Ethical issues in genetic screening for susceptibility to chronic lung disease

The extent, severity, and irreversible nature of chronic lung disorders associated with occupation dictate careful review of any potentially mitigating measure. A genetic predisposition to lung injury is known to occur in the small percentage of individuals who are homozygous for alpha-1-antitrypsin (AAT) deficiency, a defect in the protein needed for inactivating proteolytic enzymes released after lung injury. It was found that the contribution of homozygous affected individuals to the total population at risk for chronic lung disease is too small (0.5% to 2.0%) to warrant screening. Screening could be justified if the more prevalent heterozygous AAT-deficient individuals were also at greater risk. A literature review demonstrated that up to 27.2% of persons of Spanish and 12.3% of Anglo-Saxon heritage but virtually no blacks or persons of Eastern origin are heterozygous for AAT alleles. Some heterozygous phenotypes are statistically overrepresented in hospitalized populations and among workers with impaired lung function, suggesting that they are statistically at slightly greater risk for developing lung disease than are homozygous normal individuals. These data suggest that a screen for AAT carriers would be marginally acceptable scientifically, but would pose ethical questions of discrimination and equity in use of disease-detecting resources. Review of ethical criteria for screening, particularly the availability of experimental therapies, increases the cogency and reinforces the acceptability of performing occupational tests for both homozygous and heterozygous AAT-deficient persons. Currently, programs directed at early detection of symptomatic workers coupled with reduction or elimination of offending agents are scientifically and ethically more warranted than full-scale genetic screening for AAT deficiency.