which may mimic or potentiate symptoms of nicotine
withdrawal. There are conflicting data on the short-term effects of smoking abstinence
on alcohol intake. However, the data suggest that smokers attempting permanent
smoking abstinence experience decreased alcohol intake.

Research on the effects of smoking abstinence on performance indicates that
abstinence impairs performance on attention tasks. This impairment may persist for at
least 7 to IO days and is relieved by nicotine replacement. Other more complex types
of tasks as well as memory and learning have not been clearly shown to be impaired by
abstinence. The relation of improvement in attention tasks with nicotine may be due
either to withdrawal relief or to performance enhancement; findings are consistent with
both models. However. evidence more strongly suggests withdrawal relief from
receiving nicotine.

Variability in tobacco withdrawal symptoms resembles that observed for other drug
withdrawal syndromes. Several studies have suggested that expectancy influences
withdrawal effects. However, this has not been completely supported by empirical
tests. Although abstinence effects have been hypothesized to be greater in more
dependent smokers, the evidence is conflicting. Recent data indicate that smokers with
more severe withdrawal symptoms are more likely to relapse. However, no symptoms
or groups of symptoms consistently predict relapse at any given point in time.

LONG-TERM PSYCHOLOGICAL AND BEHAVIORAL CONSEQUENCES
       AND CORRELATES OF SMOKING CESSATION

Introduction

Most long-term studies of self-quitters or smokers taking part in treatment programs
only include data on smoking behavior or smoking status (Adesso 1979: Gordon and
Cleary 19X6; Orleans and Shipley 1983; Shipley. Rosen. Williams 1982); followup
measures of psychological and behavioral consequences are rarely included. Thu\.
although former smokers represent a large and growing segment of the U.S. population
(Volume Appendix). the long-tern1 psychological and behavioral consequences of
smoking cessation have not been well studied.

Very few studies of former smoker-j have employed prospective or longitudinal
designs: rather. most have used retrospective or cross-sectional designs. In the typical
retrospectivse study. subjects are asked whether after quitting or during their experience
of trying to quit, they were more or less nervous. irritable. depressed. sedentary. or
health conscious than before quitting. While relevant to the experience of a person
abstaining from tobacco, retrospective studies potentially suffer from several limita-
tions, including the absence of information about baseline group similarities or differ-

532


ences and the problem of recall bias. (See Chapter 2 for a discussion of methodologic
problems.) Successful former smokers may minimize or fail to recall their difficulties
or exaggerate their prowess (Heinold et al. 1982): recidivists may exaggerate
withdrawal problems to justify their relapse (Graham and Gibson 1971). Cross-
sectional studies do not permit the establishment of comparability at baseline. Con-
clusions from the data are therefore limited, often identifying the correlates of cessation
rather than the consequences. Both consequences and correlates of cessation will be
discussed in this Section.

Most prospective studies of smoking cessation sequelae have been conducted with
smokers participating in formal treatment programs rather than with smokers quitting
on their own (Hughes, Higgins. Hatsukami 1990). Treatment participants may differ
in several ways from self-quitters. In a recent review of findings concerning short-term
withdrawal effects, Hughes, Higgins. and Hatsukami ( 1990) noted that self-quitters had
fewer and less severe withdrawal symptoms than treated quitters; they noted. as did
Schachter (1982), that clinic populations may include a higher proportion of hardcore,
highly dependent smokers. On the other hand, treated quitters may learn new coping
skills such as relaxation, self-reward, or exercise and gain additional support for their
initial quitting efforts. Therefore, their short-term postquitting experiences may not be
representative of the 90 percent of former smokers who quit on their own (US DHHS
1988; Fiore et al. 1990). Thus. in drawing conclusions from studies of participants in
treatment programs, it is important to be aware of the possible differences between these
two populations of abstainers.

Mood, Anxiety, Perceived Stress, and Psychological Well-Being

Tobacco use has often been described as a maladaptive response to. or a way to cope
with, life stress and a way to regulate negative affect (Tomkins 1966: Billings and Moos
1981: Ockene et al. 1981: Orleans 1985; Abrams et al. 1987). Smokers often believe
that smoking helps them cope with stress and anxiety (Ikard, Green, Horn 1969). Thus.
in addition to the stress of separation from cigarettes (Tamerin 1972). abstaining from
cigarettes potentially could make the smoker feel less able to cope with stress (Abrams
et al. 1987: Marlatt and Gordon 1985) and thereby constitute a biologically based source
of stress (Grunberg and Baum 1985). If the quitter feels unable to cope with stress
without cigarettes, perceived stress may increase, and self-efficacy may decrease.
resulting in heightened anxiety and an overall negative shift in well-being. Alterna-
tively, Cohen and Lichtenstein (in press) have hypothesized that for smokers who want
to quit smoking, continued smoking may prove more stressful than cessation. and
quitting smoking may result in a more positive self-appraisal and heightened feelings
of self-esteem and personal competence. Similarly, other researchers have proposed
that smoking may cause negative self-evaluations and feelings of guilt and helplessness
among smokers who want to quit. so that quitting would result in an overall long-term
improvement in mood, self-image, and 5elf-esteem (Frerichs et al. I98 I : Knudsen et al.
1984: Schwartz and Dubitzky 1968).

Possible long-term changes in anxiety levels after quitting might also reflect quitting-
related changes in physiologic stres\ reactivity (Abrams et al. 1987). To the extent that


smoking contributes to excess physiologic stress reactivity and more ready arousal to
anxiety (Emmons et al. 1986; Williams, Hudson, Redd 1982: US DHHS 1988).
cessation might lead to stable reductions in general anxiety.

Several models have been proposed to understand the possible long-term conse-
quences of smoking cessation for depression or dysphoria (Frerichs et al. I98 I ; Hughes
1988; Hughes, Higgins, Hatsukami 1990; Tamerin 1972). Studies of withdrawal effects
have found depressed mood or dysphoria to be a common, transient withdrawal effect,
partly reflecting multiple pharmacologic effects of nicotine abstinence (Backon 1983;
Hughes, Higgins, Hatsukami 1990; US DHHS 1988). Covey, Classman, and Stetner
(in press) found that smokers with a history of major depression had more severe
symptoms of depression 2 weeks after a behavioral treatment for smoking than those
without such a history. However, some theorists have proposed that for smokers who
want to quit, quitting could result in improved mood. well-being, and self-esteem
(Frerichs et al. 198 1).

Research Results

Five cross-sectional studies have compared former smokers with continuing smokers
or relapsers on measures of mood, affect. anxiety, and psychological well-being
(Abrams et al. 1987; Giannetti, Reynolds, Rihn 1985; Orleans et al. 1983; Pederson and
Lefcoe 1976; Pomerleau, Adkins, Pertschuk 1978). Of these live studies, three found
no differences between these groups, and two found differences demonstrating more
healthy outcomes for former smokers.  Pederson and Lefcoe ( 1976) compared 46
former smokers, mostly self-quitters who had not smoked cigarettes for 1 year or longer,
with 46 current smokers volunteering for treatment. These researchers found no
differences on Jackson Personality Inventory scales that included measures of anxiety
and self-esteem. Likewise, Pomerleau, Adkins. and Pertschuk (1978) used the
Symptom Checklist (SCL-56) as a 2-year followup measure of dysphoria among 60
smoking cessation treatment participants and found no differences between quitters and
continued smokers. Mean duration of smoking abstinence was not reported. Giannetti,
Reynolds. and Rihn ( 1985) compared 47 former smokers who had been abstinent for
at least 6 months with 35 current smokers hospitalized for cardiovascular disease and
found no differences in "habits of nervous tension."

In the only study to employ multiple self-report, physiologic, and observer measures,
Abrams and colleagues (1987) found no significant differences between 22 former
smokers (mean abstinence approximately 2 years) and 22 relapsers on the State-Trait
Anxiety Inventory, but did find that former smokers reported significantly less anxiety
and had significantly lower heart rates in response to simulated smoking-related
stressors. In a study of worksite health screen participants, Orleans and colleagues
(1983) compared 525 long-term former smokers who had been abstinent for more than
I2 months (mean abstinence = approximately 9 years) with 856 current smokers and
found that the long-term former smokers had significantly better age- and sex-adjusted
scores on the Health and Nutrition Examination Survey (HANES) General Well-Being
Index, including its anxiety and depression subscales, and on the Framingham measures
of anger symptoms and anger internalization. However, there were no'differences on

534


these measures between current smokers and recent ex-smokers, those who had been
abstinent for less than 12 months.
Prospective longitudinal studies of smokers who become former smokers or remain
continuing smokers are needed to establish whether any differences between former
and current smokers existed prior to quitting, especially since baseline or "prequitting"
measures of psychological well-being and self-esteem have been found to predict
success in quitting smoking (Hall et al. 1983; Ockene et al. 1982: Schwartz and
Dubitzky 1968; Straits 1970; West et al. 1977). The few prospective studies (Table 2)
that have been conducted have either documented no significant change in psychologi-
cal factors from baseline among former smokers. or no difference in the magnitude of
change for former and continuing smokers. or have indicated improvements for former
smokers. None of these studies demonstrated long-term negative psychological chan-
ges for former smokers.
Two of the prospective studies found no significant changes in a variety of mood and
psychological measures from a prequitting baseline to long-term followup among
former smokers and no significant differences between quitters and continuing smokers
in the magnitude of such change. Pertschuk and coworkers ( 1979) asked 24 participants
in a nonaversive cognitive-behavioral treatment to complete pretreatment and 2month
followup ratings of psychological functioning. These researchers found no significant
changes in stress, affect, symptoms of psychological distress, or utilization of
psychiatric treatment as indicated by need for psychotropic medication or mental health
services, Changes from baseline to followup were not evaluated separately for quitters
and nonquitters. but these groups did not differ on 4-month followup ratings. Emmons
and associates ( 1986) studied the effects of smoking cessation on cardiovascular
reactivity to stress among quit-smoking clinic participants and found no significant
changes from baseline to a 6-month followup among 16 abstainers or 8 relapsers.
However, this study noted that an average weight gain of 5 pounds among abstainers
may have masked improvements in reactivity scores. Because weight was related to
baseline and followup cardiovascular measures, it is possible that in each of these
studies, treatment assisted quitters in avoiding persistent unwanted side effects.
Two studies of nicotine withdrawal effects that extended measurement beyond 4
weeks of abstinence have yielded no evidence for a withdrawal syndrome beyond 4 to
5 weeks (Hughes, Gust, Pechacek 1987; Gross and Stitzer 1989). These studies,
reviewed in detail by Hughes. Higgins, and Hatsukami (1990). found that adverse
postquitting changes in levels of anxiety. restlessness. impatience, irritability, and
dysphoria peaked during the first 2 weeks after quitting. returned to baseline or
below-baseline levels by 4 weeks. and remained at those levels at IO- to 36-week
followups.
Gross and Stitzer ( 1989) studied 40 smokers who quit after a j-session cessation class
and maintained biochemically validated smoking abstinence for 10 weeks while using
nicotine polacrilex gum or a placebo. Subjects completed weekly ratings of withdrawal
symptoms, including symptoms of psychological distress such as irritability. anxiety.
and impatience. Weekly followup ratings were adjusted for baseline ratings and
baseline smoking rate. For the 20 placebo subjects. mean ratings for irritability. anxiety .
and impatience increased from baseline to the first postquit weeh. returned to baseline


TABLE 2.-Prospective studies of quitting-related changes in mood, anxiety, stress reactivity, perceived stress, self-image, and
     psychological well-being

Reference

Sample 5ile

Type of study

Findings

Strengths or limitation\

Pertachuk CI al.
(IY7Y)

24 smokmg cessation clinic
participants

Emmons et al. ( IYXh)

Groaa and Stiller
(IYXY)

24 smoking cessation clinic
participant\

40 abstamer5 using nicotine
polacrilex gum or n placebo
following a 3-sesston
treatment

Stress. affect. psychological
distress. and utilization of
psychiatric treatment were
assessed at the start of treatment
and 2 mo posttreatment

Cardiovascular reactivity      No significant pre- to poattreattnent
(SBP. DBP. HR) in response to   change for abstainers (N=16) in
cognitive and physical stressors   mean SBP, DBP. or HR. and no
were assessed I wk prior to     difference in amount of change
treatment and 6 mo after       between abstainers and recidivist\
treatment               (N=U)

A IS-item withdrawal symptom
measure was completed weekly
for 10 postquit weeks

For placebo subjects. rated
symptoms of psychological distrtx
(irritability, anxiety. impatience)
increased from baselme to first
postquit week. returned to baseline
by week 4. then declined below
baseline initially, stabilizing after
5 wk; scores for active gum u\erh
declined below baseline initially.
stabilizing after 3 wk at
below-baseline levels

No significant pre- to posttreatment
change in self-reported anxiety.
depression, anger, irritabiltty,
appetite loss, msomnta,
hopelessness. dtfficulty
concentrating, apathy, use of
psychotropic medication

Although pohttreatment
scores did not dtfferentlnte
abstainer\ (N=l6) and
recidivists (N=X). thebe
groups were not compared
on pre- to posttreatment
changes

Only abstainen had a
significant weight increase
during the following
period: thih may account
for lack of reductton in
cardiovascular reactivity

Self-reported abstmencr
biologically confirmed and
baseline score\ and
baseline smokmp rate uxd
as covariates, but no
control for repeated
measurement


TABLE 2.--Continued

Sample we

Typr of study

Findings           Strength\ or limitation\

I'dlacKh (IW7)

after :I contact trc:ttmcnt with
phyhictan xivicc and active
nicotine polacrilex or placebo
gum

subject\ mted 5 withdrawal
\ymptomh relevant to mood and
psychological functioning
(anger. anxiety, difficulty
concentrating, impatience.
restlehsnrsh)

Among abstinent suhtects. these
ratings peaked at l-7 wk
postquttting, returned to bawlme by
I mo. and declined further to
below-baseline at 6 mo

Below-baseline 6-mo

ratings among nonquitters
suggest a drift in mensures
due to il repeated testing
effect

35 participant5 m u whsation
clinic for mokw with
chronic cardiopulmonary
diwaw

72 ex-\moher\ (N=7 mo
ab\tinrnt) who had quit
during the year follwinp a
worhde health wreen
(49 at comp;mie\ with health
promotion programs, 73 at
control companir\)

POMS was adminiwred before
md h mo after treiltmrnt

HANES well-being, anxiety,
and deprr\\ion scalc~ and the
Framingham anger symptom
4c;ilc'~ wcrc ximinl5terrd 31 ;L
hawlinc health scrrrn and
I-4 r followup

A meuwx of total mood
di\turhancr (anger/irritability
+ tension + anxiety + fatigue +
confusion + d~pr~\\ion/dejectiotl
- vigor) at 6 mo w;t\ \ignificmtly
negatively correlated with mohing
reduction: parallel Ggnificant
relations were noted for the ~caics
anger/irritability and ten\ion/vnxiety

Significant hawline to I-yr
improvements in the HANES
well-being and deprewon wale\
werr observed for new cx-wwher\
at treatment \ttes only: no changes
tn Framingham anger mwwrc~
were ohwrved

Analy\e\ controlled for
pretrcatmcnt mwhurc~

Analyws controlled for
uyz. wx. burlme UIUCI.
and tlurntion of nhatinrnce:
compxiwn\ with never
moher\. long-term fommcr
\mohtw. or reciclivlst\ at
twittment \ite\ were not
cwdKtrd



levels by week four, then continued to decline, stabilizing at below-baseline levels by
week six. There were significant interactions between use of the gum and the weeks
during which it was used for each of these symptoms, with nicotine polacrilex gum
significantly suppressing postcessation ratings only during the first 4 to 5 weeks after
quitting. The authors concluded that several of the most disturbing aspects of the
tobacco withdrawal syndrome appear to resolve within 4 to 5 weeks after quitting
(Gross and Stitzer 1989). Although findings suggest positive changes over baseline for
these recent quitters, below-baseline 6- to IO-week scores may reflect the effects of the
initial treatment or a repeated-testing effect.
In a similar study of the effects of nicotine polacrilex gum on tobacco withdrawal.
Hughes, Gust, and Pechacek (1987) studied 3 15 smokers for 6 months after a minimal
contact treatment involving brief physician counseling, instruction in nicotine
polacrilex gum use, and prescription of nicotine polacrilex gum or a placebo. At a
pretreatment baseline, and again at I- to 2-week. l-month, and 6-month followups,
subjects rated six withdrawal symptoms related to mood and psychological functioning
including anger, anxiety, difficulty concentrating, impatience, and restlessness in
addition to four others--craving. hunger, insomnia, and physical symptoms. For 75
subjects abstinent at 6 months, of whom 57 used nicotine polacrilex gum and I8 used
a placebo. ratings for anger, anxiety, difficulty concentrating. restlessness, and im-
patience peaked at the I- to 2-week followup, returned to baseline at 1 month, then
dipped to below-baseline levels at 6 months. Subjects receiving nicotine polacrilex
gum compared with those using placebo reported smaller increases from baseline to I-
to 2-week and I -month ratings for most withdrawal symptoms, but nicotine polacrilex
gum effects were not explored at the 6-month followup because too few subjects
continued using the gum. However, 6-month ratings were lower on many symptoms
even among 240 nonquitters, suggesting a drift in ratings due to a testing effect. In fact,
the only symptom change from baseline, which differentiated quitters and nonquitters
at 6 months, was that quitters had a greater increase in hunger than did nonquitters
(p<O.oO I ).
Hughes, Gust, and Pechacek (1987) concluded that, with the possible exception of
hunger and craving or an urge to smoke, there was no evidence for prolonged
withdrawal reactions lasting 6 months or more. (See Chapter I I for discussion of
hunger and weight effects.) However, these researchers also noted that results based
on a select group of smokers who enrolled in a study and the absence of control groups
of long-term former smokers and continuing smokers not trying to quit limit the
generalizations that can be made about the symptoms of long-term abstainers.
Two other prospective studies comparing quitters and nonquitters have documented
6-month improvements in mood and well-being among former smokers who had
participated in cessation treatments. Hall and associates ( 1983) administered the Profile
of Mood States to 35 smokers with cardiopulmonary disease both before and 6 months
after. 1 of 2 different 6session quitting treatments. Controlling for baseline scores,
they found that total mood disturbance. including anger/irritability, tension/anxiety,
fatigue. confusion, and depression/dejection, was negatively correlated with smoking
reduction (p<O.O2). That is, smokers achieving the greatest smoking reduction showed
the greatest improvements in overall mood. The same held true for the separate factors


ofanger/irritability (~~0.05) and tension/anxiety (p<O.OS). Treatment differences were
not explored.

Orleans and colleagues (lYX3) studied a group of 72 smokers who had quit in the
previous year (mean abstinence, 7 months), and compared the changes in mood and
well-being occurring among 49 quitters at 4 worksites where a range of employee health
promotion programs had been offered including smoking cessation, exercise, weight
control. and stress management. with those occurring among 23 quitters at 4 no-
treatment control worksites. The investigators controlled for age, sex, baseline values.
and months since quitting. Significant improvements in HANES well-being, anxiety.
and depression scores were observed only among former smokers at treatment com-
panies. but not among those at control companies (p<O.Ol). These results suggest that
treatment may have potentiated positive changes among new quitters. However, never
smokers, long-term former smokers, continuing smokers. or recidivists at treatment
companies were not compared.

Two studies have documented long-term, quitting-related improvements in psycho-
social outcomes among self-quitters. Prochaska and associates (in press) assessed the
processes that smokers undergo during different stages of smoking behavior change in
a 2.5-year longitudinal study of self-change among 63 self-quitters. These researchers
found significant decreases from baseline in smoking-related negative self-evaluations
(e.g.. "My dependency on cigarettes makes me feel disappointment in myself') from a
prequitting baseline for 9 subjects who progressed from the contemplation stage to the
action stage and then to maintenance, and for 54 subjects who progressed from action
to maintenance. Formal comparisons with subjects who did not progress in their stage
of change were not reported. (See Chapter 2 for a discussion of stages of change.)

