Abstract Introduction Bronchiectasis is a chronic respiratory disease characterized by chronic cough, sputum production, and recurrent lower respiratory tract infections with radiographic features of irreversible bronchial dilatation. Neutrophil elastase (NE) is believed to play a key role in the pathogenesis of bronchiectasis. NE activity was associated with airway bacterial load and radiological bronchiectasis and its activity is inhibited by anti-proteinases including serum-derived alpha-1 antitrypsin (A1AT). In this study, we sought to examine the relationship between A1AT carrier genotypes and the risk of non-cystic fibrosis (CF) bronchiectasis exacerbations. Methods This study is being conducted at the University of Florida - Jacksonville and is actively recruiting participants who have been tested for A1AT and have non-CF bronchiectasis. Participants with evidence of radiographic bronchiectasis irrespective of distribution and severity were included. Institutional review board approval was obtained and patient informed consent was waived for this study. For each patient in this cohort, we collected demographic data, data on alpha-1 genotype as well as A1AT protein levels, if available, along with details of exacerbations including steroid use, emergency room visits and hospitalizations. Frequency of exacerbations between individuals with normal and carrier genotypes was compared using Fisher’s exact test due to small expected counts. Results A total of 278 patients underwent A1AT testing out of which 76 had evidence of radiographic bronchiectasis. The average age was 63.1 years. 63% were female and 70% were Caucasian. 55% of patients had Medicare as their primary insurance payor. 37% of patients were current smokers. The most common comorbidity was hypertension (67%). 65% of patients had COPD and 15% of patients had asthma. 69 patients had PiMM genotype with the remaining patients having a carrier genotype (3 with PiMS, 3 with PiMZ and 1 with PiMP). Exacerbations occurred in 37.7% of patients with normal genotype and in 57.1% of patients with the carrier genotype. Fisher’s exact test showed no statistically significant difference (p = 0.56). The odds ratio for exacerbations in carriers compared to the normal genotype was 0.45 (95% CI, 0.09-2.23). Conclusion In this preliminary analysis of patients with radiographic bronchiectasis, there was no statistically significant increased risk for bronchiectasis exacerbations among patients with normal genotype and a carrier genotype. Notably, we found that a large number of patients with bronchiectasis also had COPD. Further analysis with a larger sample size as testing for A1AT continues may establish a relationship between A1AT genotype and risk of bronchiectasis exacerbations in the future. This abstract is funded by: None
Boppana et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: