CONTENTS

Introduction

Influence of Cigarette Smoking on the Natural History of
Byssinosis

Cigarette Smoking Patterns Among Workers Exposed
to Cotton Dust

Acute Effects of Smoking and Cotton Dust Exposure
on Respiratory Symptoms
Effects of Smoking and Cotton Dust Exposure on
Pulmonary Function Tests
Chronic Clinical Effects of Cotton Dust Exposure

Mechanisms of Cotton Dust Lung Injury
  Inflammation (Bronchitis)
  Airways Constriction

Chronic Inflammatory Lung Destruction

Cotton Dust Exposure and Mortality From Respiratory

Disease and Lung Cancer

Control of Cotton Dust Exposure

Summary and Conclusions

References

401


Introduction
Exposures to cotton, hemp, and flax dust have been associated
with two acute pulmonary responses: irritant (industrial) bronchitis
and chest tightness (byssinosis). These symptoms, often accompanied
by reduction in lung function, have occurred in 2 to 30 percent of
cotton textile workers within hours of resuming exposure following a
weekend or holiday @chilling 1956; Morgan et al. 1982). These
elements of the acute cotton dust pulmonary response may not occur
together, and may represent responses of distinct pulmonary mecha-
nisms. The exposure variables or host characteristics that lead to
cough rather than to bronchoconstriction are currently under
careful study (Hogg and Eggleston 19841. The effects of cigarette
smoking upon these different responses is also incompletely under-
stood.
In the manufacture of cotton textiles, cotton dust exposure occurs
most intensely when the tightly packed bale is opened and when
abrasive crushing and carding remove the "trash" (plant bracts and
other parts, dirt, bacteria, and fungi) and align the fibers for
spinning (Gideon and Johnson 1978). Normally, as the cotton fibers
are spun, twisted, and woven into cloth, progressively less dust is
generated. By the time cotton cloth is processed, the procedure is
practically free of cotton dust (Kilburn 1983).
Cross-sectional studies have shown that byssinosis prevalence is
greatest among cotton textile workers in the dusty preparation jobs
(e.g., carder, stripper, or grinder) (Figure 1). Byssinosis prevalence
has been related to the duration of cotton dust exposure, to the
quality of the raw cotton, and to the levels of lint-free cotton dust
(Molyneux and Tombleson 1970; Merchant, Lumsden, Kilburn,
O'Fallon et al. 1973b; Kamat et al. 1981). At a cotton dust level of 0.2
mg/m3 (lint-free dust of approximately 15 urn or less), approximately
15 percent of the cotton textile workers have some grade of
byssinosis (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973b).
While a small sex-specific effect (male disadvantage) has been noted
(Berry et al. 19741, no age effect has been shown after adjustment for
exposure (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973b; Berry
et al. 1974). Cigarette smoke interacts with cotton dust exposure in
cotton textile workers and has been associated with increased
byssinosis prevalence and severity (Berry et al. 1974). The frequency
of byssinosis has been closely correlated with the presence of chronic
bronchitis, and both symptoms have been associated with ventilatory
impairment (Imbus and Suh 1973). Cross-sectional studies have
correlated cotton dust exposure with two components of ventilatory
impairment: reduction in the baseline level of forced expiration and
reversible loss of function across a work shift. The relationship of
byssinosis and bronchitis with ventilatory impairment and its


   Z!

   2(

P
1
s   1t
6
1
3
h

   1C

    5

   c

26.2

I cotlon
[7 Cotton/Synthetic

16.2

Preparation

Yarn production    Slashing/Weaving

Miscellanecus

FIGURE l.-Byssinosis prevalence by work area and raw
        material use

NOTE- Average prevalence- cotton. 5.7. percent. cotton/synrhetlc, 4 4 percent.
SOURCE Imbus and Suh (19731.

relationship to cigarette smoking is discussed in greater detail later
in this chapter.

Influence of Cigarette Smoking on the Natural History of
Byssinosis
Cigarette Smoking Patterns Among Workers Exposed to
Cotton Dust

The smoking patterns of cotton dust exposed workers have been
reported by a number of authors and are presented in Table 1.
In summary, current studies show that male cotton workers tend
to smoke to a greater degree than do female cotton workers. Male
textile workers in Western Europe and in Canada smoke with

404


TABLE l.-Prevalence of smoking in studies of cotton workers

Study

Number and type
of population

Smoking characteristica (percent)                     Comments

Schrag and Gullett
(1970)

Kari-Koskinen and    967 female cotton workers,
Hirvonen (1970)     Finland

Merchant, Kilbum.   435 cottonsynthetic blend
et al. (1972)      workers, North Carolina

Kilburn, Kilburn     1,046 female textile
et al. (1973)      workers, North Camliia

Szymczykiewin et
al. (1970)

For et al.
(1973)

