Document V3Q3YVny2bDbmjVNJQb0Lz0Mp

7(Lr W -7^ ^ T#4 /3 - 20 - 7/ The New England Journal of Medicine KWN---------gf MAY--------- :SC T4S---------- W0V`~------- ^ Copyrighl, 1971. by the Massachusetts Medical Society Volume 285DECEMBER 2, 1971_________________________________ . Number 23 JEFFECTS OF LOW CONCENTRATIONS/6f ASBESTOS Clinical, Environmental, Radiologic and Epidemiologic Observatjorfs in Shipyard Pipe Coverers and Controls ~----- Raymond L. H. Murphy, Jr., M.D., M.P.H., Sc.D., Benjamin G. Ferris, Jr., M.D., William A. Burgess, M.S., Jane Worcester, Dr. P.H., and Edward A. Gaensler, M.D. Abstract Low-level asbestos exposure, as occurs in pipe coverers in new ship construction, has not been considered dangerous. We surveyed 101 such workers and 94 controls matched for age. duration of employment and smoking habits in a New Eng land yard. Dust exposure, under surveillance for 20 years, had been near the then recommended threshold limit value of 5 million particles per cubic foot (mppcf). "Asbestosis" was defined by presence of three or more of five standardized clinical abnor- malities including dyspnea, rales, finger clubbing, reduced vital capacity and x-ray shadows. The lat ter were judged by three observers unaware of the exposure history. "Asbestosis" was 11 times more common among pipe coverers than among controls: it was found first after 13 years of exposure or 60 mppefyears. and the prevalence was 38 per cent after 20 years. This study emphasizes that low concentrations of asbestos can lead to pulmonary fibrosis and sup ports the need for lower threshold limit values. NEW uses For asbestos are found constantly, and the number of fresh cases of asbestosis reported each year is increasing. It has been known four decades that high concentrations of dust can cause interstitial fibrosis. The biologic effects of low concentrations are still poorly defined, and informa tion useful for setting threshold limit values has been difficult to obtain. This is, no doubt, because of the many factors that must be considered to eval uate the effects of inspired dust. These include the degree of environmental contamination over a pro longed period, availability of the entire exposed population, a control group comparable in all re spects except for dust exposure and standardization of diagnostic criteria. We were able to take these aspects into account during a study of a group of shipyard pipe coverers. The concentrations of as bestos to which such workers are exposed are low1-2 except during refitting and repair work.-1-4 Our workers had been engaged solely in new ship construction'. From the departments of Physiology. Industrial Hygiene and Biosta tistics. Harvard School of Public Health, and the departments of Med icine and Surgery. Thoracic Services. Boston University School of Medicine (address reprint requests to Dr. Murphy at the Department of Physiology. Harvard School of Public Health. 665 Huntington Ave., Boston, Mass. 02115). Supported in part by a training grant (S 00044). a research grant (EC 00205). a program project grant (S 00002) and a research career award (HE-1173) from the National Institutes of Health. U.S. Public Health Service. The data contained ih this study are from a thesis submitted by Dr. Murphy to the Faculty of the Harvard School of Public Health in par tial fulfillment of the requirements for the degree of Doctor of Science In the field of Environmental Health. _ _______ We wished to determine the effect of this lowlevel exposure to ascertain whether the thresh foor ld limit value had been a reasonable guideline. In addition, we were interested in evaluating methods to detect the disease at the earliest possible stage to prevent further exposure. Environmental, clinical and epidemiologic aspects of this survey will be presented here, and studies of respiratory gas ex change will be reported subsequently. Environmental Survey The pipe coverers were employed in a private New England shipyard that had been engaged in construction of naval and commercial vessels since 1920. During World War II, it became principally a Abbreviations Used D,.: FEV,: FVC: mppcf: PF: diffusing capacity volume expired in first second forced vital capacity million particles per cubic foot peak flow destroyer-building facility. Repair and refitting work was never done. The yard was one of five investi gated by Fleischer et al.