Biomarkers of aspiration in gastroesophageal reflux-related respiratory disease: A scoping review

PURPOSE: The link between gastroesophageal reflux disease (GERD) and pulmonary damage caused by recurrent aspiration is becoming clearer; however, clinical identification remains challenging. We conducted a scoping review to summarize research on diagnostic biomarkers for detecting aspiration in patients with GERD-related respiratory diseases. METHODS: We conducted a literature search for articles published from January 1998-November 2024 via MEDLINE, ScienceDirect, the Cochrane Library, Taylor & Francis, and ClinicalTrials.gov. Articles on biomarkers for detecting GERD-related aspiration in patients with chronic cough, asthma, idiopathic pulmonary fibrosis, and allograft rejection were included. Non-peer reviewed studies, case reports, small case series, and studies on other respiratory conditions were excluded. Two reviewers confirmed the eligibility of the screened publications. The research landscape was mapped, and co-authorship network analysis was performed. The potential for biomarker translation into clinical practice was assessed using six "ideal" characteristics. RESULTS: Sixty-eight publications were included: 18 narrative reviews (26.5 %), 7 pre-clinical studies (10.3 %), and 43 clinical studies (63.2 %). Within these studies, 126 biomarkers were identified (molecular or biochemical [65.1 %], physiological [12.7 %], genetic [9.5 %], histological [8.7 %], and radiological [4 %]). Only 18 (14.3 %) were rated as highly valuable for translation. The research network analysis revealed a lack of collaborative efforts between institutions. CONCLUSION: Currently, a reliable biomarker of aspiration and GERD-related pulmonary damage is not available. However, duodenogastric products (pepsin and bile acids) in bronchoalveolar lavage fluid, functional tests (airway impedance and esophageal pH monitoring), imaging (swallow studies, chest CT, and scintigraphy), and blood biomarkers (KL-6 and antibodies against lung self-antigens) show the best potential for translation and clinical use.