Aspects of treatment in alpha 1-antitrypsin deficiency: insights derived from a Swedish PiZZ series.

Data were analysed on 158 adult Swedish alpha 1-antitrypsin deficient individuals homozygous for the proteinase inhibitor allele (PiZZ), followed from 1963-1982. The initial forced expiratory volume in one second (FEV1) increased from 1.4 l in the early cohort to 1.9 l (p less than 0.001) in the late cohort of the study period but mean age (47 yrs) and the percentage of smokers (72%) remained unchanged. Smokers were found to have significantly lower FEV1 levels (p less than 0.01) and higher (p less than 0.005) mortality than non-smokers. The differences between current and ex-smokers in mortality and FEV1 level, however, were not significant. Longitudinal analysis of FEV1 rates of decline in 80 cases with follow-up FEV1 measurements failed to detect any significant difference between current and ex-smokers but investigations were performed late in the disease process. Low initial FEV1 value was found to be significantly associated with increased mortality (p less than 0.005). In order to detect a 40% difference in the rate of FEV1 decline as an outcome variable, 253 patients plus controls must be included in follow-up studies of replacement therapy. With mortality of severely affected patients as outcome variable only, 144 treated and untreated patients would be required. The need for earlier diagnosis and intervention against smoking in these cases is emphasized.