* in 1945. The pipe cover ers prepared and applied insulating materials to machinery and pipes. The materials used and the procedures employed did not vary appreciably over the 20-year period.1 Approximately 90 per cent uf the work was done aboard ship and the remainder in a shop. PLAINTIFF'S EXHIBIT ASA-765 ASARCO ELP 0003595 1272 THE NEW ENGLAND JOURNAL OF MEDICINE Dec. 2, 1971 Figure 1. Hand-Sawing of Prefabricated Asbestos Block Aboard Ship. Aboard ship the most common procedure was wiring contoured asbestos block to pipes. Prefabri cated sections were tailored to fit bends by handsaw and knife (Fig. 1). The blocks were smoothed with cement containing 15 per cent asbestos and 85 per cent magnesia, and covered with asbestos cloth. Asbestos in fibrous form was stuffed into jackets and sewn around small pipes. Ventilation was provided by portable blowers on deck, but they were not always used. Shop work included layout, cutting, sewing, as bestos cement mixing and fabrication of pads. In 1963, a ventilation exhaust trunk was installed over the four benches. Band-saw cutting, cement mixing and pattern cutting were dustier procedures but required less than 5 per cent of man-hours, and involved intermittent work by only a few men. Pat tern cutting was done in a separate room by one man who wore a respirator. The insulating materials were largely determined by United States Navy specifications. Amosite was called for most frequently because of ite low ther mal conductivity, light weight and strength. Chrvsotile was used to a lesser extent, and croeidolite was never used. Fiberglass, cotton, calcium silicate, magnesia, hair felt and other materials were also employed, either alone or mixed with asbestos. Aerometric Analysis Dust concentrations were determined in 1945* and again in 1965 and 1966, to coincide with these studies. The same konimeter was used according to the method of Kotze.5 All dust particles in a highpower field were counted for the total dust count. Particles with a length-to-diameter ratio greater than 3 were called fibers. Both dust and fiber concentra tions were expressed in millions of particles per cubic foot of air (mppcf). Simultaneous total dust counts were made with a midget impinger in 1965 according to the Public Health Service method.6 All counts were made at the worker's breathing level at all the usual sites during usual operating conditions. A time-weighted average dust exposure was calculated by multiplying the mean* dust con centration a't various sites by the average percentage of time spent by the workers at these sites. This was expressed in mppef-years. Results of dust counts with the midget impinger -- the instrument used in setting the threshold limit value of 5 mppcf -- averaged 5.2 mppcf (Table 1). Konimeter counts, as always, were higher: in areas where over 98 per cent of the man-hours were spent the overall range was from 8.2 to 61.7 mppcf (Table 1). A weighted average, which considered the amount of time spent in these locations, as well as the number of samples taken during the three periods in 1945, 1965 and 1966, was 32.7 mppcf. Population Studies There were 101 pipe coverers employed at the Table 1. Dust Concentrations in Million Particles per Cubic Foot. A. Midget Impinger (1963)*: LOCATION Cutting room Sewing Sc fabrication bench Band-saw cutting Mixing mud Aboard ship (various) Weighted average Konimeter location YR Sewing Sl fabrication Aboard ship . 