Asbestos as a public health risk: disease and policy.
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Biomedical subjects
Publications and source records attributed to H Weill.
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Methods for deriving quantitative estimates of asbestos-associated health risks are reviewed and their numerous assumptions and uncertainties described. These methods involve extrapolation of risks observed at past relatively high asbestos concentration levels down to usually much lower concentration levels of interest today--in some cases, orders of magnitude lower. These models are used to calculate estimates of the potential risk to workers manufacturing asbestos products and to students enrolled in schools containing asbestos products. The potential risk to workers exposed for 40 yr to 0.5 fibers per milliliter (f/ml) of mixed asbestos fiber type (a permissible workplace exposure limit under consideration by the Occupational Safety and Health Administration (OSHA) ) are estimated as 82 lifetime excess cancers per 10,000 exposed. The risk to students exposed to an average asbestos concentration of 0.001 f/ml of mixed asbestos fiber types for an average enrollment period of 6 school years is estimated as 5 lifetime excess cancers per one million exposed. If the school exposure is to chrysotile asbestos only, then the estimated risk is 1.5 lifetime excess cancers per million. Risks from other causes are presented for comparison; e.g., annual rates (per million) of 10 deaths from high school football, 14 from bicycling (10-14 yr of age), 5 to 20 for whooping cough vaccination. Decisions concerning asbestos products require participation of all parties involved and should only be made after a scientifically defensible estimate of the associated risk has been obtained. In many cases to date, such decisions have been made without adequate consideration of the level of risk or the cost-effectiveness of attempts to lower the potential risk.
The dosimeter method of administering doubling cumulative doses of methacholine to measure bronchial responsiveness was standardized to control for the effects of a number of potential influencing variables. The aerodynamic mass median diameter of the challenge aerosol produced from a DeVilbiss 646 nebulizer proved to be 1.2 mu, and the mean output per inhalation 8.9 microliters. Each challenge dose comprised 5 inhalations. Cumulative doses ranged from 0.3 methacholine inhalation units (1 unit = 1 inhalation of aerosol from a 1-mg/ml solution of methacholine, i.e., 8.9 micrograms methacholine) to a possible 640 units, the maximum that was considered reasonable to avoid the risk of unacceptable systemic effects. Responsiveness was expressed as the dose provoking a 20% decline (PD20) in FEV1. Modifications in this full protocol were introduced to facilitate epidemiologic investigations. Physician assessments coupled with baseline measurements of ventilatory function allowed starting at higher dosages for persons with low probability of hyperresponsiveness, thereby shortening the time required for testing to an average of 38 min. In a validation study of 20 persons using both the full and modified protocols, no significant differences were detected between measured PD20 values (geometric means Full versus Modified, 14.83 versus 14.88; r = 0.99). The modified protocol was used to measure bronchial responsiveness in 254 workers exposed to toluene diisocyanate. It proved to be safe and acceptable. Sixty-four workers (25.2%) were found to be reactors. The frequency distribution of the PD20 values exhibited a steadily increasing trend, consistent with a unimodal distribution.
Chlorine gas, spreading from a train derailment, caused the deaths of 8 persons and the hospitalization of 23 with sublethal respiratory injuries. Twenty-five others had at least one sign of lower respiratory abnormality but were not hospitalized. One hundred thirteen who were examined for gas effects in the forty-eight hours after exposure, including 20 of 23 of those hospitalized and 21 of 25 of those not hospitalized but with respiratory abnormality, participated in follow-up studies. Probability of admission to hospital was related to distance from the spill, but by 3 wk after exposure there was no detectable difference in lung function relating to distance or apparent severity of injury. In 60 adults tested multiple times over the following 6 yr, longitudinal change in lung function showed expected differences related to smoking but none related to distance or severity of injury. The average annual change in FEV was -34 ml/yr in current smokers and -18 ml/yr in ex and never-smokers. The lack of a discernible chlorine effect in this cohort accords with the findings in most previous studies. Without pre-exposure measurements, a single, lasting reduction in lung function cannot be excluded, but there is no evidence for a persisting abnormal rate of decline.
A 29-year-old man had a persuasive history of respiratory illness following exposures to methylene diphenyl diisocyanate (MDI). He was evaluated by measuring bronchial reactivity to methacholine, both before and after controlled laboratory exposures to MDI. Despite evidence of progressive declines in FEV1 with increasing (but subirritant) doses of MDI on three consecutive days, there was no bronchial hyperresponsiveness to methacholine, before or after MDI challenge. We conclude that the absence of nonspecific bronchial hyperresponsiveness does not exclude the possibility of isocyanate asthma. In the face of a compelling history, a negative result of methacholine challenge should not deter observation or laboratory testing for specific respiratory allergy to these chemicals.
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Marine engineers undergoing routine annual chest roentgenography showed an unusual prevalence of pleural abnormalities including plaques suggestive of past asbestos exposure. A pilot survey, and a subsequent comprehensive study of the films of more than 5,000 men, showed an overall prevalence of 12% with pleural abnormality (typical calcification or plaque, or diffuse thickening). Prevalence of films classifiable for pneumoconiotic small opacities was negligible--1.2% in the pilot study. Prevalences of pleural abnormality were significantly higher among men with longer union membership, after controlling for age. Older merchant ships contain substantial amounts of asbestos-containing thermal insulation. Marine engineers often remove and reapply insulation, operations known to produce high airborne fiber concentrations. These roentgenographic survey results indicate significant past asbestos exposures of ships' engineering department personnel.
