Introduction

Chronic Obstructive Pulmonary Disease

(COPD) is manifested by chronic cough, sputum

production, wheezing and, in later stages,

dyspnea, poor exercise tolerance, and

signs/symptoms of right-sided heart failure.

Symptomatic COPD affects more than 5 percent

of the adult population, is the fourth leading

cause of death, and the twelfth leading cause of

morbidity in the United States.1,2 In more than 80

percent of cases, cigarette smoking is causally

linked to the development of COPD. Smoking

status should be assessed in all adults, and

smokers should be advised to abstain from

tobacco.

COPD is diagnosed in symptomatic

individuals through spirometric testing that

demonstrates irreversible airflow obstruction.3

Spirometry for case-finding diagnosis and

management of all adults with persistent

respiratory symptoms or having a history of

exposure to pulmonary risk factors has been

recommended in primary care settings for all

current and former smokers as well as never

smokers who have persistent respiratory

symptomsor have history of exposure to other

COPD risk factors. This report was prepared to

provide objective evidence and recommendations

to inform the work of the American Thoracic

Society (ATS), in collaboration with the

American Academy of Family Physicians, the

American College of Physicians, and the

American Academy of Pediatrics Spirometry Task

Force in clarifying usage of spirometry as part of

the management of COPD. A systematic

literature review was undertaken to address four

questions:

1. What is the prevalence of COPD and

airflow obstructions in various adult

populations as defined by: (1) spirometry

and (2) clinical examination?

2. Can use of spirometry lead to increased

smoking cessation rates?

3. Does the effectiveness of COPD-specific

therapies to improve clinically relevant

outcomes vary based on baseline severity or

change in spirometry?

4. Is prediction of future COPD status based

on spirometry, with or without clinical

indicators, more accurate than prediction

based on clinical indicators alone?

Methods

Articles published in the English language from

1966 to May 2005 were identified by searching

MEDLINE® and the Cochrane Database.

Because the individual questions addressed

different areas, the search strategies, types of

eligible studies, populations, interventions, and

outcomes varied. Emphasis was placed on studies

that assessed outcomes from adults in primary

care or population-based settings who had or were

at risk for COPD according to race, gender, age,

smoking, symptom, and spirometric status.

Evidence Report/Technology Assessment

Number 121

Use of Spirometry for Case Finding, Diagnosis, 

and Management of Chronic Obstructive

Pulmonary Disease (COPD)

Summary

Authors: Wilt TJ, Niewoehner D, Kim C, Kane RL, Linabery A, 

Tacklind J, MacDonald R, Rutks I

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

Children or individuals with asthma, or alpha-1 antitrypsin

disease were excluded. Ten cohort studies 4-13 were included to

estimate COPD/airflow obstruction prevalence and diagnostic

accuracy. Seven randomized controlled trials (RCT)14-20 met

inclusion criteria for smoking cessation studies, 52 RCT21-72

and six meta-analyses of RCT73-78 were included for assessment

of COPD-specific therapies, and five cohort studies were

included for prognosis.10, 79-82 The main outcomes according to

question were: 

1. Prevalence of airflow obstruction as determined by

spirometry and clinical examination according to race,

gender, age, smoking, and symptom status and previous

diagnosis of COPD.

2. Long-term sustained smoking abstinence rates among

smokers randomized to receive results of spirometry alone

or in combination with other interventions compared to

controls.

3. Exacerbations, hospitalizations, mortality, and respiratory

health status according to type of treatment; baseline

symptom status and FEV1; acute change in FEV1 or

slope in FEV1 over time.

4. Independent prognostic value of airflow obstruction as

determined by spirometric stage to predict future COPD

status (stage and symptoms). 

Data were used to estimate the number of adults according

to smoking status that would require symptom and spirometric

assessment and subsequent treatment to prevent COPD

exacerbations, reduce mortality or hospitalizations, and improve

smoking cessation or respiratory health status. 

Results

More than one-third of the adult U.S. population reported

respiratory symptoms compatible with symptomatic COPD.

Compared to clinical examination, spirometry plus clinical

examination improves diagnostic accuracy of clinically

significant disease in adults who report respiratory symptoms

(especially dyspnea). Based on the National Health and

Nutrition Examination Survey (NHANES) III results, 12.8

percent of adults report a current or past diagnosis of

obstructive lung disease (emphysema, chronic bronchitis, or

asthma). However, only 17.4 percent of adults reporting a

diagnosis of chronic bronchitis or emphysema (COPD) had

1987-ATS defined low lung function suggesting that many of

these individuals have normal lung function. Fewer than half of

individuals reporting a diagnosis of chronic bronchitis or

emphysema stated that they were bothered by shortness of

breath. Based on gender, age, and smoking status, between 40

and 80 percent of NHANES III participants with low lung

function as determined by spirometry in the absence of

bronchodilator testing reported no prior clinical diagnosis of

COPD. However, there were no data regarding prevalence or

type of respiratory symptoms in this group. 