509 cotton textile workera

637 men, 2,530 women

Cotton workers, 35 mills,
Great Britain

Age
17-29
30-39
4049
iw-60

CigslbY
l-14
15-24
>24

2.6

SM           EX           NS
54.7           12.0          33.3

SM
45.2
35.6

Syn. wool workers
Cottonmill workers

Men
Women

60.5
6.9

SM           NS           EX
62           31.6           6.3

36.2
21

SM
36

EX/NS

Percent smoking
~1 pack/day not
available

16.9

39.8
14.1
9.0
5.0

63.1

>53% began
smoking at 15-19
years of age


E  TABLE L-Continued

                 Number and type
   Study             of population                 Smoking characteristics (percent)                     Cmnmenta

Imbus and Suh     10,133 cotton workers.
11973)         North Carolina

Men       78
Women      43

Smokers include
ever smoked
1 cig/day for 1
Y-r

Berry et al.
(1974)

14 cotton and 2 manmade
fiber milla. Great Britain

Men       75.6
Women      56.5

Former smokers
not reported

Zwkin et al.
(1976)

Wool workers and controls

Workers   Men        47
      Women       0
Controls   Men        55
      Women       0

Khogali
(1976)

271 ginnery workers, Sudan

SM
36.5

Jones et al.
(1977)

153 cottonmill workers,
southeast United States

SMIEX
70

Almost l/2
smoken said
smoked <5
cigs/day

Bouhuys et al.
(1977)

Card and weave room
workers, South Carolina

         SM
Men      X-41
Women     15-25


TABLE l.-Continued

Study

Number and type
of population

Smoking characteristics (percent)                     Comments

Palmer et al.
(1978)

Bouhuys et al.
(1979)

203 gin workers

Textile workers, aged 245,
South Carolina

Ginnera

Pressmen

Others

Controls

Women
Carding

SM           EX
51.1          25.5
(16.0)'         (9.6)
57.1           19.1
(7.3)         (4.1)
45.5          15.1
(15.3)         (8.0)
52.3          19.2
(11.4)          (9.1)

SM           EX           NS
18           14            68
20           10            70
17           14            69
20           10            69
15           11            74

Jones et al.       Cotton and wool/synthetic
(1979)          mill workers

&,rii,g
Weaving
Others'
Men
Carding

. -
Preparing
Weaving
Others'

Mill 1
Mill 2
Mill 3
Mill 4       38.0          62.0

SM'           NS
52.6          47.2
66.9          33.1
64.8          35.2

26           44            26
37           4.5            16
50           42            8
38           37            16
20           3.5            30

NS
23.4

23.8

39.4

28.5

`( )=mean
pack-years
(1 pk/day/year)

* Includes cloth
room workers and
miscellaneous job
CAgOrieS

' Smokers include
ex-smokera


TABLE k-Continued

Study

Number and type
of population

Smoking characteristics (percent)                      Comments

Barman
(1979)

-

70 cottonmill workers

MUI
Women

Sparks and Peters
(1960)

Grimard and Adams
(1981)

Becketal
(19821

Cotton duetexposed workers

Men
Women

Textile workers, Canada

Men
Women

118 male and 162 female
cottm textile workers

Men
Workers
Controls
Women
Workers
Controls

SM           EX
44           28
58

44           28
55           -

76.6
60.4

27
16

31
43

NOTE SW Smoker; EX Exnmoker. NS. Nonrmoker


greater frequency than do American workers, with many studies
showing the proportion of smokers to be well over 70 percent.

Acute Effects of Smoking and Cotton Dust Exposure on
Respiratory Symptoms

The symptoms 01 ?ilonddy ches t t;,htness begin gradually, S or 4
hours after the cotton texrile worker returns to work. A dry cough
and shortness of breath on exertion frequently accompany the
sensation of chest tightness. However. the physiologic reaction
associated with Monday chest tightness is not confine2 to the chest.
X low grade temperature. a 20 to 3n percen: increase in the
peripheral white blood cell I polymorphonuclear ieukocyte 1 count,
and a general malaise have been frequently reported These systemic
symptoms suggest the presence of a host in!lammarory response;
however, the relationship between these systemic symptoms and the
symptom of che?t tightness is not well defined.

By 1936, an association had heen recognized between Monday
chest tightness and detectable loss of ventilatory capacity and
increased breathlessness iPrausnltz 19361. Recognition that in sus-
ceptible cotton mill workers. Monday chest tightness may be
followed by permanent respiratory disabi!ity led to the evolution of a
standard byssinosis case definition. Schilling and colleagues (19551
developed specific questions concerning Monday chest tightness for
the British Medical Research Council's respiratory symptom survey
questionnaire (British Medical Journal 1960). A positive response to
the standardized questions regarding Monday chest tightness de-
fined the presence of byssinosis.

Molyneux and Tombleson (19701 conducted one of the first
prospective studies of byssinosis. 4t the initial examination, these
investigators interviewed 1.359 workers from 14 cotton spinning
miZc and 227 -xorkers from 2 manmade fiber spinning mills in
Lancashire. United Kingdom. Followup examinations were conduct-
ed at 6-month intervals over 3 J.ears, from 1963 to 1966. Byssinosis
and bronchitis prel-alence were :Ieterl..A
                  ~;ned by the use of the Jledical
Research Council's questionnaire on respiratory sy!:iptoms [British
.Medicai .Journal 196Oi, to which :t.e Roach and Schilling t1960)
questions on chest tightness wert- added. Bjs;inosis bvas graded as
follows (Molyneux and Tombleson 197Oj.'

Grade 0: No evidence of chest tightness or breathing diffi-
    culty on the first day of the workweek
Grade 1 `2: Occasional chest tightness on !`rlondays


Grade 1: Chest tightness or difficulty in breathing on
    Mondays only
Grade 2: Chest tightness or difficulty in breathing on
    Monday and other days

Age, length of exposure to cotton dust, and smoking habit were
determined by questionnaire. Individuals were considered smokers if
they regularly smoked one or more cigarettes per day. Hexlet and
total dust air samplers were used to measure the mass concentration
of the respirable, medium, and fly components of the total airborne
dust.

Byssinosis prevalence (adjusted for age, sex, and mill type) showed
a progressive increase with increasing duration of cotton dust
exposure (Table 2) (Molyneux and Tombleson 1970). A rearrange-
ment of the data from this Lancashire mill workers study and
calculation of the Mantel-Haenszel (weighted) odds ratios (Mantel
1963) shows an interesting relationship between smoking, byssinosis,
bronchitis, and sex. A similar relationship is demonstrated by data
from studies of American cotton mill workers (Merchant et al. 1972;
Imbus and Suh 1973). Cigarette smoking was associated with an
overall 2.21-fold excess risk of bronchitis in the Lancashire cotton
mill workers (Table 3). Cotton mill workers of both sexes who smoked
had a consistently greater prevalence of bronchitis than did non-
smokers. The magnitude of the smoking effect was similar for men
12.2%fold) and women (2.16-fold). The presence of bronchitis con-
ferred an approximately twofold excess risk of developing byssinosis
(Table 4). This risk was significant for men and for women, for
smokers as well as for nonsmokers. Once the presence of bronchitis
had been controlled for, however (Table 51, cigarette smoking did not
add significant additional risk for developing byssinosis.

One may interpret these observations to show that among cotton
mill workers both cotton dust exposure and cigarette smoking
produced the symptoms of bronchitis. Bronchitis, in turn, seemed to
confer additional risk for the development of acute chest tightness
(byssinosis). Cigarette smoking, therefore, seems to facilitate the
development of byssinosis in smokers exposed to cotton dust, perhaps
by the prior induction of bronchitis. Applying an additive logit model
(6 dust levels x 3 lengths of exposure x 4 combinations of sex and
smoking habit) to these data, Berry and colleagues (1974) found that
cigarette smokers had a modest (1.4-fold) increase in the adjusted
prevalence of byssinosis when compared with nonsmokers and ex-
smokers. Two years after the initial questionnaire survey, these
investigators were able to reinterview about half of the original
population (669 cotton workers and 127 manmade fiber workers).
Incidence and remission rates were tabulated for byssinosis and
bronchitis by length of exposure, sex, and smoking status. The
incidence of both bronchitis and byssinosis was greater among

410


TABLE 2.-Prevalence (percent) of byssinosis in nine
        exposure groups

Number
in group

Prevalence
adjusted for
age. mill type.
and sex

CL4        305            52             8.8            8.0
%9        155           23 3            20.5           19.2
l&14        168           28 0            22 3           21.0
15-19        187           35.8            29 5           27.5
20-24        117           36.8            30 9           31.1
2529        115           43.5            40 2           42 4
30-34        94           30.9            302           35 1
3639        99           35 4            36.5           414
140        119           33 6            37.7           418

SOURCE Malyneux and Tombleson (19701

TABLE 3.-Age-adjusted association of bronchitis and
      smoking, by byssinosis status and sex

Smoker

   Bronchitis             Bronchitis         Chi square and
  with byssinosis        without byssinosis        odds ratio for
                                    the association of
N   Present   Absent     N   Present   Absent    smoking/bronchitis'

Yes     127
No     33

557c
554

45%
45%

Men

301   46%     54%        X*=15.20
105   21%     79%         OR = 2.28
                 cp<o.ooo1i

Women

Yes
NO

125   48%
78   33%

52%
67%

322   31%     69%        x*=21.10
268   16%     84%         OR=2.16
                 ip<0cw11

Chi Square?
Odds Ratio'.

Chi !F+quare?
Odds Ratlo3:

X2=2.83
OR=1.49
(p=O.cE!

X2=36.8
OR~2.63
,pc O.ocGlI

X*=36.3
OR~2.21
`p' O.Klol,

' Weighted by Mantel-Haenszel technique for byssmosls frequency
`Weighted by Mantel-Haenszel technique for sex dlstributlon
`Weighted by Mantel.Haenszel technique for frequency of both byssmosls and sex
SOURCE: Molyneux and Tomhleson 119701

smokers than among nonsmokers or ex-smokers of both sexes;
however, these differences were not statistically significant (Berry et
al. 1974).

