B44-06 Baseline Clinical Characteristics of Individuals in the Alpha-1 Biomarker Consortium

Abstract Introduction Alpha-1 antitrypsin deficiency (AATD) is the most common genetic etiology of chronic obstructive pulmonary disease (COPD), with considerable phenotypic variability among affected individuals sharing disease-causing variants. A multi-center longitudinal cohort study of participants with PiZZ AATD was established to examine disease heterogeneity and natural history in an era of broad access to testing and augmentation therapy. Methods The Alpha-1 Biomarker Consortium was established across nine US-based centers. PiZZ AATD participants completed clinical questionnaires, spirometry, and quantitative CT imaging on enrollment with planned 18-month and 36-month follow-up. Continuous variables were summarized as mean±SD and compared with Welch’s t-test; categorical variables with Fisher’s exact test. Two-sided p 0.05 was considered significant. Analyses were performed in R (version 4.5.1). Study design was approved by the Western Institutional Review Board-Copernicus Group (WCG). Results Of the 275 participants enrolled, 146 were on augmentation therapy at enrollment, and 129 were non-augmented. Those augmented were significantly older at time of AATD diagnosis (50±14 years vs. 39±19, p 0.001). There was an average lag time of 5.1 years between diagnosis and augmentation therapy, with initiation at an average age of 55 years. More participants on augmentation therapy had AECOPD in the year prior to enrollment (49% vs. 16%, p 0.001), with an average of 0.84 vs. 0.27 exacerbations per year across the groups. Those on augmentation therapy had a higher former smoking prevalence (47% vs. 19%), and while smoking amounts were low overall, cumulative pack-years were higher in the augmented group (7±13 pack-years vs. 2±6, p 0.001). There was a higher number of clinical COPD diagnoses in the augmented group (91% vs. 32%) vs. non-augmented, but age at COPD diagnosis was similar (53±11 years augmented vs. 55±12 non-augmented), as were rates of asthma between groups (32% vs. 35%). Airflow obstruction was more significant in the augmented group (FEV1/FVC 0.51±0.16 vs 0.74±0.14 non-augmented) with more CT evidence of emphysema (PERC15 -956±22.3 HU augmented vs. -922±24.3 non-augmented). Healthstatus scores demonstrated higher COPD symptom burden in augmented participants across SGRQ, CAT and mMRC. Conclusion A1BC is a contemporary PiZZ AATD cohort with detailed metrics of disease severity, comprised of individuals with a wide range of clinical phenotypes. As expected, participants on augmentation therapy had more cigarette smoke exposure, airflow obstruction, and emphysema compared to those not on augmentation. The longitudinal data collection and follow-up assessments will facilitate a systematic evaluation of disease heterogeneity and identify factors associated with disease severity and progression. This abstract is funded by: NIH, Alpha-1 Foundation