Observational cohort study of pulmonary exacerbations in alpha-1 antitrypsin deficiency

Background: Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant genetic disease whereby reduced levels or function of the protease inhibitor AAT lead to increased risk of emphysema. Acute exacerbations of COPD (AECOPD) have a significant impact on symptoms, quality of life and disease progression but there is limited evidence on AECOPD in AATD. We aim to characterize AECOPD in ZZ and SZ AATD patients (pts). Methods: This observational study of longitudinal data from the Birmingham (UK) Alpha-1 cohort of AATD (1996-present) comprised pts with ZZ (n=799) and SZ (n=106) phenotypes with available exacerbation data. AECOPD were defined as a change in usual sputum volume, purulence or breathlessness resulting in additional therapy. Annual AECOPD rates (mean number per patient per year) were compared with the Wald test. Results: In an unadjusted analysis, annual AECOPD rates were higher in ZZ pts compared to SZ pts (1.32 vs 0.70, rate ratio 1.88, 95% confidence interval 1.66-2.14, p<0.001). There were more frequent exacerbators (>2 AECOPD/yr) in the ZZ group than the SZ group (36% vs 17%, p<0.001, two-proportions z-test). The average duration of AECOPD in ZZ pts was 14 days; 8% were hospitalised. Among ZZ pts who were frequent exacerbators at baseline, 52% were also frequent exacerbators in the next year. Frequent ZZ exacerbators had more smoking history, breathlessness, bronchiectasis and worse pulmonary function tests compared to non-frequent ZZ exacerbators. Conclusion: In an unadjusted analysis, the AECOPD rate was higher in ZZ pts compared to SZ pts. Half of ZZ frequent exacerbators continued to be frequent exacerbators in the subsequent year.