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.

Keywords: Aspiration; BOS; Bronchiolitis obliterans syndrome; GERD; Gastroesophageal reflux disease; Lung transplantation.

Fig. 1

BALF pepsin concentrations among 100 lung transplant patients: AAT disease (AATD) (n = 7), bronchiolitis obliterans organizing pneumonia (BOOP) (n = 1), CF (n = 14), COPD (n = 38), IPF (n = 24), Jo-1 syndrome (n = 1), lymphangioleiomyomatosis (LAM) (n = 1), pulmonary artery hypertension (PAH) (n = 2), pulmonary veno-occlusive disease (n = 1), sarcoidosis (n = 4), scleroderma (n = 1), pulmonary fibrosis (PF) from work exposure (n = 1), rheumatoid arthritis RA (n = 1), dermatomyositis (n = 1), polymyositis (n = 2), and pneumoconiosis (n = 1). The BALF pepsin concentrations were highest in those with IPF.

Fig. 2

Bronchoalveolar lavage fluid pepsin concentrations among the most common indications for lung transplantation: AAT (n = 7), CF (n = 14), COPD (n = 38), and IPF (n = 24). *P < 0.05 versus all other groups (Kruskal-Wallis post-hoc analysis).