Pepsin concentrations are elevated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis after lung transplantation

Abstract

Background Aspiration of gastroesophageal refluxate has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the progression of bronchiolitis obliterans syndrome after lung transplantation. The goals of the present study were to identify lung transplant patients at the greatest risk of aspiration and to investigate the causative factors. Materials and methods From September 2009 to November 2011, 252 bronchoalveolar lavage fluid (BALF) samples were collected from 100 lung transplant patients. The BALF pepsin concentrations and the results of transbronchial biopsy, esophageal function testing, barium swallow, and gastric emptying scan were compared among those with the most common end-stage lung diseases requiring lung transplantation: IPF, chronic obstructive pulmonary disease, cystic fibrosis, and α1-antitrypsin deficiency. Results Patients with IPF had higher BALF pepsin concentrations and a greater frequency of acute rejection than those with α1-antitrypsin deficiency, cystic fibrosis, or chronic obstructive pulmonary disease (P = 0.037). Moreover, the BALF pepsin concentrations correlated negatively with a lower esophageal sphincter pressure and distal esophageal amplitude; negatively with distal esophageal amplitude and positively with total esophageal acid time, longest reflux episode, and DeMeester score in those with chronic obstructive pulmonary disease; and negatively with the upright acid clearance time in those with IPF. Conclusions Our results suggest that patients with IPF after lung transplantation are at increased risk of aspiration and a greater frequency of acute rejection episodes, and that the risk factors for aspiration might be different among those with the most common end-stage lung diseases who have undergone lung transplantation. These results support the role of evaluating the BALF for markers of aspiration in assessing lung transplant patients as candidates for antireflux surgery.

Role of gastroesophageal reflux disease in lung transplantation

“…Numerous studies have documented increased levels of pepsin in BAL of patients following lung-transplantation[35,78,79,84]. In a small study by Ward et al[79], pepsin was present in the BAL of all lung allografts, while not detected in the control group.…”

Protective Effect of Proton Pump Inhibitor for Survival in Patients with Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis

“…7,8,12,[14][15][16][17] This is supported by the lower pH or elevated concentrations of pepsin in bronchoalveolar lavage in patients with IPF. 18,19 Esophageal manometry in patients with GERD and IPF shows decreased lower esophageal sphincter pressure (LESP) with normal esophageal function, and further decreased upper esophageal sphincter pressure than LESP. 6,20 These findings may explain why typical symptoms such as heartburn are uncommon in patients with IPF.…”

Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non‐fibrotic disease among pre‐lung transplant patients

“…While proton‐pump inhibitor (PPI) therapy is widely used for symptomatic GER, the effect of acid suppression on pulmonary outcomes in IPF patients has not been definitively established, although a few studies have shown some benefits . Studies evaluating broncho‐alveolar lavage of patients with IPF demonstrated an increase in both pepsin and bile acids, suggesting that non‐acid reflux may also play a role in the pathogenesis or progression of IPF. Furthermore, Linden et al .…”