Cohen and Lichtenstein (in press) found significant long-term reductions in perceived
stress in a prospective study of I50 unaided quitters. They administered the Perceived
Stress Scale (Cohen, Kamarck. Mermelstein 1983) prior to quitting and again at 1. 3.
and 6 months after the quit date. This scale measures the degree to which individuals
perceive the stresses in their lives to exceed their abilities to cope (range=&16). For
the I2 subjects who quit and remained continuously abstinent, perceived stress
decreased significantly from a prequitting mean of 5.7 to a 6-month followup mean of
2.Y. Among 57 continuing smokers, perceived stress levels increased slightly from 6. I
prior to quitting to 6.3 at 6 months. Likewise. for the 8 1 smokers who quit but relapsed.
perceived stress levels increased slightly from a prequitting mean of 5.X to a 6-month
mean of 6.1. There were no significant differences between quitters, continuing
smokers. and relapsers in prequitting perceived stress levels. The investigators suggest
that among smokers who want to stop smoking. quitting may have a beneficial influence
on perceived stress. self-esteem. and general self-efficacy (a belief that one has the
ability to perform a specific behavior such as smoking cessation) (Bandura 1982). and
failing to quit may have opposite effects. However, these researchers also noted that a
causal explanation cannot be clearly invoked: It is possible both that perceived stress
contributed to the failure to quit smoking (Marlatt 1985a: Shiffman 1982) and that
failure to quit contributed to stress.

More prospective studies are needed to clarify the long-term postwithdrawal
psychological consequences of smoking abstinence suggested by the research reviewed

540


for this Report. Studies designed specifically to assess long-term abstinence effects
will require longer followup, larger samples of unselected quitters. and control groups
of smokers who are not trying to quit. When possible and appropriate, self-report and
physiologic and observer ratings of emotional and psychological changes should be
included (Abrams et al. 1987; Hughes. Higgins, Hatsukami 1990) with measures of
health-related quality of life (Kaplan 1988).

Self-Efficacy and Locus of Control

Self-Efficacy

Self-efficacy has been shown to be a strong mediator of smoking behavior change
and to predict short- and long-term quitting outcomes (Condiotte and Lichtenstein I98 I ;
Coelho 1984; McIntyre, Lichtenstein, Mermelstein 1983). As defined by Bandura
(1982). self-efficacy refers to one's perceived ability to perform a specific behavior.
such as resist temptations to smoke under specific circumstances: that is. self-efficacy
is a response to a stressful event rather than a global sense of personal competence. As
such, self-efficacy related to smoking cessation is likely to influence both the decision
to engage in a quit attempt and perseverance in coping after quitting (Coelho 1984;
Marlatt 1985b).

The self-efficacy measures employed in smoking cessation research have concerned
only expectations for smoking behavior control. However. several researchers have
proposed that successful smoking cessation might itself result in feelings of increased
general self-mastery and self-confidence. That is. generalized self-efficacy may be a
consequence of smoking cessation (Cohen and Lichtenstein. in press; Marlatt 1985b.c:
Prochaska et al., in press). No studies have yet examined prequitting to postquitting
changes in generalized self-efficacy.

However, the relationship between cessation and self-efficacy around smoking
control has been studied. Cross-sectional studies among smokers wanting to quit have
found that successful quitters score significantly higher on measures of self-efficacy
than either those who tried to quit and failed (Abrams et al. 1987; Barrios and Niehaus
1985; Prochaska et al. 1982) or continuing smokers (Katz and Singh 1986). These
differences may reflect that successful quitters generally have higher efficacy scores to
begin with (Fleisher et al., in press: Mothersill, McDowell, Rosser 1988; Ockene et al.
1982: Prochaska et al. 1985) or that one's expectations that smoking can be resisted
would rise significantly as a function of actual success in doing so.

Prospective longitudinal studies. with followup periods ranging from several weeks
to 2.5 years postquitting, lend support to the hypothesis that increases in self-efficacy
concerning smoking control are related to smoking cessation both for untreated self-
quitters (Prochaska et al.. in press) and for smokers enrolled in treatment programs
(Coelho 1984; Killen, Maccoby, Taylor 1984: Nicki. Remington. MacDonald 1985:
Schwartz and Dubitzky 1968). Coelho ( 1984) reported that smoking control self-ef-
ficacy scores increased significantly from a mean of 77. I at the time of enrolling in
treatment to a mean of 127.4 at 3 months posttreatment for IX subject\ M ho had quit
smoking. (Abstinence was defined as continuous nonsmohing since a quit date. but


mean duration of abstinence was not reported.) Conversely, pretreatment and posttreat-
ment means for 48 nonquitters were unchanged from 78. I to 75.1, respectively.

Two studies examined the effects of different types of smoking intervention treat-
ments on self-efficacy ratings. Killen, Maccoby. and Taylor (1984) found no differen-
ces in the amount of positive change in self-efficacy among abstainers of 4 weeks or
longer who took part in different treatments that included nicotine polacrilex gum,
nonsmoking skill training, or combined nicotine polacrilex gum and skill training.
Nicki, Remington, and MacDonald (1984) followed 53 subjects for 1 year after
treatment and found significantly greater increases in smoking control self-efficacy
among quitters and nonquitters randomized to a behavioral smoking intervention
treatment designed explicitly to enhance smoking control self-efficacy than among
those randomized to a standard control treatment (~~0.05). The mean duration of
abstinence for quitters was not reported.

Locus of Control

Measures of locus of control reflect the extent to which an individual believes that
he or she has control over personal happenings and circumstances. Measures of a
generalized locus of control reflect either expectations that one has internal (i.e.,
personal) control over the reinforcements for one's behavior, indicating an internal
locus of control, rather than believing that these reinforcements are determined by fate,
luck, or other forces beyond control (Rotter 1966), which reflects a more external locus
of control. Measures of health locus of control reflect beliefs that important health
outcomes can be controlled through behavior rather than by being at the mercy of luck,
fate, or powerful others (Wallston, Wallston. DeVellis 1978). It is possible that former
smokers would shift toward a more positive or more internal control orientation in
reaction to their successful quitting. Anecdotal evidence suggests that when smokers
quit smoking they feel both more competent and more in control of their lives and that
they experience pride in their perceived "strength of will" (Knudsen et al. 1984).

Cross-sectional studies have demonstrated that former smokers, both self-quitters and
treated quitters, exhibit significantly more internal control orientations than either those
who tried to quit and failed (Rosenbaum and Argon 1979) or continued to smoke and
did not attempt cessation (Mlott and Mlott 1974; Orleans et al. 1983; Rosenbaum and
Argon 1979). However, prequitting measures of generalized (Ockene et al. 1982) and
health-specific (Horwitz, Hindi-Alexander, Wagner 1985) locus of control also dif-
ferentiate these groups.

Locus of control may be related to the duration of abstinence. Orleans and associates
(1983) found no significant differences between 1,343 current smokers and 856
short-term ex-smokers (abstinent for <3 months) in a baseline measure of perceived
personal control over preventable illness. However, 89 medium-term former smokers
(abstinent 3-12 months) and 525 long-term former smokers (abstinent for > I2 months)
scored significantly higher on personal control than current smokers (~~0.01). A
followup conducted 1 year later showed a significant (~~0.0 I ) increase toward internal
control among 72 smokers who had quit since baseline (mean abstinence, 7 months).

542


Conversely, Orleans and colleagues (1983) found a significant shift toward more
external health locus of control of similar magnitude among 30 individuals who had
been former smokers at baseline. but who had relapsed by the l-year followup. A
similar pattern was reported by Horwitz, Hindi-Alexander. and Wagner (1985) who
followed 2 19 participants in a single-session hypnosis treatment over a I -year period.
These researchers found a significant shift (p<O.OOl ) toward a more external orientation
among 79 smokers who had tried to quit but failed, with the mean falling from 27.6
pretreatment to 24.2 at the l-year followup. The investigators suggested that general-
ized expectancies for control over one's health might be diminished by failure and by
the `*abstinence violation effect" (i.e.. when individuals take a cigarette or relapse. they
may feel guilty or depressed or believe that they are lacking in will power and may
decide they are not maintaining control over smoking) (Marlatt 198Sb). However.
Horwitz, Hindi-Alexander. and Wagner ( 1985) found no significant pretreatment to
followup shift toward an internal health locus of control among 56 continuously
abstinent quitters who had quit with hypnosis. This lack of change toward an internal
health locus of control may in part reflect that treatment using hypnosis does not
engender strong personal, internal attributions for success.

Two studies suggest that treatment factors can influence shifts in locus of control.
Orleans and associates (1983) divided 72 recent former smokers into 2 groups: 49 at
4 worksite companies where a comprehensive employee health promotion prog'am had
been introduced and 23 at 4 no-treatment control companies. The significant overall
shift toward an internal health locus of control wah accounted for wholly by the former
smokers at treatment companies. It is possible that the intervening health promotion
program emphasizing personal control over health, well-being. and preventable illness
potentiated or hastened this shift. Blittner. Goldberg. and Merbaum (1978) randomly
assigned 54 smokers seeking treatment to I of 3 conditions:  a stimulus control
treatment coupled with bogus feedback of superior self-control abilities. a stimulus
control treatment alone. or a wait list control. A statistically significant pretreatment
to posttreatment increase in internal orientation was observed only for the subjects who
received feedback to enhance their expectations of inner control ability. This group
also achieved the greatest 14-month smoking reductions (p<O.OOl ).

Thus, most of the available data suggest that smoking cessation is related to an
increase in a more internal locus of control orientation; no data indicate a shift toward
an external locus of control for abstainer>. There is some support to suggest that
treatment method may have a differential effect on an increase in internal locur, of
control orientation.

Coping and Self-Management Skills

The relation of abstinence from cigarettes to a generalized improvement in the extent
and use of coping and self-management &ills has not been studied. To the extent that
stopping smoking results in an individual'\ acquirin g or strengthening general]! ap-
plicable stress-coping and temptation-copin g &ill\. long-term benefit4 of ab\tinnics
might be expected to include the gencrali/ed use of such skills. Ho\se\er. no \tudic\
have assessed whether increases in feneralilrd \tre+copin, ~7 \hill\ occur ;I\ ;\ cons-


quence of cessation. Longitudinal studies have not included prequitting and postquit-
ting measures of generic copin p strategies. A brief review of the relation of coping to
smoking cessation and maintenance of abstinence may help to provide direction for this
line of needed research.

Shiffman and Wills (1985) have developed a conceptual framework of coping that
distinguishes stress-coping skills, that is. skills used to cope wnith general life stressors.
and temptation-coping skills, or skills relevant forcoping with a situation in which there
is a specific temptation for substance use or an urge to smoke. Folkman and Lazarus
( 1988) defined stress-coping as constantly changing cognitive and behavioral efforts to
manage specific external and internal demands that are appraised as taxing or exceeding
the resources of the person to maintain an appropriate balance between environmental
demands and resources available to the individual to meet those demands. Temptation
coping can be separated into what smokers do when faced with the immediate tempta-
tion to smoke and anticipatory coping or the strategies smokers use to maintain
commitment to abstinence and prevent temptation (Shiffman and Wills 1985).

To the extent that smoking constitutes a maladaptive response for coping with stress
and negative affects such as anxiety, depression. anger, frustration, loneliness. or
boredom (Abrams et al. 1987: Marlatt 198Sb.c: Ockene et al. 198 I ), the former smoker
must find alternative strategies for coping. The use of healthy all-purpose coping
strategies such as self-reinforcement. assertive behavior, social support, relaxation, and
exercise has proven important to success in maintaining abstinence in some studies
(Ashenberg, Morgan. Fisher 1984: Grunberg and Bowen 1985; Marlatt 1985~: Shif-
fman 1982).

However, two large worksite studies demonstrated no differences between current
and former smokers in the self-reported use of healthy and unhealthy techniques for
coping with stress (Blair et al. 1980; Orleans et al. 1983). In support of the importance
of coping skills. Katz and Singh ( 1986) found that 77 former smokers who had abstained
for 6 months or more (mean 6.7 years) had significantly higher scores on the Rosenbaum
Self-Control Schedule (a self-report measure of individual differences in applying
\elf-control or coping methods) than 52 smokers recruited for a quit-smoking treatment.
"Self-cured" and treated former smokers did not differ on this measure. The inves-
tigators concluded that former smokers may have succeeded because they possessed
better self-coping skills initially. The same interpretation could be applied to the study
by Abrams and associates (1987) in which 22 former smokers (mean abstinence 22
months) exhibited better observer-rated skills to resist the temptation to smoke than did
22 recidivists in simulations involving interpersonal smoking triggers. Shiffman ( 1982)
found that former smokers w,ho reported using cognitive and behavioral strategies to
cope with smoking temptations vvere less likely to relapse. These few studies support
the conclusion that use of skills to cope with stress and with temptations or urges to
smoke seem to be more prevalent among former smokers compared with current
smokers.

544


       Social Support and Interpersonal Interactions

Research has not addressed how smoking cessation influences the level of general or
quitting-relevant social support available to the quitter or how cessation affects the
quality of the individual's interpersonal interactions. Research on social support
processes has focused on examining baseline or posttreatment measures of social
support as predictors of quitting success (Graham and Gibson 1971: Lichtenstein.
Glasgow, Abrams 1986; Mermelstein et al. 1986; Ockene et al. 1982: US DHHS 1989).
Several studies have demonstrated that successful quitters had significantly fewer
smokers in their social networks at baseline than did continuing smokers (Eisinger
I97 I ; Graham and Gibson 197 I ; Ockene et al. 1982). Others have demonstrated that
the quitter's success stimulated quitting by others. especially spouses (Suedfeld and
Best 1977).
A few studies are relevant to the investigation of cessation effects on social support.
A large-scale. cross-sectional and longitudinal worksite study (Orleans et al. 1983)
found no differences among current smokers, former smokers. and never smokers at
baseline in satisfaction with personal relationships and interpersonal communication
or in satisfaction with coworker relationships. However, at l-year followup. 72
baseline smokers who had quit (mean abstinence, 7 months) showed a significant
decline from baseline in satisfaction with coworker relationships (p<O.Ol ) and scored
significantly lower in satisfaction with personal relationships (p<O.OS) than a group of
30 baseline former smokers who had relapsed since baseline. Whether new former
smokers were in no-treatment control companies or in treatment companies where they
benefitted from multiple health promotion programming. designed in part to boost
coworker support, did not affect changes in satisfaction with interpersonal relationships.
These negative changes in interpersonal relationships are difficult to interpret because
former smokers in this study also demonstrated decreases in anxiety and depression and
improvements in coping strategies compared with baseline. One possibility is that new
former smokers may be less tolerant of smokers in their environment. Further study is
needed to replicate and explain this isolated finding.
In contrast, Prochaska and colleagues (in press) monitored a group of 63 self-quitters
who progressed through the stages of smoking behavior change to maintain abstinence
over 3.5 years (mean duration of abstinence was not reported) (Chapter 2). They found
that their use of helping relationships continued to increase with time. Similarly.
Horwitz, Hindi-Alexander. and Wagner (1985) found that 56 successful quitters
reported significantly greater social support from spouses and friends I year after a
single-session hypnosis treatment than they did at baseline. No changes in reported
level of support were noted for 84 continuing smokers, but even 79 recidivists reported
significant increases in spouse support over baseline. Notwithstanding hypnotic sug-
gestions that "other peoples' smoke will not bother you." successful quitters reported
significantly (p<O.OS) more often expressing objections to others smoking around them
(mean=2.38) than either recidivists (mean=0.75) or continuing smokers (mean=O.SO)
at the I -year followup. Likewise. more former smokers requested nonsmoking areas
in restaurants (53 percent) and public transport (32 percent) than did recidivist5 (I2
percent and I2 percent, respectively) or continuing smokers (8 percent and 6 percent.


respectively ). This practice may have helped to minimize social pressures to smoke
commonly precipitatin g relapse (Marlatt and Gordon 1985). and helped to assure
support for maintenance. It is also possible that these practices simply resulted from.
rather than contributed to. smoking abstinence.

The results of these studies. although somewhat conflicting. suggest that former
smokers played an active role in structuring the improved support they reported as a
way of maintaining abstinence.  However, given the limited information. no con-
clusions regarding the effect of smoking cessation on social interactions can be made
at present.

Summary

Research findings provide no evidence for any long-term negative psychological
effects beyond hunger and craving. However, the available findings suggest that there
are some postwithdrawal psychological benefits that may increase with duration of
abstinence.

HEALTH PRACTICES OF FORMER SMOKERS

Introduction

Several studies have found that both good health practices and poor health practices
cluster (Belloc and Breslow 1972; Tapp and Goldenthal 1982; Verbrugge 1982:
Marsden, Bray. Herbold 1988). Self-defined former smokers appear more likely than
current smokers to engage in regularexercise and to practice other recommended health
behaviors. In general, smokers who quit and who subsequently or concurrently change
other health behaviors may represent a more distinct health-conscious group. Castro
and coworkers (1989) have suggested that cigarette smokers exhibit less healthy
lifestyles along cognitive. behavioral, and motivational dimensions. As the authors
noted, addictive behaviors seldom occur in isolation but are instead embedded within
complex behavioral chains or lifestyles. Conversely. the data presented in this Section
suggest that when individuals stop smoking. other beneficial health practices also may
emerge. Given the nature of the available data. it is not possible to determine whether
these other beneficial health behaviors reflect the characteristics of a distinct health-
conscious subgroup of smokers. emerge as part of the smokers' efforts to maintain
abstinence (e.g., increased exercise). represent a response to adverse withdrawal
symptoms (e.g.. changes in dietary practices). or are direct effects of quitting.

This Section reviews data on former smokers' physical activity and dietary practices
and use of other substances such as alcohol and other forms of tobacco. and former
smokers' profiles with regard to multiple health-enhancing behaviors. Changes in
former smokers' physical activity and dietary practices, as they relate to postcessation
weight changes, are also reviewed in Chapter 10.

The studies reviewed in Chapter 10 are longitudinal investigations in which former
and continuing smokers are compared. This Section focuses on cross-sectional data

546


from two nationwide surveys, the National Health Interview Survey (NHIS) conducted
by the National Center for Health Statistics (Kovar and Poe 1985: Schoenborn and
Benson 1988) and the Behavioral Risk Factor Surveillance System (BRFSS) coor-
dinated by the Centers for Disease Control and conducted by State health departments
(Remington et al. 1988). Both surveys provide large data sets on health behaviors in
the noninstitutionalized adult population. The limitations of drawing conclusions from
cross-sectional data apply here (Chapter 2).
For its yearly interviews, NHIS uses a multistage probability scheme sampling
technique developed in collaboration with the Bureau of the Census and employs
personnel trained for the decennial census. BRFSS uses a multistage cluster technique
of random digit dialing to select households for its yearly telephone survey. Both
randomly select a respondent from a list of residents identified when a household is
chosen.
A core set of questions each year is used in NHIS. then additional questions are added
in supplements to the core survey in keeping with each year's chosen focus. In 1985.
the NHIS special topic was health promotion, with variables such as physical activity.
dietary practices, sleep. weight, alcohol use, and smoking that were similar to those
used in the pioneering Alameda County study. The health promotion portion of the
interview was completed by an estimated 90 percent of eligible respondents (Schoen-
born and Benson 1988). In 1987. the special topic was cancer, with questions on diet.
smoking, smokeless tobacco use, alcohol use. vitamin and mineral consumption,
knowledge about cancer risks, cancer screening and preventive care, and family history
of cancer. The cancer-related portion of the interview was completed by approximately
86 percent ofeligible respondents (Schoenborn and Boyd 1989). In both NHIS surveys.
a former smoker self-reported as having smoked at least 100 cigarettes and not smoking
at the time of the survey. Mean duration of abstinence was not reported (Schoenbom
and Benson 1988; Schoenbom and Boyd 1989).
In 1987, BRFSS covered blood pressure, physical activity. weight and dieting. diet,
alcohol use, preventive practices, seatbelt use, stress, pregnancy status. use of oral
contraceptives, and use of smokeless tobacco and cigarettes. The median cooperation
rate (the ratio of completed interviews to the sum of completed interviews and refusals)
among the participating States was 84 percent (Remington et al. 1988). Similar to
NHIS. BRFSS defined a former smoker as an individual who had smoked at least 100
cigarettes in his or her lifetime and was not smoking at the time of the survey. (Mean
abstinence of former smokers cannot be calculated. However. 64 and 54 percent of
men and women, respectively, were abstinent from cigarettes for more than 5 years.)
Although these three surveys are similar, the published data available from them
differ in several respects.  Data from the 1985 NHIS. presented in Table 3. are
age-adjusted (Schoenborn and Benson 1988). Data from the 1987 NHIS. presented in
Table 4, are simple proportions with no variables controlled (Schoenborn and Boyd
1989). Data from the 1987 BRFSS were analyzed to assess the relationchips between
cigarette smoking and lifestyle and preventive practices (Table 5) and to examine the
same relationships with respect to the duration of cigarette abstinence (Table 6). The
odds ratios, presented in Tables 5 and 6. are controlled for age. ethnicity. and level of
education.


