Asthma features in severe α₁-antitrypsin deficiency: Experience of the National Heart, Lung, and Blood Institute registry

Study objectives: To describe asthma features in a cohort with α₁-antitrypsin (AAT) deficiency, and determine the impact of asthma on FEV₁ decline. Background: Asthma may be common in those with AAT deficiency, and may lead to accelerated airflow obstruction. Design: Analysis of data obtained from a 5-year, prospective National Heart, Lung, and Blood Institute registry. Setting: A multicenter registry consisting of 37 clinical centers, a central phenotyping laboratory, and a data analysis center. Participants: A cohort of 1,052 subjects with AAT deficiency. Measurements and results: Asthma was defined as reversible airflow obstruction, recurrent attacks of wheezing, and a reported diagnosis of asthma or allergy with or without an elevated serum IgE level. FEV₁ decline was calculated by least-square means with adjustments for covariables. Asthma was present in 21% of the cohort and in 12.5% of those with a normal FEV₁. Attacks of wheezing were reported in 66%, the first attack occurring at a mean ± SD age of 31 ± 16 years. Allergy and asthma was reported in 29% and 38%, respectively. An elevated IgE level occurred in 17% and was significantly associated with signs and symptoms of asthma and an allergy history. Unadjusted FEV₁ decline was less in the group without asthma and a normal IgE level (- 48.5 mL/yr) vs the groups with asthma features (≥ 64 mL/yr) [p = 0.002]. Multivariable analysis showed that bronchodilator response, age, and smoking were significant predictors for FEV₁ decline but not asthma. Conclusions: Symptoms and signs of asthma are common in AAT deficiency and may start at the age of most rapid FEV₁ loss. Adjusting for other risk factors such as bronchodilator response, asthma as defined does not lead to an accelerated FEV₁ decline. In AAT deficiency, augmentation therapy is not more effective in preventing the loss of lung function in those with asthma compared to those without.