# Does Extraesophageal Reflux Support the Development of Lung Adenocarcinoma? Analysis of Pepsin in Bronchoalveolar Lavage in Non-Smoker Patients

## TL;DR

This study found no evidence that extraesophageal reflux, measured by pepsin in lung fluid, is linked to lung adenocarcinoma in non-smokers.

## Contribution

The study provides new evidence refuting the role of extraesophageal reflux in lung adenocarcinoma among non-smokers.

## Key findings

- No significant difference in pepsin levels was found between lung adenocarcinoma patients and controls.
- After excluding hemorrhagic samples, pepsin levels were lowest in lung adenocarcinoma patients.
- The study rigorously excluded smokers and used histological verification to minimize bias.

## Abstract

In our study, we investigated the association between pepsin levels in bronchoalveolar lavage and factors such as hemorrhagic/non-hemorrhagic character of BAL, type of lung disease, tumor location, patient demographics, and smoking history. Our objective was to investigate the possible influence of extraesophageal reflux on the development of lung adenocarcinoma. Contrary to our hypothesis, we did not find significant differences in pepsin levels among patients with lung adenocarcinoma, pulmonary metastases, and lung sarcoidosis. Pepsin levels were even lower in lung adenocarcinoma patients after excluding hemorrhagic samples. By rigorously excluding smokers and carefully classifying patients, we minimized biases common in similar studies. However, our study was limited by small sample sizes, especially in the sarcoidosis group, and the absence of standardized thresholds for BAL pepsin as a reflux biomarker.

The significance of extraesophageal reflux as a risk factor in lung adenocarcinoma has been understudied. In this study, we investigated whether extraesophageal reflux leads to higher pepsin concentrations in bronchoalveolar lavage (BAL) in patients with lung adenocarcinoma compared to controls. Subjects were recruited from non-smoker patients (lifelong non-smokers and ex-smokers with more than 5 years of non-smoking history) who had undergone bronchoscopy due to pulmonary abnormalities on a CT scan and met the inclusion criteria. Based on histological verification of the lung process, the patients were divided into three groups: (1) lung adenocarcinoma, (2) pulmonary metastases, and (3) lung sarcoidosis. Lung adenocarcinoma cases were further categorized as central or peripheral. BAL samples collected during bronchoscopy were quantitatively analyzed by enzyme-linked immunosorbent assay (ELISA) to measure pepsin levels. No statistically significant difference in pepsin concentration was observed between the lung adenocarcinoma group and control groups (p = 0.135). After excluding hemorrhagic BAL samples, the pepsin concentration was significantly the lowest in patients with lung adenocarcinoma (p = 0.023) compared to the control groups. The results of the study do not support the hypothesis of a higher occurrence of extraesophageal reflux (evaluated as the amount of pepsin in BAL) in non-smoker patients with lung adenocarcinoma.