Document VJ45vX7EmvY4daJ4DBeL0nz1N
exhibit DUP-1722
Original Contributions
The Journal of the American Medical Association
Fb 5. 18*2
Voi 247. No. S
Prevalence and Incidence of Benign Asbestos Pleural Effusion in a Working Population
Gary R. Epler, MD, MPH; Theresa C. McLoud, MO; Edward A. Gaenalar, MO
Benign asbestos effusion was defined by (1) exposure to asbestos, (2) confirmation by roentgenograms or thoracenteses, (3) no other disease
3. Fireproofing product manufacturing:. 144 employees,-spase heavily exposed since
related to pleural effualon, and (4) no malignant tumor within three years. There were 34 benign effusions among 1,135 exposed workers compared with no otherwise unexplained effusions among 717 control subjects. Prevalence was dose related with 7.0%, 3.7%, and 0.2% effusions with severe (ill), indirect (II), and peripheral (I) exposure, respectively. The latency period was shorter than for other asbestos-related disorders. Benign affusion was the moat common asbestos-related abnormality during the first 20 years after exposure. Incidence studies showed 9.2 effusions per 1,000 person-years for level III exposure, 3.9 for level II, and 0.7 for level I. Most
the early 193G*,e**n annually for the laat tan year*. >u.
4. Mill A (ypenalty paper): 90 employees heavily expoeed to crocidolite in the manu facture of filter paper during a special', project between 1952 and 1956 and 126 . employees with slight exposure, teen since 1971.
5. Mill B (specialty paper): 211 employ ees manufacturing filter paper and gas
effusions were small; 28.6% recurred, and 66% were asymptomatic. There was one mesothelioma six years after effusion. Asbestos exposure should be carefully searched for In patients with ,ildlopathic,, pleural effusion.
{JAMA 1982;247:617-622)
kets, who had alight but strictly monitored exposure since 1963, seen annually for the past six years.
6. Mill C (specialty paper): 80 employee* exposed to "bonded asbestos" used for
electrical insulation since 1930, seen for
AMONG the several asbestos-related pleural manifestations, benign effu sion is the most recent to come to our
MATERIALS AND METHODS Definition
Benign asbestos effusion was defined by
the laat three years. The control group consisted of faculty
and employees of a large university. Serial films, some dating back to 1940, were
attention.1 Though still considered a four criteria, as follows: (1) direct or available because of a law requiring roent
rare complication of asbestos expo- indirect exposure to asbestos, (2) an effu genograms of school employees before:',
^ sure, the clinical and histological fea- ' sion confirmed by a transient pleural employment and every three years there- ,
tures of such effusions are now well change in serial chest films or by thora after. We located an active "three-year v
described.1'" However, these case re
ports do not permit conclusions con cerning frequency in ssbestoe-ex. posed populations. We studied serial in roentgenograms and medical records f of 1,135 employees In the asbestos
. ^ Industry and compared these with the ^records of '717 control subjects to
centesis, (3) lack of evidence for any other disease related to pleural effusion, and (4) no malignant tumor detected within three years after the effusion.
Study Populations
Two groups were selected: a "survey group" of working exposed persons seen by us- at yearly intervals at industrial sitaa
recall list," which excluded persons who L -
had been exposed to beryllium or asbestos \
at the university. We coded all filnva of the;-:,1
717 male employees oh this list seeordlag" '
to methods used during our. industrial
.surveys.
,
For comparison of clinical featursa and `
follow-up data, w* referred to a group" of,
178 asbestos exposed clinical patients'(Tfe>^; '
determine (1) the prevalence and inci and a "control group" of male employees Me 1). These included 26 with benlfa'i?,.
dence of asbestos effusions, (2) the from a large university.
pleural effusion, 12 of whom hsv^bscnfi,:?'
. duration and amount of exposure
The survey group consisted of 1,135 : described in detaiL1
. ./
,V,` associated with effusion, (3) the rela employees, including 45 women, from six
Methods of lnv#etigetlon';l^?;l'"''
4 rrr `
tionship between effusion and diffuse ^plants:
pleural thickening, and (4) the fre
X. Shipyard A (new-ship construction):
quency of subsequent mesothelioma. "93-directly exposed pipecoverers and 74
indirectly exposed shipfitters first seen in
The survey group answered a respireto^^v ' ,ry questionnaire, had a physical x*mla*-fe/'
tion, screening pulmonary function stadia*.?