TABLE 3.-Summary of data from 1985 NHIS, behaviors of ne\er, former, and
      current smokers aged 20 and older

MEN
Alcohol conwmption

Heavier drinker'
25 drmkjh

Weightidletlexercw

Never eats breahfav
Snacks dally
Less phywally actweL
Sedentaryd
Overweight'

Other

Sleep\ 56 hr

WOMEN
Alcohol conwmption

Heavier drinher"
25 drinks"

Weight/diet/exercibe

Never eats breabfast
Snack\ daily
Less physically active'
Sedentaryd
Overweight'

Other

Sleeps 56 hr

7.9
13.x

IXY
3Y.i
13.2
46.6
XI

21.5

I.1
2.2

177
37.6
IO.9
61.1
74.Y

12.7
21.2

21.5

3.7               6.1
5 .o               8.5

IY.X              37.6
41.s              35.3
2 3 .3              23.9
5x.5              61.3
73.0               17.0

lY.9

I X.Y
2x.7

33.3
3x.5
18.X
57.2
21.2

74.9

24.4

548


TABLE 4.-Summary of data from 1987 NHIS behaviors of never, former, and
     current smokers aged 18 and older

Behavior

Never wiokers
   %

MEN
Alcohol consumptron
Drmks beer tS/wk
Drinks 23 beer\/epi\ode
Drinks wine ~S/v.h
Drink\ 23 glasse\ wme/epi\ode
Drinh\ liquor Zi/wk
23 drinks/episode

Dietary practice>
3 meals/day on weekdays
3 meals/day on weekends
Avoid\ wachs weekday\
Avoid\ wackh weehends
Haa changed dret for health
220% above desirable weight

Preventive care

6.1       1% h
36.3       30.5' h
I.3       3.1dh
12.9       Il.h"h
1.7       4.X" h
30.3       25.x" h

48.6
14.3
24,s
21.0
35.0
21.9

Digital rectal exam (ever)
Blood stool test (ever)
Proctov2opic exam lever)

WOMEN
Alcohol conwmptlon
Drink\ beer tS/wk
Drinks 23 heers/epiwde
Drinkc wine tS/wk
Drink\ 23 glasse\ wme/epi\ode
Drinhr liquor ZS/wk
23 drmks/epi\ode

Dietary practices
3 meals/day on weehdays
3 meaNday on weekends
Avoids bnacks weekdays
*Avoids snack!, weekend\
Has changed diet for health
20% above desirable weight

Preventive care
Digital rectal exam (ever)
Blood stool test (ever)
Proctoscopic exam (ever)
Pap smear (within year)
Breast self-exam (withm yr)
Breast exam (monthly)
Mammogram lever)

SY.5
3X.6
24.0

0.9
17.1
1.3
7.0
0.7
13.7

so. I
14.2
26.6
22.6
3x.7
`1.3

.56.X       67.4' h
37.9       36.2" h
20.x       27.2" h
39.7       13.5" h
34.x       30.3" h
51.5         57.
3X.5       16.7" h

Former \moher\    Current smoker\
    %            %

17.1'
51. IL
1.7`
`0.2'
1.1'
15.1'

32.X'
3S.l'
`6.SL
33.6'
26.3'
33.X'

66.X" h
4-l.Yd h
27.7" h

2.3" h
17.zh
1.3" h
IO.`)" h
2.7"
14.1h

4Y.Sh
4 I .x* h
76.9
`3.4" Cl
49.0" h
?4.Xh

s9.4
33.`)'
2 I S)'





3.0'
32.7'
I .9'
17.X'
2.7'
x.0'


X.5'
29.4'
26.X
23.6
34.5'
20.3'



60.6'
35.7'
`I.1
40.7'
31.0
52.1
35.1'


TABLE K-Summary of data from 1987 BRFSS, behaviors of former smokers
     and current smokers aged 18 and older

.AdJu\ted odd\ ratio\

Behavior

Former \mvhrr\
relatl\,e to never
  \moher\

Current \mohen
relative to never
  \moher\

Former smoker\
relative to current
  \mokerr

MEN

.Alcohol conwmptwn

Any alcoholimo
2.5 drinks/episode
260 drmk\/mo
Drinkmg and drivmg

I .75"            2.1 IJ             0.82"
I .67"            2.63'             0.63'
I .7S"            3.0?"             0.58"
I .4-v'             I .YY"              0.71'

Weight/diet/exerci\e
Obese (BMI)'
Obese (Met. Llfe)d
Trying to lose pounds
More exercise
Eating fewer kcal
Physical actwity
Sedentary

I .os             0.63"              I .6x"
I .06             0.6-1"             1.63"
I.??'            0.63"             1.92"
O.YX            0.X3"            l.l7h
0.x+          O.XZh                I .w
l.lOh            0.69"             1.57"
0.9 lb             I .43"             0.64"

Preventive care
~_-
Cholesterol te\t
Flu shot part month

1.77.'               0.04              1.34"
I .OY          o.X7h              I .Ih"

Other

Use ST              l.7JJ          o.84h              `.OYJ
Use seatbelt         O.YZh            OX"             I .60"

WOMEN

Alcohol consumption
Any alcohollmo
25 drmks/epi\ode
260 drmk\/mo
Drinhing and drivmg

2.07"
I .X6'
2.xX"
I .X7"

2.w
3.35"
s .w'
1.92"

0.87"
OX"
0.52
0.65"

Weight/diet/exercr\e
Obese (BMI)'
Obese (Met. Life 1"
Trymg to lose pounds
More exercise
Eating feuer kcal
Physrcal activity
Sedentary

O.YX
0.96
1.19"
I .07
0.97
1.17"
0 X6"

0.63"
0.65"
0.75"
0.72"
0.96
0.X1"
1.7-t.'

1.59"
1.52"
I .60"
I .4x"
0.99
I .JS'l
0.69"

Preventive care

Cholesterol test
Flu shot past month

I.15
0.95

I.1 I"
O.Ylh

1 .os
I .os

550



TABLE 5-Continued

Ad,ju\ted odd\ ratw\

Behavior
______
Other

Former \moher<
rrliltive to nevrr
  \mokrrr

Current \moherr
relative to fnexer
  \moher\

U\e ST               0.73             0.16"                I 53
U\e \eatbelt             I .03             0.6?             I .h3"

Physical Activity

Evidence from the 1985 NHIS. the 1987 BRFSS, and other cross-sectional studies
suggests that smokers are less likely than nonsmokers to make regular exercise part of
their lives (Goldbourt and Medalie 1975: Schoenborn and Benson 1988: Martin and
Dubbert 1982). These differences may be the consequence of cessation and result partly
from changes in physiologic function, such as lung function, that make exercise more
pleasurable or tolerable for former smokers compared with current smokers (Castro et
al. 1989). They also may retlect the former smokers' efforts to maintain abstinence.
Blair and colleagues (1980) found mixed results in their studies of workers in a South
Carolinacompany. Among men living within a 0.5 mile of work, current smokers were
less likely than never smokers to walk to work. Among women, former smokers were
more likely than either never smokers or current smokers to walk to work. (Mean
duration of abstinence for former smokers was not reported.) There were no significant
differences between smoking categories in other measures of physical activity, such as
time spent sitting, use of stairs versus elevator, level of leisure time versus physical
activity. and participation in a company exercise program. However. many measures
for former smokers were between those of current smokers and never smokers.

The 1985 NHIS used 2 measures of physical activity, the perception of being less
physically active than others and a more rigorous definition of sedentary behavior based
on subjects' reports of participation in 23 leisure activities during the preceding 2 weeks
(Schoenbom and Benson 1988). The perception of being less physically active was
significantly more common among current smokers than former smokers and never
smokers (Table 3). When separated by sex. these differences appear to be greater for
men than for women. Men who were former smokers were significantly less likely to
report being sedentary than current smokers and not significantly different from never
smokers. Among women. former smokers were significantly less likely than current
smokers and never smokers to be sedentary.

In two studies among Navy personnel. Conway and Cronan (1988a.b) studied the
relationship among smoking. exercise. and physical fitness. The first study (Conway
and Cronan 1988a) included 3.035 Navy personnel randomly selected from a group
who volunteered to participate in an evaluation of physical fitness and health. Both


TABLE 6.-Summary of data from 1987 BRFSS, behaviors of former smokers
     aged 18 and older by duration of abstinence

Behavior

MEN

Alcohol consumption
Any alcohol/ma
>5 drinks/episode
260 drinks/m0
Drinking and driving

Weight/diet/exercise
Obese (BMIJh
Obese (Met. Life)'
Trying to lose pound\
More exercise
Eating fewer kcal
Physical activity
Sedentary

Preventive care

Cholesterol test
Flu shot past month

Other

Use ST
Use seatbelt

WOMEN

Alcohol consumption
Any alcohol/ma
i1S drinks/episode
%Odrinks/mo
Drinking and driving

Weight/diet/exercise
Obese (BMIjh
Obese (Met. Life)'
Trying to lose pounds
More exercise
Eating fewer kcal
Physical activity
Sedentary

Preventive care

Cholesterol test
Flu shot past month

Adjusted odd\ ratlos by duration of abrttnence

13-21 mo relative to
I-12-moquitters

1.01               I .02
I .03               I .os
I 00               I .26
1.27               I.14

l.51d            1 .16L
I .45"            1.38"
I .02               I.18
0.85               I .06
0.92               I .16
0.98               1.13
I .02              0.88

0.94              I .03
0.88              0.96

0.64"
I .02

I .02            I .2R"
0.97              I .03
1.30              I .03
I .55              0.60

1.28            1.31"
1.07               1.16
1.17               1.15
0.97               I.10
1.10              1.01
I .os               1.06
0.95              0.95

0.89               I .05
1.26              0.97

25-60 mo relative to     261 mo relative to
I-1 2-mo quitter\      I-I?-moquitters

0.97            0.73"
I .09            I .22"

1 .09
0.95
I .09
I.17

I .13"
I .39"
I .08
0.86
1.37
I .25*
O.Sd

0.98
0.95

I .22"
0.83
1.15
0.72

I .42"
1 .30d
I .w
0.98
0.90
I.1 I
0.90

0.88
I .04

552


TABLE 6.-Continued

Adjusted odds ratios by duration of abstinence

Behavior


Other

13-24 mo relative to     25-60 mo relative to
l-l 2-mo quitters      I-I?-moquitten

261 mo relative to
I-I?-moquitter\

Use ST
Use seatbelt

0.49              0.27               I .07
I .28"              I.14            1.24.

NOTE: BRFSS=Beharlordl Ri\k Factor Survetllance Syrtem: ST=\mokelev tobacco
`Signtticantly different from I-12.mo quttten lp4.051. There were no significant difference\ nmung the three
categories of cesmon >I yr.
"BMI=body ma\\ index.
`Met. Life=Metropohtan Life hetght and weight Index.
SOURCE: Samet and W&t\. unpublished analye\ of the 19X7 BRFSS.

never smokers and former smokers engaged in significantly more exercise sessions per
week than did current smokers. Current smokers exercised for significantly less time
per session and had significantly lower overall physical fitness scores compared with
never smokers or former smokers. In a second study. the same authors examined the
association between physical fitness and smoking among 1,357 Navy men (Conway
and Cronan 1988b). Again, current smokers had poorer levels of physical fitness with
lower scores than former smokers or never smokers on tests of cardiorespiratory and
muscular endurance. Overall, never smokers performed better than former smokers
and current smokers. In both studies, participants were young, with an average age of
26 years (study 1) and 28 years (study 2). suggesting that both decrements associated
with smoking and improvements associated with quitting can appear at an early age.

A cross-sectional study of 78 1 runners found that as mileage increased, the percentage
of self-defined former smokers also increased (Macera, Pate, Davis 1989). These
investigators suggested that high-mileage runners seemed to quit smoking at a higher
rate than low-mileage runners. Although the sample size was probably too small to
show significant differences and the data were cross-sectional, the results support both
empirical and anecdotal data about the relationship between abstinence from smoking
and increased participation in exercise. Gordon and Polen ( 1987) studied 1,061 men
and women who participated in smoking cessation clinics at Kaiser Permanente medical
facilities from 1980 to 1983. Men and women who had increased their exercise after
program participation were more likely to be abstinent from smoking 7 to 12 months
later. These studies suggest that increasing exercise may be part of a former smoker's
efforts to remain abstinent, a direct consequence of cessation, or both. The study by
Gordon and Polen ( 1987) lends support to the first hypothesis.

The 1987 BRFSS allows a comparison among current smokers, never smokers, and
former smokers on a range of health practices (Table 5). Two measures of physical
activity were used. One asked a very general question about any physical activity in
the past month, including nonaerobic activities, such as gardening. as well as major
aerobic activities. The second identified sedentary lifestyle as the lowest category on


a complex scale of life activities. On both measures. men and women who had quit
smoking were more active than nev'er smokers. who were in turn more active than
current smoLer\. Among men, those who had been smoke-free for more than 5 years
here significantly more active and less sedentary than neu quitters, those who had been
abstinent less than I year. This difference was not significant among women.

Prospective investigations of changes in physical activity after smoking cessation
have indicated either no change or an increase in activity (Chapter IO). An additional
prospective study focusing on exercise specifically. rather than weight changes, also
found increased exercise among quitters.  In a l-year study of a large worksite
population, Orleans and associates ( 1983) found that 71 recent ex-smokers (mean
abstinence, 7 months) significantly increased their self-rated levels of activity compared
with 347 continuing smokers (~~0.01) and that the ex-smokers achieved significant
increases (p<O.O I ) from a prequitting baseline in the frequency of activities involving
moderate exertion, such as walking or climbing stairs. Gordon and Cleary (1986)
analyzed data from the 1979-1980 National Survey of Personal Health Practices and
Consequences and found a more limited positive relationship. Aerobic exercise in-
creased for women who tried to quit smoking but was not related to successful quitting
in the last year among women or to any change in smoking behavior among men.

More studies are needed to clarify the effects of smoking abstinence on the level of
physical activity. The relationship between increased physical activity and smoking
abstinence may be a consequence of cessation, may reflect more successful quitting
among smokers who have a higher level of prequitting physical activity. may be
evidence that former smokers use exercise as a strategy to avoid smoking, or as a way
to deal with the possible adverse effects of weight gain. or may be due to some
combination of these possibilities. The cross-sectional nature of the data available do
not permit a conclusion with regard to these alternatives.

Dietary Practices

Cross-sectional data from NHIS. BRFSS, and other studies present a mixed picture
of the dietary practices of smokers, former smokers, and never smokers. Schoenbom
and Benson (1988). reporting on the 198.5 NHIS, found that current smokers are more
likely to skip breakfast than never or former smokers (Table 3). This finding is
consistent with the 1987 NHIS data showing that both former and never smokers are
more likely than current smokers to eat no more than or no less than three meals a day
(Schoenbom and Boyd 1989) (Table 4). As shown in Table 4, whether former smokers
are more likely. less likely, or equally likely to eat three meals than are never smokers
depends on gender and whether the day is a weekday or weekend day. Two NHIS
surveys present contradictory results on snacking. The age-adjusted 1985 study indi-
cated that among women, former smokers are the most likely to snack, but that there
was no significant difference among men (Table 3). Raw percentages in the 1987 NHIS
data show that among men, former smokers avoid snacks more than either never or
current smokers, but that among women. there is essentially no difference (Table 4).

BRFSS data (Table 5) indicate that former smokers are the most likely group to be
"trying to lose weight," although no more likely than never smokers to be obese.

554


Similarly, the 1987 NHIS data show that former smokers of both sexes are the most
likely to report that they have changed their diet for the sake of their health (Table 3).
In these same NHIS data. not controlled for age, men who are former smokers are more
obese than never smokers, although women who are former smokers and never smokers
are equally likely to be obese.  Among the 10.000 Israeli men in Goldbourt and
Medalie's 1975 study of Government employees. former smokers (duration of
abstinence not noted) consumed fewer calories and were more likely to be on some sort
of special diet for weight loss, diabetes, heart disease, hypertension. or ulcers. Former
smokers surveyed for all three of these data sets may have initiated special diets or quit
smoking following the diagnosis of illness. However, the Israeli data demonstrate that
among those individuals who had experienced heart attacks or peptic ulcers, former
smokers were more likely to report themselves compliant with their diets than current
smokers (Goldbourt and Medalie 1975).

Former smokers often report retrospectively that they increased food consumption
when they quit smoking (Carmody et al. 1986). The first part of this Chapter and a
review by Hughes, Higgins, and Hatsukami (1990) indicate that increased hunger and
appetite are common smoking withdrawal reactions, often extending beyond the initial
4-week withdrawal period. However, most longitudinal studies of changes in dietary
practices after quitting have examined only short-term changes (Chapter IO). The
majority of these studies have found evidence for increased dietary intake, especially
of sweet foods and simple carbohydrates, after quitting. In a prospective study Orleans
and coworkers (1983) found approximately a 6-pound weight gain at l-year followup
over baseline for 72 former smokers who had been abstinent from cigarettes for an
average of 7 months. These researchers also found evidence for significant (p<O.Ol)
improvements in overall nutritional practices for former smokers.

Better dietary behavior among former smokers when compared with current smokers
may reflect changes made by former smokers in their efforts to remain abstinent. a
response to their concerns regarding possible weight gain, or an overall desire to be
healthy that is motivated by smoking cessation. Adequate data are not available to
permit an assessment of these alternative hypotheses.

Use of Other Substances

Other Tobacco Products

In data from the United Kingdom, the cessation of cigarette smoking has been linked
to the increased use of other smoked tobacco products, including pipes and cigars, by
men (Jarvis 1984). These researchers noted that many of the alleged gender differences
in cigarette smoking cessation rates are due to the adoption of pipe and cigar use by
men. Comparable analyses have been performed on data from the 1987 NHIS Cancer
Epidemiology and Control Supplement (Schoenbom and Boyd 1989) (Volume Appen-
dix). When former cigarette smokers who used any other forms of tobacco were
reclassified as smokers, the difference in cessation rates between men and women
decreased.


Data from the I987 NHIS indicate that the overall prevalence of the use of smokeless
tobacco products and cigars or pipes is low; the prevalence of use ranges from 3.0 to
5.2 percent for men and from 0 to 0.5 percent for women: former cigarette smokers are
more likely than never cigarette smokers to be current smokers of pipes or cigars (Table
7). Because the prevalence of pipe or cigar smoking increases as a function of age, it
is important to use age adjustments in future investigations of the relationship between
cigarette cessation and pipe or cigar smoking.

Alcohol

Smokers are more likely than nonsmokers to drink alcohol and use other drugs (Istvan
and Matarazzo 1984: US DHHS 1988). Cross-sectional data from the 1983 NHIS
(Kovar and Poe 1985) show a strong association between smoking status and daily
alcohol intake (Figures 3 and 4): former smokers tend to be heavier drinkers than are
never smokers, and daily alcohol intake increases with heavier smoking (Kozlowski
and Ferrence 1990). The drinking and smoking scales differ for men and women to
compensate for the relative rarity among women of very heavy drinking and heavy
smoking: at the same levels per day as men, fewer drinks per day are required for women
than for men to be placed in the "heavy drinking" category.

In the 1987 NHIS, alcohol consumption was divided into beer, wine, and liquor
consumption. Published data report on the proportion of respondents consuming "5 or
more drinks per week" and "3 or more drinks on days you drank" for each category.
These data are generally consistent with the 1983 (Figures 3 and 4) and the 1985
age-adjusted NHIS data (Table 2) and with the age-, education-, and ethnicity-adjusted
data from the 1987 BRFSS (Table 5) in showing lower alcohol consumption among
former than among current smokers but higher than among never smokers. These data
regarding alcohol consumption of former smokers are also consistent with data
presented previously in this Chapter on the short-term effects of smoking abstinence
on alcohol consumption (Hughes and Hatsukami 1986; Olbrisch and Oades-Souther
1986; Puddey et al. 1985).

