Eight patients with pulmonary emphysema associated with α1-antitrypsin deficiency have been compared with 20 patients who had emphysema of equal severity but normal plasma α1-antitrypsin. The two groups differed significantly in the radiological distribution of the lesions; the lower zones were predominantly affected in all the patients with α1-antitrypsin deficiency. Among the 20 ‘non-deficient’ patients, however, the main lesions were in the upper zones in 11 and in the lower zones in seven; in two patients the upper and lower zones were equally affected. Bullae occurred in 20 of the 28 patients and were found with equal frequency in the two groups.
All 28 patients had dyspnoea on exertion which developed on the average 12 years earlier in those with α1-antitrypsin deficiency. Chronic bronchitis occurred in 62.5 per cent of those with the deficiency and in 70 per cent of those without; among those who did develop chronic bronchitis, the mean age of onset was similar in the two groups. There was little relationship in either group between the age of onset of chronic bronchitis and that of exertional dyspnoea. The trypsin inhibitory capacity was not related to the presence or absence of chronic bronchitis. The body-weight was substantially below the expected value in both groups.
Twenty-nine per cent of the patients with severe emphysema who had attended the Unit during a six-year period had α1-antitrypsin deficiency. This unexpectedly high figure is not explained by selection in favour of younger patients or patients with actual bullae.
The mean trypsin inhibitory capacity in obligatory heterozygotes was very significantly less than that of the controls. Among the non-deficient patients, however, it was not significantly reduced, whether the upper or the lower zones were predominantly affected, suggesting that there is no excess of heterozygotes in this group. Our findings support the general concept that heterozygotes for recessively inherited disorders do not normally manifest the clinical features of the fully developed disease. However, the similarity of the non-deficient patients with lower zone disease to the patients with α1-antitrypsin deficiency, suggests that the former may have a related biochemical disorder.