1965. Asbestos1 had been used..regularly consisting of force vital c*pedty;(f5WS^0",
From tit* Ivan* Memorial Depenment of CtWS*
cal Aeeeareii, Department of Medicine (Or Epler), and in* Thoracic Sarvfcaa, Department e* Surgery
since 1980..
: and Its time derivatives, including a fowifwt-?'
2. Shipyard B (submarine new construc expired volume la 1 s, and also a slagle-W-:,
tion and refitting): 317 employees, inefud- breath diffusing capacity (Db)," Ooaupa^*^1'
(Dr Oeeneler), Boston University Medical Canter, ing diractly exposed pipecoverers and tional histories, obtained hy.-spe^uji^f'i
and the Department of Radiotoay, Massachusetts. . sweepers and indirectly exposed welders, trained physicians, included a liating'of
Oenerpl Hoapttsl and McLoud), Boaton.
Harvard
Medical
School
(Or..
i.
lead bonders, and other* seen annually `
.past
jobs
and
exposures,
present' jolt';
Reprint requests to 80 E Concord SI, Seaton, since 1976. Asbestos had been used from . description,-year first exposed, and 'totids
'
MA 021 IB (Dr Oeenelet).
1952 to 1975.
'. years exposed. Dust exposure hadbseha
JAMA, Feb 6, 1982--Voi 247, No. 6
A Benign Aebeeto* Effusion--Epler et *| air
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related to obvious disorders, 18 of which were pleural or pulmonary malignancy (Table 1).
Pravaiance of Banign Asbastos Effusion
The overall occurrence of one or more asbestos effusions in the survey group was 3.1% (Fig 1 and 2), while there were no otherwise unexplained effusions in the control group (Table 1).
Dose Response
In the first four plants listed in Table 2, where there were many employees at each exposure level, there was an obvious relationship between exposure and prevalence of asbestos effusions. These prevalences ranged from 7.2% to 143% at level III and ranged from 0% to 43% at level I. In the fifth plant, mill B, where exposure had .been recent, slight, and carefully controlled, there were no documented effusions. In mill C, there were few level III exposed employees left at the time of our first survey. For the entire survey group, the prevalences of asbestos effusion were 7.0%, 3.7%, and 0.2% at expo* sure levels III, II, and I, respectively.
There was also a relationship to occupation (Table 3). Asbestos effu sions were most common among asbestos pipecoverers (7.3%) (Fig 1 and 2), less common in asbestos prod uct'- and paper machine operators (5.3%), and least common among shipfittera, maintenance personnel, and welders. The fact that effusions were seen in level II exposures and in an office executive (Table 8), and have been seen in the wife of an employee," ' suggests that the requisite exposure threshold may be low.
Latency
The latent period, that is, the inter val between first exposure and clini cal evidence of disease, is shown for several asbestos-related disorders in Fig 3. Only persons exposed at level II or III were included, because only for these was onset of exposure precisely known. There were so eases of asbestosis, pleural plaques, or calcific*-' tions during the first ten years after initial exposure. These three manifes tations increased steadily over subse quent years. The latent period for benign asbestos effusion was shorter.
FH> 2.--Chest roentgenograms ot 51-year-old shipyard pipecoverer had been normal for 18 yaars (left). Three months later, pleuritic chest pain developed on right side, as well as pleural-based density (right). Exploratory thoracotomy for "mesothelioma" showed encapsulated bloody eSusion. Patient has remained well for three years.
Table 2.--Prevalence and Incidence of Asbestos Effusion
Industry and Exposura Uevsl
Shipyard A
Shipyard B a.
.8
i
Asbsstos products a
> 1 '-
Pspsr mlN A a
7
9. 1
Pspsr milt B a
it
7
i ...
Pspsr mill C .a .
-,r
BurvsyOroup a
E.
Total Total Control Subjects
No. of Employees
S3 74
128 78 112
27 71 48
70 80 128
8 18 187
4 36 .40
338 388 61V 1,135 717
Asbestos Effusion, No. (%)
8(8.2)
1(1.4)
8(7.1) 3(3.8) 0(0.0)
1353 887'
408
.... 7.3.
,13 .
4(14.8) 6(16) : I <**>'
4(6.7) 0(10) . 0(00) V,.;,
350 1010 v 330
14.8 "5.8 " 4*4'i.r4.3 ..
338 - 13.4 79 . ...-;288_u-.'.
-
0(0.0) o<oh) 0(0X1.- . . ;
80 . . ae-'-'
241-.'.=:;.
. .