Spirometry, when used in primary care settings for case

finding of all adults with persistent respiratory symptoms or

having a history of exposure to pulmonary risk factors, is likely

to label a relatively large proportion of individuals as diseased

with airflow obstruction but who do not have respiratory

symptoms or whose symptoms are unlikely to affect their

health status. Conversely, spirometry is normal in a relatively

large percentage of adults who report respiratory symptoms

including dyspnea, the respiratory symptom having the greatest

impact on quality of life. Prevalence and severity of airflow

obstruction and symptomatic COPD vary widely according to

definitions utilized and country and populations studied. The

percentage of adults having normal spirometry and no

respiratory symptoms (normal/asymptomatic) ranged from 56

to 91 percent. Compared with previous definitions of airflow

obstruction, use of recent criteria tripled the number of adults

being labeled as “at-risk” or having “low lung function” (from

6.8 to 20 percent). Normal spirometry with chronic sputum

production (“at-risk”) was present in 7.2 percent of subjects. An

additional 13.9 percent of adults had prebronchodilator

spirometrically detected airflow obstruction (mild, moderate, or

severe to very severe airflow obstruction = 7.2 percent, 5.4

percent, and 1.5 percent respectively). Prevalence was higher in

current smokers and older individuals. The percentage of

individuals reporting respiratory symptoms increased with

airflow obstruction severity. However, one-third of individuals

with normal spirometry reported respiratory symptoms (21

percent reported shortness of breath). Some of these individuals

may have had asthma and thus might have normal spirometry

at the time of testing. Approximately, 21 percent of individuals

with severe to very-severe airflow obstruction (similar to Global

Initiative for Obstructive Lung Disease Stage 3,4) were

asymptomatic and 35 percent did not report shortness of

breath. 

Smoking cessation is the most important factor in reducing

the development and/or progression of airflow obstruction and

symptomatic COPD. All adults should be asked about

smoking and current smokers encourge to quit. However,

evidence indicates that baseline symptom and spirometric status

are of limited clinical use in reliably predicting a patient’s future

likelihood of quitting smoking. Spirometric testing as a

motivational tool to improve smoking cessation rates is unlikely

to provide more than a small benefit. Results from

observational studies of spirometry are mixed. RCT of other

biomarkers used as motivational tools for smoking cessation are

generally negative. The only randomized controlled trial that
assessed the independent contribution of spirometry and

counseling on smoking cessation rates reported a nonsignificant

1 percent greater quit rate at 12 months in the group assigned

to receive spirometry plus repeat counseling compared to repeat

counseling alone (6.5 percent vs. 5.5 percent). Quit rates were

lower in the spirometry group than in participants who

received repeat counseling plus nicotine replacement therapy

(7.5 percent). Two other studies approximated an independent

effect and their results were mixed. The self-reported 6-month

point prevalent abstinence rates for the intervention group

assigned to receive spirometry in combination with advice plus

carbon monoxide values were lower than the group that

received advice alone (9 percent vs. 14 percent). The one study

that showed an improvement in smoking cessation rates

compared a 50-minute educational intervention with a group

that received the educational intervention plus a questionnaire

and discussion of symptom status, spirometric results, and

carbon monoxide levels. At 12 months, the biologically verified

point prevalent quit rates were 20 percent in the intervention

group and 6.7 percent in the control group. Four other trials

that evaluated spirometry demonstrated an improvement in

smoking cessation but all included concomitant interventions

proven to increase abstinence.

Spirometry is useful for determining at what threshold of

airflow obstruction initiation of therapy is likely to improve

clinical outcomes in adults with bothersome respiratory

symptoms. However, monitoring with spirometry to guide

additional therapy or to initiate interventions in individuals

who do not report bothersome respiratory symptoms does not

appear to be beneficial. COPD trials typically were of short

duration, they involved subjects with an established clinical

diagnosis of COPD who had moderate to severe respiratory

symptoms, frequent COPD exacerbations, and severe to very

severe baseline airflow obstruction, and they used varying

outcome definitions for exacerbations. On average,

interventions reduced the relative risk of exacerbations by 20 to

25 percent and the absolute risk by 5 to 6 percent. Treatments

improved measures of dyspnea and respiratory functional

status, although the average improvement from inhaled

bronchodilators and corticosteroids on validated health status

measures failed to achieve a predetermined level of clinical

significance. However, some individuals will notice greater and

clinically significant improvement in respiratory symptoms.