1945 1965 1966 1945 1965 1966 "Instrument used in setting threshold limit value of 5 mppcf. AVERAGE CONCENTRATION (MPPCF) 5.7 3.0 10.0 0.8 7.2 5.2t NO. OF SAMPLES 2 12 10 15 12 to CONCENTRATIONS (MPPCF) rangem average 10.6-12.3 14.2-30.2 12.9-32.8 25.3-89.0 8.2-61.7 18.3-35.7 11.4 23.4 23.1 49.2 21.4 25.9 % FIBER 0.5-0.8 0.1*2.7 0.1-3.8 0.2-2.4 0.1-0.7 0.1-0.7 tSimultaneous counts with Konimeter equaled 24.4 mppcf. ASARCO ELP 0003596 Vol. U85 No. '23 LOW CONCENTRATIONS OF ASBESTOS-MURPHY ET AL. IU73 Yard in November, ISJfiS. One hundred and one controls were selected from the 486 shipfitters and pipefitters employed at the time of the survey. To match them for age and duration of employment, cards with this information only were inspected in sequence, and the first worker whose age was with in one year of a pipe eoverer was selected provided he had spent approximately the same time at the Yard. All pipe covercrs participated, but seven of the selected controls refused, leaving 94 individ uals. Methods Questionnaire A questionnaire on respiratory symptoms7 was administered by one observer. It was adapted from that previously given extensive trials by Fletcher and others.8'10 Past History The company medical records of all workers were examined for symptoms, signs and diagnostic im pressions presumably related to cardiorespiratory disease. Physical Examination Physical examination was made by one physician with particular attention to breath sounds in each of eight locations. In 1966, tape recordings were made. Adventitious sounds were defined according to the nomenclature of Chamberlain." To evaluate club bing, a tracing of all fingers was made in the frontal and lateral projection. The hyponychial angle of the right index finger was measured according to Regan et al.,13 and an angle of 198 or greater was consid ered indicative of clubbing. Spirometry Maximal forced expirations were recorded with a Stead-Wells spirometer, and peak flow with a Wright Peak Flow Meter. The order of tests was randomized. Five recordings were made, and the average of the last three was used to calculate the forced vital capacity (FVC), the volume expired in the first second (FEVj) and the peak flow (PF). Methods of calibration and analysis were previously described13; normal predicted values derived from a population study of a New England town were used.14 Roentgenologic Examination Posteroanterior and lateral views were exam ined independently by three radiologists after identification had been masked and the films had been randomly interspersed. Results were coded as follows: 1, no abnormality; 2, abnormality not con sistent with asbestosis; 3, questionably consistent with asbestosis; 4, consistent with slight asbestosis; 5, consistent with moderately advanced asbestosis; and 6, consistent with advanced asbestosis.* The reported results represent the combined readings of the three observers. Prevalence o( Other Disease The prevalence of tuberculosis was assessed from the roentgenograms, skin testing and sputum cul ture. The criteria of Fletcher and Tinker'* were used to calculate the prevalence of nonspecific chronic obstructive lung disease. Simple and com plex bronchitis was defined according to Reid et al.,r Results Description of the Populations The control group, matched for age and duration of employment, was similar to the exposed group in color, height, weight, marital status and location of residence (Table 2). The majority of both groups had spent their lives in the general vicinity of the shipyard town. All were blue-collar workers who received hourly wages. The pipe coverers had been employed at the Yard for an average of 17.4 years, and the controls for 17.1 years. With shipbuilding for defense, the work force var ies with national crises. When not working at the Yard, members of both groups most commonly en gaged in fishing, lumbering and general outdoor construction work. Cumulative years in dusty occu pations other than pipe covering did not differ in the two groups. One pipe eoverer had been a" sandhog for five years, and one control had spent five years shoveling