To explore the mechanisms of asbestos-related perturbations of the immune system, we evaluated the in vitro cell-mediated immunity of five asymptomatic asbestos workers with hypergammaglobulinemia and decreased T-cell numbers. These results were compared with those in 10 matched controls. Analysis of T-lymphocyte populations revealed decreased absolute numbers of OKT4+ (helper/inducer) T cells in the peripheral blood and phytohemagglutinin (PHA)-stimulated mononuclear cell cultures of the workers. When chrysotile asbestos was added to PHA cultures, expansion of OKT4+ cell populations was disproportionately inhibited in workers' cultures. Furthermore, control proliferative responses to PHA became indistinguishable from initial worker responses. These effects were incompletely explained by the cytotoxic effects of asbestos on cultured lymphocytes. We conclude that both in vivo and in vitro exposure of mononuclear cell populations to asbestos may lead to a diminution of helper-inducer T-cell numbers. In asbestos-exposed individuals, this latter lymphocyte subpopulation appears to be especially sensitive to in vitro asbestos exposure. Although the clinical implications of these findings are unclear, we hypothesize that many of the immunologic abnormalities that occur in asbestos workers could be explained by direct asbestos effects on the OKT4+ immunoregulatory population.
Immunoregulatory disorders have been implicated in the pathogenesis of asbestosis. We therefore compared the immunologic status of a well-characterized group of 31 current and former asbestos-cement workers with that of a group of 52 healthy controls, after adjustments had been made for the possible confounding effects of age, race, and smoking. The asbestos workers had significantly decreased percentages and numbers of both B and T lymphocytes in peripheral blood and a paradoxical IgG hypergammaglobulinemia. Analysis of T-lymphocyte subpopulations revealed that total T-cell numbers (OKT3+), helper-inducer T-cell numbers (OKT4+), and suppressor-cytotoxic T cell numbers (OKT8+) were decreased by similar proportions. These decreases were negatively correlated with time elapsing since the end of exposure to asbestos. In both workers and controls, lymphocyte proliferative responses to phytohemagglutinin (PHA) were correlated positively with the number of OKT4+ cells and negatively with age and serum IgG levels. When adjustments had been made for these confounding variables, no differences in PHA responses were noted between workers and controls. No relationship was detected in the workers between any of the immunologic aberrations noted and (1) radiographic category of pneumoconiosis, (2) estimates of cumulative asbestos exposure, or (3) abnormalities of pulmonary function. These data suggest that the immunologic perturbations we have noted in asbestos-exposed individuals are epiphenomena, unrelated to the pathogenesis of asbestosis itself.
Serum specimens from 144 workers exposed to asbestos cement dust were examined for the presence of ANA, RF, immunoglobulins, and IC. These immunologic findings were compared with chest radiographic changes. A high percentage of workers had polyclonal hypergammaglobulinemia, and there was a statistically significant association between elevated levels of IgG and IgM and radiographic classification. Although a significant number of workers had an increased prevalence of ANA and elevated levels of IC, there was no correlation between these parameters and chest radiographs. These findings support B cell hyperactivity in workers exposed to asbestos and suggest that autoantibody production and IC are not directly involved in disease pathogenesis.
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Toluene diisocyanate (TDI) sensitivity accompanied by nonspecific bronchial hyperresponsiveness occurs in approximately 5% of occupationally exposed workers. We report the case of a 32-yr-old worker followed longitudinally after removal from isocyanate exposure. TDI reactivity was lost 11 mo after removal from exposure and nonspecific bronchial hyperresponsiveness resolved after 17 mo. Bronchial reactivity to radishes (Raphanus sativus), which developed concurrently with TDI reactivity, was lost 2 yr later. Immunopharmacologic results show that the worker's initial decreased ability of lymphocytes to produce cyclic AMP returned to near normal after 2 yr. IgE antibodies to a human serum albumin tolyl monoisocyanate conjugate were still present at this time.
Three hundred seventy-two workers were examined at two coffee processing plants in New Orleans. Workplace dust concentrations were relatively low, and respiratory symptom prevalences were not different in various areas of the plants. After controlling for other variables, men with lengthy employment and exposure to dust of green (unroasted) coffee had lower mean residual FEV1 values (regression coefficient, -0.011 L/yr employed, p less than 0.05). Similarly, workers with serum IgE antibodies to green coffee beans had lower mean residual FEV1 (-0.244 L, p less than 0.05). Each effect remained significant after controlling for the other. In a subset that included all workers exposed to green coffee, acute changes in expiratory flow rates were not related to differences in exposure. The finding of adverse impacts of exposure and sensitization, in a work force relatively free of overt asthma, has important implications for worker health protection.
Annual decline in lung function determined longitudinally is often compared with predicted decline determined cross-sectionally. To test this comparison, spirometric data were collected 5 times over 5 yr from 52 adult male Caucasians. The age regression coefficient for FEV1 and FVC, determined cross-sectionally at each visit, was more than twice the longitudinal annual change computed from the same data as the mean of the slopes of each subject's regression lines. The discrepancy persisted even when the first visit was deleted to reduce learning effects on longitudinal estimates. This discrepancy may be partly explained by the sensitivity of cross-sectional analyses to past noxious influences, whereas longitudinal analyses are sensitive only to influences that continue to affect annual decline during the study period. We also found historical evidence of an increase in height-specific VC, which would artifactually steepen cross-sectionally determined regression lines. Thus, observed longitudinal changes of study cohorts should be compared with control longitudinal data.