Few studies reported information on hospitalizations, but in

those that did reduction was 4 to 7 percent. Mortality was

similar between treatment and control groups, though there

were relatively few events and the available information cannot

rule out an improvement with long term inhaled treatment.

Information related to the effectiveness of short-acting inhaled

medications used for acute symptomatic rescue therapy was not

available. 

Benefits from interventions are mostly limited to reduction

in exacerbations in patients having activity limiting respiratory

symptoms and severe to very severe airflow obstruction (FEV1

<50 percent predicted). Five large studies of greater than 1-year

duration (one assessing a short-acting anticholinergic and four

evaluating inhaled corticosteroids) found little to no

improvement in respiratory outcomes among subjects with

mild to moderate airflow obstruction or those with normal

airflow but having chronic sputum production (“at risk”

individuals). Analysis of one of these studies that enrolled a

subgroup of individuals that had mild to moderate airflow

obstruction but denied respiratory symptoms demonstrated

that ipratropium did not prevent development of symptoms at

3 years of followup. Subgroup analysis of other studies

indicated that treatment benefit was almost exclusively confined

to adults with bothersome respiratory symptoms and severe to

very-severe airflow obstruction. Five additional comparative

studies of long-acting inhaled b-agonists and corticosteroids

indicated that combination therapy was similar to

monotherapy regarding exacerbations (ARR 1-2 percent) and

mortality (ARR 0-1 percent). Combination therapy with shortor long-acting beta-agonists plus anticholinergics was not

superior to anticholinergics alone but did reduce exacerbations

versus short-acting beta-agonists (ARR = 6 percent). Adverse

effects of inhaled interventions during the study followup

periods were generally mild but included bone loss, thrush, dry

mouth, and serious cardiovascular events. About 50 percent of

subjects remained compliant with therapy. Withdrawals from

therapy were greater in subjects assigned to placebo than to

active treatments. 

Studies have not examined the value of spirometry to

monitor need for additional therapy or to identify candidates

for treatment among patients who do not report symptoms. It

is unlikely to be beneficial because data indicated that: (1)

clinical improvement was not associated with an individual’s

spirometric response to therapy; (2) treatments other than

smoking cessation did not alter the rate of spirometric decline

over time; (3) there was wide intra-individual variation in

spirometric decline; (4) higher doses of inhaled interventions or

combination therapy were not superior to lower doses or to

monotherapy; and, (5) interventions were not effective in

asymptomatic individuals or those with mild to moderate

airflow obstruction.

Based on NHANES III results if all “at risk” adults (i.e.,

smokers and ex-smokers regardless of symptom status as well as

never smokers with persistent respiratory symptom) undergo an

office-based spirometric test then nearly two-thirds of the adult

3
4

population, approximately 110 million adults, would receive

spirometric testing.

• If a primary care clinic was comprised of 10,000 adults

with similar demographic, smoking, symptom, and

spirometric status as NHANES III respondents then

6,588 would undergo spirometric testing, 129 (1.3

percent) would be potential candidates for COPD therapy

and 7 (0.08 percent) would have reductions in

exacerbations (i.e., an estimated 1,010 current smokers,

960 former smokers, and 2,043 never smokers would

undergo spirometric and respiratory assessment to identify

candidates for treatment consisting of an inhaled

bronchodilator or corticosteroid to prevent an individual

from having one or more exacerbations).

• If subjects with moderate airflow obstruction (FEV1 50-

80 percent predicted; approximately Global Initiative for

Obstructive Lung Disease Stage 2) benefit to a similar

magnitude as severe to very severe airflow obstruction,

then 529 adults (5.3 percent) would be candidates for

treatment and 32 adults (0.3 percent) would benefit from

having at least one exacerbation prevented compared with

placebo. Approximately 76 (0.8%) would report a

clinically noticeable improvement in respiratory health

status. Reserving testing and treatment for individuals

with respiratory symptoms (especially dyspnea, exercise

intolerance, or exacerbations) would maintain benefits.

• If spirometry was targeted to individuals with dyspnea,

regardless of smoking status, the number needed to screen

and treat for severe to very severe airflow obstruction

would be 475. 

These estimates assume individuals with airflow obstruction

and respiratory symptoms have COPD as the cause of their

symptoms and that effective detection by clinical examination

and treatment would not have occurred without spirometry.