411


TABLE 4.-Age-adjusted association of bronchitis and
     byssinosis by smoking status and sex

Association of byssmosls and bronchicls

Odds ratio

p-Value

Men and women combined

Cigarette smoker

Sonsmoker

1.73         00002

3.13       <O.cxMl

Combmed smoking status

Men

Women

1.80         0.001

2.25        <O.oool

Combined overall                    2.02       < O.oool

SOURCE. Data from Molyneux and Tombieson (1970)

TABLE 5.-Age-adjusted association of byssinosis and
      smoking by bronchitis status and sex

   Association of byssmosis and smoking

   Men and women combined

    Bronchitis present

     Bronchitis absent

   Combined bronchitis status

     .Men

     Women

   Combined overall

SOURCE Data from Molyneux and Tombleson 11970).

Odds ratio     pValue

0.82         0.39

1.44         0.03

1.19         0.45

1.17         0.36

1.18         0.23

More than 10,000 Burlington Industries textile employees (95
percent of the workforce) from 19 plants participated in a 1970
survey conducted by Duke University with the cooperation of
Burlington Industries and the North Carolina State Board of Health
(Imbus and Suh 1973). Each participant received the modified
British Medical Research Council Respiratory Questionnaire for
determining the prevalence of byssinosis and bronchitis. Byssinosis
was graded according to the classification of Roach and Schilling
(1960). Chronic bronchitis was defined as grade 0, no evidence of
sputum production; grade 1, simple chronic bronchitis; and grade 2,
chronic bronchitis with an exacerbation (Imbus and Suh 1973).
Smokers were defined as those regularly smoking one or more
cigarettes per day (Molyneux and Tombleson 19701. Forced expira-
tion was measured in all participants before the beginning of the
work shift on the first day of the workweek. Approximately 80

412


FIGURE 2.-Byssinosis prevalence by grade, smoking
       status, and dust level among men working in
      synthetic/wool mills and cotton/blend mills,
       North Carolina, 1970-1971
SOURCE: Merchant. Lumsden. Kilburn. O'Fallon et al. (1973ai

percent underwent spirometry again 6 hours into the work shift
(Imbus and Suh 1973).

Like Molyneux and Tombleson (1970) in their study of the
Lancashire mill workers, the North Carolina investigators found
that smoking was responsible for a doubling of the bronchitis risk
and that the presence of bronchitis was strongly associated with
byssinosis. After controlling for the effect of bronchitis, there was no
additional significant smoking effect on the risk of chest tightness at
the observed dust levels. Cigarette smoking seemed to play a greater
role in byssinosis prevalence as cotton dust levels rose (smoking-
cotton dust interaction). Figure 2 shows no cigarette smoking effect
on byssinosis prevalence at low dust levels. However, at the highest
dust levels, cigarette smoking was found to interact with cotton dust
exposure to substantially increase the acute symptom prevalence
(Merchant et al. 1972; Merchant, Lumsden, Kilburn, O'Fallon et al.
1973a).

No "safe" level of cotton dust exposure has been identified for
cigarette smokers (Merchant, Lumsden, Kilburn, O'Fallon et al.
1973b). However, among nonsmokers, these investigators found no
case of byssinosis below a cotton dust level of 0.2 mg/m3. An

413


.l  2  3  4  .5           1            15           2

               Median dust level (mg/mJ)

FIGURE 3.-Byssinosis prevalence by median dust level
      among current smokers and those who never
      smoked, preparation and yarn area workers,
      linear regressions and fitted profit dose-
        response curves

NOTE. Group 1 ION. smokers. group 2 IM. nonsmokers
SOURCE Merchanr. Lumsden. Kllburn. O'Fallon et al t1973bl

examination of a large population found one case in a nonsmoker
below this level (Figure 3). Workers with byssinosis who stopped
smoking but did not change their work area lost their byssinosis
symptoms (Merchant et al. 1972). These observations suggest that
there may be a "safe" level of cotton dust in the absence of other
inhaled irritants. Cigarette smoking seems to lower this threshold of
susceptibility to chest tightness below the present limits of cotton
dust detection. At least in some individuals, this threshold may be
restored by smoking cessation.

The repeated demonstration of a linear dose-response relationship
of symptoms with cotton dust levels led to the development of cotton
dust exposure standards to protect the majority of the workforce
(Roach and &hilling 1960; McKerrow et al. 1962; Merchant et al.
1972; Merchant, Lumsden, Kilburn, O'Fallon et al. 1973b). The

414


American Congress of Government Industrial Hygienists' I ACGIH)
early cotton dust standard was based upon the work of Roach and
Schilling (19601, which concluded that 1 mg/m" gross (total) dust was
a safe level for occupational exposure. Further study, however, found
that the biologic activity of cotton dust resided primarily in the
respirable dust fraction McKerrow et al. 1962). The use of total dust
as the only measure of exposure has sometimes resulted in a
misleading lack of association between cotton dust level and
byssinosis symptoms (McKerrow et al. 1962; Molyneux and Tomble-
son 1970; Merchant et al. 1972).

