Abstract Background Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition predisposing to early-onset emphysema and liver disease. While the ZZ genotype is well-recognized as conferring an increased risk of lung and liver disease, the clinical significance of the SZ genotype remains less well-defined. SZ genotypes result in AAT levels which span the ‘putative protective threshold’ of 0.57g/L or 11μM. The SZ genotype confers a variable risk of developing lung disease influenced by environmental exposures, particularly cigarette smoke. This study aims to characterize lung health in SZ individuals at diagnosis and over time. Methods We included individuals with confirmed SZ genotype attending the National Centre of Expertise for AATD and enrolled in the Irish National AATD Registry. We evaluated demographic data, smoking history, and index status. Lung index cases refers to patients tested for AATD because of respiratory symptoms or abnormal lung function. Non-lung index refers to patients tested for AATD due to other reasons, such as liver symptoms or a family history of AATD. Pulmonary function tests (PFT) and lung imaging were analysed at baseline and on longitudinal evaluation. The rate of lung function decline was compared between subgroups . Results 142 participants with SZ genotype were evaluated with a mean age of diagnosis of 47 years. 53% of this cohort are ever-smokers with a mean pack year history of 23.19. To date, 73.3% are non-lung index referrals and 26.7% are lung index. Lung index SZ participants were diagnosed at an older age of 54.11 versus 45.7 years in the non-lung index cohort (p = 0.04). Lung health at diagnosis differs according to smoking status and index status. Mean FEV1 (% predicted) in ever-smokers was 82.88% versus 101.4% in never-smokers (p 0.0001). Ever-smokers had evidence of obstruction at diagnosis with a FEV1/FVC ratio of 0.67 versus 0.78 in never-smokers (p = 0.0001). Ever-smokers also had a lower DLCO (% predicted) of 78.72% versus 88.92% in never-smokers (p = 0.0187). Lung indexes had baseline FEV1% of 71.46% versus 97.59% (p 0.0001). Lung indexes had airflow obstruction at diagnosis (FEV1/FVC 0.61) compared to non-lung indexes (FEV1/FVC 0.75) (p = 0.0011). We will also present longitudinal lung outcomes. Conclusion This study explores the natural history of lung health in SZ AATD. Preliminary observations suggest that smoking and index status are key determinants of pulmonary function. The findings have implications for clinical monitoring, counselling regarding smoking cessation, and early detection of respiratory disease in SZ individuals. This abstract is funded by: None
McHugh et al. (Fri,) studied this question.