In the 1987 BRFSS survey, two measures of alcohol were used: the amount consumed
and whether drinking and driving occurred together (Tables 5 and 6). Men and women
who had quit smoking drank significantly more than never smokers and were sig-
nificantly more likely to drink and drive. However, former smokers drank significantly
less than current smokers and were significantly less likely to drink and drive.

The intermediate position of former smokers seen in the 1987 BRFSS and the 1985
NHIS is paralleled in the 1987 NHIS by the percentage of both sexes who drink five
beers or more per week, the percentage of women who drink three glasses or more of
wine when they drink wine, and the percentage of men who drink three drinks or more
when they drink liquor (Table 4). In the 1987 NHIS, male former smokers are
significantly less likely than either comparison group to have three beers or more when
they drink beer or three glasses or more of wine when they drink wine. Although a very
small percentage of adults drink wine or liquor five times or more per week, men who
are former smokers are more likely than current or never smokers to drink this often.
Female former smokers are more likely than current or never smokers to drink wine

556


TABLE 7.-Percent distribution of persons aged 18 and older by tobacco product and use status, according to gender and
     cigarette smoking status, United States, 1987

Tobacco product
and use status

Total

  Both genders

Never     Fomler
wlokers     smokers

Current
smokers

          Men                          Women

     Never    Former    Current           Never   Former   Current
Total   \moker>   smohers   smoher5     Total   smokers  wwkers   smokers

Total

Chewing tobacco
Never
Former
Current

Snufl
Never
Formrr
Current

Pipe
Never
Former
Current

Cigars
Never
Formrr
Current

100.0     IWO

93.X      96.7
4.2       I .x
2.0       I .s

Y5.Y      Y3.3
2.4       I.1
1.7       I .6

01.1      Yl.4
7.3       I .7
I .6       0.x

8Y.X      02.0      X7.6    02.5
7.3       5.x       x.3     4. I
2.`)       2.2       4.0     3.4

04.3      94.x      02.3    Y4.6
3.x       3.5       4.7     2.4
I .Y       I .6       3.0     3.0

79.3      x0.7      8 I.5    Y3.Y
IX.5       7.0      15.2     4.4
2.2       2.3       2.3     2.2

x03      x0.7      Xl.7    Y2.S
16.3       6.2      13.1     4.4
3.2       3.1       5.2     3. I

I(w).0     Ion.0     100.0

x3.s     X.5.3     YY.3
I I.Y     IO.6      0.4
3.6      4. I      0.3

00.9     Y0.S     YY.2     YY.0
h. I      6.4      0.4      0.3
3.0      3.1      0.5      0.7

x5.`)     x03     YY.7
30.4     IS.1      0.3
3.7      4.4     (HP

x7.x     x0.x     YY.6     YY,X
2h.Y     I I.5      0.3     O.ll'
5.3      7.X     0. 1,'     0.0"

loo.0

09.3
0.3
0.4

lot).0
00"

I00.0     Iwo



YY.2     YY.2
0.6      0.6
0.2"     02



00.2     YY.4
0.5      0.5
0.3"     0. I"



YY.2     YY.5
0.x      0.4
0.0:'     0."'



09.4     YY.2
0.6      0.6
0.0"      0. I"


  Never  Fommr <l-lo/day 11-2Olday 213lday 3lWday

SMOKING STATUS

* l/day 0 2-3/day 0 4-6,fday O L7lday

FIGURE 3.-Drinking relative to smoking status for men, 1983 NHIS (Kovar
       and Poe 1985)

NOTE: Samples for each category are. from never smoker to hewlest smoker. 1.397. X74.295.653.
263. 100. S7. NHIS=Natlonal Health IntervIew Survey.

SOURCE: Kozlowrki and Ferrence (1990).

five times or more per week; they are as likely as current smokers to drink liquor this
often. However, this represents a very small proportion of women. Female former
smokers are less likely than current smokers and no more likely than never smokers to
drink three beers or more when they drink beer or to have three drinks or more when
they drink liquor.

These cross-sectional data are consistent with other cross-sectional data that
demonstrate a relationship between alcohol use and smoking status (Istvan and
Matarazzo 1984). However, the contribution of tobacco cessation to alcohol and drug
use by individuals with alcohol and drug problems is unknown (Sobell et al. 1990). The
majority of smokers consume approximately 1 pack per day, and most smokers do not
have serious alcohol problems. The most significant effects might be seen in those few
individuals who both smoke very heavily, more than 40 cigarettes per day, and use
drugs or alcohol heavily (Kozlowski and Ferrence 1990). Bobo (1989) and Miller,
Hedrik, and Taylor ( 1983) reported data that indicate that smoking cessation does not

558


          Fofmw  4.1Oldmy ll-2Oiday 214Ww ,3Vdy

SMOKING STATUS

     aNever !!?&12/yr    NIvrrHuvy
     O tc+luvy rnl/deyU~2/dy

FIGURE 4.-Drinking relative to smoking status for women, 1983 NHIS
       (Kovar and Poe 1985)

NOTE: Samples for each category are. from never smoker to heavle\t
smoker. 2.661,789. SOS, 7X6.10.5. 176. NHIS=National Health Interview Survey.

SOURCE: KoAow4.i and Ferrence ( 1990).

impair the course of treatment for alcohol problems and may be associated with better
outcomes.

Studies of Multiple Health Habits

It is of interest to examine not only single behaviors, such as diet or exercise, in
relation to smoking cessation, but also combinations of behaviors. Use of alcohol and
other substances, use of other tobacco products, coffee consumption. physical activity,
and diet have been the health behaviors studied most widely in conjunction with
smoking and smoking cessation.

Schoenbom and Benson (1988) reported on the following eight unhealthy behaviors
surveyed in the 1985 NHIS: sleeping 6 hours or less, skipping breakfast, snacking daily.
being less physically active than other persons of the same age, being sedentary in terms
of leisure-time sports activities, being significantly overweight (IO percent or more
based on the 1983 Metropolitan Life Insurance Company standards). drinking heavily


(an average of two drinks or more/day), and having five drinks or more on IO days or
more. The authors used age-adjusted percentages to eliminate age as a confounding
factor. With the exception of snacking and being overweight, current smokers engaged
in unhealthy habits at significantly higher rates than never smokers (Table 2). Former
smokers more closely resembled never smokers than current smokers. Fewer former
smokers and never smokers than current smokers slept 6 hours or less, never ate
breakfast, were less physically active, or were sedentary. However, former smokers
tended to snack daily and be overweight in slightly higher percentages than current
smokers. which is concordant with the previously noted findings regarding dietary
practices and smoking abstinence.

Marsden, Bray, and Herbold (1988) examined substance use and other health prac-
tices in a large cross-sectional study of more than 17.000 military personnel. These
researchers found the number of positive health practices inversely related to use of
alcohol. illicit drugs, and tobacco. On the basis of a very preliminary retrospective
study of 35 heart disease patients. Finnegan and Suler (1985) concluded that former
smokers (mean duration of abstinence, unspecified) were more likely to maintain diet
and exercise changes. Former smokers may have represented a particularly adherent
subgroup of patients, but the authors postulated that success in maintaining diet and
exercise changes may have been influenced by the psychological effects of attempting
cessation.

Maron and colleagues (1986) examined seatbelt use in a sample of high school
students and found modest but significant negative effects of smoking, frequency of
getting drunk, and illicit drug use (cocaine and marijuana), and positive effects of
"heart-healthy nutrition" and physical activity on seatbelt use. In a study of 874
community college students, Castro and associates (1989) found that moderate-to-
heavy smokers had exhibited more unhealthy behaviors than nonsmokers. As in some
of the other cross-sectional studies reported here, these investigators did not distinguish
former smokers from never smokers.

Among males. former smokers interviewed as part of the 1987 BRFSS (which
examined multiple health behaviors) were more likely than current smokers but less
likely than never smokers to use seatbelts. However. among females, never smokers
and former smokers were equally likely to use seatbelts, and both were significantly
more likely to use seatbelts than current smokers (Table 3). Long-time quitters were
more likely than new quitters (<I year) to use their seatbelts, although this association
was small and significant only for men who had been abstinent from smoking cigarettes
for 5 years or more and for women abstinent for 1 to 2 years and for 5 years or more
(Table 5).

Among Multiple Risk Factor Intervention Trial (MRFIT) participants. Schoenen-
berger (1982) found that smokers who had quit between baseline and a 3-year followup
survey made successful changes across a number of dimensions. Former smokers were
more likely to avoid gaining weight, to lower their serum cholesterol, and, if hyperten-
sive, to lower their blood pressure. Supporting the conclusions of Schoenenberger
(1982) regarding MRFIT participants, Tuomilehto and associates (1986) studied a
random sample of 2, I 19 Finnish subjects at 2 points in time and found that both men
and women who had quit smoking between baseline and the 5-year followup reduced

560


their fat intake, increased their physical activity. and made more attempts to reduce
body weight than did current smokers.  Baseline differences suggested that these
quitters (duration of abstinence not specified) may have been more health conscious at
the outset.

Orleans and colleagues (1983) performed a prospective analysis of health behavior
changes experienced by 72 employees quitting smoking between baseline and year one.
As part of the "Live for Life" program they included baseline health behavior values.
age, and sex as covariates. Their findings indicated an overall positive shift in healthy
lifestyle with improvements in subjective health status, emotions, and well-being. New
ex-smokers (average abstinence, 7 months) showed improvements over baseline in
resting pulse. perceived personal control over preventable illness, knowledge of health
risks, overall nutrition practices, regular moderate exercise. and seatbelt use. The only
negative changes were body mass and weight changes associated with slightly less than
a mean 6-pound weight gain, which took place along with an improvement in overall
nutrition, and declines in job satisfaction measured by satisfaction with growth oppor-
tunities and personal relationships on the job.

Summary

In the absence of more systematic longitudinal research, data from cross-sectional
and longitudinal studies suggest that abstinence from smoking is related to improve-
ments in other positive lifestyle behaviors contributing to overall good health. These
behaviors may be used by the former smoker to prevent relapse (e.g.. exercise), to cope
with adverse withdrawal symptoms (e.g., increased food intake as a response to
increased appetite), or as part of a commitment to a healthier lifestyle. Exercise may
help new quitters to remain abstinent and to avoid or minimize weight gain. The data
from the MRFIT (Schoenenberger 1982) and other large data bases (Friedman et al.
1979) confirm that former smokers often take active steps to lower their disease risks,.
These studies should alleviate concerns that smoking cessation may result in unhealthy
lifestyle shifts through unwanted symptom substitution.

Given the strong association between smoking and other kinds of substance use. it is
important to know if smoking cessation impairs the ability to stop other drug use. The
limited evidence suggests that this is not the case (Bobo 1989; Miller. Hedrih. Taylor
1983). How multiple drug use and multiple drug withdrawal may interact with cigarette
smoking and its cessation is an area requiring study.

PARTICIPATION OF FORMER SMOKERS IN HEALTH-SCREENING
                  PROGRAMS

The literature presented earlier in this Chapter suggests that former smokers are more
likely than current smokers to engage in a variety of health-enhancing behaviors, such
as regular physical activity.  Another area in which improvement may occur for
individuals who stop smohin g i\ participation in. or benefits from. health-screening
programs. Participation in programs of health screening by those who are presumably
healthy and asymptomatic is ;I health-enhancing or health-protective behavior. much


like wearing vzatlxlts or performing regular exercise.  This participation is to be
distinpui\hed from health \creeninp bought for diagnostic purposes. Calnan and Rutter
( 1986) cautioned, however. that there are important conceptual difference\ between
behavior5 such as not smoking or regular flossing and utilization of screening. In the
first case. the emphasis is on the individual performing the recommended action. In
the second, the individual makes a decision to use the service. but a professional
performs the procedure. Smokers exhibit a decreased propensity to use preventive
services in contrast to nonsmokers. The data suggest that former smokers occupy an
intermediate position between current and never smokers in their seeking of health
screening.
Data from the large Johnson and Johnson "Live for Life" worksite trial discussed
earlier showed that current smokers were less willing than former or never smokers to
complete health risk assessments (Shipley et al. 1988). A survey of randomly selected
nonrespondents to the "Live for Life" health screening found that significantly more
nonrespondents reported ever having smoked cigarettes and significantly more female
nonrespondents currently smoked (Settergren et al. 1983). Additional support for the
position that smokers may have lower response rates to health risk appraisals is provided
by Seltzer, Boss& and Garvey (1974). who found current smokers significantly less
likely than never smokers to respond to a health questionnaire.
One source of data about the health-screening practices of former smokers consists
of results from a 1988 nationwide randomized survey of American Association of
Retired Persons (AARP) members aged 50 and older to assess differences among
current smokers, former smokers (abstinent for 1 week or longer with a mean duration
of 19.3 years), and never smokers (Rimer et al. 1990). In addition to the usual
quitting-related variables. respondents were asked about their use of health services,
including routine cardiovascular and cancer screening. Questionnaires were received
from 3. I79 persons, a %-percent response rate. In this older population for whom
health screening is especially important. the never, current, and former smokers differed
significantly on utilization of screening (Table 8). The results suggest that smoking
may act as a deterrent to appropiiate use of screening services for older smokers and
possibly for younger smokers as well, or that there is a general unhealthy approach
taken by smokers. That former smokers were more likely to avail themselves of
preventive checks and services than current smokers suggests that former smokers may
have a more preventive health orientation than current smokers. may participate in
screening as an approach to maintain abstinence, or may be concerned about the effects
of smoking on their health. As with exercise and other health promotion practices. the
data are retrospective: therefore. it cannot be determined if the former smokers were
always different from current smokers in their health screening habits or if they changed
as a result of cessation.

The results of the AARP survey suggest that with time former smokers may resemble
never smokers in their use of screening services. Maintaining health was the primary
reason for quitting among former smokers who responded to the AARP survey; perhaps
the subset of smokers who quit was more health conscious at the outset. Or having quit.
former smokers may be more willing to take a proactive stand to maintain their health.
It is also possible that having admitted vulnerability to the harms of smoking and

562


TABLE 8.-Physician visits and medical tests within the past year among
     AARP members aged 50 and older, by smoking status

Current      Former
smokers     smokers
(N=339)    (N=l489)
II%       47%

Never
smokers
(N=l316)
42%

Overal I
(N=3147)
100%

p-value'

Physician visit
(21)

77        88         86        X6        <O.ool

Complete physical or
checkup

Blood pressure check

Electrocardiogram


Stool blood test

50        60         60        59        <O.OOl




79        90         x7        x7        <O.OOl


41        52         4s        4X        <o.oo I


28        3x         36        36        <o.oo I

Digital rectal
examination

23        34         30        31        <O.OOl

Mammogram
(women only)

24        41         36        36        co.0 13

Pap smear (women only)

33        43         39        40        <0.006

NOTE: All rates are age adjusted.  AARP=Amencan Aw~~atwn of Retired Perwn\
"Current smoker\ vs. former or never hmoken.
SOURCE: Rlmer er al. (IWOL

experiencing the benefits of quitting, former smokers are more amenable to adopting
other health-enhancing behaviors.  This would be consistent with the tenets of the
Health Belief Model (Janz and Becker 1984) and with preliminary findings about the
increased value of health expressed by self-defined former smokers (Tipton and
Riebsame 1987).

In two measures of disease prevention assessed in the 1987 BRFSS data, male former
smokers appeared to be more health conscious than current smokers and at least as much
as never smokers (Table 5). These individuals are significantly more likely than never
smokers to have had their cholesterol tested in the past year; never smokers. in turn, are
more likely than current smokers to have had this test. Although former smokers were
slightly more likely than never smokers to have had a flu shot in the past month, this
difference was not statistically significant.  Both former smokers and never smokers
were significantly more likely to have had the shot than were current smokers. Female
former smokers were more likely to have had their cholesterol tested than were never
smokers, but were not significantly different from current smokers. Women in all three
smoking categories were similar, indicating no statistically significant differences in
their probability of having received a flu shot in the past month. Among former

563


smokers. length oftime since cessation did not predict any differences in either ofthese
behaviors among men or women.

The 1987 NHIS data show higher rates of preventive care among former smokers
than among never or current smokers (Table 4). Women who hadquit were significant-
ly more likely to report ever having had a digital rectal exam. a stool blood test. and a
proctoscopic exam. Women who had stopped smoking were also significantly more
likely to have had a Pap smear or a breast examination within the past year and to ever
have had a mammogram. However. women did not differ by smoking status in their
practice of monthly breast self-examination. These data did not control for age and
may reflect the greater number of former smokers in the higher risk ages. in addition
to the unavoidable problems inherent in cross-sectional data such as not being able to
determine the order of smoking cessation and preventive care.
A study of participation among 600 female members of a health maintenance
organization showed that female smokers were less likely than former smokers or never
smokers to complete a health risk assessment or to obtain mammograms (Rimer et al.
1988. 1989). When residents of a large retirement community were surveyed about
their health habits, Chao and colleagues (1987) found differential use of several
screening tests. including blood pressure, fecal occult blood tests, mammograms, and
Pap tests among current smokers. former smokers. and never smokers, with former
smokers having the highest rates of screening. Macrae and colleagues (1984) studied
581 individuals vvho completed health questionnaires before being offered fecal occult
blood tests. These researchers found that whereas smokers were not less likely to
decline the initial offer, they were significantly less likely to comply, that is. to follow
through with the test. These same investigators suggested that smokers may have been
more susceptible to interpersonal pressure publicly. but later succumbed to a strategy
of defensive avoidance. Although Macrae and associates ( 1983) did not distinguish the
screening behavior of never smokers and former smokers. other studies reported here
suggest that these groups would have been similar.

The suggestion that former smohers are more oriented to prevention and early
detection is also consistent with Verbrugge's (1981) conclusions that smokers have
poorer health. increased risks due to smoking. and are more oriented to remedial as
opposed to preventive health actions.  As smokers move toward maintenance of
nonsmoking. they appear to value their health more highly (Tipton and Riebsame 19X7:
Horwitz, Hindi-Alexander. Wagner 1985). This finding is consistent with the greater
utilization of screening found among AARP former smokers (Rimer et al. 1990). These
findings undoubtedly are affected by the relationship between socioeconomic status
(SES) and preventive care utilization. That is. lovver SES is associated with less use of
preventive services (Dutton 1986). To the extent that they are represented dispropor-
tionately among those of lower SES, current smokers will be at risk for underuse of
age-appropriate prevention and early detection services.

The literature about the health screening practices of fomrer smokers is suggestive
but inconclusive. It appears that former smokers are more likely than current smokers.
but perhaps less likely than never smokers. to seek regular cardiovascular and cancer
screening C.

564


SUMMARY

The data suggest that as the duration of abstinence lengthens, former smokers begin
to resemble never smokers in their utilization of health screening and their participation
in a variety of health-enhancing behaviors, such as physical activity. However, it is not
clear if former smokers are different from current smokers at the outset, if the method
of cessation affects these outcomes. or if the reason for quitting affects subsequent
health practices. There is reason to believe that former smokers, especially those who
quit while they are healthy, come to value their health more and take health-enhancing
action as an extension of this valuing (Tipton and Riebsame 1987). These conclusions
are consistent with the Health Belief Model (Janz and Becker 1984) and the Protection
Motivation Theory (Prentice-Dunn and Rogers 1986). Longitudinal. prospective
studies would make an important contribution to understanding these issues.

Increased participation in screening and other health-enhancing behaviors also may
result from enhanced self-esteem and an increased sense of self-control. Ockene and
colleagues (1988) concluded that successful behavior change is likely to promote a
perception of general self-efficacy. The perception of oneself as capable may general-
ize to other areas of one's life. Kronenfeld and associates (1988) stressed that it may
be difficult for most people to change multiple habits simultaneously. Having gained
a sense of mastery from stopping smoking, former smokers may attempt to improve
other health practices. However, some studies suggest that former smokers seem to
undertake a number of health-enhancing steps proximally, if not simultaneously
(Schoenenberger 1982; Friedman et al. 1979; Gerace et al., in press). For example,
quitters in MRFIT (baseline smokers who were biochemically verified ex-smokers at
the sixth annual visit) reported a greater decrease in their number of alcoholic drinks
per day and sucrose consumption than nonquitters (Gerace et al., in press).

CONCLUSIONS

1, Short-term consequences of smoking cessation include anxiety, irritability, frustra-
tion, anger, difficulty concentrating, increased appetite. and urges to smoke. With
the possible exception of urges to smoke and increased appetite. these effects soon
disappear.