High correlations between byssinosis symptoms and respirable
dust levels were observed, using the vertical elutriator to sample
dust of an aerodynamic diameter of 15 pm and less (Merchant,
Lumsden, Kilburn, O'Fallon et al. 1973131. In Figure 3, cigarette
smokers are shown to have a slightly higher prevalence of byssinosis
symptoms than nonsmokers at each measured dust level. A linear
dose-response model fits the data at low dust levels. At respirable
dust levels from 0.1 to 0.75 mg/m3, the byssinosis prevalence in
nonsmokers rose from 5 to 24 percent, and in smokers, from 8 to 53
percent. The tapering of the dose-response curve at higher dust
levels has been attributed to self-selection by less susceptible cotton
workers (Kilburn 1983).

To minimize the acute symptoms and to inhibit possible chronic
consequences, the Occupational Safety and Health Administration
(OSHA) (US DOL 1981) has modified the permissible exposure limits
to acknowledge the importance of the respirable fraction of cotton
dust (approximately 15 pm or less aerodynamic equivalent diame-
ter). The OSHA standard specifies that employees engaged in yarn
manufacturing may not be exposed to respirable cotton dust levels
greater than 0.200 mg/m3 over an g-hour average, and employees
assigned to the slashing/weaving processes can be exposed to no
more than an 8-hour average of 0.750 mg/m3 of cotton dust (US DOL
1981). No specific accommodation has been made to recognize the
increased byssinosis susceptibility of cigarette smokers.

Effects of Smoking and Cotton Dust Exposure on
Pulmonary Function Tests

In a cross-sectional study of 61 textile workers on carding
machines, Zuskin and colleagues (1975) found a rough correlation
between the grade of byssinosis and the l-second forced expiratory
volume (FEV,) before dust exposure. These observations confirm
those of Merchant, Halprin and colleagues (1974) (Figure 41. It is
suggested that those with byssinosis symptoms start the workweek
with a lower FEV, than those without symptoms (age, height, sex,
race unaccounted for), and at least for the individuals with byssinosis
grade l/2, that overnight exposure cessation is insufficient for

415


Uondav

Tuesday

Vvedwsday

\

    230 730     2.30
Thursday      Friday

Tme (davs)

FIGURE 4.-FEV, during &day exposure of 25 carders
SOI'RCE \lerchant Ha!pnn ct ~1 !`I:;

complete respiratory recovery and that a longer abstinence period (a
weekend. for example) is necessary to restore preexposure levels of
ventilatory function (Merchant, Halprin et al. 19741.

The baseline (initial) ventilatory function, measured as percent of
predicted FEV, and forced vital capacity (FVC), showed that among
nonsmokers (Table 61, a mild decrease was noted in those with
bronchitis alone (without byssinosisl and a more marked decrease
was observed in those with byssinosis alone (without bronchitis). In
men. the lowest value tr'as observed among bronchitics with byssino-
sis. Smoking further reduced the baseline ventilatory function in
every category (except nonbroncbitic, byssinotic women). (The au-
thors pointed out that the small sample size may have made the
slightly higher ventilatory function value among this group of
women somewhat uncertain.) There was also an interaction of the
effects of cigarette smoking with cotton dust exposure upon baseline
forced expiration, similar to that found for symptoms of chest
tightness (Merchant, Lumsden, Kilburn, O'Falion et al. 197313).

Studies of pulmonary function among 61 textile workers showed
that cotton dust exerts its acute effect primarily upon the conducting
airways rather than upon the gas-exchanging parenchyma (Zuskin
et al. 1975). Zuskin and colleagues observed a significant reduction


TABLE 6.-Average percentage of predicted FEV, in
       smokers and nonsmokers with and without
      byssinosis and bronchitis

Average percent of predicted FEV,
     (sample size!

Subjects

Male nonsmokers

Nonbyssinotic       Byssinotic

Nonbronchitlc
Bronchitic

Male smokers

89.4 (9931           84.5 1281
88.2 (591            80.1 (161

Nonbronchitic
Bronchitic

Female nonsmokers

85.9 13.1721          81.5 (1571
61.2 14341           73.7 11091

Nonbronchitic
Bronchitic

Female smokers

857 (1.7291          76.6 (471
82.9 (681            78.4 (11)

Nonbronchitic
Bronchitic

82.6 (1,213)          77.0 WI,
81.3 (93)            73.5 (151

SOURCE: lmbus and Suh (19731

across a workshift in FEV, and midexpiratory flow at 50 percent
(MEFsoQ) and a statistically significant increase in residual volume.
In contrast, plethysmographically determined total lung capacity (a
measure of alveolar volume) and the single-breath diffusing capacity
(a measure of gas diffusion) were unchanged.

