Bpifa1 Expression In Asthmatics

Introduction: Studies on the ubiquitous airway protein bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1) have revealed important roles in reducing eosinophilic airway inflammation, relaxing airway smooth muscle, and defending against microbial infection. Aims and Objectives: The objective of this study was to test the hypothesis that BPIFA1 expression is reduced in asthmatics. Methods: BPIFA1 protein levels were measured by ELISA from bronchoalveolar lavage (BAL) supernatants from twenty mild asthmatics and twenty normal volunteers who underwent research bronchoscopy at our center. BPIFA1 gene expression in airway epithelia was analyzed from seven transcriptomic studies involving 355 asthmatics and 193 controls (Tsai et al. ERJ. 2018;51). Results: The concentration of BPIFA1 was significantly lower in BAL samples from asthmatics compared to normal volunteers (9 + 3 vs. 38 + 8 ng/mL, p<0.005). This decrease in BPIFA1 concentration in asthmatics was independent of gender, asthma control medication, and atopic status. Meta-analysis of BPIFA1 expression in epithelia obtained by bronchial brushings was found to be consistently down regulated in asthmatic subjects compared to normal volunteers. Overall, the reduction in BPIFA1 expression was both statistically significant (p=2.3x10-3) and of large effect (-0.5). Conclusions: BPIFA1 protein and BPIFA1 mRNA expression is reduced in the airways and airway epithelia of asthmatics, respectively, suggesting that reduced protein levels are due to down-regulation of expression rather than degradation. Further research characterizing BPIFA1 levels in larger numbers of asthmatics with well-defined phenotypes will help determine if BPIFA1-deficiency contributes to asthma pathogenesis.