Meta-analysis of Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis

BACKGROUND: The relationship between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) is controversial. Current guidelines recommend that clinicians use regular antacid treatment, while two recent meta-analyses of antacid therapy in IPF were inconclusive. The objective of this study was to examine the evidence regarding the association between GERD and IPF through a systematic review and a meta-analysis, with special reference to the methodologic quality of the observational studies. METHODS: The MEDLINE, EMBASE, Ovid, and Web of Science (1966-May 2018) databases were searched for original articles published in any language, and we then systematically reviewed the bibliographies of the retrieved articles. Observational studies (cohort and case-control studies) were selected if they allowed the calculation of a measure of association relating GERD to IPF. RESULTS: Eighteen case-control studies including 3,206 patients with IPF and 9,368 control subjects met the inclusion criteria of the meta-analysis. The meta-analysis indicated that GERD is associated with IPF (OR, 2.94 [95% CI, 1.95-4.42]; P homogeneity < .0001). Overall, the results remained consistent whatever the data source (clinical studies vs databases) or the type of control subject (healthy volunteers, patients with respiratory diseases other than interstitial lung disease, or patients with non-IPF interstitial lung disease). In a meta-regression, after controlling for smoking, GERD and IPF were not related. CONCLUSIONS: GERD and IPF may be related, but this association is most likely confounded, especially by smoking. Our confidence in the estimate of association is low because it is exclusively from case-control studies.