In Figures 5 and 6 are shown the effects of byssinosis, bronchitis,
and smoking on FEV, measured before and after 6 hours' work,
adjusted to a base age of 40 years. People with bronchitis alone
(without byssinosis) and people with byssinosis alone (without
bronchitis) experience a decline in FEV, during the workday. People
with a combination of both conditions, however, show the greatest
decrement. Although forced expiration change across a work shift
also shows a strong association with dust levels (Merchant, Lumsden,
Kilburn, O'Fallon et al. 1973131, the relationship of cigarette smoking
to the cross-shift decline in function is less clear. Merchant,
Lumsden, Kilburn, O'Fallon, and colleagues (1973a) found no
smoking effect on acute ventilatory function change within any dust
level, over all dust levels, or as part of a dust times smoking
interaction (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973a).
Zuskin and colleagues (1969) and Jones and colleagues (1979)
reported similar observations. However, Haglind and Rylander

417


Men

NEY. NBR         NBY, BR        BY. NBA          BY, BR
            B

3.400

2.700

m Nonsmokers        wm~mma Smokers

FIGURE 5.-Byssinosis, bronchitis, and smoking effects on
      FEV, in men before and after 6 hours' work,
      adjusted to base age 40 years
NOTE B. before work. A. after 6 hours' work.
SOURCE. Imbus and Suh cl9731

(1984) found that cigarette smokers seemed to have a lower effect
threshold. Among cigarette smokers, the threshold for a 5 percent
decrease in FEV, was 0.58 mg dust/m3, compared with a threshold
in nonsmokers nearly threefold greater (1.63 mg/m3). These results
confirmed the findings of Merchant and colleagues (1975) among a
group of 12 cotton workers in an exposure chamber. In addition to
the lower threshold, Haglind and Rylander (1984) reported a larger
FEV, decrease among smokers than among nonsmokers at the same
exposure levels. These findings and the others previously mentioned
suggest that cigarette smoke may enhance the airways reaction to
cotton dust.

Cross-shift change in ventilatory function has been shown to
depend upon the type of cotton dust as well as the level (Table 7)

418


     Women
2.500 _

       NBY. NBR       NBY. BR         BY, NBR         BY. BR

      B
2.400 '

                   B

- Nonsmokers

FIGURE 6.-Byssinosis, bronchitis, and smoking effects on
       FEV, in women before and after 6 hours'
      work, adjusted to base age 40 years
NOTE. B. before work: A. after 6 hours' work
SOURCE. lmbus and Suh Cl9731

@chilling 1956; Roach and Schilling 1960; Merchant, Lumsden,
Kilburn, O'Fallon et al. 1973b; Merchant et al. 1975; Castellan et al.
1984). Under the conditions of an experimental card room (using
carding machines under typical commercial production conditions),
concentrations of gravimetric elutriated cotton dust and the corre-
sponding acute FEV, change were measured (Table 7). In Figure 7 is
shown the significant association of dust concentration and ventila-
tory response found by Castellan and colleagues (1984). Bacterial
endotoxin, a contaminate of cotton dust, was found in this study to
correlate even more closely with a decline in ventilatory function,
but Diem and colleagues (1984) found that the across-shift decline
was more closely correlated with the log dust level than with the
number of gram negative rods or log endotoxin level.

419


TABLE 7.-Slopes of dose-response regressions for
      individual cottons, using vertically elutriated
      gravimetric dust as an exposure index

Change Ipercentage per mg/m3 of dust!

Cotton type                         FVC        FE\`,       FEF-us

Cahfornia jtnct middling                 4.9 '         -0.4 i        14.0'
California strict low middling               -2.3 =         -3.4 3       -l&O3
Califorma strwt low middling spotted          -273         -3.1 3       -13.2*
Texas stnct low middling                 -2.33         -2.9 3       -18.45
Texas strict low middling spotted             -3.6 3         x2=       -27.33
Mississippi strict low middlmg              -3.1 3         -3.53       -20.1 3
Mkssippi strict low middling spotted         -15.93        -24.4 a       43.6 3

SOTE Regrewons based on spirom?tnc responses of 54 persons FVC=forced vital capacity, FEV, =forced
expnatory volume m 1 second; FEF-~7 = maximal flow at 75 percent of expired vital capaelty.
1 p=not s1gmflcant
*p'ooI
`p/OooOl.

SOURCE Ca~tellan et al. r19841

Chronic Clinical Effects of Cotton Dust Exposure

Nonreversible reduction in forced expiration is usually caused by
an increase in airways resistance (particularly in the small airways),
a reduction in elastic recoil (emphysema), or both (Bates et al. 1971).
Chronic cough and sputum production may be a nonspecific irritant
reaction to particle deposition in the conducting airways. Similar
reactions have been seen in cigarette smokers and workers exposed
in dusty trades including mining (coal and metal), manufacturing
(cement and plastics), and foundry work (Morgan and Seaton 1975;
Hank&on et al. 1977; Morgan 1978; Kilburn 1983).

Chronic airflow obstruction is associated with increased age-ad-
justed total mortality and respiratory disease mortality. However,
once adjustment has been made for airflow obstruction, cough and
chronic mucus hypersecretion (the symptoms of chronic bronchitis)
have little additional predictive value for chronic obstructive lung
disease (COLD) mortality (Peto et al. 1983). Since there are both
significant morbidity and mortality consequences associated with
the development of chronic obstruction but not with simple bronchi-
tis, it is important to determine whether the acute symptoms of
bronchitis and chest tightness associated with cotton dust exposure
are associated with chronic airflow obstruction to a greater extent
than could be explained by cigarette smoking alone.

