Exploring the overlapping burden of alpha-1 antitrypsin deficiency and bronchiectasis: insights from the US BRR

<bold>Background:</bold> Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed hereditary condition characterized by reduced serum AAT levels. While AATD is a known risk factor for early-onset COPD, its role in bronchiectasis (BE) remains less clear, warranting further investigation. <bold>Methods:</bold> We analyzed cross-sectional data (2008–2023) from the US Bronchiectasis and NTM Research Registry (US BRR). AATD status was physician-reported, with genotype or phenotype data assessed when available. Patients with CF, primary immunodeficiency, or PCD were excluded. Demographic and clinical characteristics were compared between patients with and without AATD at enrollment. <bold>Results:</bold> Among 5,002 patients with BE (mean age 67±13 yrs, 80% female, 40% ever-smokers), 122 (2.4%) had AATD, 33% of whom carried the clinically severe ZZ or SZ genotype. Patients with AATD-BE were younger (63±12 vs. 67±13 yrs) and had lower FEV₁% predicted (71±23 vs. 75±22). Dyspnea was more prevalent in AATD-BE (68% vs. 59%, p=0.047), while wheezing was less common (16% vs. 25%, p=0.02). NTM disease was less frequent in AATD-BE (28% vs. 39%, p=0.03). No significant differences between the groups were observed in cough, hemoptysis, fatigue, smoking history, or Pseudomonas aeruginosa chronic colonization. AATD-BE patients had higher odds of exacerbations (OR=1.7, 95% CI: 1.2–2.6) but similar hospitalization rates in the two years before enrollment. <bold>Conclusion:</bold> In this cohort of patients with BE, a higher proportion of patients with AATD-BE reported exacerbations and dyspnea and had worse lung function at a younger age compared to non-AATD BE. Further studies should explore genotype-phenotype correlations in this population.