2. Smokers who abstain from smoking show short-term impairment of performance
on a variety of simple attention tasks, which improves with nicotine administration.
Memory, learning, and the performance of more complex tasks have not been
clearly shown to be impaired. Whether the self-reported improvement in attention
tasks upon nicotine administration is due entirely to relief of withdrawal effects or
is also due in part to enhancement of performance above the norm is unclear.
3. In comparison with current smokers, former smokers have a greater perceived ability
to achieve and maintain smoking abstinence (self-efficacy) and a greater perceiv,ed
control over personal circumstances (locus of control).
4. Fomler smokers, compared with current smokers, practice more health-promoting
and disease-preventing behaviors.


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578


    VOLUME APPENDIX
NATIONAL TRENDS IN SMOKING
      CESSATION

579


CONTENTS

Introduction  .....................................................

Sources of Data  ..................................................
National Center for Health Statihtict Surve>\  .........................
Office on Smoking and Health Survelh ..............................

Measures of Quitting Behavior  ......................................
Percentage of Former Smokers in the Entire Population
Percentage of Ever Smoher\ Who Are Former Smokers ("Quit Ratio")  
The Smoking Continuum .........................................
Other Measures .................................................

Trends in the Proportion of Ever Smoker\ Who .,\rc F'~~wI~ Smoker\
("Quit Ratio") ..................................................
Trends by Gender ...............................................
Trends by Race.. ...............................................
Trends by Age  .................................................
Trends by Level of Educational Attainment  ..........................

Long-Term Abstinence and Relapse  ..................................
National Health and Nutrition Examination Sur\,e! Epidemlolo~ic
  FollowupStudy ...............................................

The Smoking Continuum ...........................................
Percentage of Ever Smokers Who Have Never Tried to Quit
Percentage of Those Smohing at I? Month\ Prior to ;I Sur\,c! Inter\ ieu
  Who Quit for at Least I Day During Those 12 blonth~ ................
Percentage of Ever Smokers Who Had Been Ah\tincnt for Lc\\ Than I YLYII
Percentage of Ever Smokers Who Had Been Ah\tinent for I to 1 Year\
Percentage of Ever Smokers Who Had Been Ah\tincnt for at Least 5 Year\
Interpretation of Continuum Findings  ...............................

5x3

5x3
5x3
5x-t

5x-l
5x5
sxs
sxs
sxx

606
606
606
607
A07

Other Measures Related to Smoking Cessation  . 60X

Intention to Smoke in 5 Years  .-. ..................................
Receipt of Advice to Quit From a Doctor  ............................

Conclusions  .....................................................

References  ......................................................

60X
hOC)

610

63


INTRODUCTION

This volume appendix discusses national trends in smoking cessation over the last
25 vears. specifically updating and expanding descriptions of the national trends in
quilting activity presented in previous Surgeon General's reports (US DHHS 1980.
1983, 1988, 1989a). This Section does not provide a detailed discussion of psychoso-
cial, pharmacologic, and behavioral factors known to be related to cessation, because
this information is available from other sources (US DHEW 1979; US DHHS 1980,
1988. 1989a).

Data are utilized from 5 national cross-sectional surveys on adult tobacco use that
were performed by the Office on Smoking and Health (OSH) (formerly the National
Clearinghouse for Smoking and Health) and the I2 National Health Interview Survey
(NHIS) supplements and the National Health and Nutrition Examination Survey
(NHANES) Epidemiologic Followup Study (NHEFS), both performed by the National
Center for Health Statistics (NCHS). The surveys were conducted between 1965 and
1987. The national surveys and the measures of quitting activity are described below,
followed by a discussion of the data.  Information on smoking cessation during
pregnancy is also included in Chapter 8.

Information on smoking behavior was obtained from these surveys by means of
self-report(i.e., without biochemical validation). Asdiscussed in Chapter 2. self-report
is considered a valid measure of smoking status in cross-sectional surveys. although
some underreporting of daily cigarette consumption likely occurs.

SOURCES OF DATA

National Center for Health Statistics Surveys

Survey data collected by NCHS and available for inclusion in this Report were
derived from the 1965, 1966.1970, 1974, 1976, 1977, 1978, 1979. 1980,1983. 1985.
and 1987 supplements to NHIS and the 1982 to 1984 NHEFS. Cigarette smoking status
(current, former, and never) is assessed in the same manner in all surveys. The
constructs assessed on the NHIS supplements vary from survey year to survey year.
Variables assessed include attempts to quit smoking among current smokers, duration
of abstinence among former smokers, and receipt of advice to quit from a doctor.

NHIS, a cross-sectional household interview survey, samples the civilian, noninstitu-
tionalized population of the United States (NCHS 1958, 1985. 1989). Weighting
procedures are used to provide national estimates. Sample sizes for the smoking
supplements (ages 20+) vary from approximately 9,700 in 1980 to over 80,000 in 1966.

NHEFS was a followup study of persons enrolled in NHANES-I, which assessed
lifetime patterns of cigarette smoking behavior among current and former smokers.
Whereas NHANES-I participants were drawn from a national probability sample of the
civilian, noninstitutionalized population, NHEFS participants included only those who
underwent the medical examination in NHANES-I. Personal interviews with each
participant or a proxy (for deceased NHANES-I participants) were completed for
12,200 of the 14,407 original examinees. Proxy interviews were conducted with I.697

583


representatives of deceased NHANES-I examinees. The interval between NHANES-I
and NHEFS was about 10 years (Madans et al. 1986: NCHS 1987).

Office on Smoking and Health Surveys

OSH has commissioned five national surveys of tobacco use among adults in this
country, referred to as the Adult Use of Tobacco Surveys (AUTSs). The surveys ask
detailed questions designed to assess the knowledge. attitudes, and practices of adults
regarding all forms of tobacco use. These cross-sectional surveys were conducted in
1964,1966, 1970. 1975, and 1986 (US DHEW 1969,1973,1976; US DHHS 1989b).

The similar or identical wording of several standard questions for all five surveys
facilitates comparisons. Constructs assessed included tobacco use behavior, intentions
regarding future smoking behavior among ever smokers. and receipt of a doctor's
advice to quit smoking.

Some differences in the conduct and design of the studies occurred. The mode of
interviewing changed with time. The 1964 survey obtained data solely from personal
household interviews. Whereas personal household interviews were the major mode
of data collection in the 1966 survey. telephone interviews and mailed questionnaires
were also used to collect data from eligible household members not available when the
interviewer was present in the house. The 1970 and 1975 surveys conducted telephone
interviews when possible and personal household interviews in nontelephone
households. The 1986 survey was conducted entirely by telephone. The I964 and 1966
surveys drew samples only from the contiguous United States. Other AUTSs collected
data from residents of all SO States.

The actual number of respondents for each survey was 4,635 in 1964,4,06 I in 1966,
5.191 in 1970, 12,029 in 1975, and 13.031 in 1986(US DHEW 1969. 1973, 1976: US
DHHS 1989b). In each survey, weighting procedures were used to adjust for an
oversampling of ever smokers in the original study population. Comparisons between
the 1986 AUTS and the others will not be exact. because the 1986 AUTS weights to an
estimate of the adult U.S. population. whereas the other surveys weight to their
respective sample sizes.

MEASURES OF QUITTING BEHAVIOR

As documented in several previous Surgeon General's reports (US DHEW 1979; US
DHHS 1988. 1989a) and discussed in Chapter 2 of this Report. smoking cessation is a
multifactorial process for overcoming an addictive behavior. One model characterizes
this process as having several stages-precontemplation. contemplation, action, and
maintenance (Prochaska and DiClemente 1983: Chapter 2). People frequently cycle
and recycle through the various stages (marked by frequent relapse episodes) on their
way to becoming long-term ex-smokers (Prochaska and DiClemente 1983; Cohen et
al. 1989). This analysis of national trends in smoking cessation will use several
measures to describe the quitting process. The 1989 Surgeon General's Report (US
DHHS l989a) discusses three measures of quitting behavior. These interrelated
parameters are discussed below.

584


Percentage of Former Smokers in the Entire Population

This measure of quitting behavior has been used to calculate the number of former
smokers in the population. Based on data from the 1987 NHIS. for example, 23.6
percent of the 162.6 million civilian, noninstitutionalized adults 20 years of age and
older were former cigarette smokers.  There were. therefore, approximately 38.5
million former smokers 20 years old or older in the United States in 1987. The
percentage of former smokers in the entire population is limited as a measure of quitting
activity primarily because it does not take into account the percentage of the population
that has ever smoked (and thus is "at risk" of quitting). It also does not differentiate
between people who have been abstinent for a short period and people who have
maintained abstinence for several years (US DHHS 1989a).

Percentage of Ever Smokers Who Are Former Smokers ("Quit Ratio")

By dividing the number of ever smokers into the number of former smokers.
perspective is given to the magnitude of quitting in a population. The term "quit ratio"
has been used to describe this measure (CDC 1986: Pierce. Aldrich et al. 1987; US
DHHS 1988. 1989a: Fiore et al. 1989) and is the term used below; this measure has
also been termed the "quit rate" (Kabat and Wynder 1987) or the "cessation rate" (Jarvis
1984). The term "ratio" is mostly used in sciences when the numerator and the
denominator are two separate and distinct quantities (Elandt-Johnson 1975). "Quit
ratio" is used here, even though the numerator is included in the denominator. because
of its repeated use in the literature as well as in previous Surgeon General's reports.
The percentage of ever smokers who have discontinued smoking indicates the
prevalence of abstinence (Ossip-Klein et al. 1986).

In 1987, 23.6 percent of the population were former cigarette smokers and 29.1
percent of the population were current smokers. The quit ratio among ever smokers
was 44.8 percent; that is, nearly one-half of all living adults who ever smoked cigarettes
had quit. Quit ratios by gender and age were recently published for 36 States and the
District of Columbia based on 1988 data from the Behavioral Risk Factor Surveillance
System (Anda et al. 1990) (Table I).

The measure is limited because it treats all former smokers equally, regardless of
duration of abstinence. It also classifies current smokers who had never tried to stop
smoking in the same manner as it does current smokers who had been abstinent for a
long period of time and relapsed shortly before the time of the survey (US DHHS
1989a).

The Smoking Continuum

The I989 Surgeon General's Report defined a 1 O-category smoking continuum based
on data from the 1986 AUTS. This continuum expanded on the smoking status variable
(current, former, and never) to incorporate the timing and duration of quit attempts (US
DHHS 1989a). Respondents were asked whether they had ever made a serious attempt
to quit, and if the response was affirmative, they were then asked about the timing of


TABLE I.-Quit ratio" in selected States, by age group and gender-BRFSS, 1988

             I x-34          3544,         S(L64           25s          MW        Wonlrn          Total

SlLlk        (h   (fYS% Clhl %   l+Ys% (`I)    %  (+Ys% Cl,     %   (+Ys% Cl)   %  (*OS% CI)   `k   (WS'/i <`I)    %    (It').S'ir (`I)

Ald%l~~~;l

Arimm
California

Connecticut

District of

Columbia

Florida
Georgia
Hawaii

Idaho

Illinoi\

Indiana

Iowa
Kentucky
Maine
Maryland
Massachusetts
Michigan
Minnesota
Misouri

Montana

143

4.5,s

40. I

3X.6



37.2

43.7

3Y.S

33.7

43.6

2s. I

23.1

30.0

22.6
3x.3

41.1

35.2

37.4

41.2

3.5.x

45.7

(7.0)
(7.Y)

(5.7)
(7.4)


(8.X)
(7.4)
(S.6)
(7.1)
(7.1)
(6.7)

(5.5)
(Y.2)
(S.b)
(7.2)
(Y.0)
(6.6)
(7.0)
(4.4)
(7.1)
(9.6)

`II.3

54.2

54.3

40.0



45.4

45.3

40.3

45.0

4Y.2

42.6

41.2

503

33.h

so.4

45.6

50.x

s0.s

ss.2

43.`)

5X.X

(7.3)

(X.0)

(5.h)
(7.3)


(Y.9)
(7.2)
(X.7)

(7.6)

(6.`))

(6.6)
(S.X)
(10.5)

(6.9)
(7.4)
(X.3)
(7.0)
(7.3)
(4.3)

(73)
(7.7)

54.3   (X.3)
61.2   (9.`))
64.3   (6.Y)
60.7   (Y.3)



56.5  ( I I .h)
S2..?   (7.7)
S2.1 (12.7)
61.5   (Y. I )
sx.3   (X.3)
S3.h   (X.0)
51.`)   (6.7)

55.4  (12.3)

4x.2   (7.0)
65.3   (X.4)
S7.Y   (Y.9)
X).X   (Y.5)
5.5.0  (10.7)
64.6   (5.4)
57.5   (X.41
5x.x   (X.2)

65.X

67.0

65.6

74.`)

SY.4
77.6

70.2

7O.Y

77. I

64.1

79. I

71.1

63.6

72.7

70.`)
75.5

b.5 .Y

76.0

79.1

7Y.O

( IO. I )
(X.8)
(7.X)
(X.0)


(12.5)
(5.7)
(17.2)
(9.Y)
(6.2)
(X.3)
(5.`))
( IO.`))
(7.0)
(X.7)
(Y.3)
(7.1)
( 13.4)
(S.0)
(7.0)
(7.1)

47.4   (5.6)    37.3

60. I   (6.2)     40.x

56.4,   (4.4)     49.3

ss. I   (6.4)     so.4

52.0   (X.0)    43.4

5x.5   (4.X)     so.4

44.2   (7.2)     4h.6

49.6   (5.X)     44.3

61.3   (S.5)     44.2

4x.9   (5.3)     42.4

51.6   (4.4)    41.2

60.2   (X.1)     3Y.l

42.6   (4.`))     31.1

h0.S   (5.Y)     44.5

s3.0   (7.1)     4x.0

56.2   (6.3)     47.6

52.0   (6.4)     45.5

60.4   (3.4)     49.2

54.7   (6.1)     43,s

62.0   (6.4)     s4. I

(S.9)
(6.0)

(45)
(.5.X)


(7.3)
(S.2)

(6.X)
(6.3)
(5.5)
(5.2)
(4.6)
(7.1)
(4.5)
(5.5)
(h.5)
(5.2)
(5.X)
(3.X)
(5.4)
(6.2)

43.2

5.5.4

53 7

52.x

47.6

s4.x

4S.3

47.3

s4.0

3.5.x

47.0

so.7

27.x

53.2

SO.6

51.`)

4X.Y

5.5.4

4Y.b

SX.6

(4.1 )
(4.3)
(3.1)
(4.3,


(5.5)
(3.5)
(5.2)
(3.3)
(7.Y)
(3.h)
(7.2)
(S.X)
(3.4,
(4. I )
IS 0)
(4.2)
(43)

l3.5)

(4. I )
(4.S)


TABLE l.-Continued

state

   1 X-34         3549          so-64         265           Men         Women          Total

%  (2995% CI)   %   w50/, CI)    % (+9s%cI)    %  (H58 Cl)   %  (k9sx CI)   % ( f')S%, CI     %   (FWE Cl)

Nebraska
New Hampshire
New Mexico
New York
North Carolina
North Dakota

Ohio
Oklahoma
Rhode Island
South Carolina
South Dakota
Tennessee
Texas

Utah
Washington
West Virginia
Wisconsin
Median
prevalence

39.6   (7.4)      57.6
35.2   (7.0)      53.0
3x.4   (X.7)      47.0

29.8   (7.4)     42.7
37.0   (6.X)      47.5
3x.7   (7.1)      so.9
30.6   (6.5)     42.3

37.1   (9.1)     43.6

34.7   (6.4)      44.x

2x.9   (5.X)      41.5

37.4   (9.2)      52.3

29.0   (4.X)      40.9

3X.X   (X.6)     45.7
33.5   (7.5)      50.9
37.7   (7.3)     54.X
3X.S   (7.1)     43.4
35.0   (6.9)      92.0

37.2

47.0

(8.3)      57.6
(7.4)      60.3
(9.2)      53.4
(8.1)      66.3
(6.7)      47.9
(6.X)      62.2
(7.6)      57.4
(8.6)      55.9
(6.X)      55.6
(6.6)      58.7
(8.6)      60.8
(5.7)      49.5
(8.4)      53.7
(X.1)      6X.3
(7.5)      53.7
(6.5)      49. I
(7.3)      62.2

57.5

(9.0)
(9.9)
(9.X)
(X.9)
(8.5)
(7.9)
(9.0)
(10.2)
(X.5)
(7.6)
(9.2)
(6.X)
(10.5)
(I 1.3)
(X.7)
(7.2)
(X.5)

74.5   (7.X)
74.2   (9.2)
64.7   (I 1.7)
x0.3   (X.2)
72.3   (7.0)
73.3   (7.4)
67.3   (X.4)
62.9   (13.4)
60.X   (7.2)
72.2   (X.X)

71.1    (X.7)
67.2    (7.9)
69.3   (12.5)

x0. I    (Y.2)
x2.5    (7.9)
69.4   (7.2)
76.0    (9.1)

71.1

59.0   (9.9)
s3.x   (6.1)

40.4   (7.3)
54.2   (6.X)
so.4   (5.7)
5x.3   (5.1)
s-2.0   (h.2)

53.4   (7.0)

51.1   (5.h)
46.0   (5.1)

55.6   (5.X)
43.4   (4.S)
52.5   (6.7)
65.2   (5.X)
5x.2   (5.X)
54.5   (5.2)
63.X   (S.6)

94.2

47.2   (6.1)      54.0

4X.6   (6.0)      51.5

46.3   (7.0)      4x.0

46.X   (6.5)      SO.5

43.4   (5.2)      47.3

45,s   (5.6)      53.1

31.4   (5.7)      44.9

3Y.b   (6.7)      47.5

44.6   (51)      47.x

42. I   (S.4)      44.4

SO.5   (6.7)      53.4

3Y.4   (4.1)      4 I .x

41.4   (6.X)      47.9

40.5   (X.6)      5h.h

46. I   (5.X)      53.0

3X.4   (5.0)      47.6

46.3   (6.7)      56.5



44.6           so.5

(4.3)
(4.6)
(5.2)
(4.7)
(3.9)
(3.X)
(4.2)
(S.1)
(3.X)
(3.8)
(4.3)
(3.2)
(4.X)
(5.0)
(4.2)
(3.7)
(4.4)

    NOTE: BRFSS=Behavioral Rl\k Factor Survedlance System.
   "Ddmed as the percentage ofever vnokcn who were former amoken at the time ot the survey
    hConfidrncr interval.
     SOURCE: BRFSS IYXX (Anda et al. IYYO)
z
-4


their most recent quit attempt. This measure provides information on the recent quitting
history of the population (Pierce, Giovino et al. 1989: US DHHS 1989a). The trend
analyses presented below will use an eight-category continuum (Table 2) among ever
smokers to incorporate data from the 1978, 1979. 1980, and 1987 NHISs. As opposed
to the 1986 AUTS, the questions asked in these NHISs do not permit a dichotomous
classification of current smokers who had never tried to quit according to interest in
quitting.

In addition to a description of the overall smoking continuum, several segments of
the continuum, or measures derived from the continuum, will be described separately.
These measures include the following:

o The percentage of ever smokers who have never tried to quit;

o The percentage of people smoking at I2 months prior to a survey interview who
had been abstinent for at least I day during those 12 months:

o The percentage of ever smokers who had stopped smoking for less than 1 year:


o The percentage of ever smokers who had stopped smoking for I to 4 years: and

o The percentage of ever smokers who had stopped smoking for at least 5 years.

Other Measures

Respondents to AUTSs were asked to estimate the possibility that they would be
smoking 5 years after the survey. This question gives a measure of intention to smoke.
Finally, respondents to several NHISs and to all OSH tobacco use surveys were asked
if a physician had ever advised them to stop smoking.

TRENDS IN THE PROPORTION OF EVER SMOKERS WHO ARE
      FORMER SMOKERS ("QUIT RATIO")

Using data from NHISs for I965 to 1987. trends in the proportion of ever cigarette
smokers in the U.S. adult population who have stopped smoking cigarettes (quit ratio)
are presented by gender and by race in Figures 1 and 2. respectively. Trends for the
total adult population. as well as trends by age and by education, are shown in Table 3.
These data, with the exception of the age-specific estimates. are age-adjusted to the
1985 population. In thes,e analyses. the quit ratio was regressed on the calendar year
of data collection. The R- statistic. supplied for each trend analysis. is a measure of the
strength of the linear relationship. R' values may range from 0 (no linear trend) to 1 .O
(a perfect positive or negative linear relationship).