gravel. There were no exposures to material likely to cause pneumoconiosis in less than five years of exposure. Respiratory Questionnaire The significant differences in positive responses appear in Table 2. Smoking habits were similar: according to our classification,18 two thirds of both groups were "present smokers" (Table 2). Physical Examination Dry, crackling rales with a. "close-to-the-ear" sound (cellophane rales) were a most striking finding in some pipe coverers. They could be dear ly identified over background noise in the tape re cordings, whereas occasional fine rales could not be distinguished. Such rales not only were significantly more common in the pipe coverers (Table 2) but also were heard more often in multiple sites. For example, they occurred in three or more sites in seven pipe coverers but never in the controls. 'Four years after these interpretations were made, a modification of the international Scheme for Classification 'of the Radiopmphic Ap pearance of Pneumoconioses was proposed that was believed to he suitable for interpretation of asbestosis.*1 Our classification corre* spends approximately as follows: "I". 0/0: ''3". 0/1: "4''. I/O. 1/1 md 1/2: "5". 2/1. 2/2 and 2/3; and "6". 3/2. 3/3 and 3/4. ASARCO ELP 0003597 1274 THE NEW ENGLAND JOURNAL OF MEDICINE Dec. a. I!)7I Table 2. Summary of Selected Results. Finding Age(yr) Height (in) Weight (lb) RESPIRATORY SYMPTOMS Cough - day - winter Cough -- day -- summer Cough 3 yr Phlegm - day - winter Phlegm - day - summer Wheezing apart from colds Breathlessness (Fletcher 1U or more) Shortness of breath. ( flight MHeart trouble*' or "high blood pressure'* SMOKING CATEGORY Never smoked Ex*smoker Present smoker Uncertain recording PHYSICAL EXAMINATION Basilar rales: Right lower lobe Left lower lobe 2 or more sites Clubbed fingers -- hyponychial angle >198* PULMONARY FUNCTION FVC (liters) FEV, (liters) PF (liters/min) FVC % of predicted ROENTGENOLOGIC PANEL INTERPRETATION (1) Normal (2) Other abnormality (3) Questionable asbestosis (4) Slight asbestosis (5) Moderately advanced asbestosis (6) Advanced asbestosis 101 Pipe Coverers MEAN 41.5 67.9 168.0 SD 11.6 2.3 23.5 NO. rOSITIVE % POSITIVE 31 30.7 21 20.8 25 24.8 39 38.6 34 33.7 29 28.7 38 37.6 26 25.7 20 19.8 no. rosmve 7 27 67 0 % POSITIVE 6.9 26.8 66.4 0 NO. POSITIVE % POSITIVE 94 Controls MEAN so 40.9 68.4 174.7 11.6 2.7 27.5 NO. POSITIVE POSITIVE 18 19.1 9 9.6 9 9.6 23 24.5 (2 12.8 15 16.0 23 24.5 6 6.4 15 16.0 NO. POSITIVE 7 23 62 2 % POSITIVE 7.4 24.5 66.0 2.1 NO. POSITIVE % POSITIVE 23 16 16 20 MEAN 3.9 3.0 478.8 92.7 NO. POSITIVE 28 2 27 31 9 4 22.8 15.8 15.8 19.8 SO 0.76 2: 0.77 237.9 2: 1.3 % POSITIVE ' 27.8 1.9 26.7 30.7 8.9 4.0 5 7 4 5 MEAN 4.3 3.6 526.3 102.7 NO. POSITIVE 52 8 13 19 2 0 5.3 7.4 ' 4.2 5.3 so 2: 0.87 = 0.74 2:84.6 2: 1.7 % POSITIVE 55.5 8.5 13.8 20.1 2.1 0 f Value NS NS NS NS <0.005 <0.01 <0.05 <0.005 <0.01 <0.05 <0.005 NS NS NS NS NS <0.005 NS <0.01 <0.005 <0.001 <0.001 <0.001 <0.001 <0.001 Wheezes, rhonchi and moist rales were present equally often in both groups. Ventilatory Tests There was a marked difference in mean FVC (Table 2). Peak flow and FEV, were also significantly lower in the exposed workers, and were close to the predicted level in the control group (Table 2). Roentgenologic Findings Moderately advanced (code 5) or advanced asbestosis (code 6) was diagnosed six times more fre quently in pipe coverers than in the controls, whereas slight asbestosis (code 4) occurred only 1.4 times more frequently (Table 2). For each of the three observers, the chances were good'that the classification agreed with the exposure history when the readings were moderately advanced or advanced; the chances were much smaller when the classifi cation was questionable or slight asbestosis. Of the two controls with a reading of "moderately advanced asbestosis," one had previously recognized pulmonary fibrosis after smoke inhalation 30 years ago, and the other had bullous emphysema with diffuse