Association between Pepsin in Bronchoalveolar Lavage Fluid and Prognosis of Chronic Fibrosing Interstitial Lung Disease

Abstract

Chronic fibrosing interstitial lung disease (ILD)s are characterized by chronic progressive fibrosis of lung which include idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPF is an irreversible fibrotic lung disease which results in respiratory failure. Although NSIP and CTD-ILD can be improved or stable by treatment with corticosteroid or immunosuppressant, some of them progress to fibrotic lung diseases. Aspiration of gastric contents is suggested as an aggravating factor of ILDs. We measured pepsin, a marker of gastric aspiration, in bronchoalveolar lavage (BAL) fluid of chronic fibrosing ILD patients to evaluate the association between BAL fluid pepsin and prognosis of chronic fibrosing ILDs. Patients with chronic fibrosing ILDs, who underwent bronchoscopy between December 2010 and April 2015 were prospectively enrolled. Pepsin levels were measured using a commercial ELISA kit. Clinical characteristics, lung function data, and mortality were analyzed. Fifty-one patients with chronic fibrosing ILDs were enrolled (26 with IPF, 15 with NSIP, and 10 with CTD-ILD). Pepsin levels in BAL fluid were 69.87 ± 74.16 ng/mL in IPF, 110.68 ± 94.93 ng/mL in NSIP, and 101.87 ± 88.44 ng/mL in CTD-ILDs. There were no statistically significant differences in BAL fluid pepsin levels among patients with the different chronic fibrosing ILDs. In multivariate regression analysis, higher BAL pepsin levels were associated with higher mortality (adjusted odds ratio [aOR] = 1.021, p = 0.025). BAL fluid pepsin may be used as a prognostic marker for predicting mortality in chronic fibrosing ILD patients.

Keywords: aspiration; bronchoalveolar lavage fluid; interstitial lung disease; pepsin; pulmonary fibrosis.