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

Abstract

BACKGROUND: Acid gastroesophageal reflux is a common problem in non-cystic fibrosis bronchiectasis and COPD. Invasive methods are used to diagnose gastroesophageal reflux, but the ability to detect pulmonary microaspiration of gastric contents using this method is unclear. A noninvasive option to detect pulmonary microaspiration is to measure pepsin in exhaled breath condensate (EBC), but this has not been related to esophageal pH monitoring in these lung conditions. This study aimed to measure pepsin concentrations and pH in EBC and to determine the relationship to gastroesophageal reflux in bronchiectasis or COPD. METHODS: Subjects with bronchiectasis (n ‫؍‬ 10) or COPD (n ‫؍‬ 10) and control subjects (n ‫؍‬ 10) completed 24-h esophageal pH monitoring for detection of acid gastroesophageal reflux, measuring the percentage of reflux time in the proximal esophagus and the DeMeester score (DMS). Concurrently, 3 samples of EBC were collected from each subject, and pH was measured and pepsin concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: EBC pepsin was detected in subjects with bronchiectasis (44%) or COPD (56%) and in control subjects (10%). A diagnosis of gastroesophageal reflux was not associated with a higher concentration of EBC pepsin in bronchiectasis (P ‫؍‬ .21) or COPD (P ‫؍‬ .11). EBC pepsin concentration did not correlate with DMS (r s ‫؍‬ 0.36) or proximal reflux index (r s ‫؍‬ 0.25) in subjects with bronchiectasis or with DMS (r s ‫؍‬ 0.28) or proximal reflux index (r s ‫؍‬ 0.21) in patients with COPD. EBC and sputum pepsin concentrations were moderately correlated in bronchiectasis (r s ‫؍‬ 0.56) and in COPD (r s ‫؍‬ 0.43). CONCLUSIONS: Pepsin is detectable in EBC samples in bronchiectasis and COPD. Although no association was found between pepsin concentrations and a diagnosis of gastroesophageal reflux, a moderate relationship between sputum and EBC pepsin concentrations suggests that EBC pepsin may be a useful noninvasive marker of pulmonary microaspiration.

Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24‐hour esophageal impedance/pH monitoring in pediatric patients

“…Gastro‐esophageal reflux is common in infants and children and can be assessed using diagnostic tests such as esophageal pH monitoring and MII/pH . Salivary pepsin has been studied as a potential noninvasive diagnostic method for gastric reflux in adults and children . Because pepsin is normally produced only by gastric chief cells in the stomach and is absent from the oropharynx, the presence of pepsin in the saliva is evidence that a gastro‐esophageal reflux event has reached the oropharynx.…”

“…Measurement of gastric pepsin 3b (pepsin A‐4) in the oropharynx has been studied as a noninvasive method to detect oropharyngeal reflux in both adults and children . Because pepsin A is normally found only in gastric juice, it has been hypothesized that GER events positively correlate with the presence of oropharyngeal pepsin .…”

“…Measurement of gastric pepsin 3b (pepsin A-4) in the oropharynx has been studied as a noninvasive method to detect oropharyngeal reflux in both adults and children. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] Because pepsin A is normally found only in gastric juice, it has been hypothesized that GER events positively correlate with the presence of oropharyngeal pepsin. 8 To test this hypothesis, we analyzed individual saliva samples collected at varying time periods following impedance-detected GER episodes for the presence of gastric pepsin Additionally, we used validated GERD questionnaires 19,20 to objectively assess clinical symptoms in all subjects.…”

Current and future perspectives in the management of gastroesophageal reflux disease

“…Another direct, but not widely used, test is pepsin immunoassay in bronchial lavage and saliva or the measurement of pepsin in exhaled breath condensate. This latter test detected microaspiration in 56% of patients with COPD, but did not correlate to 24‐h pH monitoring results . Assessing bile acids in saliva and bronchial lavage is less useful in clinical practice, but again correctly demonstrates the microaspiration in the lung.…”

“…This latter test detected microaspiration in 56% of patients with COPD, but did not correlate to 24-h pH monitoring results. 102 Assessing bile acids in saliva and bronchial lavage is less useful in clinical practice, but again correctly demonstrates the microaspiration in the lung.…”