0(0.0) . ! K3.6) '
own) ;
23(7.0) : 11(17} 1(0.8),. 35(11)' 0(0.0)
: *3. - , -7330
/-I8
3.600 ; : 3.798
8,718 8,833
.',i 0.0 -**>
' ii'fe'B.B' f 8.3
0.0
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JAMA, Feb 5, 1982--Vo) 247, No. 6
Benign Asbestos Effusion--Epler of al
JExpoaura
Laval 111
It
1
Table 3.--Job Descriptions ot Employees*
Job Title Pipacovarara, aabaatoa Atbastot mixar Aabaatoa iwHpfifi Machine operators
Sltlpfttara Maintananca Othera Machina oparatorat Pipacovarara, ibarglaaa Offca Othars
NO. Of Employaaa
191 no se 114 41
31 109 206
71 59 175
N-1.I35. tOne each: welder, lead bonder, aebeatoe aupply room worker.
(Did not work with aebeatoe.
60 -
50 -
>>
a. 40
uEi
Aebestos Ellusion Pulmonary Fibrosia Pleural Plaquea Pleural Calcification
112
Effuaion, No. (%) 14(7.3)
7 (6.4) 2(7.1) 6(5.3) 1(2.4) 1 (3.2) 3t (2 8) 0(0,0) 0(0.0) 1(1.7) 0(0.0)
19
tery disease in three, and diabetea in one. in none was there any evidence of tuberculosis at the time or subse quently. Two thirds reported no symptoms during their effusion, even when told of their condition (Fig 1) (Table 4). In contrast, more than one half (53.8%) of the 26 clinic patients with asbestos effusions had pleuritic pain.
Roentgenographic Features
Most asbestos effusions were small (Fig 1), and a few presented bilateral ly (Table 4). Plaques were seen in one fifth, calcifications in only one, and moderate to severe asbestosis in less than 10%. AH of these three manifes tations wen uncommon because they are usually late complications, while asbestos effusion often occurs rela tively early (Fig 3). Follow-up films showed blunted costophrenic angles in virtually all cases, and residual diffuse pleural thickening was seen in one half (Table 4).
30
c 20
.10
40-49
Fig 3.--Aebeatoe-related manifeatatlona among employaaa expoaad to aabeatoa at level II
or 111. Grouping la acoording to yeara alnce firat expoaura. Number of employeea in each group Indicated above cotumna. Benign.aabeatoa eftuaiog waa obaerved earlier than other manifeatatione: It waa the only aabeatoa-related diabnler obaerved during firat ten yeara after expoaure and waa moat common during firat 20 yeara.
It wu th* only manifestation seen within tan years, and it waa the most common abnormality during the first * 20 years (Pig 8). The possibility that latency is dose related could not be proved by these data. Although the latent period was shorter (188 years) for the 23 workers exposed at level III than for the 11 employees exposed at level II (15.2 years), this difference was not statistically significant.
Incidence
Serial chest roentgenograms were : available for up to 45 years. There
fore, the number of new asbestos ! effusions u per 1,000 person-years of
observation could be calculated (Ta ble 2). This analysis indicated an annual occurrence of nine asbestos effusions per 1,000 employees exposed at level III, four for those at level II, and fewer than one per 1,000 for those at level I.
Clinical Findings
The mean age at the time of the first benign asbestos effusion was 46.1 years, and two workers were only 28 years old. Eight also had chronic bronchitis, one had asthma, and four had had childhood pneumonia. Con current medical problems included hypertension in three, coronary ar-
Follow-up and Prognoais
The mean follow-up after initial asbestos effusion was 9.7 years, with
a range of three to 27 years. Recur rent benign effusions developed in ten
persons (28.6%), sometimes on the same side, more often on the opposite side (Fig 1). Physical findings con sisted of bilateral crackles in one third, and there were pleural friction ' rubs in two. The FVC was reduced.in one half, and Dsb was reduced in two
thirds. Few had evidence of Airflow obstruction (Table 5). .