linear opacifications. Medical-Record Review Forty-seven pipe coverers and 35 controls had notations concerning cardiopulmonary complaints, an insignificant difference (p greater than 0.05). However, pleurisy, pleural effusion and pleural rub were noted 13 times in pipe coverers and four times in controls. Other notations that acre more common in pipe coverers included hrinn. hiti- .10 and three), influenza (15 and four) and d>'pnc.i five and zero). Prevalence of Asbestosis To assess the prevalence of this disease it Ix-i.mie necessary to define criteria. Manifcstaimii- must commonly reported in persons with kumui i-l.. ^tnsis were used19-0: dyspnea on climbing mu' liigi.t .if stairs or less; basilar rales in two nr mure -u.-s. clubbing of the fingers -- that is, a hypmn. in.d .mule of 198 or greater; a vital capacity of less than mi per cent of the predicted value; and a meiitgeimgram consistent with moderately advanced nr ud- 1 ASARCO ELP 0003598 Vul. -J85 No. `23 I.OW CONCENTRATIONS OF ASHESTOS --MURPHY ET AL. 11275 vauccd asbestosis (codes 5 or 6). The ivsencc of at least three of these sinus teas defined arbitrarily as necessary for an e/iic/cmio/onie diagnosis. By this definition, 11 pipe eoverers had "asbestosis"; all 11 had roentgenograms coded 5 or 0, nine had reduced vital capacities, nine clubbing, eight basilar rales, and eight exertional dyspnea. Also, hy this definition, one of the controls had "asbestosis" -- the worker who had pulmonary fibrosis after smoke inhalation. Respiratory Gas Exchange In subsequent surveys, one and three years later, we studied the role of several physiologic tests in defining and detecting this disease. Pipe eoverers had significantly reduced single-breath and exercise steady-stat'1 diffusing capacities (D,} v. liercas air ways resistance, specific conductance, ventilation, carbon dioxide tension and dead space were not significantly different. Physiologic evidence of ob structive disease was equally common in both groups. All workers with clinical "asbestosis" had severely reduced D,, corroborating our clinical cri teria (Murphy, R. L. H., Jr., Caensler, E. A., Red ding, II. A., et al: Unpublished data). Figure 2 shows the relation of data on respiratory gas exchange to our clinical findings. Our diagnostic criteria that focused on marked abnormalities corre lated highly with impaired D,. However, Figure 2 also suggests that clinical findings of lesser severity may reflect interstitial lung disease. Prevalence of Other Respiratory Diseases Skin hypersensitivity to 5 tuberculin U of PPD was not significantly different in the two groups. All persons with 5 nun or more of induration submitted X*Roy SIB JU I Clubbing Ory Rales 3t 191 (91 !9t 2 I 0 Dyspnea w<* Copcc % 2 I o <tQ 13*90 >30 Table 3. Chronic Nonspecific Obstructive Respiratory Dis ease. Cat f.gory 1 - no obstructive lung dis ease 2 -- chronic bronchitis only* 3 _ asthma only* 4 -- chiontc obstructive lung disease <?nlyt Comuin OIOSS 2+3 3+4 2+4 2 + 3+4 lot Pll'F, Covt ni.n. % 71.3 IR.it 0 3.0 1.0 5.9 0 0 94 SntpvAitn Coni Kins W 6S.I 25.5 0 3.2 0 2.1 0 l.l 'PWcg'i* fu'm chcM at least t\ l!<iuVdv.. 4 t!.t\;./'vV. tor at } >r. ? r;o for past Aschm.t tf/a.'iiOsct/ bv ,i phjsicun still present. iWhcciinp or whistling must U.i>s or nights, or worker has to stop for breath when walking at own pace on the level, or <60** of FVC. three 24-hour sputum specimens, none of which were positive for Mycobacterium tuberculosis. Nonspecific obstructive lung disease was slightly but not significantly more common in the control group and among cigarette smokers (Table 3). Among workers with this syndrome, approximately 73 per cent of the pipe coverers and 65 per cent of the controls smoked cigarettes. Asbestosis and Its Relation to Dust Exposure By our scheme, "asbestosis" was never diagnosed in persons with less than 10 years of cumulative exposure, with a progressive increase thereafter (Fig. 3). If uniform exposure over the working ca reers is assumed, certain conclusions can he reached from dust counts made with the midget impinger. No "asbestosis," as defined above, oc curred in men exposed for less than 60 mppef-years; 20 per cent of those exposed for 75 to 100 mppefyears were considered to have asbestosis, and the prevalence was 3S per cent in those with exposure for more than 100 mppef-years. 