Based on 2004 Red Book prices the annual long-acting inhaled

drug costs would be over $4.5 billion to treat the estimated 4

percent of adults with dyspnea and severe to very-severe airflow

obstruction (n = 4,630,000). If combination therapy was

routinely used instead of monotherapy, effectiveness would be

similar but drug costs would be considerably higher. Compared

to diagnosis and treatment based on clinical examination alone,

spirometry may reduce the number of symptomatic individuals

who are diagnosed with, and treated for, COPD but do not

have airflow obstruction of severity that is likely to benefit from

treatment. 

Spirometry provides independent prognostic value regarding

respiratory symptoms, morbidity, and mortality, though level of

dyspnea is a better predictor of symptom progression and

mortality. Baseline spirometry predicts rate of spirometric

decline over time in male smokers. Spirometric levels may be

useful as a guide for initiation of inhaled medications and

pulmonary rehabilitation among individuals having disabling

respiratory symptoms, especially frequent exacerbations.

Subjects with chronic sputum production and normal

spirometry (Stage GOLD 0 condition) are not at increased risk

for developing airflow obstruction compared to individuals

without chronic sputum production, and more than half of

these subjects do not have chronic sputum production after 10

years of followup. 

Discussion

Spirometry in addition to clinical examination improves

COPD diagnostic accuracy compared to clinical examination

alone and it is a useful diagnostic tool in individuals with

symptoms suggestive of possible COPD. The primary benefit

of spirometry is to identify individuals who might benefit from

pharmacologic treatment in order to improve exacerbations.

These include adults with symptomatic, severe to very severe

airflow obstruction. In individuals where a diagnosis of asthma

is suspected bronchodilator responsiveness, testing may be

indicated. The evidence does not support widespread use of

spirometry in primary care settings for all adults with persistent

respiratory symptoms or having a history of exposure to

pulmonary risk factors for case-finding, improving smoking

cessation rates, monitoring the clinical course of COPD, or

adjusting COPD interventions.

Routine spirometric testing in primary care settings is likely

to result in considerable testing and treatment costs, resource

utilization, and health care personnel time. It might reduce the

number of individuals being labeled as having COPD or

receiving disease-specific treatment in the absence of severe to

very-severe airflow obstruction. However, it is likely to label a

large number of individuals (many not reporting bothersome

respiratory symptoms or having nondisabling symptoms) as

diseased who would not benefit from testing or treatment.

Treatment effectiveness (beyond short acting medications used

for “acute rescue therapy”) is largely limited to reducing

exacerbations among subjects who have bothersome dyspnea,

frequent exacerbations, and severe to very-severe airflow

obstruction. Nearly all the benefit from treatment could be

obtained by reserving spirometry for those having activity

limiting respiratory symptoms and targeting therapy to those

who have reached a spirometric threshold of airflow obstruction

of approximately a FEV1 less than 50 percent predicted.

Spirometric response to therapy or change over time has not

been shown to be associated with clinical outcomes, nor does it

appear to be beneficial in modifying therapy. Future studies

should be conducted to determine if spirometry improves
smoking cessation rates; if treatment effectiveness in established

COPD varies according to an individual’s baseline or followup

spirometric value; if treatment benefits individuals with airflow

obstruction and moderate to no reported respiratory

symptoms; or if therapy improves the rate of decline of FEV1.

Spirometry provides independent prognostic value for

predicting respiratory and overall morbidity and mortality. 

Availability of the Full Report

The full evidence report from which this summary was taken

was prepared for the Agency for Healthcare Research and

quality (AHRQ) by the Minnesota Evidence-based Practice

Center, under Contract No. 290-02-0009. It is expected to be

available in September 2005. At that time, printed copies may

be obtained free of charge from the AHRQ Publications

Clearinghouse by calling 800-358-9295. Requesters should ask

for Evidence Report/Technology Assessment No. 121, Use of

Spirometry for Case Finding, Diagnosis, and Management of

Chronic Obstructive Pulmonary Disease (COPD). In addition,

Internet users will be able to access the report and this

summary online through AHRQ’s Web site at www.ahrq.gov.

Suggested Citation

Wilt TJ, Niewoehner D, Kim C, Kane RL, Linabery A,

Tacklind J, MacDonald R, Rutks I. Use of Spirometry for

Case Finding, Diagnosis, and Management of Chronic

Obstructive Pulmonary Disease (COPD). Summary, Evidence

Report/Technology Assessment No. 121. (Prepared by the

Minnesota Evidence-based Practice Center, under Contract No.

290-02-0009.) AHRQ Publication No. 05-E017-1. Rockville,

MD: Agency for Healthcare Research and Quality. August

2005.

