Pepsin like activity in bronchoalveolar lavage fluid is suggestive of gastric aspiration in lung allografts

Abstract

Background: A biologically plausible link between gastro-oesophageal reflux (GOR), aspiration, and lung allograft dysfunction has been suggested, but there is no systematic evidence indicating the presence of gastric contents in the lung. We have tested the hypothesis that pepsin, as a marker of aspiration, is detectable in bronchoalveolar lavage (BAL) fluid of allograft recipients who had not reported symptoms of GOR. Methods: Standardised 3660 ml surveillance BAL fluid samples from 13 chronologically sequential stable lung allograft recipients without chronic rejection (10 patients treated with a prophylactic proton pump inhibitor) were studied. Lavage supernatants were assayed by an ELISA based on a monospecific goat antibody for pepsin/pepsinogen. Pepsin levels were compared with those from four normal volunteer controls. Results: Pepsin levels were measurable in all allograft recipients, in keeping with gastric aspiration (median 109 ng/ml (range 35-1375)). In the control group the pepsin levels were below the limit of detection. Treatment with a proton pump inhibitor was not correlated with pepsin levels. There was no correlation between BAL fluid neutrophils and pepsin levels.Conclusion: These data demonstrate lung epithelial lining fluid concentrations of pepsin in lung allograft recipients which are much higher than blood reference levels, with no detectable pepsin in controls. This provides direct evidence of gastric aspiration, which is potentially injurious to the allograft.

Exhaled Breath Condensate Pepsin: Potential Noninvasive Test for Gastroesophageal Reflux in COPD and Bronchiectasis

“…The timing of EBC sample collection was selected at random and was irrespective of reflux symptoms; this may influence the ability to fully describe the relationship between gastroesophageal reflux and EBC pepsin. The relationship may also be influenced by the overall EBC pepsin concentrations, which are lower than median levels evident in bronchoalveolar lavage samples (8.3-541 ng/mL) in lung transplant recipients 10,11,14,[40][41][42] and in individuals with pharyngeal reflux (up to 200 ng/mL). 12,36,43 This lower concentration may be at the limit of the detection threshold for the enzyme-linked immunosorbent assay used in this study, which may influence the ability to detect a relationship in some patients.…”

“…However, this lack of association is consistent with some reports of pepsin present in upper airway samples in individuals with lung disease in whom a diagnosis of gastroesophageal reflux could not be confirmed by esophageal pH monitoring. [9][10][11][12][13]39 The DMS that was used to define gastroesophageal reflux in this study considers not only the frequency of reflux episodes but the position in which they occur (upright or supine) and their duration. 27,40 Short isolated reflux episodes that result in occult aspiration and influence pepsin concentrations in EBC and sputum may be sufficiently infrequent to be detected by esophageal pH monitoring.…”

“…Currently, pepsin may be detected in saliva, tracheal aspirates, or bronchoalveolar lavage fluid using proteolytic enzyme analysis 9 or immunoassays. [10][11][12][13][14] Although it has been recently demonstrated that pepsin is detectable in easily obtainable sputum samples of patients with COPD and bronchiectasis, 6 this method imposes limitations for individuals who are not regular producers of sputum or in conditions not associated with sputum production.…”

Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid

“…[2,3] Patients who reflux gastric content into the pharynx are at increased risk for aspiration, which can result in pulmonary complications such as chronic cough, asthma, pneumonia, fibrosis, and allograft rejection. [4][5][6] It is estimated that almost 10% of patients with GERD experience pulmonary manifestations; [4] although it is often difficult to effectively gauge the pulmonary consequences of GERD. [7] While pH monitoring is the gold standard for diagnosing GERD clinically, it is not an effective tool for predicting or identifying aspiration.…”

Gastro-oesophageal reflux disease and non-asthma lung disease

“…ROSEN et al [108] recently reported a series of 50 children undergoing bronchoscopy and combined oesophageal pH and impedance monitoring, and found no correlation between the LLMI and reflux events, endoscopic oesophagitis or response to fundoplication. Other BAL markers of aspiration, bile acids and pepsin, have been identified in patients with GERD and lung disease [115][116][117][118], but currently these markers have not been adequately studied as routine diagnostic tests.…”