12 it 22 :r t n // h Figure 2. Relation between 0, (Steady State at Rest. D,SS, R; Exercise. D,SS. Ex: Single Breath, 0,SB) and the De gree of Five Clinical Abnormalities among Pipe Coverers and Controls (Figures at Bottom Represent Numbers of Sub jects with the Indicated Abnormality). Discussion Building-insulation workers move from site to site and are confronted by varying situations and specifications, making supervision and assessment of dust exposure difficult. An important study confined to such workers hy SelikofF, Churg and Hammond' showed that almost xh of 1117 workers were con sidered to have roentgenologieallv evident ashestnsis; prevalence was directly related to duration of exposure. By contrast, shipboard pipe eoverers en gaged in new vessel construction have a mine uniform exposure. Fleischer et al.,* in a sliuK al ready alluded to, found only three eases of ashe-insis among 1074 pipe eoverers, and these three had been exposed for 20 or more years. Therefore, tinauthors (bought that such pipe covering was not a ASARCO ELP 0003599 1270 Till-: NEW ENGLAND JOURNAL OI' MEDICINE Dec. 2. 1971 Figure 3. Relation of "Asbestosis" to Duration of Expo sure. "Asbestosis" was never diagnosed in persons with less than 10 years of cumulative exposure, and the prevalence was 38 per cent in those exposed (or more than 20 years. One member of the control group had "asbestosis." dangerous occupation. More recently, Man-3 reported five cases of disability anion,!' 60 to 80 shipyard pipe covcrers; lie questioned whether this was caused by massive exposure during removal of old insulation or from many years of exposure by sus ceptible persons during all types of insulation work. Our principal objective was to determine the prevalence of asbestosis in pipe covcrers who had not engaged in repair work. Diagnostic criteria were based on recognized symptoms and signs of this disease because an `exact assessment would have required pathological material. These signs and symptoms have been reported in other defined populations of asbestos' workers with similar fre quency.18,11,11,14 The prevalence of shortness of breath among our pipe covcrers (Table 2) was similar to the 12 to 26 per cent in other asbestos workers.**"** In unex posed North American populations this percentage has ranged between 2.6 and 5.77,1B,1',,1'i -- quite comparable to our own control group with 6.4 per cent. Rales in two or more sites were found in 15.8 per cent of the pipe covcrers -- a rale not very different from the 13 to 14 per cent reported by others in asbestos workers.11,1* In our study the observer was unaware of the roentgenographic findings at the time of ausculta tion. Nevertheless, 33 per cent of workers with codes 5 and 6 roentgenograms had rales in two or more sites. Drcesscn cl al.-1 reported rales or other adventitious sounds in 49 per cent of those with "ground-glass" markings, whereas Vigliani3- heard such sounds in 70 per cent of workers with abnor mal roentgenograms. Clubbing of the fingers in 19.8 per cent of pipe eoverers was more frequent than that in other studies11,14; also, the 5.3 per cent prevalence in the controls was slightly larger than in other normal groups.17 However, the mean hyponychial angle of controls considered clubbed was only 200 as com pared to that of the dubbed pipe eoverers, which' was 208. Vital-capacity measurements were usually tacking in the earlier survt,ys.,,11,J1 Klcinfeld14 reported an average FVC of SI per cent of predicted in 56 workers exposed for more than 14 years, hut he used different prediction formulas. The mean FVC of 4.0 liters in 21 Australian