The alpha-1 foundation research registry: smoking history and obstructive lung disease in alpha-1 antitrypsin deficiency patients in the united states

<bold>Introduction</bold>: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that affects the lungs and liver. While smoking is known to exacerbate lung damage in individuals with AATD, the effect can vary depending on genotype. <bold>Aim:</bold> To examine smoking history among AATD genotypes and the impact on lung disease. <bold>Methods:</bold> The Alpha-1 Research Registry is a retrospective patient-reported cohort of 3450 AATD patients. 1156 patients provided information regarding smoking history. <bold>Results:</bold> 712 patients reported to be current or ex-smokers (age 55 +/- 12.8 years) and 444 patients were non-smokers (age 56.7 +/- 13.8 years). Among ever-smokers, 38% were ZZ and 26% were MZ ; in non-smokers, 42% ZZ, 27% MZ. In ZZ ever smokers, 86% reported diagnosis of obstructive airway disease, 42.6% current oxygen use, and 65.7% current augmentation use vs. ZZ non-smoker 84.4% reported diagnosis of obstructive airway disease, 41.7% current oxygen use and 68.3% current augmentation use. In the MZ ever smoker, 66% reported diagnosis of obstructive airway disease, 20.7% current oxygen use and 20.7% current augmentation therapy; in MZ non-smokers, 49% reported a diagnosis of obstructive airway disease, 16.2% current oxygen use and 17.9% current augmentation use. <bold>Conclusion:</bold> The ZZ genotype was associated with higher incidence of obstructive lung disease with higher supplemental oxygen usage, irrespective of smoking status. Smokers with the MZ genotype had increased obstructive lung disease prevalence as compared to non-smokers. This highlights the importance of screening efforts to identify at risk individuals for targeted smoking avoidance or cessation efforts.