- Gastroesophageal reflux disease (GERD) is associated with idiopathic pulmonary fibrosis (IPF), but the link disappears after adjustment for smoking.
- Authors: “Our confidence in the estimate of association is low because it is exclusively from case-control studies…[which] are particularly susceptible to threats to internal validity through unmeasured confounders.”
- Editorial calls meta-analysis “methodologically elegant,” adding, “when reported associations are weak…we confront the limits of observational epidemiology, making the leap from association to causation treacherous.”
Why this matters
- Existence of GERD-IPF causal link is debated.
- IPF guidelines recommend antacid treatment.
- All but 3 studies had higher proportions of smokers and ex-smokers among the IPF group.
- GERD and IPF were associated: OR, 2.94 (95% CI, 1.95-4.42).
- 1 study that adjusted for smoking as confounder linked IPF to:
- Total reflux episodes: OR, 4.9 (P=.03); and
- Increased reflux exposure time: OR, 4.0 (P=.05).
- Upon meta-regression taking smoking into account: OR, 0.66 (95% CI, 0.34-1.27).
- No publication bias detected.
- Systematic review and meta-analysis of 18 observational (all case-control) studies (3206 IPF patients and 9368 controls) probing links between GERD and IPF diagnoses.
- Funding: None.
- GERD and IPF diagnostic criteria varied across studies.
- Aggregate rather than individual data analyzed.