The contribution of the acute byssinotic symptoms (grades l/2 and
1) to the subsequent development of airflow obstruction and the
chronic forms (grades 2 and 3) of byssinosis is not well documented
(Douglas et al. 1984). The term "byssinosis" is often applied to the
acute response to inhalation of cotton dust as well as to the

420


-12oL  1   '   -   .   .   1   .   ,   .   .   .
   0.00    0 10    0 20    0 30    0 40    0 50    060

A               Elutnatec oust bng/m')

00

-10 0

-12.0
    0    100   200   300    400    500   600    700

B              Elutnated endotox~n (ng/m3)

FIGURE `I.-Percentage of change in forced expiratory
       volume in 1 second (FEV,) (mean*SE) for
      each subgroup of people exposed for 6 hours
       to a clean room and to dust from various
      cottons (54 persons in two equal-sized
      subgroups; seven different cottons)
NOTE 4 Plot of change ,n FE\`, `percen?~ versus vertically elutnated al&me- grawnetr~ dust concentratmn
Imgtm3~. B Plot of change I" FE\`, qx?rcentl versus rertirall~ elurnated anborne endotoxln conwntratmn Ing m3r
SOCRCE Casrellan Ed al ~19R.t

421


permanent dyspnea with impaired function. Although a link of
pathogenesis between the two has been assumed, and is supported by
finding impairment in textile workers without other exposures, no
longitudinal study has been done that documents this transition
(Kilburn 1983).

Nevertheless, chronic airflow obstruction has been found more
frequently in cotton textile workers than in control populations
(Bouhuys et al. 1977; Wegman et al. 1983). Obstruction has been
found particularly among the older, cigarette-smoking cotton textile
workers (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973a; Beck,
Maunder, and Schachter 1984). Whether cotton textile workers are
compared with a control population of synthetic fiber and wool
workers (Merchant, Lumsden, Kilburn, O'Fallon et al. 1973a), with
farmers and workers from other industries (Bouhuys et al. 19691, or
with the population of a rural town (Beck, Schachter, and Maunder
1984), there is a cross-sectional correlation between occupational
exposure to cotton dust and impaired ventilatory function.

Followup studies that document a greater fall in ventilatory
function among those with byssinosis help to establish the transition
between acute and chronic effect (Bouhuys and Zuskin 1976). Beck,
Schachter, and Maunder (1984) have compared the frequency of
pulmonary function abnormality among South Carolina cotton
textile workers with the pulmonary function survey results among
residents of a Connecticut community. These researchers report that
both byssinosis and smoking were associated with subsequent
impairment of age- and height-adjusted respiratory function. They
found that even asymptomatic cotton textile workers had significant
lung function impairment compared with controls. In general, cotton
textile workers had lower lung function among smokers and
nonsmokers, for both men and women and among those with and
without symptoms, but these differences were only statistically
significant for the nonsmoking asymptomatic female subgroup (the
subgroup with the largest number of individuals). Smokers also had
lower FEV, than nonsmokers in each of the subgroups. However, in
the absence of cotton dust measurements, nonoccupational factors
related to control selection may be postulated to have contributed to
these findings (Tockman and Baser 1984).

Other followup studies of cotton textile workers provide inconsis-
tent support for the importance of byssinosis to subsequent ventilato-
ry impairment. Zuskin and Valic (1975) reported on a lo-year
followup of selected members of a worker cohort exposed to coarse
cotton dust. These investigators found both an increased prevalence
of byssinosis on followup examination and approximately twice the
rate of mean annual decline in FEV, among men who had byssinosis
initially, compared with those who later developed it or to those who
did not report this symptom. Smoking was not found to contribute

422


significantly to the development of byssinosis. Contrasting results
were reported by Berry and colleagues (19731, who examined cotton
textile workers at several plants and found that the cotton textile
workers had a 54 mL per year decline in FEV, compared with 32 mL
per year in workers in the synthetic textile mill; however, most of
this excess decline could be attributed to workers in only one mill.
FEV, declined 19 mL per year faster in smokers than in nonsmokers.
However, despite these differences between the cotton workers and
the control group, no difference in annual FEV, decline was found
between the subjects with and without byssinosis symptoms. Cotton
textile workers with acute (grades 0 or 11 byssinosis symptoms and
those with bronchitis following cotton dust exposure may be a subset
of the population at risk of further ventilatory deterioration. The
sensitivity and specificity of these symptoms for subsequent lung
injury is yet to be established by cohort studies.

