Antacid Medication and Antireflux Surgery in Patients with Idiopathic Pulmonary Fibrosis A Systematic Review and Meta-Analysis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumoniawith impaired survival. Previous guidelines recommend antacidmedication to improve respiratory outcomes in patientswith IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana del Torax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacidmedication or 2) undergo antireflux surgery to improve respiratory outcomes?"Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Metaanalyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacidmedication,when two studieswere aggregated, therewas no statistically significant effect on disease progression, defined as a 10% ormore decline in FVC,more than 50-mdecline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03).Aseparate study that could not be included in themetaanalysis found no statistically significant effect on disease progression when defined as a 5% ormore decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progressionwhen defined as a 10% ormore decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, therewas also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26).Neither antacid medications nor antireflux surgerywas associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patientswith IPF,most ofwhomhad not had abnormalGER confirmed. Well-designed and adequately powered prospective studieswith objective evaluation forGER are critical to elucidate the role of antacidmedication and antireflux surgery for respiratory outcomes in patientswith IPF.