WHILE SMOKING is a well-established risk factor for emphysema in α1-antitrypsin deficiency (AATD), never-smokers with severe AATD can also develop lung disease. The international EARCO Registry provides valuable insights into the prevalence and characteristics of lung disease among never-smokers carrying the PI*ZZ genotype.
Characteristics of Lung Disease in α1-Antitrypsin Deficiency Never-Smokers
This observational and cross-sectional study analysed 914 PI*ZZ individuals, comparing 472 active or former smokers with 442 never-smokers. Researchers evaluated lung function, disease prevalence, and the use of augmentation therapy, focusing on differences between index and non-index cases among never-smokers.
Never-smokers were generally older, more often female (58.8% vs 43.9%), and exhibited better lung function, with a mean FEV1 of 81.3% predicted compared to 48.4% in smokers. Lung disease remained common, affecting 75% of never-smokers, although smokers showed higher overall prevalence at 98.5%. Interestingly, bronchiectasis was more frequent among never-smokers (28.6% vs 17.7%).
Augmentation therapy was received by 34.9% of all patients, including 19.2% of never-smokers. Among these never-smokers, 72.7% were index cases, who were older and had lower FEV1 than non-index cases, suggesting more severe disease. Non-index never-smokers generally exhibited healthier profiles and higher quality of life. Factors associated with fixed airflow obstruction in never-smokers included lower BMI, male sex, comorbidities, and pulmonary exacerbations.
Clinical Implications α1-Antitrypsin Deficiency Management
The study demonstrates that never-smokers with severe AATD are not immune to lung disease. While never-smokers often have milder symptoms, a subset develops significant airflow obstruction that warrants augmentation therapy. Identification of index cases appears critical, as these patients are more likely to experience severe impairment.
These findings highlight the importance of early detection, ongoing monitoring, and individualised care strategies for all patients with severe AATD, regardless of smoking history. Clinical management should consider patient characteristics such as sex, BMI, comorbidities, and exacerbation history to optimise outcomes.
Reference
Premuda C et al. Lung disease in never-smokers with severe α1-antitrypsin deficiency: the EARCO Registry. ERJ Open Research. 2025;11(6):01279-2024.