References

1. Murray CJ, Lopez AD. Alternative projections of mortality and

disability by cause 1990-2020: Global Burden of Disease Study.

Lancet. May 1997;349(9064):1498-504.

2. Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD.

Chest. Feb 2000;117(2 Suppl):5S-9S.

3. Global Initiative for Chronic Obstructive Lung Disease. Global

strategy for the diagnosis, management, and prevention of chronic

obstructive pulmonary disease. Available at:

http://www.goldcopd.com/revised.pdf, 2004.

4. Bakke PS, Baste V, Hanoa R, et al. Prevalence of obstructive lung

disease in a general population: relation to occupational title and

exposure to some airborne agents. Thorax. Dec 1991;46(12):863-70.

5. de Marco R, Accordini S, Cerveri I, et al. An international survey of

chronic obstructive pulmonary disease in young adults according to

GOLD stages. Thorax. Feb 2004;59(2):120-5.

6. Isoaho R, Puolijoki H, Huhti E, et al. Prevalence of chronic

obstructive pulmonary disease in elderly Finns. Respir Med. Sep

1994;88(8):571-80.

7. Mannino DM, Ford ES, Redd SC. Obstructive and restrictive lung

disease and markers of inflammation: data from the Third National

Health and Nutrition Examination. Am J Med. Jun 2003;114(9):758-

62.

8. Mannino DM, Gagnon RC, Petty TL, et al. Obstructive lung disease

and low lung function in adults in the United States: data from the

National Health and Nutrition Examination Survey, 1988-1994. Arch

Intern Med. Jun 2000;160(11):1683-9.

9. Pena VS, Miravitlles M, Gabriel R, et al. Geographic variations in

prevalence and underdiagnosis of COPD: results of the IBERPOC

multicentre epidemiological study. Chest. Oct 2000;118(4):981-9.

10. Vestbo J, Lange P. Can GOLD Stage 0 provide information of

prognostic value in chronic obstructive pulmonary disease? Am J

Respir Crit Care Med. Aug 2002;166(3):329-32.

11. Viegi G, Pedreschi M, Pistelli F, et al. Prevalence of airways

obstruction in a general population: European Respiratory Society vs

American Thoracic Society definition. Chest. May 2000;117(5 Suppl

2):339S-45S.

12. von Hertzen L, Reunanen A, Impivaara O, et al. Airway obstruction

in relation to symptoms in chronic respiratory disease—a nationally

representative population study. Respir Med. Apr 2000;94(4):356-63.

13. Buffels J, Degryse J, Heyrman J, et al. Office spirometry significantly

improves early detection of COPD in general practice: the DIDASCO

Study. Chest. Apr 2004;125(4):1394-9.

14. Humerfelt S, Eide GE, Kvale G, et al. Effectiveness of postal smoking

cessation advice: a randomized controlled trial in young men with

reduced FEV1 and asbestos exposure. Eur Respir J. Feb

1998;11(2):284-90.

15. Li VC, Kim YJ, Ewart CK, et al. Effects of physician counseling on

the smoking behavior of asbestos-exposed workers. Prev Med. Sep

1984;13(5):462-76.

16. Richmond R, Webster I. Evaluation of general practitioners’ use of a

smoking intervention programme. Int J of Epidemiol. Sep

1985;14(3):396-401.

17. Risser NL, Belcher DW. Adding spirometry, carbon monoxide, and

pulmonary symptom results to smoking cessation counseling: a

randomized trial. J Gen Intern Med. Jan-Feb 1990;5(1):16-22.

18. Rose G, Hamilton PJ. A randomised controlled trial of the effect on

middle-aged men of advice to stop smoking. J Epidemiol Community

Health. Dec 1978;32(4):275-81.

19. Segnan N, Ponti A, Battista RN, et al. A randomized trial of smoking

cessation interventions in general practice in Italy. Cancer Causes

Control. Jul 1991;2(4):239-46.

20. Sippel JM, Osborne ML, Bjornson W, et al. Smoking cessation in

primary care clinics.[see comment]. J Gen Intern Med. Nov

1999;14(11):670-6.

21. Aalbers R, Ayres J, Backer V, et al. Formoterol in patients with chronic

obstructive pulmonary disease: a randomized, controlled, 3-month

trial. Eur Respir J. May 2002;19(5):936-43.

22. Ambrosino N, Bruletti G, Scala V, et al. Cognitive and perceived

health status in patient with chronic obstructive pulmonary disease

surviving acute on chronic respiratory failure: a controlled study.

Intensive Care Med. Feb 2002;28(2):170-7.

