Publications

PURPOSE

Many occupational factors can cause asthma or reactivate preexisting disease. We carried out a critical review and synthesis of the available literature to estimate the proportion of adult asthma that is attributable to workplace factors.

METHODS

We reviewed published citations from 1966 through May 1999 as well as recent abstracts of studies providing risk estimates for asthma among various occupations. We extracted published attributable risk estimates, derived others from published data, and extrapolated estimates from the incidence rates of occupational asthma. We used a semiquantitative score to rank studies based on their characteristics.

RESULTS

We obtained 43 attributable risk estimates from 19 different countries: 23 were published estimates, 8 were derived from published data, and 12 were extrapolated from incidence data. The median value for the attributable risk of occupationally associated asthma was 9%(25th to 75th interquartile range: 5% to 19%). The derived estimates (median attributable risk = 25%) were significantly greater than published values (median = 9%, P = 0.002), whereas the extrapolated estimates were significantly lower (median = 5%, P = 0.04). The 12 highest scored studies based on their characteristics yielded a median risk estimate of 15%.

CONCLUSION

Occupational factors are associated with about 1 in 10 cases of adult asthma, including new onset disease and reactivation of preexisting asthma.

Work disability due to respiratory disease, especially asthma, is common and costly among working age adults. The goal of this analysis was to characterize the risk factors for such disability. We analyzed data from the Swedish part of the European Community Respiratory Health Survey (ECRHS), a random population-based sample of adults age 20 to 44, enriched with symptomatic subjects at increased likelihood of having asthma. We analyzed structured interview data available for 2,065 subjects and further analyzed methacholine challenge and skin prick test data for 1,562 of these. We defined respiratory work disability as reported job change or work loss due to breathing affected by a job. We used binary generalized linear modeling with a log link to estimate disability risk. Eighty-four subjects (4%) reported such work disability. This increased to 13% among those with asthma (45 of 350 subjects). Adjusting for covariates, occupations at high risk for asthma were associated with disability (prevalence ratio [PR] 1.8; 95% confidence interval [CI] 1.1 to 3.0), as was self-reported regular exposure to environmental tobacco smoke (ETS) at work (PR 1.8; 95% CI 1.1 to 3.1) and self- reported job exposure to vapors, gases, dust, or fumes (VGDF) (PR 4.3; 95% CI 2.2 to 8.6). Workplace ETS exposure was also associated with methacholine challenge-positive asthma reported to be symptomatic at work among male subjects (PR 4. 2; 95% CI 1.8 to 9.8), whereas high asthma-risk occupations were associated with this outcome among female subjects (PR 2.7; 95% CI 1. 05 to 7.1). Respiratory work disability, defined as breathing-related job change due to work loss, was associated with workplace exposures themselves, even after taking into account other covariates. Better control of workplace exposures, including workplace ETS, may reduce work disability caused by respiratory conditions, especially adult asthma.

Repeated treatment of female rats with the synthetic estrogen ethynylestradiol (EE(2)) increases the formation of the cyclosporine A (CyA) metabolites AM1c and AM9 by 3-fold, whereas the formation of AM1 and AM4N is not significantly enhanced. The formation of all four CyA metabolites was inhibited by greater than 80% by the CYP3A-selective substrate midazolam or polyclonal anti-rat CYP3A IgGs in liver microsomes of untreated and EE(2)-induced rats. In contrast, anti-rat CYP2C6 IgGs had little effect, indicating the involvement of a CYP3A but not 2C6 in this EE(2)-stimulated CyA metabolism. Semiquantitative reverse-transcriptase polymerase chain reaction was used to determine the mRNA content for four CYP3A genes (CYP3A2, CYP3A9, CYP3A18, and CYP3A23) in livers of control and EE(2)-treated female rats. EE(2) selectively induced CYP3A9 by 3.3-fold whereas the expression of CYP3A18 and CYP3A23 was slightly decreased; neither CYP3A2 mRNA nor CYP3A1 mRNA was detectable in these EE(2)-treated livers. To determine whether rat liver microsomal CYP3A9 was indeed responsible for the EE(2)-stimulated CyA metabolism, a recombinant CYP3A9 was heterologously expressed in Escherichia coli. When functionally reconstituted, this enzyme was active in metabolizing CyA preferentially to its AM9 and AM1c metabolites as compared with CYP3A4. These findings thus support the notion that the increased CyA-metabolizing capacity of EE(2)-treated female rat liver microsomes is due to the induction of the CYP3A9 enzyme.