In* the survey"jroup three persona have died, two from asbeatosi*,snd
one from a mesothelioma that devsl-
oped six years after the first offgsipn. ; Mortality wu greater amongotjf:$6.
clinic patients with asbestos effusion^
Five have died: two from Infections,.',
one from metastatic hypsrnsphrojrna,
and two from mesothelioma niais and
16 years after the first effuaira^^.;
COMMENT "
Asbestos and other fibrouxiaijieates >
are virtually unique among.
mental hazards as a cause ofpltUFtl
manifestation!. Hyaline plaqui$Mp'
readily associated with asbeatig*,isUni-
cally, because of the almost inVAtishle
history of exposure, howevsr^jcl^U&t .
or brief, and epidemiologiqi^ly^'bsT
cause of their exi
SSAs"
620 JAMA, Feb 5, 1982--Vol 247, No. 5
Benign Asbestos Effusion' , ...... f *1 -o ''&&&& o
DU 009456
nized that the International Clnasifi- disorders occurred in the same pa
catioh for -the Pneumoconioses al tient in nonrelated fashion. It is also
lowed for a distinction from possible that the pleural drift of
plaquea.'u> Our longitudinal observa asbestos fibers caused mechanical
tions suggest that the sudden appear irritation resulting first in effusion
ance of diffuse thickening frequently and eventually in mesothelioma. Fi
was caused by an effusion. Among our nally, it is possible that the earlier
35 workers with asbestos effusion, effusion was the first manifestation
54% had residua in the form of of the tumor. Mesothelioma grows
diffuse thickening (Pig 1). Further along interstitial planes and is de
more, among the 1,135 employees, tected roentgenographically only late,
there were 44 with diffuse pleural and, therefore, its "doubling time"
thickening greater than 5 mm, and of cannot be determined. It well may be
these, almost one half had had a that in some patients this lesion
previous asbestos effusion, By con initially grows rather slowly. The
trast, there were 127 with typical spontaneous cessation of pleural exu
plaques, but the development of the dation, the disappearance of most
plaques never seemed to be related roentgenographic residua, and the
temporally to the effusion.
usually long-term stable course there
Mesothelioma,' the other well-rec after suggest that most of our "be
ognized asbestos-related pleural com nign asbestos effusions" were indeed
plication, generally is thought of as a benign. However, our follow-up was
rapidly growing and quickly fatal not long enough to determine the
tumor. Therefore, we excluded from incidence of mesothelioma after as
our count of benign asbestos effusions bestos effusion.
all persons who had a follow-up of
Historically, idiopathic pleural ef
less than three years. However, there fusion was generally attributed to
has been a report of malignant meso tuberculosis, and, among younger
thelioma of 17 years' duration," and persons, two thirds eventually showed
others have indicated that effusions development of active disease." Even
sometimes occurred several years be now some textbooks and reviews on
fore the histological confirmation of a pulmonary disease deal at length
mesothelioma.*-" In our "survey with the concept of idiopathic effu
group," one person was recognized to sion presumably due to tuberculosis
have a mesothelioma six years after and make no mention of benign
his initial "benign" effusion, and in asbestos effusion. Our study suggests
* our clinic group, two had such a that in the general population, effu tumor nine and 16 years after initial sions without immediately apparent
effusion. There are several possible cause have become extremely rare,
- explanations: inasmuch as both a while in the asbestos exposed, they
benign effusion and mesothelioma are are relatively frequent (Table 1). In relatively common in the- asbestos our ambulatory consultation practice,
exposed, it may be that the two asbestos exposure has become the
most common cause of pleural effu sion.' Mesothelioma presents the principal differential diagnostic prob lem to benign asbestos effusion. Our experiences and those of others sug gest that benign effusion often occurs relatively soon after initial exposure, sometimes within ten years (Fig l) and in two thirds within 20 years1'*'1
(Fig 2 and 3), while mesothelioma usually is seen more than 20 and often 30 to 40 years later. Pleuritic pain is the most frequent symptom in both conditions though benign effu sion goes entirely unnoticed by more than one half of patients (Table 4), Roentgenogrifttfc signs of other asbestos-relaMdjiliaase such as plaques or pulmooarif =Jbroais (asbestosis)
may be aberat both in benign asbes tos effusion and mesothelioma, and the presence of plaques or asbestosis is not helpful in differentiating between the two.
It has been estimated that there are somewhere between 2 million and 6 million persons with significant asbestos exposure in the United States.** A prevalence of 3.1% benign effusions in the asbestos exposed should alert physicians to the impor
tance of this disorder in the different tial diagnosis of "idiopathic" effu sion.
This study was supported in part by program project grant HL 19717 and career award HL 1173 from tha Nation*! Heart, Lung, and Institute, National Institutes of Hsalth, Public Health Service.
Ths authors wish to thank Kelvin H, HD, for permlealon to inspect strisl roentgeno grams of employ*** of Massachusetts Institute of Technology, Boston. The Warren E. Collins Co of Braintree, Uaae, donated equipment for survey studio*.
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422 UAUA,-F*b 4. 1982--Voi 247, No. 5
*BqalQq Mbwato* HfiitJ'm--
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n
