Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry

Authors: Eden E, Hammel J, Rouhani FN, Brantly ML, Barker AF, Buist AS, Fallat RJ, Stoller JK, Crystal RG, Turino GM
Publication: Chest
Keywords: adult, aged, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency, analysis, analysis of variance, Asthma, blood, complications, deficiency, diagnosis, epidemiology, female, forced expiratory volume, heart, humans, Immunoglobulin E, infusions, intravenous
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

STUDY OBJECTIVES:

To describe asthma features in a cohort with alpha(1)-antitrypsin (AAT) deficiency, and determine the impact of asthma on FEV(1) 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. FEV(1) 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 FEV(1). 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 FEV(1) decline was less in the group without asthma and a normal IgE level (- 48.5 mL/yr) vs the groups with asthma features (> or = 64 mL/yr) [p = 0.002]. Multivariable analysis showed that bronchodilator response, age, and smoking were significant predictors for FEV(1) decline but not asthma.

CONCLUSIONS:

Symptoms and signs of asthma are common in AAT deficiency and may start at the age of most rapid FEV(1) loss. Adjusting for other risk factors such as bronchodilator response, asthma as defined does not lead to an accelerated FEV(1) 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.

By, Eden E, Hammel J, Rouhani FN, Brantly ML, Barker AF, Buist AS, Fallat RJ, Stoller JK, Crystal RG, Turino GM