We studied the relationships among neutrophil elastase, smoking, and pulmonary function in 32 subjects with intermediate alpha₁-antitrypsin deficiency (Pi MZ phenotype). Nineteen subjects were detected in population studies, and 13 were detected in a family study of patients with chronic airway obstruction. Of the 32 subjects, 10 less than 30 years of age and 12 more than 30 years of age had normal lung function. The remaining 10 subjects, all more than 30 years of age, had abnormal lung function as determined by one or more of the following indices: maximal expiratory flow, specific conductance, closing capacity, slope of phase III of the single-breath N₂ test, lung elastic recoil, or upstream resistance.

The neutrophil elastase content of all Pi MZ subjects as a group was not significantly different from that of a control group of 26 subjects of Pi M phenotype. However, in Pi MZ subjects more than 30 years of age, those with abnormal lung function had greater neutrophil elastase content than did those with normal lung function. The 12 MZ subjects more than 30 years of age with normal lung function had less neutrophil elastase content as compared to the 20 M control subjects more than 30 years of age. In Pi MZ subjects more than 30 years of age, neutrophil elastase content correlated significantly with tests of maximal expiratory flow, airway conductance, closing capacity, and slope of phase III, whereas smoking showed a correlation with the latter 4 measurements, but not with tests of maximal expiratory flow. Neutrophil elastase and smoking interacted as significant factors related to abnormal lung function in Pi MZ subjects more than 30 years of age.

We conclude that in MZ antitrypsin-deficient subjects neutrophil elastase content is a significant risk factor related to lung function abnormalities and that neutrophil elastase and smoking interact in producing abnormal lung function in Pi MZ subjects.