asbestos workers did not differ much from that of our pipe eoverers. Hunt's exposed population18 is difficult to compare because knowledge of the diffusing capacity is re quired for interpretation. Our regression equations were derived from a population survey,1'* Since such surveys include disabled people, they generally yield lower values than surveys of industrial work ers. For example, our pipe eoverers had an average FVC of 92.7 per cent based upon our population survey, whereas it was only 75.2 per cent with the use of normal values from 2770 persons engaged in heavy labor and mining.18 Pipe eoverers over the age of 55 had a mean FVC that placed them in the same category as workers with advanced silicosis.18 The FVC of all pipe eoverers was also lower than the mean of paper-mill, flax and polyurethane-loam workers.*s,ls,m Concerning radiographic findings, some observers have considered early changes evidence of asbesto sis,1,31,11 whereas others have not.11,23,31,34 At any rate, our 19.9 per cent prevalence of moderately ad vanced or advanced asbestosis (codes 5 and 6) was much higher than the 0.27 per cent in the only other survey of shipyard pipe eoverers engaged in new vessel construction,1 but it was about the same as in building-insulation workers.1 Effect of Duration of Exposure and Age The prevalences of clinical signs and symptoms of "asbestosis" increased with duration of exposure (Fig. 4). The prevalences also rose with age (Fig. 5), ` and therefore the association between age and cumulative years of exposure was high (r equal to 0.7, p equal to 0.001). The advantage unique to this study was that the control group allowed examina tion of the relative importance of age: in the con trols there was no clear association between age and these abnormalities except in vital capacity (Fig. 5). Accuracy of Diagnosis How likely is it that the 11 workers considered to have "asbestosis" did indeed have this disease':' They were offered a medical examination, including ASARCO ELP 0003600 Vo!. 2S3 No. 23 LOW' CONCENTRATIONS OF ASBESTOS--MURl'HY ET AL. * Pve Cm. II 20 26 29 Controls 10 21 21 32 IS 10 1277 - X Dyspnea -- X Rales ---- 'i Clubbing -- % VC.<80 --X-Roy 566 Ch 40 30 9 20 tj 10 4? Figure 4. Increases with Duration of Exposure in Preva lence of Dyspnea. Rales, Clubbed Fingers, Reduced Vital Capacity and Roentgenologic Abnormalities. detailed pulmonary-function studies, by a group of internists not associated with this study. In the eight who consented, no illness other than ashestosis was discovered to account for the signs attd symptoms. Two of these men have since died, and both had severe ashestosis. Of the remaining three who refused detailed examination, two have died; autopsy in one showed ashestosis and cor pulmo nale, and the other died of bronchopneumonia. The accuracy of a "negative" diagnosis is much more difficult to assess. Only one worker so classified has died. His history, physical examina tion and ventilatory-function studies had all been normal at the time of this survey, and his chest roentgenogram showed slight ashestosis (code 4). When he died of peritoneal mesothelioma, the lungs showed minimal chronic interstitial pneumo nitis. Conclusions should not he drawn from this single case, hut the prevalences reported here proba bly are too low. Our subsequent surveys were de signed to investigate this possibility. What is the likelihood that other disease caused the findings that we attributed to ashestosis? Medical-record review, the respiratory questionnaire, physical examination, skin testing, sputum examina tion and roentgenograms did not uncover any excess cardiac disease, tuberculosis or other pulmonary disease. There was no significant dilfcrence in smoking habits in the entire population of pipe coverers and controls. Asbestosis and Dust Exposure The concept of a dose-response relation was intro duced by Merewelher amt Price in I930,'3 Imt the first information useful for calculating threshold lim- Age, Years -101 Pipe Coverers ---- 94 Controls Figure 5. Higher Prevalences of Clinical Abnormalities Seen in Older Pipe Coverers but Not in Older Controls. Since the association between age and cumulative years of exposure (Fig. 4) was high (r equal to 0.7, p less than 0.001), the importance of aging in relation to these abnor malities was reviewed in the controls: no clear association with age was found except in vital capacity. it values came from Dreessen et al. in 1938.