5
23. Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking

intervention and the use of an inhaled anticholinergic bronchodilator

on the rate of decline of FEV1. The Lung Health Study. JAMA. Nov

16 1994;272(19):1497-505.

24. Bourbeau J, Rouleau MY, Boucher S. Randomised controlled trial of

inhaled corticosteroids in patients with chronic obstructive pulmonary

disease. Thorax. Jun 1998;53(6):477-82.

25. Bourbeau J, Julien M, Maltais F, et al. Reduction of hospital

utilization in patients with chronic obstructive pulmonary disease: a

disease-specific self-management intervention.[see comment]. Arch

Intern Med. Mar 2003;163(5):585-91.

26. Brooks D, Krip B, Mangovski-Alzamora S, et al. The effect of

postrehabilitation programmes among individuals with chronic

obstructive pulmonary disease. Eur Respir J. Jul 2002;20(1):20-9.

27. Brusasco V, Hodder R, Miravitlles M, et al. Health outcomes

following treatment for six months with once daily tiotropium

compared with twice daily salmeterol in patients with COPD. Thorax.

May 2003;58(5):399-404.

28. Burge PS, Calverley PM, Jones PW, et al. Randomised, double blind,

placebo controlled study of fluticasone propionate in patients with

moderate to severe chronic obstructive pulmonary disease: the

ISOLDE trial. BMJ. May 13 2000;320(7245):1297-303.

29. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and

fluticasone in the treatment of chronic obstructive pulmonary disease:

a randomised controlled trial.[see comment][erratum appears in

Lancet. 2003 May 10;361(9369):1660]. Lancet. Feb 8

2003;361(9356):449-56.

30. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of

once-daily inhaled tiotropium in chronic obstructive pulmonary

disease.[see comment]. Eur Respir J. Feb 2002;19(2):217-24.

31. Celli B, Halpin D, Hepburn R, et al. Symptoms are an important

outcome in chronic obstructive pulmonary disease clinical trials:

results of a 3-month comparative study using the Breathlessness,

Cough and Sputum Scale (BCSS). Respir Med. Jan 2003;97(Suppl

A):S35-43.

32. Chapman KR, Arvidsson P, Chuchalin AG, et al. The addition of

salmeterol 50 microg bid to anticholinergic treatment in patients with

COPD: a randomized, placebo controlled trial. Can Respir J. MayJun 2002;9(3):178-85.

33. Cockcroft A, Bagnall P, Heslop A, et al. Controlled trial of respiratory

health worker visiting patients with chronic respiratory disability. Br

Med J (Clin Res Ed). Jan 24 1987;294(6566):225-8.

34. COMBIVENT Inhalation Solution Study Group. Routine nebulized

ipratropium and albuterol together are better than either alone in

COPD. Chest. Dec 1997;112(6):1514-21.

35. COMBIVENT Inhalation Aerosol Study Group. In chronic

obstructive pulmonary disease, a combination of ipratropium and

albuterol is more effective than either agent alone. An 85-day

multicenter trial. Chest. May 1994;105(5):1411-9.

36. Dahl R, Greefhorst LA, Nowak D, et al. Inhaled formoterol dry

powder versus ipratropium bromide in chronic obstructive pulmonary

disease. Am J Respir Crit Care Med. Sep 2001;164(5):778-84.

37. Donohue JF, van Noord JA, Bateman ED, et al. A 6-month, placebocontrolled study comparing lung function and health status changes in

COPD patients treated with tiotropium or salmeterol. Chest. Jul

2002;122(1):47-55.

38. Engstrom CP, Persson LO, Larsson S, et al. Long-term effects of a

pulmonary rehabilitation programme in outpatients with chronic

obstructive pulmonary disease: a randomized controlled study. Scand J

Rehabil Med. Dec 1999;31(4):207-13.

39. Finnerty JP, Keeping I, Bullough I, et al. The effectiveness of

outpatient pulmonary rehabilitation in chronic lung disease: a

randomized controlled trial. Chest. Jun 2001;119(6):1705-10.

40. Gallefoss F, Bakke PS. Impact of patient education and selfmanagement on morbidity in asthmatics and patients with chronic

obstructive pulmonary disease. Respir Med. Mar 2000;94(3):279-87.

41. Griffiths TL, Burr ML, Campbell IA, et al. Results at 1 year of

outpatient multidisciplinary pulmonary rehabilitation: a randomised

controlled trial. Lancet. Jan 29 2000;355(9201):362-8.

42. Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of

fluticasone propionate (250 microg)/salmeterol (50 microg) combined

in the Diskus inhaler for the treatment of COPD. Chest. Sep

2003;124(3):834-43.

