Genetic influences in the development of emphysema in persons with normal serum proteins

This review has failed to uncover convincing evidence to support the existence of familial emphysema in patients with normal serum proteins. Although a large number of studies have documented that non-A1PI hereditary factors are important in the development of nonspecific chronic obstructive pulmonary disease, it is far less certain that emphysema accounts for this familial occurrence. To the contrary, most existing evidence fails to support this possibility. Nevertheless, the issue remains unsettled and incompletely studied. Further investigations should include a major effort to identify young persons, 20 to 45 years of age, with emphysema alone but without A1PI deficiency. Based on prior reports, 76 it is likely that such persons will be found. As emphasized by Kazazian, "this is the group that should be studied for the presence of a single mutant gene in the homozygous state." 42 It is possible that several or many rare single-gene causes of emphysema await discovery. Careful family studies of young emphysematous subjects are indicated as well to determine whether emphysema-producing genes also constitute a risk factor in heterozygous persons. If such patients and families are discovered, further hypotheses will have to be drawn-up and carefully investigated to attempt a better understanding of the etiology and pathogenesis of emphysema.