Deficient alpha-1-antitrypsin phenotypes and persistent airflow limitation in severe asthma

SummaryBackgroundPersistent airflow limitation is common among patients with severe asthma, but its pathogenesis has not been fully clarified. Severe alpha-1-antitrypsin (AAT) deficiency is a risk factor of chronic airflow limitation and emphysema, and partially deficient phenotypes have been associated with an accelerated decline in lung function. We hypothesized that partial deficiency of AAT (non-PiM AAT phenotype) is a risk factor of persistent airflow limitation in asthma.MethodsIn 122 patients with severe asthma (86 females; age (median (range)): 44.0yr (18–75)) postbronchodilator FEV1 and FEV1/VC were measured and the AAT phenotype was determined. Persistent airflow limitation was defined as postbronchodilator FEV1 or FEV1/VC<75% pred. with TLC>75% pred.ResultsSix patients (4.9%) had a non-PiM phenotype (1 MF, 3 MS, 1 MZ and 1 SZ). Of the 58 patients with persistent airflow limitation only 1 patient (1.7%) had a non-PiM phenotype vs. 7.8% among the patients without persistent airflow limitation (P=0.21). Postbronchodilator FEV1/VC (% pred.) was higher in the non-PiM patients than in the PiM patients (P=0.02), the other lung function parameters were not different. Linear regression analysis showed no association between AAT phenotype and FEV1% predicted (P=0.26).ConclusionsAAT heterozygoty does not seem to be an important risk factor of persistent airflow limitation in patients with asthma. Although confirmation by longitudinal follow-up studies with larger sample sizes is needed, these results suggest that routine assessment of the AAT phenotype is not indicated in asthmatic patients even if they exhibit fixed airflow limitation