43. Hermiz O, Comino E, Marks G, et al. Randomised controlled trial of

home based care of patients with chronic obstructive pulmonary

disease. BMJ. Oct 2002;325(7370):938.

44. Hiller FC, Alderfer V, Goldman M. Long-term use of Viozan

(sibenadet HCl) in patients with chronic obstructive pulmonary

disease: results of a 1-year study. Respir Med. Jan 2003;97(Suppl

A):S45-52.

45. Jolliet P, Tassaux D, Roeseler J, et al. Helium-oxygen versus air-oxygen

noninvasive pressure support in decompensated chronic obstructive

disease: A prospective, multicenter study.[see comment]. Crit Care

Med. Mar 2003;31(3):878-84.

46. Jones PW, Bosh TK. Quality of life changes in COPD patients treated

with salmeterol. Am J Respir Crit Care Med. Apr 1997;155(4):1283-

9.

47. Laursen LC, Lindqvist A, Hepburn T, et al. The role of the novel

D2/beta2-agonist, Viozan (sibenadet HCl), in the treatment of

symptoms of chronic obstructive pulmonary disease: results of a largescale clinical investigation. Respir Med. Jan 2003;97(Suppl A):S23-33.

48. Littlejohns P, Baveystock CM, Parnell H, et al. Randomised controlled

trial of the effectiveness of a respiratory health worker in reducing

impairment, disability, and handicap due to chronic airflow limitation.

Thorax. Aug 1991;46(8):559-64.

49. Lung Health Study Research Group. Effect of inhaled triamcinolone

on the decline in pulmonary function in chronic obstructive

pulmonary disease. N Engl J Med. Dec 2000;343(26):1902-9.

50. Mahler DA, Donohue JF, Barbee RA, et al. Efficacy of salmeterol

xinafoate in the treatment of COPD. Chest. Apr 1999;115(4):957-65.

51. Mahler DA, Wire P, Horstman D, et al. Effectiveness of fluticasone

propionate and salmeterol combination delivered via the Diskus

device in the treatment of chronic obstructive pulmonary disease. Am

J Respir Crit Care Med. 2002 Oct 15 2002;166(8):1084-91.

52. Monninkhof E, van der Valk P, van der Palen J, et al. Effects of a

comprehensive self-management programme in patients with chronic

obstructive pulmonary disease. Eur Respir J. Nov 2003;22(5):815-20.

53. Paggiaro PL, Dahle R, Bakran I, et al. Multicentre randomised

placebo-controlled trial of inhaled fluticasone propionate in patients

with chronic obstructive pulmonary disease. International COPD

Study Group. Lancet. Mar 1998;351(9105):773-80.

6
54. Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment

with inhaled budesonide in persons with mild chronic obstructive

pulmonary disease who continue smoking. European Respiratory

Society Study on Chronic Obstructive Pulmonary Disease. N Engl J

Med. Jun 1999;340(25):1948-53.

55. Rennard SI, Anderson W, ZuWallack R, et al. Use of a long-acting

inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with

chronic obstructive pulmonary disease. Am J Respir Crit Care Med.

Apr 2001;163(5):1087-92.

56. Ries AL, Kaplan RM, Myers R, et al. Maintenance after pulmonary

rehabilitation in chronic lung disease: a randomized trial. Am J Respir

Crit Care Med. Mar 2003;167(6):880-8.

57. Ringbaek TJ, Broendum E, Hemmingsen L, et al. Rehabilitation of

patients with chronic obstructive pulmonary disease. Exercise twice a

week is not sufficient! Respir Med. Feb 2000;94(2):150-4.

58. Rossi A, Kristufek P, Levine BE, et al. Comparison of the efficacy,

tolerability, and safety of formoterol dry powder and oral, slow-release

theophylline in the treatment of COPD. Chest. Apr

2002;121(4):1058-69.

59. Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of

budesonide/formoterol in the management of chronic obstructive

pulmonary disease. Eur Respir J. Jan 2003;21(1):74-81.

60. Tashkin DP, Ashutosh K, Bleecker ER, et al. Comparison of the

anticholinergic bronchodilator ipratropium bromide with

metaproterenol in chronic obstructive pulmonary disease. A 90-day

multi-center study. Am J Med. Nov 1986;81(5A):81-90.

61. van der Valk P, Monninkhof E, van der Palen J, et al. Effect of

discontinuation of inhaled corticosteroids in patients with chronic

obstructive pulmonary disease: the COPE study. Am J Respir Crit

Care Med. Nov 2002;166(10):1358-63.

