Characteristics and Outcomes of Chronic Bronchitis in Alpha-1 Antitrypsin Deficiency Related Lung Disease: A Retrospective Longitudinal Analysis

Abstract

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with lung disease such as early-onset emphysema and chronic obstructive pulmonary disease (COPD). The presence of chronic bronchitis may accelerate disease progression in AATD patients, but few studies have specifically examined this phenotype. Objectives: To investigate the characteristics and outcomes such as FEV1 decline, DLCO decline, exacerbations frequency, and mortality of AATD patients with chronic bronchitis compared to those without chronic bronchitis. Methods: This retrospective cohort analysis utilised clinical data from the REDcap registry for 236 PiZZ and PiSZ AATD patients. Participants were categorised based on chronic bronchitis diagnosis and genotypes. Characteristics were compared between groups. Multiple linear regression analysis, logistic regression analysis, mixed linear model, and survival analysis are done to investigate outcomes including lung function decline, exacerbation frequency, and mortality among those patients. Results: Patients with chronic bronchitis (35% of the cohort) demonstrated significantly worse baseline lung function. FEV1 decline was steeper in PiZZ chronic bronchitis patients (-1.61% predicted/year, - 52 ml/year) versus PiZZ without chronic bronchitis (-1.07% predicted/year, - 31.5 ml/year). In the PiSZ genotype, the chronic bronchitis group similarly showed accelerated decline (-1.85% predicted/year, - 64 ml/year) versus the PiSZ without chronic bronchitis (-0.67% predicted/year, - 21 ml/year). Female sex was associated with higher odds of frequent exacerbations in both PiZZ and PiSZ individuals. There was no significance in terms of mortality between the groups. Conclusion: Chronic bronchitis in AATD is associated with impaired lung function and worse clinical outcomes compared to AATD alone. This high-risk phenotype warrants additional research into tailored interventions and closer monitoring. Larger longitudinal studies are needed to confirm the results and elucidate underlying mechanisms.