Followup studies of cotton textile workers have been weakened by
several sources of bias. Self-selection of workers for continued
employment in dusty environments introduces bias into studies that
examine only the currently available workforce, who may be
healthier than workers who have left the industry. Berry and
colleagues (1973) reported that less than half of the subjects were
available sufficiently often to calculate an annual FEV decline.
Merchant, Lumsden, Kilburn, O'Fallon, and colleagues (197313)
reported substantial evidence of selection away from dust exposure
in the cotton textile industry, which results in the presence of
relatively resistant workers in dustier areas at the time of cross-
sectional surveys. As Beck, Schachter, and Maunder (1984) have
shown, it is feasible to survey the retired workforce in addition to
those currently active in order to account for workers who retire
prematurely because of poor respiratory health. To finally determine
the magnitude of the cotton dust effect on chronic lung function of
cotton textile workers, studies must carefully distinguish the sepa-
rate indices of cotton dust lung injury, and impairment rates must be
tabulated over the entire population at risk. However, documenta-
tion of the association between exposure and lung injury will become
increasingly difficult as industrial hygiene control reduces the levels
of occupational cotton dust exposure.

Mechanisms of Cotton Dust Lung Injury

Epidemiologic observations have suggested that cigarette smoking
and cotton dust have complementary effects on the airways. A
discussion of the mechanisms of cotton dust lung injury may
facilitate an understanding of this interaction.

42.1


Inflammation (Bronchitis)

Considerable effort has been devoted to the search for specific
agents responsible for the symptoms and changes in lung function
associated with cotton dust exposure. These investigations have
focused upon water-soluble extracts found in the cotton bract. An
animal model has been developed that partly reflects the sequence of
clinical findings seen in cotton textile workers. Hamster inhalation
of condensed vegetable tannins from card room floor sweepings
stimulated the recruitment of leukocytes to the trachea, bronchi,
and small bronchioles, with a time course similar to that of
byssinosis symptoms in humans (Kilburn, Lynn et al. 1973). Tannins
isolated from cotton bract have been shown to cause pneumocyte
lysis (Ayars et al. 1984). Other agents in cotton dust have also been
found to have pharmacologic activity (Hitchcock 1974; Ainsworth et
al. 1979). Compounds that have been identified in cotton bract
extract in significant concentrations include tannin, 5-hydroxytryp-
tamine, endotoxin, and histamine (Rylander 1981; Bouhuys and
Lindell 1961; Rohrbach et al. 1984; Russell et al. 1982).

Pharmacologic activity has also been isolated from the compo-
nents of bacteria and fungi found in cotton bract. Studies by Cinkotai
and colleagues (1977) have demonstrated a close relationship be-
tween the prevalence of byssinotic symptoms and the airborne
concentration of gram-negative (endoagar) bacteria. In Figure 8 are
shown a close correlation between byssinotic symptoms and levels of
gram-negative bacteria, a more variable relationship with gram-
positive (nutrient agar) bacteria, and no relationship with fungi or
with airborne dust. Human exposure to airborne gram-negative
bacteria may result in symptoms related to the presence of endotox-
in lipopolysaccharide within the bacterial cell walls (Rylander 1982).
This material could activate complement (Wilson et al. 1980) with
subsequent generation of anaphylatoxins, release of histamine and
leukotactic substances, and induction of an inflammatory response.

Cotton bales from different geographic areas may be contaminated
with different levels of gram-negative bacteria. Cottons grown in dry
areas with irrigation were found to have smaller amounts of gram-
negative bacteria (Rylander et al. 1985). The culturing of viable
organisms was found to be a misleading index of byssinosis potency,
however, because endotoxin activity persists after bacterial death
(Rylander et al. 1985). Airborne endotoxin levels correlated with
byssinosis symptoms, blood neutrophil levels, and airways response
(Rylander et al. 1985). Castellan and colleagues (1984) have reported
a high correlation between endotoxin exposure and ventilatory fall
in experimental exposures (part B of Figure 7). Their data show no
evidence for an endotoxin exposure t,hreshold, but this conclusion
depends on the validity of the four outlying observations presented
in the figure. In an experimental card room, Haglind and Rylander

424


B
tt
h 40
F
a,
a

  30

  20

  IO

10    2.0    30 40   150
Awborne dust less "fly" (mglm~)

1oKl 2ooo   3coo   4cm

     Endoagar bacterra (n/ma)
c cotton malls       * Wwlm~ll
C cotton waste mills    A Tea packtng plant
o Willowing mill      A Pipe tobacco factory

        0
C
     0
0

        0
         0
I+
  Q 0
  @

loo00     2oooo     75mo
Numenl agar bacrerla (n/m')

O D

    0
0

0
     0
QO
       0        o
?
                      25ocm

          Fungi (n/ml)

FIGURE &-Concentration of endotoxins in airborne dust
      correlated with the prevalence of byssinotic
       symptoms
SOURCE Clnkotai et al f19771

(1984) found a dose-response relationship between the average FEV,
decrement across a work shift and the amount of airborne dust or
endotoxin. These data have been used to suggest that endotoxin
contamination of cotton, rather than the plant dust itself, is
responsible for the byssinosis syndrome. However, Buck and col-
leagues (1984) have reported that cotton bract extract contains a
bronchoconstricting agent or agents distinct from endotoxin and
have suggested that an interaction may exist between the effects of
endotoxin and these other agenb; Diem and colleagues (1984) have

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