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 alpha(1)-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 (greater than or equal to64 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.