alpha 1-Antitrypsin deficiency and susceptibility to lung disease

This subject concerns the complex interrelationship of a genetically determined protein deficiency, enzymes which are inhibited by that protein, environmental challenges such as cigarette smoke and industrial pollutants, and the occurrence of obstructive lung disease (Fig. 1). Unequivocal establishment of an etiological role for AAT deficiency, especially of intermediate degree, has proven to be difficult. Confounding variables such as enzyme concentration in PMN and PAMs, duration of exposure to potential environmental hazards, differences in laboratory methods utilized in measuring AAT and in studying pulmonary function all require investigation. The definitive study, incorporating all of these and other factors, has yet to be conducted. No single, clear-cut conclusion can be drawn from analysis of present studies. In those circumstances in which heterozygotes appear to be predisposed to COPD, phenotypic screening of the population at potential risk, such as industrial workers may be appropriate. Conversely, in conditions in which no association is demonstrated, such screening would not be justified. Perhaps, the best one can do is to suggest a "Scotch verdict"; that is, the issue of causation is not proven.