GERD has no causal impact on susceptibility and prognosis of idiopathic pulmonary fibrosis

The findings published in BMC Pulmonary Medicine did not reveal any evidence of a causal relationship between GERD and the diffusing capacity of the lung for carbon monoxide (DLco), forced vital capacity (FVC), and transplant-free survival (TFS) of patients with IPF.

Idiopathic pulmonary fibrosis is a severe and progressive fibrotic lung disease. IPF patients have an abysmal prognosis, with a median survival of 3-5 years following the diagnosis and a survival rate of only 66% at three years after lung transplantation. GERD encompasses a constellation of distressing complications and symptoms that arise due to the reflux of stomach contents into the oesophagus.

Previous studies have shown a relationship between GERD and the susceptibility as well as the prognosis of IPF, with the potential confounding factor of smoking not adequately addressed. In light of this, Di Sun & Qiao Ye from Capital Medical University in Beijing, China, conducted an MR study to investigate the causal effects of GERD on the prognosis and susceptibility of IPF while excluding smoking.

GERD was chosen as the exposure variable and genome-wide association data was employed to examine its association with forced vital capacity, susceptibility, transplant-free survival, and diffusing capacity of the lung for carbon monoxide in IPF patients as the outcome variables.

The inverse variance weighted (IVW) method was used to perform MR analyses, and sensitivity analyses were conducted using the MR-Egger intercept test, MR-PRESSO outlier test, Cochran’s Q test, and leave-one-out sensitivity analysis. Additionally, a multivariable MR (MVMR) analysis by adjusting for smoking was conducted to mitigate the potential effects of smoking on MR estimates.

The study led to the following findings:

· The univariable MR analysis demonstrated no causal effect of GERD on FVC (βIVW = 26.63, SE = 48.23), DLco (βIVW = 0.12, SE = 0.12), and TFS (HRIVW = 0.87) in patients with IPF.

· Sensitivity analysis revealed no evidence of heterogeneity, horizontal pleiotropy, or outlier single nucleotide polymorphisms.

· The MVMR analysis showed no causal effect of GERD on susceptibility to IPF after adjusting for smoking (ORIVW = 1.30). These findings were consistent in the replication cohort.

“Our findings indicate that the association of GERD with susceptibility to IPF may not be directly causal and could be explained by confounding factors, particularly smoking,” the researchers wrote. “Furthermore, no observed causal effect of GERD on DLco, FVC, and TFS of idiopathic pulmonary fibrosis was found.”

Reference:

Sun, D., Ye, Q. Mendelian randomization analysis suggests no causal influence of gastroesophageal reflux disease on the susceptibility and prognosis of idiopathic pulmonary fibrosis. BMC Pulm Med 23, 517 (2023). https://doi.org/10.1186/s12890-023-02788-8