*1 They found clear-cut asbestosis among those exposed to dust concentrations exceeding 5 ntppcf, and none at lower concentrations. Therefore, tentatively, they regarded 5 mppcf as a threshold value.11 These ob servations were confirmed by Vigliani.14 In retro spect, the choice of 5 mppcf, on the basis of the data then available, was open to question; in the dust counts in the textile mills no distinction was made between cotton and asbestos fibers. Kutlheimore, among those who were exposed at or just above this threshold (that is, 5.0 to 9.9 mppcf). 13 of 19 were considered to have ashestosis after 10 years, and six of 37 after only five years. In relation to the dose-times-tiine relation, over l/x the woikers exposed to 100 mppef-years had ashestosis. Divid ing 100 mppef-years by the recommended threshold ASARCO ELP 0003601 1278 THE NEW EXCt.AXD JOURNAL OK MEDICINE Dec. 2, 1971 limit value of 5 inppcf sliottld have prompted tlie conclusion that the risk of ashestosis was great after only 20 years of exposure. Indeed, other observa tions have suggested that ashestosis becomes evi dent after approximately this degree of total dust exposure: Wells35 began to see the disease after 50 to 60 mppef-years, and Fulton3 reported a 17 per cent prevalence after exposure from 27 to 75 tnppcfyears. In our study, ashestosis became evident after a total exposure of 60 mppef-years, and the earliest ease was found after 13 years of employment. Fleischer's prevalence in the same shipyard was much lower because, in 1945, less than 10 per cent of the workers had been exposed for more than 10 years. These observations indicate that prolonged exposure to low concentrations of asbestos is haz ardous, and support the lowering of the threshold- limit values. We arc indebted to Drs. Kenneth T. Bird, Eugene P. Pendergrass and Alfred L. Weber, who read, graded and classified (he roentgenograms, and to Mrs. Lee Slocum, who wrote the computer programs. References 1. SetikofF IJ. C'hurg J. Hammond EC: The occurrence of ashestosis among insulation workers in the United States. Ann NY Acad Sci 132:139*155* 1965 2. Ftcischer WE. Vitcs FJ Jr. Gadc RL. ci al: A health survey of pipe covering operations in constructing naval vessels. J Ind Hyg Toxicol 28:9-16. 1946 3. Marr \VT: Asbestos exposure during naval vessel overhaul. Am Ind Hyg Assoc J 25:264-268. 1964 4. Stumphitis J, Meyer PB: Asbestos bodies and mesothelioma. Ann Occup Hyg 11:283-293. 1968 5. Miners Phthisis Prevention Committee: Final report, Johannes burg. Union of South Africa, 1919 6. American Conference of Governmental Industrial Hygienists, 1962: Air sampling instruments (Document B-3-3U. Cincinnati, Ohio. 1963 7. Ferris BG Jr, Anderson DO: The prevalence of chronic re spiratory disease in a New Hampshire town. Am Rev Rcsp Dis 86:165-177. 1962 8. Fletcher CM, Elmes PC. Fairbairn AS. et al: The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br Med J 2:257-266. 1959 9. Higgins ITT: Respiratory symptoms, bronchitis, and ventilatory capacity in random sample of an agricultural population. Br Med J 2:1198*1203. 1957 10. Fairbairn AS. Wood CH. Fletcher CM: Variability in answers to a questionnaire on respiratory symptoms. Br J Prev Soc Med 13.: 175-193, 1959 11. Chamberlain EN. Ogilvie C: Symptoms and Signs in Clinical Medicine: An introduction to medical diagnosis. Eighth edition. Bristol. England. Wright and Sons. 1967 12. Regan GM. Tapg B. 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Harrisburg, 1935 ASARCO ELP 0003602