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

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease ) be treated with antacid medication or ) undergo antireflux surgery to improve respiratory outcomes?" 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 ) compared antacid medication to placebo or no medication or ) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.