Treatment of Gastroesophageal Reflux in Patients With Idiopathic Pulmonary Fibrosis A Systematic Review and Meta-Analysis

BACKGROUND: Gastroesophageal reflux (GER) is common in patients with idiopathic pulmonary fibrosis (IPF) and has been proposed as a potential contributor to disease progression and exacerbation. Whether treatment of GER improves health outcomes in patients with IPF is controversial. Our objective was to review the efficacy and safety of GER treatments in IPF. METHODS: We performed a systematic review and meta-analysis, using MEDLINE, Embase, Central (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov. These databases were searched from their inception, and Google Scholar and conference abstracts were searched until September 2017 without language restrictions for randomized and observational studies evaluating the effects of pharmacologic or nonpharmacologic treatment. Primary outcomes were IPF-related mortality and all-cause mortality. Evidence was evaluated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The study was registered with PROSPERO (#CRD42017076257). RESULTS: Thirteen observational studies were identified through the search strategy, and eight were included in the meta-analysis. Pharmacologic treatment of GER was associated with a significant reduction in IPF-related mortality as compared with no GER treatment (unadjusted risk: HR, 0.60; 95% CI, 0.38-0.97; P = .04; I-2 = 0%; three studies; N = 2,033; adjusted risk: HR, 0.45; 95% CI, 0.24-0.84; P = .01; I-2 = 0%; three studies; N = 2,033) but not all-cause mortality (unadjusted: HR, 0.73; 95% CI, 0.45-1.2; P =.22; I-2 = 46%; three studies; N = 1,316; adjusted: HR, 0.76; 95% CI, 0.31-1.84; P = .54; I-2 = 89%; four studies; N = 1,585). The quality of evidence for these outcomes was low. CONCLUSIONS: Low-quality evidence suggests pharmacologic treatment of GER is associated with a reduction in IPF-related mortality but not overall mortality. Randomized trials of antacid therapy in IPF are needed.