For patients with idiopathic pulmonary fibrosis (IPF), the use of medication for gastroesophageal reflux disease (GERD) may improve survival time, researchers found.
Patients who used GERD medications had a median survival time of about 65 months, compared with about 29 months for those who did not use the drugs (P<0.01), according to Joyce Lee, MD, of the University of California San Francisco, and colleagues.
Over the study period, IPF patients who used drugs for reflux had a 53% reduced relative risk of death after adjustment for multiple confounders (HR 0.47, 95% CI 0.24 to 0.93), the researchers reported online in the American Journal of Respiratory and Critical Care Medicine.
"There is equipoise among pulmonologists as to how aggressively to diagnosis and treat gastroesophageal reflux in patients with idiopathic pulmonary fibrosis," they wrote. "There are no convincing data demonstrating a clinical benefit to treatment of gastroesophageal reflux in this setting and there are risks to medical and surgical treatment."
"While preliminary," they concluded, "these findings support the hypothesis that gastroesophageal reflux and chronic microaspiration may play important roles in the pathobiology of idiopathic pulmonary fibrosis."
Although GERD has been shown to be common in patients with IPF -- which was confirmed in the current study -- its significance in terms of outcomes is not clear.
To explore the issue, Lee and colleagues examined data from 204 patients with idiopathic pulmonary fibrosis who were being treated at two academic medical centers -- UCSF and the Mayo Clinic in Rochester, Minn.
Most of the patients (69%) were men, and the average age was 70. At baseline, the mean forced vital capacity was 69% predicted and the mean diffusing capacity for carbon monoxide was 47% predicted.
High-resolution CT provided radiologic fibrosis scores. At baseline, the median score -- the percentage of the lung affected by fibrosis -- was 17%.
As observed in previous studies of idiopathic pulmonary fibrosis, gastroesophageal reflux was a common problem in these patients -- 34% reported symptoms of gastroesophageal reflux, 45% had a history of GERD, 47% reported use of GERD drugs (either proton pump inhibitors or H2 blockers), and 5% reported use of Nissen fundoplication.
Although all of those factors were associated with longer survival time in unadjusted analyses, only the use of reflux medications remained a significant predictor in a multivariate analysis.
"There are several possible explanations for the results of our study," Lee and colleagues wrote. "The most straightforward is also the most controversial; that the treatment of gastroesophageal reflux is beneficial to survival in idiopathic pulmonary fibrosis."
They noted that the results are consistent with two previous studies linking treatment of gastroesophageal reflux and stabilization of idiopathic pulmonary fibrosis.
"It is hypothesized that gastroesophageal reflux may impact progression in idiopathic pulmonary fibrosis through microaspiration of gastric droplets causing either slowly progressive lung injury and fibrosis or by triggering acute exacerbation of [the lung disease]," they wrote. "Suppressing the acidity of gastric contents may reduce the injury caused by microaspiration."
But there are other possible explanations, according to the researchers, including confounding by unmeasured factors. For instance, they wrote, patients who are treated for reflux may be more likely to receive other medical interventions that lengthen survival.
Also, gastroesophageal reflux could cause patients to seek medical attention sooner and thus receive a diagnosis of idiopathic pulmonary fibrosis earlier in the course of the disease.
A final possibility, the authors stated, is that the association between reflux and lung disease is real, but that reflux develops in response to the fibrosis, and not the other way around.
Ultimately, Lee and colleagues wrote, the findings need to be validated in future studies, which should collect information on 24-hour pH and/or esophageal impedance testing, dosing, duration, and compliance with reflux therapy, and effectiveness of acid suppression therapy.
Primary source: American Journal of Respiratory and Critical Care Medicine
Source reference: Lee J, et al "Gastroesophageal reflux therapy is associated with longer survival in idiopathic pulmonary fibrosis" Am J Respir Crit Care Med 2011; DOI: 10.1164/rccm.201101-0138OC.