The presence of pepsin in the lung and its relationship to pathologic gastro‐esophageal reflux

Abstract

Background Pepsin has been proposed as a biomarker of reflux related lung disease. It is the goal of this study to determine 1) if there is a higher reflux burden as measured by pH-MII in patients that are pepsin positive in the lung and 2) the sensitivity of pepsin in predicting pathologic reflux by pH, MII and EGD. Methods We recruited children between the ages of 1–21 with chronic cough or asthma undergoing bronchoscopy, esophagogastroduodenoscopy (EGD), and multichannel intraluminal impedance (pH-MII) probe placement. The reflux profiles were compared between those patients that were pepsin positive and negative; proportions were compared using Chi square analyses and means were compared using t testing. Key Results Only the mean number of non-acid reflux events was associated with pepsin positivity (0.04). The sensitivity and specificity of pepsin in predicting pathologic reflux by pH-MII or EGD was 57% and 65% respectively. The positive predictive value of pepsin in predicting pathologic reflux by pH, MII or EGD was 50% (11/22) and the negative predictive value was 71% (20/28). There was a significantly higher mean LLMI in patients that were pepsin positive compared to pepsin negative patients (81±54 vs. 47±26, p=0.001). Conclusions and Inferences Lung pepsin cannot predict pathologic reflux in the esophagus but its correlation with lung inflammation suggests that pepsin may be a important biomarker for reflux-related lung disease.

Salivary Pepsin Lacks Sensitivity as a Diagnostic Tool to Evaluate Extraesophageal Reflux Disease

“…Previous studies evaluated salivary pepsin for predicting reflux burden. However, although initial studies suggested a relationship between BAL pepsin and proximal acid reflux measured by pH-metry, studies using pH-MII failed to corroborate these earlier findings 10,12,32 . One of the limitations of using BAL pepsin as a biomarker is that sampling requires bronchoscopy under anesthesia, which is again both expensive and invasive.…”

“…Pepsin is a proteolytic enzyme produced in the stomach, so its presence in the oropharynx and tracheobronchial tree suggests reflux and resultant aspiration. Higher pepsin levels have been reported in tracheal aspirates and bronchoalveolar lavage (BAL) fluid from children with chronic cough and proximal reflux (as measured by pH-metry), and may represent more severe pediatric lung disease 9–12 . Bronchoscopy is an invasive diagnostic procedure, therefore alternative methods to measure pepsin are sought.…”

Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs

“…As described above, several studies have demonstrated that pepsin regulates the physiology of airway epithelial cells (18,32,34), including cell survival and generation of inflammatory cytokines (18). Given the known enzymatic action of pepsin and injurious effects of other nonacidic components of gastric juice on lung parenchyma, the potential implications of gastric reflux in the pathobiology of pulmonary fibrosis are evident.…”

Chronic cough

“…21 Pepsin levels in the lung only weakly correlated with non-acid reflux burden and did not correlate with any other reflux parameters. 21 Another recent study found that pepsin levels were similar in patients with and without cough. 20 At this time, the routine use of pepsin levels to diagnose cough related reflux cannot be recommended and the search for biomarkers with adequate sensitivity and specificity remains elusive.…”

“…19–21 However, a recent study in children determined that pepsin levels in the lung for predicting reflux disease (by pH or pH-MII) had a PPV of only 50% and NPV of 71%. 21 Pepsin levels in the lung only weakly correlated with non-acid reflux burden and did not correlate with any other reflux parameters. 21 Another recent study found that pepsin levels were similar in patients with and without cough.…”