Trends by Gender

As shown in Figure 1. the quit ratio for both genders has been increasing in an
approximately linear fashion (R-=0.94 for males and 0.97 for females) since 1965, and

5X8


TABLE d.-Cigarette smoking continuum by year, percentage of ever cigarette smokers, NHISs, United States, 1978-87, adults
      aged 20 and older

Cigarette smoking continuum

I. Current smokers who had never tried to quit
2. Current smokers who had quit previously but
not in past year

3. Current smokers who had quit for <7 days
in past year

4. Current smoker5 who had quit for >7 days in
past year

5. Former smoker\ who had quit within past 3 mo

6. Former smokers who had been abstinent for
3-12 mu

7. Former smokers who had been abstinent for
I-S yr

X. Former smokers who had quit 25 yr earlier

Percentage of those smoking during the year prior
to the survey who tried to quit during that year
(Categories 3+4+5+6 divided by 1+2+3+4+.5+6)

Percentage of those smoking during the year prior
to the survey who quit during that year and were
still abstinent at the time of the survey
(Categories S+6 divided by 1+2+3+4+5+6)

  197x                  I979                    IYXO                 10x7


  25.9                  26. I                    25.4                  1X.Y

  22.7                  2 I .4                    23.1                  20.0


  6.6                   6.0                    5.9                  7.0


  KS                   X.6                    7.x                  x.4


  I.3                   1.6                     I .4                  1.x

  2.7                  2.6                    2.7                  2.X


  Y.0                  IO.0                     Y.5                  IO.4


  23.3                  23.6                    24.1                 20.7
-___           .-

2X.2                  2x.4                    26.X                 34.0

6. I                   6.3                     6.7                  7.x

NOTE: NHIS=NAonal Health Interview Survey
SOURCE: NHlS\ IY7X. 197'). 19X0. 1987.


z
0    60

                                                MALES   FEMALES
                      Slope of Regression Line      0.70      0.76
-........_._..__________________________--------------.------.-.--....-..-..---- !f -----....____ !E! __________ !!L?! _________

I    1    I    I    I    I    I    I    I    I   I    I    I    I    I   I    I    I    I    I   I    I   I

1964            1969              1974             1979             1984

YEAR

FIGURE I.-Trends in the quit ratio, United States, 1965-87, bv gender
NOTE: Quit ratio ib the proportion of ever \mohers who are former \moher\. NH`IS=N;it ionnl Health
Intreview Survey; OSH=Office on Smoking ond Health.
SOURCE: NHIS!, IOhS. IYhh. lY70. 1974, lY7h. 1077. lY7X. 1979. IYXO. lYX3. IYXS. IYX7: OSH.
  1. 1 1.


  40






  30







  20



3 10
s
E
z
E  0

Whites    Blacks

                        Slope of Regression Line      0.72      0.45
                              I32        0.96      0.86
______________---__-____________________~--~--------------------~----~--------------------~..~~~~-~~~~~-~~-~.~~~~~~-~-~.~~~-~---

  I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I
                                      I
964            1969              1974             1979              1984

YEAR

FIGURE 2.Trends in the quit ratio, United States, 1965-87, by race

    NOTE: NHlS=National Health Interview Survey; OSH=Office on Smoking and Health.
    SOURCE: NHISs 1965. 1966, 1970, 1974, 1976, 1977, 1978, 1979, 1980. 1983, 1985, IYX7: OSH,
22   unpublished data.


TABLE .X-Trends in quit ratio ( %) (percentage of ever cigarette smokers who are former cigarette smokers), by age and by
     education, NHISs. United States, 1965-87, adults aged 20 and older

Year

I Y65"

I YM

20-2-l

17.x

17.0

  Age (yr)                                Educational level
                        Lr\s than       Hngh
                                      school         Some
                  h!gh school                        (`allege
25-u      4SA4     xl5     graduate      praduatc      college      graduate

22.6       30.0     1x.7

`3.4       30.0     SO.5        33.3           2x.0         28.7         30.1

1070             3s.1        20.x      3.X       36.1      S6.Y        3x. I           33.6          34.9         3x.2

1974             7h.J        2O.Y      3.3       3Y.7     57.x        3X.0          35.2          36.6         47.')

I Y7h             37.1        22.0       X4       JO.4     5Y.h        3Y.S           35.0          37.'         36. I

1077             36.X        22.0       ?Y.fl       3.5     5x.7        3x.3           34.0          36.X         4X.6

197x             3X.5        22.x      7 I .Y       40. I     62.4        3x.7           36.3          4 I .o         4Y.7

I Y7Y            34.0        27.h       3 I .x       32.4     61.7        30.x           36.7          37.5         SO.6

I YXO             NO        73 7
                         --.-       33.0       40.0     hl .o        3Y.3          36.5          40.6         4x.7

3x.7          `II.2         S4.Y

40.5          46.0         61.1

`Il.1          4.5.5         SC). I




0.5s          0.74         0 xx

0.0s          0.0x         0. I3

0.92          O.YO         0 x3


the rates of increase for both are also similar (0.70 percentage points/year for males and
0.76 percentage points/year for females). The quit ratio has been consistently higher
for males than for females. Using data from the 1970 and I975 AUTSs. Jarvis (1984)
reclassified as current smokers males who gave up smoking cigarettes but who con-
tinued to smoke cigars and/or pipes. When the use of other forms of smoking tobacco
was considered, the difference between males and females in the quit ratio (termed as
the "cessation rate" by Jarvis) was reduced by more than two-thirds.

Data from the 1987 NHIS Cancer Epidemiology and Control supplement (Schoen-
born and Boyd 1989) were analyzed to update the work of Jarvis (Table 4). The
weighted percentage of ever cigarette smokers who were former cigarette smokers
among males was 48.7 percent. The corresponding number among females was 40. I
percent. When former cigarette smokers who smoked cigars and/or pipes were reclas-
sified as current smokers (without changing the denominator). the prevalence of
cessation among ever smokers became 45 percent for males and 40 percent for females.
Furthermore, when former cigarette smokers who used any other form of tobacco
(cigars, pipes, snuff, and/or chewing tobacco) at the time of the survey were classified
as current tobacco users, the figures became 42. I percent for males and 39.9 percent
for females (OSH, unpublished data).  Thus, reclassification of former cigarette
smokers who were smoking cigars and/or pipes as current smokers reduced the
difference in the quit ratio between males and females from 8.6 to 5.0 percentage points.
Former cigarette smokers who were using any other form of tobacco were reclassified
as current tobacco users, and this reclassification further reduced the difference to 2.2
percentage points.

Trends by Race

Trends by race are presented in Figure 2; The quit ratio among both whites and blacks
has been increasing steadily since 1965 (R&=0.96 for whites and 0.86 for blachs). While
the change per year since 1965 is higher for whites (0.72 percentage points/year) than
it is for blacks (0.45 percentage points/year), the lines have been essentially parallel
since 1974 (Fiore et al. 1989). Use of the 1987 NHIS data to reclassify as current
smokers all former cigarette smokers who were smoking cigars or pipes reduced the
quit ratio from 46.4 to 44.2 percent among whites and from 3 I .S to 30.2 percent among
blacks. Further reclassification, as current tobacco users, of former cigarette smokers
who were using any other form of tobacco reduced the numbers to 42.5 percent for
whites and 29.1 percent for blacks (OSH, unpublished data).

Trends by Age

Table 3 provides information on the quit ratio stratified by age. For all age categories.
the quit ratio increased from 1965 to 1987. The rate of change was highest in the age
categories of 45-64 years and 65 years and older. Reclassification of the I987 data to
account for cigar and pipe smoking and for any other tobacco use lowered the numbers
from 23.8 percent to 23.4 and 22.2 percent. respectively. among the 20-24-year-olds:
from 37.2 percent to 35.6 and 34.3 percent. respectively.among 25-G-year-olds; from


4Y.2 percent to 46.4 and 35.0 percent. respectively. among 4%64-year-olds; and from
69.1 percent to 66.2 percent and 62.8 percent, respectively, among those 65years-old
and older (Table 4) (OSH. unpublished data). A detailed analysis of trends in the quit
ratio by age for the period 197-I through I087 has been completed (Novotny et al., in
press).

Differences in quit ratios between age groups may reflect actual differences in
quitting activity by age-that is. older persons may be more prone to quit and maintain
abstinence than younger smokers, perhaps because of the occurrence of smoking-
related symptoms or illness. However, continuing smokers are less likely than former
smokers to survive to old age (Chapter 3): this selective mortality will artifactually
increase the quit ratio among older age groups.

TABLE 4.-Effect of adjusting for use of other tobacco products on quit ratio
     (percentage of ever cigarette smokers who are former cigarette
      smokers), 1987, NHIS, United States

Quit ratio (%)

Adjusting for

UnadyNed"

Adjustmg for
cigar\/pipe\h

ciE"r"/pipe\/~nuff/~hewin@
    tobacco`

Gender

  Males
  Females

Race

  White5
  Black>

.Age (yr)

xb-21
7.5-4-I
35-64
   265

Education (yr I

  <I2
   I?
13-1s
   216

Overall

a.7
JO. I

46.4
31.5

23.x             73.4
37.'             35.6
-19.2             46.4
6Y.2             66.2

45.0
JO.0

44.7
30.'

3x.1
3Y.2
44.Y
57.3

12.x

42.1
39.0

17.2
29.1

17 7
_-._
34.3
45.0
62.X

SY4


Trends by Level of Educational Attainment

Table 3 shows the quit ratio among college graduates is consistently higher than the
ratios among persons with less than high school graduation. high school graduation, or
some college education. Also, the rate of increase per year rises as the educational level
increases (0.44, 0.55,0.74. and 0.88 percentage points/ year in persons with < 12, 12,
13-15, and 16 or more years of education, respectively). From 1966 to 1977 the quit
ratio among high school dropouts was higher than the ratios among the two middle
education categories; the reason for this is unclear.

Reclassification of the 1987 NHIS former cigarette smokers based on the use of other
tobacco products did not affect the magnitude of the relationships between education
categories (Table 4). After reclassification, the quit ratio dropped from 39.7 percent to
38.1 and 35.2 percent in the less-than-high-school-graduation category, from 40.9
percent to 39.2 and 37.8 percent in the high-school-graduation category, from 46.9
percent to 44.9 and 43.5 percent in the some-college category, and from 61.4 percent
to 57.3 and 56.6 percent in the college graduation category (OSH, unpublished data).

LONG-TERM ABSTINENCE AND RELAPSE

The prototypical pattern of relapse after cessation among group clinic participants
was first published by Hunt, Bamett, and Branch ( 197 1) and is cited in the 1988 Surgeon
General's Report (US DHHS 1988). The relapse curve for smokers indicates that
approximately 65 percent of all quitters relapsed within 3 months of quitting; another
10 percent relapsed from 3 to 6 months postcessation. About 3 percent more of the
original sample of quitters relapsed from 6 to 12 months postcessation.

Because smokers who attend quit-smoking classes are likely to be different from
smokers who attempt to quit on their own (Fiore et al. 1990). the probability of quitting
success in one group may not apply to the other. Indeed, the results of a meta-analysis
of 10 prospective studies of people attempting to quit without any assistance or using
only self-help materials suggested that about 24 percent of those study participants who
were continuously abstinent at the 6-month followup relapsed before the l-year
followup (Cohen et al. 1989); the corresponding percentage in the study of clinic
attendees (Hunt, Bamett, Branch 197 I) was 12 percent, as calculated using the percent-
ages in the previous paragraph.

Few prospective studies of cessation have observed participants for longer than 1
year (Schwartz 1987; Glasgow and Lichtenstein 1987). Relapse data after 1 year of
continuous abstinence are not presented in some of the intervention studies that include
followup periods of more than 1 year (e.g., Lando and McGovern 1982; Lichtenstein
and Rodrigues 1977; Ockene et al. 1982; West et al. 1977). In the Multiple Risk Factor
Intervention Trial, 15 percent of the special-intervention group and 16 percent of the
usual-care group who were abstinent from cigarettes at both the first- and second-year
followup assessments reported recidivism during the third or fourth year of followup
(Ockene et al. 1982).

Hammond and Garfinkel (1964) provided data from the Cancer Prevention Study I
(CPS-I) on a cohort of 65.709 male former smokers (aged 30-89) who were re-

595


interviewed after 2 years. Of those who had been abstinent for less than I year at
baseline. 37.3 percent were smoking cigarettes again at followup. Of those who had
been abstinent for at least I year but less than 2 years or for 2 years or more at baseline,
19.1 and 4.6 percent. respectively. were smoking cigarettes again at the 2-year followup
interview.

In another report also based on CPS-I. Hammond and Garfinkel (1963) further
subdivided the duration of abstinence at baseline for males aged SO to 69. For those
abstinent for 2 to 4 years. 5 to 9 years, and 10 years or more at baseline, 8.7,4. I. and
2.2 percent, respectively, were smoking cigarettes at the 2-year followup interview.

Kirscht, Brock. and Hawthorne (1987) surveyed a probability sample of 3,073
Michigan adults in 1980. In 1982. completed followup questionnaires were obtained
from 2,l 10 members (68.7 percent) of the original sample. In 1980,23.0 percent of the
entire sample were ex-smokers. Of those ex-smokers who had been abstinent for less
than 6 months in 1980,38.7 percent were smoking again when they completed the 1982
questionnaire. Among those ex-smokers who had been abstinent between 6 and 23
months in 1980,29.5 percent were smoking in 1982. Among those abstinent between
24 and 1 19 months or for 120 months or more in 1980,9.5 and 2.3 percent, respectively,
reported that they were smoking again when the 1982 survey was conducted.

National Health and Nutrition Examination Survey
    Epidemiologic Followup Study

Data from NHEFS (NCHS 1987; Madans et al. 1986) were used to assess lifetime
patterns of quitting in a sample of the adult population (OSH. unpublished data).
Reconstructed cigarette smoking prevalence from NHEFS shows good agreement with
self-reported smoking status recorded during the original NHANES-I interview
(Machlin. Kleinman. Madans 1989).

The description of quitting and relapse discussed below is limited because only quit
attempts of 12 months or more were assessed and the reclassification of former cigarette
smokers who smoked cigars or pipes as current smokers is not always possible. Quit
attempts that occurred before the age of 2 I were not considered.

As shown by NHEFS data in Figure 3. of the 6.360 ever cigarette smokers. 55.2
percent had stopped \moLin, (7 cigarettes for at least I year at some point before the
NHEFS interview. Of the\e. 37.6 percent relapsed after at least I year of maintaining
abstinence. Of those who relup\ed. 33.0 percent quit again for at leasr 1 year. Among
those who quit again for at least I Jear. 35.2 percent relapsed a second time. These
data indicate that at least one-third of all e\`er smokers who quit for at least I year will
eventually relapse.

The product-limit method (Lee IWO) was used to estimate the relapse rate after the
first I-year period of abstinence. As shown in Figure 3. most of the relapse after the
first l-year abstinence period occurred within a few year\. About 2X percent of ever
smokers who attained abstinence for at least I ).ear relapsed Nithin 5 years of quitting.
Another 7 percent of the original sample of ever smokers who had quit for 1 year or
more relapsed within the next 5 lears. Thu\. about one-third (35 percent) of former
smokers who have maintained abstinence for at least I year may eventually relapse.

596


TOTAL NUMBER OF EVER REGULAR
  CIGARETTE SMOKERS

NEVER QUIT FOR AT           6,460
LEAST 1 YR      /H /--      ----__ ----
2,704 (41.9%) --      RELAPSED AFTER
         FIRST QUIT c----------- _---

QUIT ONCE FOR AT
LEAST 1 YRa
3,566 (55.2%) __

NEVER QUIT AGAIN  _N 1,340 (37.6%; 20.7%) .--.,__

648 (48.4%; 10.0%)' d                           ---.-
                             QUIT FOR A SECOND TIME

            RELAPSED AFTER      FOR AT LEAST 1 YRd

            SECOND QUlT  ----- --- 576 (43.0%; 8.9%)'   ~- .~ .__

203 (35.2%: 3.1%)"

FIGURE 3.-Flowchart of quitting history, attempts lasting longer than 1 year,
        NHEFS

NOTE: NHEFS=National Health and Nutrition Examination Survey (NHANES-I) Epidemiologic
Followup Study.

"Of the 6.640 ever regular cigarette smokers, I.55 quit within the year preceding the NHEFS interview.
Data on the first quit attempt were missing for 35 people (4 were current smokers. 6 were former smoker\.
and 25 were deceased at the time of the interview).

`Of the 3.566 people who quit for at least I year. data were not available on I6 t IS were former
smokers and I was deceased at the time of the interview).
`The first number represents the percentage of the reference number one row above (e.g.. I.340 i\
37.6% of 3366): the second number represents the percentage of the total number of ever regular cigarette
smokers in this sample (e.g., I.340 is 20.7% of 6.460).

`Of the I.340 people who relapsed after their first 21 -yr period of abstinence. 74 quit within the year
preceding the interview and 26 never returned to regular smoking. Data were not available on I6 other\
( I I were current smokers. 3 were former smokers, and 2 were deceased at the time of the interview).
`Of the 576 people who quit twice for at least I yr. data were not available for 2 (both were former

    --.__
DID NOT Q2T RELAPSE
AFTER FIRST QUlTb
2,210 (62.0%; 34.2%)

DID NOT RELAPSE
-. AFTER SECOND QUITe
371 (64.4%; 517%)'

smokers at interview).


1       2       3        4       5       6        7       8        9        10       11

YR AFTER STOPPING SMOKING

FIGURE 4.-Estimated duration of abstinence on first l-year or longer quit
     attempt, product-limit method, N=3,363
SOURCE: NHANES-I Epidemiologic Followup Study 1982-84: OSH. unpublished data.


THE SMOKING CONTINUUM

A number of surveys have sought detailed information on respondents' quitting
histories. An eight-point smoking continuum among ever smokers can be developed
from the 1978. 1979. and 1980 NHIS tobacco supplements. the 1986 AUTS. and the
1987 NHIS. Smoking continuums for the four NHlSs are presented in Table 2. and are
similar over time.

The data in Table 2 can be used in various ways. For example, by focusing on those
who were smoking during the year before the survey (categories I through 6). the
proportion that tried to quit during that year (categories 3+4+5+6 divided by categories
1+2+3+4+5+6) and the proportion that quit during that year and were still abstinent at
the time of the survey (categories S+6 divided by categories 1+2+3+3+5+6) can be
estimated. The proportion who tried to quit during the year before the survey was higher
in 1987 (34 percent) than in 1978. 1979. and i980 (27 to 29 percent). The proportion
who quit during the year before the survey and were still abstinent at the time of the
survey remained stable at 6 to 8 percent from 197X to 1987.

Data are presented below on various components of the smoking continuum. Data
from NHIS years not included in Table 2 are often presented in the following sections
because, whereas these surveys did not provide all the questions necessary to construct
a complete continuum, enough information to define one or more components of the
continuum was collected. These data are broken down by education (Table 5 and
Figures 5-9) because educational attainment is a strong sociodemographic predictor of
smoking and quitting behavior (US DHHS l989a: Pierce, Fiore et al. 1989). Data from
other stratified analyses (i.e., gender, race, and age) are also presented in Table 5. The
data on the continuum have been age-adjusted to the overall 1985 population.

Percentage of Ever Smokers Who Have Never Tried to Quit

There is no overall clear and significant trend from 1974 to 1987 in the percentage
of ever smokers who have never tried to quit. Education has a consistent effect on
quitting--lower levels of educational attainment are associated with a higher prob-
ability of never having tried to quit (Figure 5).

The difference between genders in the proportion of ever smokers who have never
tried to quit has been decreasing with time (Table 5). While the proportion of females
in this category has been decreasing over the years, it has remained fairly constant for
males. The data also show that. on average. over time, females are more likely than
males to have never tried to quit smoking.

Trend data broken down by race show that blacks have been consistently more likely
than whites to have never tried to quit smoking; however. the difference between the
races has been narrowing with time. The data also show that the likelihood of having
ever tried to quit smoking increases with age. For all age categories. the percentage of
ever smokers who have never tried to quit has been decreasing with time (especially
for the oldest age group).


