Gastroesophageal reflux disease (GERD) is more prevalent in patients with idiopathic pulmonary fibrosis (IPF) than in the general population, and it’s been proposed that GERD plays a pathogenic role in IPF. One hypothesis is that refluxate extending into the proximal esophagus leads to microaspiration, which in turn triggers fibrosis. Previous studies of GERD have relied on multichannel intraluminal impedance and pH testing (MII-pH), which has substantial limitations including the need to count reflux episodes.

Now, researchers at Brigham and Women’s Hospital have linked more advanced impedance metrics to the prognosis of patients with IPF. Gastroenterologists in the Division of Gastroenterology, Hepatology and Endoscopy, including Vikram Rangan, MD, Lawrence F. Borges, MD, MPH, and Walter W. Chan, MD, MPH, director of the Center for Gastrointestinal Motility, and colleagues present the findings in The American Journal of Gastroenterology.

Methods

The retrospective study included 124 adults with IPF who underwent esophageal function testing, including MII-pH, as part of routine evaluation before lung transplantation. Three advanced MII-pH metrics were calculated:

• Postreflux swallow-induced peristaltic wave (PSPW) index, a marker of chemical clearance of refluxed contents in the esophagus, with lower values reflecting impairment of clearance

• Distal and proximal mean nocturnal baseline impedance (MNBI), a potential marker of long-term reflux severity as it reflects longer-term intrinsic electrical conductivity of the esophageal wall, and thus esophageal mucosal integrity, in the absence of reflux and swallowing during quiescent periods overnight

Pulmonary function testing (PFT) was performed at the time of MII-pH and at the one-year post-transplant visit. Parameters examined were the change in forced expiratory volume in one second (FEV₁), change in % predicted FEV₁, change in forced vital capacity (FVC), and change in % predicted FVC.

Advanced Impedance Metrics and PFT Decline

Lower baseline values of all three impedance metrics correlated with more negative changes over one year in all four PFT parameters examined. The magnitude of correlation was similar across parameters.

Multivariable Analyses

In adjusted analyses, the impedance parameters remained associated with:

• Lower distal MNBI—more decline in FEV₁ (β, 0.0038; P=0.0061) and more negative change in % predicted FVC (β, 0.0029; P=0.016)

• Lower proximal MNBI—more decline in FEV₁ (β, 0.0045; P=0.024) and more negative change in % predicted FVC (β, 0.0038; P=0.025)

• Lower PSPW index—more decline in FEV₁ (β, 41.9; P=0.049)

In the analysis of distal MNBI, the use of a proton pump inhibitor seemed to have a protective effect on lung function:

• Positive change in % predicted FEV₁—β, 8.91 (P=0.025)
• Positive change in % predicted FVC—β, 6.98 (P=0.052)

Traditional GERD Metrics

Traditional metrics on MII-pH (acid exposure time, bolus exposure time and the total number of reflux episodes) were not significantly associated with PFT decline, either overall or with regard to changes in % predicted FEV₁ or % predicted FVC in multivariable models.

Therapeutic Implications

These results are further evidence of the role for GERD in IPF pathogenesis. They also suggest advanced MII-pH could identify patients with IPF who are good candidates for aggressive antireflux therapy.