A16-08 Severe Alpha-1 Antitrypsin Deficiency - Are Never- Smokers Disease Free?

Abstract Introduction Alpha-1 antitrypsin deficiency (AATD) is an under-diagnosed hereditary condition resulting from mutations in the SERPINA1 gene. Severe AATD (e.g., ZZ and Z Null genotype) can result in premature lung disease and airflow obstruction, especially in smokers. As smoking is directly linked to risk of lung disease, we evaluated never smoking individuals to assess their lung health at diagnosis and over time. Methods This is a retrospective Irish National AATD registry study. We evaluated 300 severely deficient ZZ participants attending our national centre of expertise in AATD. We evaluated baseline demographics at the time of diagnosis including age, smoking status and indication for testing. We evaluated lung health at diagnosis and on longitudinal assessment. Results Mean age of diagnosis was 45 years with no difference noted between ever and never smokers (47 v 42 years p = 0.28). 37% of our ZZ population are never smokers. Mean FEV1 % was 89% in never smokers compared to 64% in ever smokers (p = 0.0001). However, we note a significant heterogeneity in presentations amongst never smokers with a range in FEV1 % from 16 -142%. FEV1/FVC ratio was 0.72 at diagnosis in never smokers compared to 0.53 in ever smokers (p = 0.0001) with a range of 0.23-0.95 noted in never smokers. CT Thorax at diagnosis revealed evidence of early disease even in the setting of preserved spirometry. Baseline CT Thorax revealed 65% of never smokers had an abnormal first CT with 43% having emphysema and 69% bronchiectasis on initial lung imaging. In comparison, 82% of ever smokers had an abnormal first CT. Irish Longitudinal follow up of 300 ZZ registry participants, demonstrates that even never smokers experience a significant decline in lung function - see figure 1 below. Conclusion Two-thirds of ZZ never smokers have an abnormal CT at diagnosis highlighting structural disease is extremely common even without smoke exposure. People with AATD are diagnosed too late as evidenced by the radiological abnormalities at diagnosis and lung function decline even in never smoking individuals. Despite increased awareness of AATD and our national targeted detection program, we are still diagnosing people in their mid-40s with established COPD, even in never smokers. Consideration should be given to more effective screening and therapeutic interventions before significant disease burden is established. This abstract is funded by: None