Lung allograft injury improves after gastroesophageal reflux surgery by donor-derived cell-free DNA kinetics

Gastroesophageal reflux disease (GERD) and bile acid micro-aspiration are risk factors for the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Donor-derived cell-free DNA (dd-cfDNA) is a clinically validated plasma biomarker for acute rejection but also detects other types of allograft injury and can potentially be used to detect GERD and micro-aspiration. Here, we report a five-case single-center series of LT patients with confirmed GERD and micro-aspiration, treated by Toupet fundoplication and adjunctive laparoscopic procedures. dd-cfDNA fraction measured pre- and post- intervention demonstrated a decreasing trend in the state of molecular injury: 3.24% (IQR, 1.675-8.71) vs. 0.75% (0.165-1.825; p = 0.0625), respectively. All patients experienced clinical improvement (assessed by spirometry or resolution of recurrent aspiration pneumonia events). These data suggest that dd-cfDNA may have expanded utility as a non-invasive clinical tool to identify molecular injury sequelae of gastroesophageal reflux. Given the limited effective treatment options for CLAD, we envision an opportunity for the use of dd-cfDNA to reduce the risk of CLAD development when GERD is involved.