Anti-reflux therapy and mortality in patients with idiopathic pulmonary fibrosis and gastroesophageal reflux disease: a systematic review and meta-analysis

Gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) frequently coexist, with GERD potentially exacerbating IPF progression through microaspiration and pulmonary inflammation. This systematic review and meta-analysis assessed the impact of anti-reflux therapy, including proton pump inhibitors and H2-receptor antagonists, on mortality outcomes in IPF patients with concurrent GERD. A systematic search identified six eligible studies, including 2874 patients, for quantitative synthesis. Results indicate that anti-reflux therapy may reduce IPF-related mortality, with a pooled relative risk (RR) of 0.79 [95% confidence interval (CI): 0.55-1.33], although this finding was not statistically significant. However, no significant effect was observed on overall mortality (pooled RR: 0.97, 95% CI: 0.74-1.25). Study heterogeneity was moderate (I²=60%), reflecting variability in study designs, populations, and therapeutic regimens. The observational nature of most studies highlights the need for randomized controlled trials to better understand anti-reflux therapy’s role in IPF management. While anti-reflux therapy was associated with a potential reduction in IPF-related mortality (RR: 0.79, 95% CI: 0.55-1.33), no significant effect on overall mortality was observed (RR: 0.97, 95% CI: 0.74-1.25). Future research should also evaluate the long-term safety of anti-reflux therapy, given concerns about complications such as infections and renal impairment. This analysis underscores the importance of tailored treatment approaches in IPF patients with GERD to optimize clinical outcomes.