TABLE 5. --Selected measures of quitting activity (%), NHISs, United States, adults aged 20 and oldera

Overall

   Gentler             Kate              Age (~0                 Educalion or)

MdlC    Femule     Whw\    nkh    XL24    2.544    45-M    26.5      <I?     12     L-15    216

Ncvcr trIcd 10 LIUII"
      IY7-I     223     20. I
      I YX7      IX.7     IX.5
      'L1C.W     23.4     '2 fl

Qlll tot- ill lc;I\I I da)'
      lY7X     27.x     25.x
      IYX7      31.6     31.1
      ML211     2X.11     76.7
OII IC\\ 111x1 I 41"
     I Yh.5"      4.6     4.X
      10x7      4.6     4.5
      MWl      4.3     4.3
Ott I-l yr'
     I Y)hz=lC      X.0     x.7
      IYX7      to..5     IO.'
      MCXIl      Y.2     Y.4
otl 2s yri' IYhS'     12.1     14.0
      IYX7     3.x     32.x
      MUI1     11.7     24.3

25.x
IO.5
2.5 6

30.2
32. I
2Y.h

4.2
4.7
4.4

6.7
10.x
4.0

x.7
2.53
17.5

31.1
17.7
22.6

26.0
30.6
27. I

4.x
4.5
3.3

X.2
I I .o
0.4

12.7
30.9
20.x

34.4     2X.5     22.x     22.4     l6.S
26.5     26.6     20.3      I 6.Y     I I .o
30. I     3 I .7     24.7     22.2     IS.3

36.5     41.6     27.X     22.5     26.4
37.7     40.6     32.6     26.5     29.X
35.0     38.X     20. I      22.3     26.5

2.9      5.1      4.7      3.9     4.x
4.`)      6.2      5.5      3.6     2.5
3.7      6.`)      5.0      2.9     2.6

6.1      6.5      7.x      7.6     IO.0
7.3     I I.6     IO.0      10.4     x.4
7.1     IO.0      Y.X      7.6     x.7

X.3      I.2      7.3      IS.4     30.2      12.2
20.7      4.7     `2. I     36.7    5X.3      22.4
14.3      2.0     IS.?     27.0     46.4      IX.1

26.3
253
2x.0

26.7
29.0
21.4

3.0
4.1
3.0

7.4
7.7
7.0



35



30



25



20



15

go
s
is5
ii
Q-0

YEARS

    <12 yr
- Education

                        ?16 yr
+   12yr
   Education   + 13-15 yr
                 Education    -a-  Education

FIGURE S.-Percentage of ever smokers who never tried to quit, by education,
      United States, 197447

  SOURCE: NHlSs 1974, 1976, 1978. 1979, 19X0. 1987; OSH, unpublisheddata.
5


                                         //
                                                   I I
1978            1979           1980                      1987

YEAR

  m cl2 yr   w 12yr    p`
                       13-15 yr   111 216 yr

        Education       Education       Education        Education

FIGURE &-Percentage of persons smoking at 12 months prior to the survey
      interview who quit for at least I day during those 12 months,
      United States, 197840, 19X7, by education
<Ol `KC-F  Nv)tlS\ l`b7X I Q7c) IUXO I')X7. O`GII. unrwhl~\hrd d;it;~.


8

6

4

                                                                           __________________





.____-____ -_                                                                         ____________





                              --_____--____



  I

I    I    I    I    I    I    I    I    I    I    1    I    I    I    I    I    I    I    I    I    I    I    I    I

1965            1970            1975            1980            1985            1990
YEAR

+   <12 yr     -8   12yr
    Education         Education   ++ 13-15 yr
                               Education  * E%z%h

FIGURE 7.-Percentage of ever smokers who had been abstinent for less than
      1 year, United States, 1966437, by education
SOURCE: NHISs 196f1. 1970. 1978, 1979, 1980. 1983. 198.5. 1987; OSH. unpublished data.


I    I    I    I    I    I    I    I    I    1    I    I    I    I    I    I    I    I    I    I    I    I    I    I

1965             1970            1975             1980             1985             1990

YEAR

e   <12 yr    +   12yr
    Education        Education   + 13-15 yr
                               Education   ++ 216yr
                                             Education

FIGURE &-Percentage of ever smokers who had been abstinent for l-4 years,
     United States, 1966437, by education

SOURCE: NHlSs 1966. 1970, 197X. 1979, 1980. 1983. 19X5. 1987: OSH, unpublisheddata.


  50





  40





  30





  20

8
s 10
5
; *
c-8 0

____________-___________________________------------------------------------------------------------------------------------





  I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I    I

1965             1970            1975            1980             1985            1990

YEARS

    Cl2 yr
- Education

+   12 yr
   Education   + 13-15 yr
                 Education  * E~~~~`on

FIGURE 9.-Percentage of ever smokers who had been abstinent for 5 years or
      more, United States, 1966-87, by education
SOURCE:  NHISs 1966, 1970, 1978, 1979, 1980, 1983, 1985, 1987: OSH. unpublished data.


Percentage of Those Smoking at 12 Months Prior to a Survey Interview Who
      Quit for at Least 1 Day During Those 12 Months

The percentage of those smohing at I:! months prior to a survey interview who
stopped for at least I day during those 12 months is a measure of quitting activity-that
is,, quitting attempts-independent of the success of those attempts. Trend data show
that this percentage was slightly higher in 1987 than in the 3 earlier years (1978. 1979.
and 1980) in all educational strata (Figure 6).

Data show an effect of all demographic variables (gender, race, education, and age)
on quitting for at least 1 day (Table 5). Females are significantly more likely to be in
this category than are males. Blacks, more than whites, are more likely to have been
abstinent for I day or more. Although the effect of education is not statistically
significant, the data suggest a positive trend. Overall, the likelihood of being abstinent
for at least I day tends to be higher in the more highly educated groups (Figure 6).
especially in 1987. Finally, there is a J-shaped relationship between quitting for at least
I day and age. The proportion in this category is highest in the two younger age groups,
lowest in the 45-64.year-old group. and intermediate in the oldest ape group.

Percentage of Ever Smokers Who Had Been Abstinent for Less Than 1 Year

The data in Figure 7 show trends. analyzed according to education. in the proportion
of ever smokers who. at the time of the survey, had been abstinent for less than I year.
In general, no stable trend over the years or absolute change in this proportion from
1965 to 1987 is seen. This lack of a consistent pattern is also evident when the data are
classified by gender, race, and age. In every subgroup. the proportion of ever smokers
who had been abstinent for less than I year in I985 increased; the reason for this increase
is unclear. Data from the 1988 NHIS. which were not available when this Report was
prepared, should help clarify recent trends in this measure of quitting.

The data show effects of most of the demographic variables on the likelihood of being
in this category (Table 5). In general. the two younger age groups are more likely than
the two older age groups to have been abstinent for less than 1 year. A higher proportion
of whites than blacks have been abstinent for less than I year. However, given that the
trend in this proportion has been generally stable for whites and increasing for blacks,
the gap between the races has closed with time. The level of education is positively
associated with the likelihood of being in this category. Those with the least education
(<12 years) are slightly less likely to be recent quitters compared wcith other education
groups.  There is no difference between the sexes in the likelihood of being in this
category.

Percentage of Ever Smokers Who Had Been Abstinent for 1 to 3 Years

Figure 8 presents data on trends in the proportion of ever smokers. who at the time
of the survey had been abstinent from 1 to 4 years, are stratified by education. While
no consistent patterns appear across time, the data show that education is positively
associated with being abstinent for 1 to4 years. Those with the highest education level


( 16+ years) are the most likely to have quit I to 4 years earlier. and those with the lowest
educational level (<12 years) are the least likely.

The data also show that for 1965-1978, the proportion of males who had been
abstinent for I to 4 years is slightly higher than that for females (although across the
entire time period 1965-87, there is no difference in the proportions between the sexes).
Given that the proportion off cigarettes for 1 to 4 years has been increasing significantly
for females and remained stable for males with time, the gap between the genders has
closed (Table 5). Whites are more likely than blacks to have been abstinent for I to 4
years. The data do not show any consistent patterns with respect to age.  Across time.
on average, the proportion of those in the 45X34-year age group in this category is
slightly lower than in the other age groups.

Percentage of Ever Smokers Who Had Been Abstinent for at Least 5 Years

Data on the proportion of ever smokers who, at the time of the survey. had been
abstinent for 5 years or more show positive trends with time for the overall population
and for every population subgroup (trends across education shown in Figure 9).
Overall, the proportion of ever smokers in this category has more than doubled from
12.4 percent in 1965 to 29.8 percent in 1987. Data from the 1955 Current Population
Survey (the first large survey of tobacco use conducted among a probability sample of
the U.S. population) indicate that 5.0 percent of those who ever smoked cigarettes were
abstinent for at least 4.5 years in 1955 (Haenszel, Shimkin, Miller 1956).

The data also show strong effects of all four demographic variables on the likelihood
of being abstinent for at least 5 years. Figure 9 shows that those with the most education
(l6+ years) are the most likely to have been abstinent for 5 years or more than those in
the other categories. On average, over time, the data show that increasing education
is associated with increasing likelihood of being in this category (Table 5). Also seen
in the data are a gender effect (males are more likely than females to have been abstinent
for 5+ years), a race effect (whites are more likely than blacks to be in this category ).
and a strong effect of age (increasing age is associated with increasing likelihood of
being abstinent for at least 5 years). The age effect is due, at least in part. to the fact
that older persons have had a longer opportunity to quit and maintain long-term
abstinence compared with younger persons. The gaps between the races and across age
groups (and to a lesser extent, across education) have been increasing with time.

Interpretation of Continuum Findings

In the period spanned by these data, a slightly increasing proportion of smokers are
attempting to quit and are maintaining abstinence. Slightly less than a third of the
people who were smoking at 12 months before the 19X7 survey quit smoking for at least
1 day during those I2 months. Trends categorized by sociodemographic subgroups
show that females. blacks. younger persons. and more highly educated persons are more
likely than the appropriate comparison groups to have quit for at least I day during rhe
last year.


One way to determine whether these quit attempts have been successful is to examine
trends in the proportion of ever smokers who have been abstinent for I to 4 years.
Although blacks are more likely than whites to have quit for I day or more, whites are
more likely to have successfully maintained abstinence for 1 to 4 years. Younger
smokers are more likely to have quit for 1 day or more than older smokers; however,
there are only small absolute differences across age groups in the percentage who have
been abstinent for 1 to 4 years. The positive trend across educational categories with
respect to quitting for I day or more parallels important differences seen in the
likelihood of being abstinent for I to 4 years. Those with the lowest level of education
were the least likely to make an attempt to quit and the least likely to maintain long-term
abstinence. Those with the highest level of education were the most likely to have made
a quit attempt and the most likely to maintain long-term abstinence. Finally. although
females were more likely than males to have quit for at least I day. there were no gender
differences in abstinence for 1 to 4 years.

The data on the increasing proportion of ever smokers who have been off cigarettes
for at least 5 years show that more ever smokers are entering this category by
successfully quitting and abstaining than are exiting by death or relapse. Overall, this
proportion has increased 242 percent between 196.5 and 1987. Consistent with other
data showing that males began quitting earlier than females (Fiore et al. 1989),
proportionately more males than females are in this category. Similarly, whites began
quitting earlier, and are therefore, more likely than blacks to have stopped smoking for
5 years or more. There is also evidence that those with the highest level of education
have been abstinent for a longer period than those with less education. Finally, older
people were more likely to have been abstinent for at least 5 years. This positive
relationship reflects the accumulation of successful quitters with age and, probably to
some extent, the benefits of cessation on survival.

OTHER MEASURES RELATED TO SMOKING CESSATION

Intention to Smoke in 5 Years

Intention to smoke or quit is a predictor of future smoking behavior (Collins, Emont,
Zywiak, in press: Cummings et al. 1988; Pierce, Dwyer et al. 1987; Pederson, Basker-
ville. Wanklin 1982). Current and former smokers responding to the five OSH-spon-
sored surveys of tobacco. use were asked to assess the likelihood that they would be
smoking in 5 years. There is little change in the responses of former smokers since
1964. In each survey year. fewer than 3.2 percent of all former smokers responded that
they would be smoking again in 5 years. Thus. former smokers overestimate the
likelihood that they will remain abstinent. (See the previous Section, Long-Term
Abstinence and Relapse.)

In Table 6, the predicted likelihood of future smoking behavior among current
smokers is presented for each survey year by gender. The sharp dropoffs that occurred
between 1966 and 1970 may have occurred a\ a result of the widespread television
broadcast of antismoking public service announcements (PSAs) from 1968 to 1970


TABLE 6.-Percentage of those intending to smoke in 5 years, by gender,
     AUTSs, United States, 1964436, current smokers aged 21
       and older

Year

Definitely will be smoking   Probably nilI be smoking

Male       Female       Male       Female

Total (definitely + probably I

Male       Female

1964      25.2        20. I         SO.6       9.4       75.x       74.5

1966      22.3        15.6        53.7       55.3       76.0       7 I .O

1970      IO.9        IO.2         39.1        11.1       50.0       s1.3

1975       11.7        12.0         31.2       AS.9       55.9       57.9

1986       7.3         6.4        35.2       3x.x       42.6       lS.3

VOTE:  AUTS=Adult Lks of Tobacco SW-W!
SOCRCE: Al:TS\ lYh4. IYM. lY70. 1975. IYXh

under the Federal Communications Commission's Fairness Doctrine (US DHHS
1989a). Longitudinal data collected between 1964 and 1975 supported the hypothesis
that the Fairness Doctrine PSAs influenced smokers' attitudes about quitting (Horn
1979). The percentage of smokers who "thought seriously about giving up smoking"
increased from 56 percent before the PSAs to about 85 percent at the end of. and 5 years
after, the PSAs. The proportion of smokers who tried to quit and the overall cessation
rate also increased over the same timeframe.

The slight increases in intention to smoke from 1970 to 1975 might reflect a decay
effect after the removal of the antismoking commercials. The reduction between 1975
and 1986 could reflect an increase in antismoking activity. such as the growth of the
nonsmokers' rights movement (US DHHS 1989a).

Receipt of Advice to Quit from a Doctor

Advice to quit smoking by a doctor increases patient cessation rates (Glynn. Manley,
Pechacek, 1990; Kottke et al. 1988; Schwartz 1987; US Preventive Services Task Force
1989). Data from Table 7 show that the percentage of current smokers who report
having ever been advised by a doctor to stop smoking increased steadily for both
genders between 1964 and 1987. Male current smokers were 3.1 times more likely to
report having received advice from a doctor to stop smoking in 1987 than in 1964;
female current smokers were 3.2 times more likely to have reported receipt of such
advice in 1987 than in 1964.

The data for former smokers, while less consistent, also show increases with time.
Male former smokers were I .5 times more likely to report having received advice from
a doctor to stop smoking in 1987 than in 1964. Female former smokers were 2.1 times
more likely to report having received such advice in 1987 than in 1964.
In summary, large increases in the percentages of current and former smokers who
reported having received advice to quit occurred between 1976 and 1987.

609


I~.4lSl,E 7.--Percentage N ho report ha\ ing e\ er rewi\ ed ad\ ice to quit from a
     doctor, by smoking status and gender, United States, 196187,
     adults aged 21 and older

AUTS IYM
AUTS IYhh
ACTS IY70
NH6 1`471
AUTS I')75
NHIS lY7h
AUTS IYXh
NHIS 1'4x7

CONCLUSIONS

I. By 1987. more than 38 million Americans had quit smoking cigarettes. nearly half
of all living adults who ever smoked.

2. The percentage of ever cigarette smokers who are former cigarette smokers (quit
ratio) has increased from 29.6 percent in 1965 to 44.8 percent in 1987 at an average
rate of 0.68 percentage points per year. The quit ratio has increased among men
and women, among blacks and whites. and among all age and education subgroups.
Between 1966 and 1987, the rate of increase in the quit ratio among college
graduates was twice the rate among high school dropouts.

3. About one-third of all former cigarette smokers who have maintained abstinence for
at least I year may eventually relapse. As the duration of abstinence increases,
relapse becomes less likely.

4. Quitting activity. as measured by the proportion of people smoking at I2 months
before a survey who quit for at least I day during those I2 months, has increased
slightly over time. Between 1978 and 1987. this proportion increased from 27.8 to
3 I .6 percent.

5. Female smokers were more likely than male smokers to have quit smoking cigarettes
for at least 1 day during the previous year; however, there were no gender differen-
ces in the proportion abstinent for I to 4 years. Men were more likely than women
to have been abstinent for 5 years or more. These findings do not take into account
the use of tobacco products other than cigarettes.

610


6. Black smokers were more likely than white smokers to have quit for at least I day
during the previous year. Blacks, however. were less likely than whites to have
been abstinent for I year or more.

7. Younger smokers (aged 20 to 44) were more likely than older smokers to have quit
for at least I day during the previous year.

8. Smokers with less education tend to be less likely to have quit for at least I day
during the previous year compared with those having more education. In addition,
those with lower levels of education are less likely to have been abstinent for I year
  or more.

9. In 1964, about three-fourths of all current smokers predicted that they would
"definitely" or "probably" be smoking in 5 years. In 1986, fewer than half of all
current smokers felt the same way. Moreover, while more than 20 percent of current
smokers in 1964 predicted that they would "definitely" be smoking in 5 years. only
about 7 percent of current smokers in 1986 so predicted.

IO. Current smokers in 1987 were more than three times as likely as current smokers
in 1964 to report having received advice from a doctor to stop smoking.

hl I


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h I 5


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1977.

