Pepsin, a Biomarker of Gastric Aspiration in Lung Allografts

Stovold, Rachel; Forrest, Ian; Corris, Paul A.; Murphy, Desmond M.; Smith, Jaclyn A.; Decalmer, S; Johnson, Gail; Dark, John H.; Pearson, Jeffrey P.; Ward, Chris

doi:10.1164/rccm.200610-1485oc

Cited by 161 publications

(116 citation statements)

References 33 publications

(34 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…30 Sputum and EBC pepsin concentrations were tested using a locally developed enzyme-linked immunosorbent assay based on a monospecific antibody to porcine pepsin. 11,32 Polystyrene microtiter plates (MaxiSorp, Nunc, Roskilde, Denmark) were coated with goat anti-pepsin antibody, diluted in carbonate-bicarbonate buffer at 0.1 g/mL, and incubated for 4 h. After washing, wells were incubated with a blocking buffer (1% bovine serum albumin) and stored at 4°C overnight. For the assay, wells were washed, and enzyme controls (for standard curve) and clinical samples were added in duplicate.…”

Section: Sputum and Ebc Sample Collectionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Sputum and Ebc Sample Collectionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2014

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“…It was declared that pepsin and bile salt, acts as biomarkers of microaspiration specific to gastrointestinal tract (GIT), have been measured in respiratory tract. Normally there is no pepsin in lower respiratory tract and not always GER patients have elevated pepsin level in their BAL fluid [12]. Interestingly, the highly specific and sensitive method for diagnosing GER -associated with respiratory tract aspiration is measurement of pepsin level in BAL.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Bronchoalveolar Lavage Pepsin Level in Idiopathic Pulmonary Fibrosis

Said¹,

Alsowey²,

Ibraheem³

2017

Zagazig University Medical Journal

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Background: Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause.Recently, there is increasing evidence supporting a relationship between gastroesophageal reflux, microaspiration, and IPF, since the diagnostic gold-standard for microaspiration remains unknown. So, the aim of this study is to assess the presence of chronic microaspirates by bronchoalveolar lavage pepsin level in these patients. Patients and method: A case -control study was conducted at Chest Department and outpatient clinics Faculty of Medicine, Zagazig University hospitals in the period from (February 2013 till January 2016) on thirty patients with stable interstitial lung diseases (ILD).they were divided into two groups: 15 patients (group I) with stable idiopathic pulmonary fibrosis (IPF), another 15 patients (group II) stable ILD other than IPF. Both groups underwent pulmonary function tests (PFTs), Pulmonary HRCT and Bronchoscopy. Measurement of bronchoalveolar lavage pepsin level was done for all patients. Results: 80% of IPF patients complained from gastroesophageal reflux with a statistically significant decrease in PaO 2 , FEV 1 and FVC than in non IPF patients.Bronchoalveolar lavage pepsin level was (43.711.4ng/ml) in IPF group, which was significantly higher than non IPF group (32.710.5 ng/ml).Also total cell count in IPF patients were increased significantly including neutrophils, alveolar macrophages and red blood. Increased reticulation on HRCT for IPF patients group were associated with higher BAL pepsin levels (p <0.01). Regression coefficient revealed the most powerful predictor of IPF severity were; HRCT findings: reticulation score,honeycombing score[(Odds ratio(95%CI)=5.3 (1.9 to14.9), 7.8 (2.7 to 22.3)respectively],pepsin level[(Odds ratio(95%CI)=4.6 (1.9-11.4)],FEV1 and FVC[(Odds ratio(95%CI)=3.7 (1.6 to 8.9), 3.2 (1.4 to 7.5)respectively].while gastroesophageal reflux symptom [(Odds ratio(95%CI)=1.04(0.94-1.14)] was the least powerful predictor. Conclusion: Gastroesophageal reflux or microaspiration is common in patients with IPF, associated with elevated levels of pepsin in BAL fluid.

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