62. van Noord JA, de Munck DR, Bantje TA, et al. Long-term treatment

of chronic obstructive pulmonary disease with salmeterol and the

additive effect of ipratropium. Eur Respir J. May 2000;15(5):878-85.

63. van Noord JA, Bantje TA, Eland ME, et al. A randomised controlled

comparison of tiotropium and ipratropium in the treatment of

chronic obstructive pulmonary disease. The Dutch Tiotropium Study

Group. Thorax. Apr 2000;55(4):289-94.

64. Vestbo J, Sorensen T, Lange P, et al. Long-term effect of inhaled

budesonide in mild and moderate chronic obstructive pulmonary

disease: a randomised controlled trial. Lancet. May

1999;353(9167):1819-23.

65. Vincken W, van Noord JA, Greefhorst AP, et al. Improved health

outcomes in patients with COPD during 1 yr’s treatment with

tiotropium. Eur Respir J. Feb 2002;19(2):209-16.

66. Wadbo M, Lofdahl CG, Larsson K, et al. Effects of formoterol and

ipratropium bromide in COPD: a 3-month placebo-controlled study.

Eur Respir J. Nov 2002;20(5):1138-46.

67. Watson PB, Town GI, Holbrook N, et al. Evaluation of a selfmanagement plan for chronic obstructive pulmonary disease. Eur

Respir J. Jun 1997;10(6):1267-71.

68. Wedzicha JA, Bestall JC, Garrod R, et al. Randomized controlled trial

of pulmonary rehabilitation in severe chronic obstructive pulmonary

disease patients, stratified with the MRC dyspnoea scale. Eur Respir J.

Aug 1998;12(2):363-9.

69. Weinberger M, Murray MD, Marrero DG, et al. Effectiveness of

pharmacist care for patients with reactive airways disease: a

randomized controlled trial. JAMA. Oct 2002;288(13):1594-602.

70. Weinberger M, Oddone EZ, Henderson WG. Does increased access

to primary care reduce hospital readmissions? Veterans Affairs

Cooperative Study Group on Primary Care and Hospital

Readmission. N Engl J Med. May 1996;334(22):1441-7.

71. Weir DC, Bale GA, Bright P, et al. A double-blind placebo-controlled

study of the effect of inhaled beclomethasone dipropionate for 2 years

in patients with nonasthmatic chronic obstructive pulmonary disease.

Clin Exp Allergy. Jun 1999;29 Suppl 2:125-8.

72. Calverley PM, Boonsawat W, Cseke Z, et al. Maintenance therapy

with budesonide and formoterol in chronic obstructive pulmonary

disease. Eur Respir J. Dec 2003;22(6):912-9.

73. Sin DD, McAlister FA, Man SF, et al. Contemporary management of

chronic obstructive pulmonary disease: scientific review. JAMA. Nov

2003;290(17):2301-12.

74. Dear K, Holden J, Andrews R, et al. Vaccines for preventing

pneumoccal infection in adults. Chochrane Database System Review.

2003;4:CDD000422.

75. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of

beta-agonists in patients with asthma and COPD: a meta-analysis.

Chest. Jun 2004;125(6):2309-21.

76. Steurer-Stey C, Bachmann LM, Steurer J, et al. Oral purified bacterial

extracts in chronic bronchitis and COPD: systematic review. Chest.

Nov 2004;126(5):1645-55.

77. Barr RG, Bourbeau J, Camargo CA, Ram FSF. Inhaled tiotropium for

stable chronic obstructive pulmonary disease. The Cochrane Database

of Systematic Reviews 2005, Issue 2. Art. No.: CD002876.pub2.

78. Nannini L, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid

and longacting beta-agonist in one inhaler for chronic obstructive

pulmonary disease. The Cochrane Database of Systematic Reviews

2004, Issue 3. Art. No.: CD003794.pub2.

79. Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow

obstruction, dyspnea, and exercise capacity index in chronic

obstructive pulmonary disease. N Engl J Med. Mar

2004;350(10):1005-12.

80. Enright RL, Connett JE, Bailey WC. The FEV1/FEV6 predicts lung

function decline in adult smokers. Respir Med. Jun 2002;96(6):444-9.

81. Burrows B, Knudson RJ, Camilli AE, et al. The “horse-racing effect”

and predicting decline in forced expiratory volume in one second

from screening spirometry. Am Rev Respir Dis. Apr 1987;135(4):788-

93.

82. Fletcher C, Peto R. The natural history of chronic airflow obstruction.

Br Med J. Jun 25 1977;1(6077):1645-8.

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AHRQ Pub. No. 05-E017-1

August 2005

ISSN 1530-440X