616


GLOSSARY

AARP
ACS
AR
AUTS
BM
BMI
BP
BPS
BRFSS
BUPA
CASS
cc
CCDPHP

CDC
CHD
CI
cig
CNS
co
COHb
COPD
CPS
CPS-I
CPS-II
cv
CVD
DBP
DHEW
DHHS
DLCOSB
DPA
DSM-III-R
FEV I
FVC I
HANES

American Association of Retired Persons
American Cancer Society
attributable risk

Adult Use of Tobacco Survey
bone mass
body mass index
blood pressure
Baseline Prevalence Survey
Behavioral Risk Factor Surveillance System
British United Providence Association
Coronary Artery Surgery Study
closing capacity
Center for Chronic Disease Prevention
and Health Promotion
Centers for Disease Control
coronary heart disease
confidence interval
cigarettes

central nervous system
carbon monoxide

carboxyhemoglobin
chronic obstructive pulmonary disease
Center for Preventive Services
Cancer Prevention Study I
Cancer Prevention Study II
closing volume
cardiovascular disease
diastolic blood pressure
Department of Health. Education. and Welfare
Department of Health and Human Services
carbon monoxide diffusing capacity
dual photon absorptiometry
Diagnostic UIKI Stutistiwl MUI~MI~ cfMerltcr/ Disordo-s
I -set forced expiratory volume
I -set forced vital capacity
Health and Nutrition Examination Survey

617


HB,Ag
HCN
HDL-C
HA10
HR
IARC
LDL-C
Ml
MMEF
MRC
MRFIT
NCHS
NCI
NHANES-I
NHEFS
NHIS
NHLBI
NNS
OSH
PBI
PCA
PDL
PEF
PHS
POMS
PPA
ppd
PSA
REE
RR
SBP
SCN -
SD
SES
SGA
SIDS
SPA
ST
STD
TLC
TQ
vc
WHO
WHR

hepatitis B surface .mtigen
hvdrogen c\ snide
high-den\it) lipoprotein chole\trrol
health maintenance organization
heart rate
International Agency for Research on Cancer
lowdensity lipoprotein cholesterol
myocardial infarction
mid-maximum expiratory flow
Medical Research Council
Multiple Risk Factor Intervention Trial
National Center for Health Statistics
National Cancer Institute
National Health and Nutrition Examination Survey I
NHANES Epidemiologic Followup Study
National Health Interview Survey
National Heart, Lung. and Blood Institute
National Natality Survey
Office on Smoking and Health
penile brachial index
percent cortical area
predicted diffusing capacity
peak expiratory flow
Public Health Service
Profile of Mood States
phenylpropanolamine
packs per day
public service announcement
resting energy expenditure
relative risk
systolic blood pressure
thiocyanate
standard deviation
socioeconomic status
small gestational age
sudden infant death syndrome
single photon absorptiometry
smokeless tobacco
sexually transmitted disease
total lung capacity
Fagerstrom Tolerance Scale
vital capacity
World Health Organization
ratio of waist to hip circumference

618



INDEX

Absenteekm. Xc)

Abstinence duration
atherosclerosis wveritk. I YY-NO
  bladder cancer. I64
cerehrovascular dijea\e. 152-25X
COPD mortalit). MS
cllr4ifying smohinf atu\. 26-27
CHD mortality. 205-2 15. 223
disease development. l2Y
educational attainment. 606-608
laryngeal cancer. 131-132
locus of control. 533
lung cancer diagnosis. 13-l 3 I
lung ciincer risk patterns. I IO- 12.
    122-126
multistage models. 13-l 7X
MI risk. 203-101
overall mortalit\. 7X-N)
relapse. 33-1-t. W-5YX
respiratory symptom\. 303
self-efficacy. 53 I
3mohinf continuum. 606-607
withdrawal symptom\. 529-530
Abstinence
long-term. 5Y5-5YX
pertormxwe. 525-533
Age at cessation. lung c;uicer. 175-l 76


oral i'ancer. Ii 1 - IS2
pancreatic cancer. 155-l SC)
American Cancer Society Cancer
  Prr\ ention Stud! -I. 26. 1XlY.
   75-7X. I IO. 17-k. I `X. 2.50. 30X.
   131. SOS-SO6
American Cax.w Swirl> C;rncer
  Pre\,ention Studyll. 1X. 7X-7Y.
   I IO. 124. 1 `Y. 1.32. I SC). 171.
   `lS.`11.`15 350 `5' 75X,
             _. -- . -- -. -.

   iox. 34s

Anal cancer. 172-l 76
Analytic issues of consequence
   assessment. SS-S7
Anxiety. 5.33-51 I
Aortic aneurym. 2-I I
Arrhythmias. 195
Arteriosclerosis obliterans. 244
A\ses\ing smohing cessation. see
  Chapter 2
.4\thma (4ee also Airway
  respomiveness)
nosology. 27Y-3X0
respiratory symptom\. 36
Atherowlerosis
CHD development. IYl-lY3
severity. IYY-200
.L\ttrihutahle ri4h. pregnancy outcome.
   3Y3-3%

R

Behav ioml consequence\ of ceskon.
  we Chapter I I
Behavioral measures. 15-J I
Bias. 36.18. 53-55
Biochemical marherr. 33-37
Birth&eight
cessation after conception. 383-3X7

ce\Wion before conception.
    382-3X.3
continued smohins. 3X 1-3X2
loIt. attributable rik N-3YS
mohing and cessation. 379-3237
Bladder cancer. 159-l 65
Blood oxygen deliwry. CHD
  development. IYS-lY6
Body fat di\trihution. lYS
Body height. we Chapter IO
Bogw pipeline. 37
Bone 104s. WC Osteoporosis
Bone mineral content. W&UC)
Breast cancer. I69
Breathlessnes\, see Respiratory
  symptoms
British Physicians Study. 7Y. I 10. 118.
  -70s. 30x. 33 I
Bronchitis (see also Rcbpiratory
  infections)
mortality. .?J2-315
nosology. 27Y

Caffeine we. cessation. S23-525
Cancer\. nonrespirutory. see Chapter 5:
  \ee also specific bites
Cancers. respiratory. \ee Chapter 1: see
  alw specific \ite\

Carbon monoxide. M-35
C'rrrdiovawular disease risk. estimated

   cessation effects. I97
Cardiovavzular diseases. see Chapter 6
Carotid artery plaques. 216
Cas+ontrol study design. 39-50
Cerebral blood flow. 216. 25 I
Cerebrovascular disease
abstinence duration. 37-15X


age factors. 3 I
  ca\e-control studie4. 2KP24Y

  cross-\ectional \tudie\. 2-16
de\ elopment. I Y6
  inter\,ention \tudie\. 3 I
oral contraceptives. 75X-260
prospective cohort \tudit'\. 21Y-750
wiohing and cc\wtion. 215-260
vmohing hi\tor\. 3 l-252
wmmarv of ob\ervstional qudiet.

    151

Cervical cancer. 165-l 60

Ceswtion
consequence\ a\\essment. 16-57
proces\ and heha\,ior a\w\vnent.
    `216
rate. \ee Quit ratio
xtaze modsl. 22-2-I
    c
time trend\. pregnanq. 393
timing. bil-thweight. 3X3-386
Chapter conclusions. Y- I1
Chronic obstructive pulmonary disease
FEVI decline. 33X-333
mortality. 3-l l-338
nosologj,. 27Y-25
patients. 31534X
Cigar smoking
3s cigarette replacement. 555-556
lung cancer. 12-LI25
trend\. 593
Cigarette consumption
bladder cancer. I61
cerebrovascular di\ea\e. 25 I-752
FEVI decline. 329-333
lq ngc;il cancer. I.32
lung cancer. 11-l
MI ri\h. 703

oral cancer. I.5 I - IS2

overall mortality. 7X-M). X6
pancreatic wicer. 15.5
prefnanc! . 3YO-393
LIttight gain. 501-501
Cohort \tud! de\ifn. 1X-4Y
Conclusion\
chapter. YP I1
1 olume. x

Contextual i4w3. biochemical

   ~l\w\\nlt`nt. 17-k
Coping shill\. 513-S4-l
Coronary arty sp;~wl. CHD
  dcwlopment. I OS
Coronar! heart divzrhe (CHD)
cro\5-wclion;il Gudiek 1 YY-200
cc'\\ation. 147-730
development. lYLlY6
niortal~t!. 3JS-2I!4. 227-220
patwnt\. 72%23Y
rich factors. 1Y71YY

Cotinine. 36-37
Cough. see Rrqiratory synptoms
Craving. 573-524
Cro4~+ectional stud!, de\ign. 171X

0

D-fentluramine. weight control.
   soi-so1
Demographic factor\
prqnanc! outcomc~. attributable
    rich. 3Yi-3YS
\mohing and ccs\ation during
   pregnant> 3YOk3Y.J
Deprc\sic,n. 5.73%51 I
Diahetlc\. CHD mortalit!. 22 I-222
Diet. SOO-502
Dietar! ch;mge\. 4X-L-M
I>ict:rr! prxtiLy\. 554-555


Dlt`fuslnp capacity. former wiohcrs.                 F

   327-3'8

Disease developnicnt. Atinence
   duration. 129

DNA adduct lwels. IN- I IO
Duodenal ulcers (see also Peptic ulcers)
healing. 132-133
recurrence. -133-439
Duration of abstinence. see Abstinence

   duration

Dyspnea. see Respiratory symptoms

E

Ecologic study design. 47
Ectopic pregnancy. 375-376
Educational attainment

abstinence duration. 606608
quit ratio. 595
smoking continuum. 5999608
Emphysema
mortality. 342-345
nosology. 179
Endometrial cancer. 169- I71
Energy expenditure. 487l90
Enhancement models, performance.
   52-526
Esophageal cancer. 153-l 55
Estrogen metabolism
osteoporotic fractures. 44334-t
premature menopause. 398
Ethnic factors
abstinence duration, 606608
quit ratio. SO3
smoking and cessation during
   pregnancy. 39 i-393
smoking continuum. 599%608
Ex-smokers. see Former smokers

Fertility
female. 372. 373-37s

male. 304-409
Fetal growth. 373. 379-387: see also
  Birthvveight
Fetal mortality. 376-379
Forced expiratory volume in I second
  (FEVI)
cross-sectional population studies.
    308-3 I6
decline. 328-337.345-347
longitudinal population studies.
    318-337
Fibrinogens. former smokers. I94
Food intake. 484386

Former smokers
absenteeism, 89
anal cancer. 172-l 76
atherosclerosis severity, 199-200
bladder cancer, I64
breast cancer, 169
cerebrovascular disease, 246260
cervical cancer, 166-169
dietary practices, 554-555
diffusing capacity, 327-328
early menopawe risk, 30X-400
endometrial cancer. I69- I72
esophageal cancer, 15% IS5
established COPD. 355-348
fibrinogen levels, I94
health practices. 546-56 I
health screening. 56 l-564
health status. 87-9 I
hepatocellular cancer. 176
HDL-C levels. 192-193
kidney cancer. I72


Ieukemi;l. I76
lung cancer ri& pattern\. I IO- I27
medical care utilization. X7

Ml wr\,i\ 31 200-771
         ` .

oral cancer. 117-l S2

ovarian cancer. I72
over311 mortalit!. 7X-X0
pcnilc c3nccr. 172-l 76
phq\ical xtivit!. SS l-554
population pcrccntafe. CXS
pulmonary function. 30X-337
re\pir;~toq \\mptoni\. 2X.5-305
stomach cancer. I76
Fractures. see O\teoporosi\
Framingham Heart Stud!. X0.
  2 I X-22 I. 30-23s. 250. 25x.
  453,1Y71YX
Frequency issue\. \elf-reports. 27-7X

G

Gastric secretion. smohinp. J2Y430
Gastric ulcer4 (\ee alw Peptic ulcers)
healing. 440
recurrence. 3301-l I
Gastrointestinal physiolog . wioking.
   42Y3.30

Gender factors

abstinence duration. 606-60X
alcohol consumption. 556-S%
bladder cancer. I61
diet. 1X53X6
dietary practices. SSA-555
esophageal cancer. I S2- IS5
MI survi\xl. 237
oral cancer. I17
o\~er3ll mortalit>. X0
pancreatic c3nccr. IS5
physical activit>. 55 l-551

H

Health practlc'e\. tormcr \mohcrs.
   S-K-S6 I
Health rish ch;mgc\,. -4Y7-500
Health \creenlng. former wohers.
   S6l-S6-l

Htxlth \t;rtu\. X7-Y I
Hemorrhagtc \trohc. WC
   Cerehro\ascular diwacc
Hepatocellular cancer. I76
High-densit) lipoprotein chole\terol
  (HDL-CJ Ic\el\. former smokers.
   ICI?-IYi
Hormones. male reproduction. 10 I

I

Imn~unc \steni. respirator\ infection\.

305-30x

ImpotcYlc~. malr. -102-w
Infertilit!

female. 372. 371-375

male. 1OS-4OY

I~lflue~l~;~. we Respirator! infection\
Inhalation practice\. lung cancer. 12-l
IntentIon to cmohe. SXX. 60X-hoc)
Intermittent claudication. 213-714
Intcrpcrwnal intfxiction~. 545-516
Intrr~tsntion trial\. \tudJ dc~i~n. 50-Y I
Inter\ it3 \. 15-29


Ii

Kidnc! cancer. 172

1,

Laryngeal cancer. Ii I - 132
Leukemia. I76
Locus of control. 542-513
Long-term p\ychologicul and
  beha\ ioral consequence\ and
   correlates. 532-546
Lung c;mccr

abstinence duration. I IO-I 31.

a E e at cessation. 125-l 76
airs ay histopatholosy. I OX- I OY
wiohing and cessation. lO7- I3 I
cigar smoker4. I25
cigarette consumption. I24
DNA adduct levels. I OY- I IO
diagnosis. I2Y-I 3 I
inhalation practice\. 12-l
multl\tqe models. 126-l 3X
nonfilter cigarettes. 124 12.5
pathophbsiologic mechanisms ot

  \mokinf. 107-l IO
pipe smohcw I25
\mohincy duration. 122-l 23
     2
smohino hi\tor\ I Z7-1 26
     C     . -

Major conclusions. X
Measures of cessation. 2216
Measures of quitting beha\,ior. 5X4-SXX
Medical care utilization. X7

Clcnopause. premature. 3Y6400
Zletabolic rate. 4X71YO
`Llethodologic i\\ues of consequence
  ;I\\c`sslllcllt. 5 l-57
Mrthodologie\. cexttion a\eswicnt.
  \ec Chapter 3
Mi\clas~ificntion of smoking st;ltu\.
  4Y. 5 I. 52-55

Mood. 533-5-l I
Morbidity (\ee alw Chapter 3: specific

   caLl\es)
peptic ulcers. 13 1332
respiratory. 2X5-30X
Mortality (see alw Chapter 3: specific

   causes)
bronchitis. 331-33.5
COPD. 31 1-315.347-34X
cohort studies. 75-X3
emphysema. 341-335
fetal. neonatal. and perinatal. 371.
    376-37Y
overall. intervention studies. X&X6
peptic ulcers. 332.
weight. 4Y l3YS
Mouth c;mcer. jee Oral cancer
Multiple health habit\. 559-561
Multiple primary cancer\. 176-l 77
Multiple Rish Factor Intervention
  Trial. 34. 2X. SO-S I. 53. X6.
  227-`2X. 333-33s. 4%. 3YX.
   560-56 I. SYS
Multistage models. lung cancer.
   136-11X
Myocardinl infarct (MI) risk
ca\exontrol studies. 200-20-l
cigarette consumption. 203
cohort studie\. 20S-393
                 --
healthy persons. 200-379

624


intervention trials. 223-220
Ml patients, 22Y-23Y
recurrent. 230-73Y

N

National Health and Nutrition
  Esamination Sur\e>,. 21. 30. 4.3 I.
   1s3.sx3-sx1

National Health Interview Sur\e>. 3.
  390-39 I. 537-561.5X3-5x4
National trend5 in smohing ce\\ation.
  we Appendix

Neonatal mortality. 379-3X I
Neoplasms. see Cancer\: we LIIW
  specific sites

Nicotine polacrilek gum
weight control. 502-503
lvithdraual \)mptorn\. 518. 53Y
Nicotine M ithdraival. 52 l-532
Nonbehavioral measure\. 3 116
Nonfilter cigarettes. lung cancer.
   134-1'5

0

Obesity. 3Y0497
Obstructive airways divzase\. see
  Chapter 7

Occupational factors. respirator!
  symptoms. 2Y6-2YY
Oral cancer

kohol conwmption. IS I - I32
cigarette consumption. I5 l-l 51
former smoLer5. I-$7- I57
gender facton. I.47
5nioAing xld ce\s;ition. I17- 152
Oral contrucepti\ e\. cerebra\ ;I\CLI~:II
  diwaw. 25X-700
Osteoporosis. 44.345;

O\teoporotic fractures. 44YL-453
Oi arian cancer. I72
O\ eweight. xl\ crw nicdical and
  p\>cho\ocial outcomes. 4YO4Y7

P

Pxncreatic caiccr. I55- I30
Pathoph! \iolofic nicchaii\m\ ot
   wlohln~
  cartlio\ ;I\~LII:II. diw;rw\. I Y I - I Y7
I;ir> ycal C~IIlCt'l'. I3 I
lung cwccr. 107-l IO
male reproduction. 40040I
preyancb. 37 l-371
premature ~iienop;~uw. 396-39X
osteoporo\l\. I-ii-444
respirator> di\e;iw. 77Y-2X.5
shin ~rinhling. 4531.56
Penile c;uiccr. 171-l 76
Peptic ulcer di\e;iw. 17%41~
Peptic ulcer\
morbidit!,. -Ii ILL32
mortalit>. 4.32
Pcrfomwicc. aktinencc. 525-526. 5.30
Perinatal mortalit!
attrihutahlc ri4. iY.JLWS
\niohing and ceswtion. 376-37Y
Pei-ipheral ;irtc'l-ial occItisi\e dixe;l\e.
   2-l I-211
Peripheral artel-! diw,tw
dC\ clopllkwt. I%. 21.3
progno\i\. T-13-744
PIlen\ I~~rop~inolanlirle. ~4 tight control.
   503.-504
Phleynl production. \c`c Ke\pirator!
   `! lllp,loln\
f'h! \ic;il ;ii,ti\ 11) 4S6. .i5 I --554
f'ti! SICI;II~ .id\ ic,c`. 5%. 6tN


Kac~al t`ac,tor.\. \c'c E!I~IIIC Factor,
Kccidi\ i\m. 595--5YX: \c`c AIYO Kclapc
Kcducrion 01' ~tnok~n~. prcy;tnc>.
   7X7-.3X9
R~lapw. 23-21. 53Ok53 I. 5Y5-5YX
Report
coticlu4ion~. X
de\ cloptlletlt. x-9
05 ervich . 5-7
Reproduclion
fetnale. 37 IL-W

male. 10010v
Reproduction. see Chapter X
Ropiratory cancers. we Chapter 4
Respirator!, diwuw\. \ec Chapter 7
Respiratory function te\th. we
  Spirometric parameter\: Stii~ill
  airway\ function
Respiratory infection\. 305-30X
Respiratory morbidit!,. mohing
   cr\\at;on. 2X5-308
Re\piratorl symptotn~
ah\tinence duration. 303

asthmatic\. 1X6

ce\3ation clinics. 2X5-7X7
cro3\-sectional population studic\.
    2Xx-296
longitudinal Gudiw 7YY-305
occupational !yoiip\. 7061YY
rc\ awl. pooihlr mechaniwi\. 301
w-tohing anti ct`\\ation. 1X5-305
wiohinp hi\lor! . 3Y-3Oi


Self-report tneawres. 3-2Y
Self-monitoring. 29
Sexual acti\ ity. male. IOI-U)4
Sexual behavior. cervical cancer. I66
Shorme\s of breath. see Re\ptratorl
  symptoms

Skin urinhling. 153456
Small airways function. smoking
   cessation. 323-327
Stnohing and ce\ation wrveys.
   methodoio~~\ 5X'-.5X4
           t- .
Smoking behavior chanc7e "-21
                 t .--
Smohin~ charucteri~tic~. see Inhalation
  practice\

Smohing continuum
abstainers for lesh than I Jear. 606
abstainer\ for I to 1 years. 606-607
ab\taitwr\ for 5 \`ear\. 607
defir,ition. 5X5-58X
smokers never trying to quit. SYY
smoker\ quitting for at least I day
  during I ?-month period. 606
Smoking duration. lung cancer.
   122-123

Stnoking history
cerebrovascular disease. 25 l-252
FEV I. 30X-3 16.328-337
lungcancer. I??-126.13%12X
respiratory symptom\. ZYY-303
Smoking interventions
cerebrovaxular dizea\e. 25 I
CHD mortality. 22&2?Y
overall mortality. X3-86
pregnancy. 3X7-.3X9
&eight control. SOO-502
Social wpport. 535-516
Spam. coronary arter! I Y5
Sperm qualit!. JO-l-lOY

Spirometrtc p;tr;lmeter~. smohing
   cessation. 3 IY-32.2
Spontaneou\ abortion. 372. 376
Statistical coti~ider3tiotis. 52
Stomach c:tncer. I76

S1re\4. 533-S-I I
Strobe patients. ce\\;ttion. 760
Studv design. 16-S I
Subaruchnoid hemorrhage. 2IY. 150.
   `.5X-260
Surrogate ;i\w5wxnt\. JO-3 I
Survival progtiwi\
lung cancer. l2Y- I3 I
MI patients. 7iO-33Y

T

T lymphocyte\. 306-307
Temporal i\we>. wit`-report\. 77-7X
Tertninolog\~. ahse\stnent. 33-31
Thiocyanate. 35-36
Thrombosi\. CHD de~~loptncnt.
   lY3-I95
Time trend\ in mohing and ce\\;ttion.
  pregn;inc>. iY3
Tobacco conwt~~p~iot~. e\oplugr~~l
   cancer. I52- I S-l
Tracheal mttcou\ \.elocit>. 304

U.S. Veteran\ Stud!. 10. 7Y. I IO. 12-t.
   12s. I'X. l2Y. 132. IS I. 15'.
   155. IM. l71-17h.217-`IX.
  2s I-25'. 345.112
Lllcrr healing ;tncl recurrence. 4321-i I
lilcer occurrt'nc`c'. -17%4.3~
L;lccr\. 4et' 21~ kpiic ulc`t`t-\: Ga\trtc
  ulcer\: Duotlen~tl LIICC`I-\


Weight control \trategie\. SOO-SO-1
Weight c\cling. 197195
      ,
Weight gain (we ;1lx~ Chapter IO)
pregnancy. 373
rish and amount. 473483

c;1use5.483190

Weight. mortality. 19 I495
Weigh-rclattxl health rid>. 497-500
Well-being. psychological. 533-511
Whesre. \ee Respiratory \ynptoms
Withdraual symptoms
relapse. 5X-53 I
relief. performance. 525-526
timecourse. S? I. 519-530
variability. 526-529
Wrinhlinp. skin. 453456