Review of the Kilburn and Warshaw Chest article--airways obstruction from asbestos exposure.
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Biomedical subjects
Publications and source records attributed to H Weill.
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Fourteen cohorts of asbestos-cement workers have been studied. These studies have demonstrated exposure-response relationships for lung cancer, mesothelioma and asbestosis. For lung cancer, relatively consistent results have been observed, with risk two-fold or less in 13 of the 14 cohorts. Among New Orleans workers, excess risk was restricted to those with X-ray evidence of asbestosis. Workers employed at least 21 years but without X-ray abnormalities, experienced no elevated risk, while those with small opacities (1/0 or higher) had substantially elevated risk (SMR > 400). Exposures in these two groups had been similar. These results suggest that asbestosis may be a necessary precursor for asbestos-induced lung cancer; if so, then the no-threshold model for lung cancer risk is inappropriate since there is general agreement that very low exposures will not result in radiologically detectable lung fibrosis. Further data on this potential link are needed. As in other industries, mesothelioma risk was strongly related to amphibole exposure, especially to crocidolite in asbestos-cement pipe manufacture. A cluster of cases has recently been reported in a family amosite-cement business. Among New Orleans workers, risk of asbestosis was related to cumulative exposure but there was little evidence of risk below 30 f ml-1-years. Progression of asbestosis in these workers was slow, related to past cumulative exposure and not related to lung function decline. Asbestosis risk is therefore not likely to develop in workers under current controlled exposure conditions.
In this report of a 5-yr longitudinal study of workers employed at six cotton textile mills, exposure and across-shift FEV1 change were evaluated as possible predictors of the annual change in FEV1 for yarn manufacturing workers. A total of 611 workers had three repeatable spirometric tests, over at least 3 yr, and at least one (average of three) across-shift test, while always working the same shift. The "same shift" criterion controlled for the effect of diurnal variation. Average exposure was determined from measures of lint-free elutriated cotton dust in combination with job histories. This study found a significant association between the acute and chronic effects of cotton dust exposure. Both exposure and across-shift change proved to be significant predictors of annual change, and excess annual declines in FEV1 were predicted even for exposures of 200 micrograms/m3 and across-shift drops in FEV1 of 200 ml. These results suggest that, to prevent dust-related chronic decline in lung function, current smokers should be excluded from yarn manufacturing work and exposures should be reduced below 200 micrograms/m3, to approximately 100 micrograms/m3.
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A survey of workers in seven man made mineral fibre (MMMF) production plants, the subject of a previous report, was conducted, with other blue collar workers serving as regional comparisons. Based on the median reading of chest radiographs by five readers, a low prevalence of small opacities, all at the 1/0 and 1/1 profusion levels, was again found: for workers with MMMFs, 23/1435 (1.6%); for comparison workers, 2/305 (0.7%). Spirometric measurements indicated generally healthy populations, and were not related to presence of opacities. Ninety three per cent (21/23) of MMMF workers with opacities worked at the two plants with the highest exposures to fine fibres, resulting in a dose-response relation across plants. For one location, the prevalences of opacities for the MMMF and comparison workers were not significantly different (5.9% (13/220) v 3.1% (2/65)). No comparison x ray films were obtained for the MMMF plant with the highest prevalence (6.6%), so a second phase of the study was conducted, with pre-employment films from these two plants. On this second reading, the prevalence of opacities was lower; there were no significant differences between the two groups of films, and no relation between opacities and exposure indices. There was considerable inter and intrareader variability. These results indicate no adverse clinical, functional or radiographic signs of effects of exposure to MMMFs in these workers.
