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Updated: Jul 5, 2025
Author Spotlight: Investigating the Key Factors of Obliterative Bronchiolitis After Lung Transplantation
Published on: November 10, 2023
Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft
Rayoun Ramendra1, Allen Duong1, Chen Yang Kevin Zhang1
1Toronto Lung Transplant Program, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.
Background:
Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant.
Methods:
Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs.
Results:
PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4.
Conclusions:
Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.
Insights
Airway pepsinogen A4 (PGA4) is a novel biomarker for aspiration in lung transplant recipients. Elevated PGA4 levels predict chronic lung allograft dysfunction (CLAD) and indicate a need for anti-reflux surgery.
Area of Science:
- Pulmonary Medicine
- Transplantation Immunology
- Gastroenterology
Background:
- Aspiration is a significant risk factor for poor outcomes following lung transplantation.
- Current biomarkers like airway bile acids may be confounded by gastrointestinal motility.
- Previous studies on total airway pepsin have yielded inconsistent results regarding post-transplant outcomes.
Purpose of the Study:
- To investigate the utility of airway pepsinogen A4 (PGA4) as a specific biomarker for aspiration.
- To determine if airway PGA4 can predict adverse outcomes, specifically chronic lung allograft dysfunction (CLAD), in lung transplant recipients (LTRs).
Main Methods:
- Compared PGA4 expression in lung tissue versus other pepsinogens.
- Quantified total pepsin and PGA4 in bronchial washings from LTRs.
- Assessed PGA4 association with aspiration markers and CLAD risk in two independent LTR cohorts.
- Evaluated PGA4 changes post-anti-reflux surgery in a third cohort.
Main Results:
- PGA4 is expressed in the stomach but not native lung tissue.
- Airway PGA4 levels, unlike total pepsin, correlated significantly with aspiration.
- Elevated airway PGA4 was associated with an increased risk of developing CLAD in LTRs.
- Anti-reflux surgery led to a reduction in airway PGA4 levels.
Conclusions:
- Airway PGA4 serves as a reliable biomarker for aspiration in lung transplant recipients.
- PGA4 measurement can identify LTRs at high risk for CLAD.
- Routine PGA4 assessment during surveillance bronchoscopy can guide the decision for anti-reflux interventions.
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