B44-08 Alpha-1 Antitrypsin Carrier Genotype and the Risk of COPD Exacerbations: An Update

Abstract Introduction Alpha-1 Antitrypsin (A1AT) is a member of the serpin family of serine protease inhibitors. It has antiprotease activity and inhibits serine proteases including neutrophil elastase. It is produced by the liver and severe A1AT deficiency is associated with lung and liver disease and is inherited in an autosomal codominant pattern. Studies have shown that patients with A1AT carrier genotypes and those who smoke are at increased risk for developing COPD and having recurrent exacerbations as well as other chronic lung diseases. We present an updated analysis examining the relationship between A1AT carrier genotypes and the risk of COPD exacerbations (COPDe). Methods This is an ongoing study that is actively enrolling patients and being conducted at the University of Florida - Jacksonville. The study population includes patients with confirmed obstruction on spirometry who have undergone testing with AlphaIDTM. IRB approval was obtained, and patient informed consent was waived for this study. We collected demographic data, alpha-1 genotype and protein levels, if available, along with number of COPDe. A chi-square test was used to compare groups, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results We collected data from a total of 174 patients. The average age of patients was 65 years. 54% were female. 70% were identified as Caucasian. 59% had Medicare as their primary insurance payor. 37% were current smokers. The most common comorbidity was hypertension (75%). 23% of patients had concomitant bronchiectasis. 87% (152) had a normal genotype (PiMM) while the remaining were heterozygous. Of these, 11 were PiMS, 8 were PiMZ, 2 were PiMF and 1 was PiSZ. Exacerbations occurred in 52.6% of patients with PiMM genotype (80 of 152) and 50% of patients with the heterozygous genotype (11 of 22). 6 of 11 patients with PiMS had exacerbations as well as 4 of 8 patients with PiMZ and 1 patient with PiSZ. There was no statistically significant association between alpha-1 genotype and exacerbation status (p = 0.93). The OR for exacerbations in the heterozygous group compared with the normal group was 1.11 (95% CI 0.45-2.71). Conclusion In this updated cohort, being heterozygous for A1AT was not associated with a statistically significant increased risk for COPD exacerbations. As patient enrollment and A1AT testing continues, further analysis with larger sample sizes may provide further insight into the relationship between A1AT carrier genotype and COPDe which may in turn guide individualized management and improve outcomes. This abstract is funded by: None