Exposures to toluene diisocyanate (TDI) were studied for effects on respiratory health of workers in two plants manufacturing polyurethane foams. Intensive personal monitoring was used to characterize job exposures. Of 4,845 12-min personal samples, 9% exceeded 5 ppb and 1% exceeded 20 ppb. Initial questionnaire and spirometry were obtained in 386 workers (88.7% of target population). Current smoking was associated with lower mean FEV1 and FEF25-75, but percent predicted (% pred) means were normal in all smoking categories. Multiple regression showed significant adverse effects of cumulative TDI exposure on initial level of FVC and FEV1 of current smokers, and an effect at borderline significance (p less than 0.063) on FEF25-75 over all smoking categories. Logistic regression showed that chronic bronchitis was more prevalent among those with higher cumulative exposures, after controlling for smoking, age, and sex. Methacholine (MCh) reactivity was associated with reduced airway function, -8.5% pred for FEV1 and -20.0% pred for FEF25-75. In 227 with adequate follow-up, the slopes of annual change were abnormal, for example, FEV1 of -67 ml/yr in current and -53 ml/yr in never smokers. Men had worse FEV1 declines than did women, -71 ml/yr versus -43 ml/yr. TDI exposure, lifetime or concurrent, had no significant effect on slopes, despite its demonstrated effects on initial level of lung function and on prevalence of chronic bronchitis.
A prospective mortality study of 839 men employed in the manufacture of asbestos cement products in 1969 examined lung cancer risk in relation to lung fibrosis seen on chest x ray film, controlling for age, smoking, and exposure to asbestos. Twenty or more years after hire, no excess of lung cancer was found among workers without radiographically detectable lung fibrosis, even among long term workers (greater than or equal to 21.5 years); nor was there a trend in risk by level of cumulative exposure to asbestos among such workers. By contrast, employees with small opacities (greater than or equal to 1/0; ILO classification) experienced a significantly raised risk of lung cancer (nine observed deaths v 2.1 expected), even though their exposures to asbestos were similar to the exposures of long term workers without opacities. In this population, excess risk of lung cancer was restricted to workers with x ray film evidence of asbestosis, a finding consistent with the view that asbestos is a lung carcinogen because of its fibrogenicity.
To evaluate the effectiveness of the current workplace standards in preventing chronic health effects from cotton dust exposure, a 5-yr longitudinal study of a large multimill population of cotton textile and synthetic process workers, employed at a major U.S. textile company, was conducted. To control for and assess the effect of type of work area on annual change in lung function, we limited the analysis to those 1,817 subjects who, throughout their textile work history at the company, worked exclusively in cotton yarn manufacturing or slashing and weaving, or in synthetic textile mills. The expected effect of smoking on average annual change in lung function was demonstrated for both cotton and synthetic workers. Despite lower overall dust exposure, cotton yarn workers exhibited steeper annual declines in lung function than did workers in slashing and weaving; this difference persisted within each smoking category, indicating a dust potency effect. There were mill differences in annual change in lung function among cotton workers, potentially masking an exposure effect. A smoking-work area interaction persisted after adjusting for mill differences, with the largest annual declines observed in cotton yarn workers who smoke. A significant dose-response relationship was seen in cotton yarn manufacturing between annual declines in FEV1, FVC, and FEF25-75 and average exposure by mill, and the larger declines were found in mills using the highest percentage and lowest grade of cotton. Synthetic textile workers had larger declines than did cotton textile workers, which were not explained by smoking or duration of employment. Unrecognized and unmeasured causative exposures or selection bias could explain this result.(ABSTRACT TRUNCATED AT 250 WORDS)
From an original prospective cohort of 244 current and ex-workers in two asbestos cement plants, longitudinal radiographic data covering ten years were available for 165 and lung function data covering about six years for 150. Estimates of average and cumulative dust exposure were available for each participant, all men. Radiographic progression (onset or worsening) was assessed by comparing earliest and latest films side by side. Annual changes in lung function were computed by fitting regression lines to all the data points. Small opacities (ILO category 1/0 or higher) were found in 16% of initial films, and progression of small opacities occurred in 13% of film pairs. Average and cumulative dust exposure were each significant determinants of the initial presence of small opacities, and were determinants of the progression of both parenchymal and pleural abnormalities. There was greater likelihood of progression if an abnormality was initially present, and a greater likelihood of progression in the plant that had systematic use of some crocidolite. Initial levels of lung function were related to smoking, exposure to dust, and initial radiographic status. Mean annual declines in lung function were modest (FVC-0.017 l/y, FEV1-0.020 l/y) and were related to smoking but not exposure to dust, initial radiographic status, or radiographic progression. Both plants used mainly chrysotile asbestos and exposure levels declined severalfold after 1960. Our findings suggest a waning effect of the larger remote dust exposures on recent annual change in lung function. This accords with human and experimental pathology data showing the relatively low resistance of chrysotile fibres to chemical alteration and clearance.
Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.
Several groups of researchers, at the request of government agencies in various countries, have reviewed the literature on the health effects of asbestos exposure and derived quantitative estimates of the risks from such exposures. Because of differences in the area of responsibility of the different agencies, these estimates have inevitably been based on different assumptions concerning exposure (concentration, number of years of exposure, initial age, and number of hours per week). The lifetime cancer risk estimates derived in 6 reports are compared here, after adjustment to a common set of exposure assumptions appropriate for students attending schools containing asbestos products. Estimates are found to be reasonably similar, remaining differences being primarily due to differences in assumptions concerning parameter values of the models and the background risk of lung cancer. The various administrative processes used by the US agencies are also compared, and recommendations made for US government agencies involved in the derivation of risk estimates for exposures of general public concern.
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In a study of the mortality experience of 6931 employees of two New Orleans asbestos cement products manufacturing plants over 95% were traced. Chrysotile was the primary fibre used in both plants. Plant 1 also used small amounts of amosite and, later, crocidolite irregularly whereas plant 2 used crocidolite steadily in pipe production. Previously reported exposure concentration estimates were revised, based on additional air sampling data and re-evaluation of these data. Workers in the two plants had similar duration of employment (overall, a mean of 3.8 years) and estimated exposure concentration (a mean of 7.6 million particles per cubic foot (mppcf)). Mortality was similar for these plants and comparable with Louisiana rates for all causes combined, nonmalignant causes, and primary cancers of specified sites other than lung. Short term workers from both plants showed raised and similar risk of lung cancer, but risk among longer term workers differed--for example, for workers employed over one year there was no excess in plant 1 (16 observed, 17.2 expected) but a significant excess in plant 2 (52 observed, 28.9 expected, p less than 0.001). After excluding short term workers, risk of lung cancer in plant 2 showed a significant trend with estimated cumulative asbestos exposure; using a conversion of 1.4 fibres/ml = 1 mppcf, the slope of the line was 0.0076. The slope for plant 1 was 0.0003. Among all workers (the 6931, plus 167 early employees) ten mesotheliomas had occurred up to 1984: two from plant 1, eight from plant 2. In plant 2 a case-control analysis found a relation between risk of mesothelioma and duration of employment (p less than 0.01) and proportion of time spent in the pipe area (p less than 0.01), thus adding to the evidence of a greater risk of mesothelioma from crocidolite than chrysotile asbestos. A review of the mortality findings of eight cohorts of asbestos cement workers is presented.
Quantitative test criteria have been developed to assess the acceptability of spirometric tracings. Most automated spirometers have been programmed with the criteria in order to assist in data collection. These instruments compare computed parameters from the collected tracings with the criteria and, after 3 acceptable FVC maneuvers have been collected, print out a statement indicating that "tests meet acceptability criteria." Technicians, nurses, and even their medical supervisors are beginning to rely on these statements as assuring overall test quality. However, a review of actual curves indicates that unacceptable results can be obtained from tests that comply with these standards. Although quantitative test criteria are a positive step toward quality assurance, they should be treated as they were developed, as "minimum" criteria. All curves should be inspected for visible defects, especially if the results are used to follow subjects longitudinally.
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Longitudinal measurement is increasingly used to quantify the effects of recent and ongoing influences on lung function, whether treatments of groups of patients, or exposures of working or community populations. The variability in an estimate, eg, mean annual change in FEV1, comes from two sources; variability from true differences in annual change among individuals (called signal), and variability from measurement error (called noise). Signal is useful variability, potentially relatable to explanatory variables, and noise is extraneous. Assuming the variance of true differences remains constant, any increase in noise produces a calculable fall in the proportion of signal in the total observation, which fall we term "signal decay". This is not a function of the number of individuals, which influences rather the statistical power to determine that observed differences are not likely from chance alone. Imprecision in the estimation of individuals' rates of change is a major source of signal decay. Within practical limits, this can be compensated for by increasing the length of the study. Higher rates of subject attrition cause signal decay, in addition to loss of statistical power and susceptibility to survivor bias. Increasing the frequency of testing, within a study of constant length, has little effect on signal and noise, but interval testing protects against secular bias and minimizes data loss from subject attrition.