Should All IPF Patients Be Treated for GERD?
Lee JS, Ryu JH, Elicker BM, et al
Amer J Respir Crit Care Med. 2011;184:1390-1394
Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal disease of unknown cause. Although there is no known cure, there have been indications that gastroesophageal reflux disease (GERD) is often present and may contribute to disease progression, possibly due to microaspiration of reflux gastric contents. Some small studies have suggested that treatment of GERD may slow the progression of IPF. The present much larger study attempts to determine the frequency of GERD in patients with IPF and whether medical or surgical treatments are associated with prolonged survival. The study was observational and included data on the treatment and duration of survival of 204 patients from 2 major academic medical centers.
GERD was present by history in 34%-45% of participating IPF patients; 47% received GERD medications and 5% had Nissen fundoplication surgery. Median survival time of patients who received a diagnosis of GERD was 1499 days vs 920 days for those who were not diagnosed with GERD (P < .01). However, patients who received treatment for GERD, either a proton-pump inhibitor or histamine blocker, survived significantly longer than those who did not (median of 1967 days vs 896 days [P < .01]). Nissen fundoplication prolonged survival similarly. After adjustment for potentially confounding factors, the only predictor of prolonged survival apart from lung function was GERD therapy.
The prognosis of IPF is as dire as that of lung cancer, with a median survival between 2 and 3 years. Its cause and pathophysiology are unclear, and current therapies provide limited benefit. Thus, a treatment that may prolong survival, especially one that is already available and the safety of which is known, is of considerable interest. Lee and colleagues' study goes some of the distance to fulfilling that need. The results suggest that any of the currently available GERD treatments can prolong median survival by almost 3 years, namely by a factor of more than 2.
But the study has some limitations. First, it was an observational study rather than a prospective, randomized treatment study. The 2 groups, those who received GERD treatment and those who did not, seemed to be reasonably well-balanced; however, the decision to treat GERD may not have been uniformly applied. There may also be other unknown confounding factors. Second, it would have been interesting to know whether GERD medications only benefited patients who had symptoms or a diagnosis of GERD, but that analysis was not reported. The study also doesn’t explore whether a patient with IPF must have a diagnosis of GERD to benefit from GERD therapy. Third, the observation that patients who had symptoms or a diagnosis of GERD had longer survival than those who did not seems to contradict the hypothesis that GERD contributes to IPF progression.
Despite these limitations, the potential ability to prolong survival of patients with this aggressive disease, the need for IPF treatments, and the safety and general availability of oral treatments for GERD all argue in favor of their greater use in IPF. The substantial prolongation of life in this study speaks for itself. Clearly, a prospective trial with a randomized, double-blind treatment assignment would be needed to confirm the benefit but may pose ethical concerns.
Abstract
Gastroesophageal Reflux Therapy Is Associated With Longer Survival in Patients With Idiopathic Pulmonary Fibrosis
Lee JS, Ryu JH, Elicker BM, et al
Amer J Respir Crit Care Med. 2011;184:1390-1394
Study Summary
Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal disease of unknown cause. Although there is no known cure, there have been indications that gastroesophageal reflux disease (GERD) is often present and may contribute to disease progression, possibly due to microaspiration of reflux gastric contents. Some small studies have suggested that treatment of GERD may slow the progression of IPF. The present much larger study attempts to determine the frequency of GERD in patients with IPF and whether medical or surgical treatments are associated with prolonged survival. The study was observational and included data on the treatment and duration of survival of 204 patients from 2 major academic medical centers.
GERD was present by history in 34%-45% of participating IPF patients; 47% received GERD medications and 5% had Nissen fundoplication surgery. Median survival time of patients who received a diagnosis of GERD was 1499 days vs 920 days for those who were not diagnosed with GERD (P < .01). However, patients who received treatment for GERD, either a proton-pump inhibitor or histamine blocker, survived significantly longer than those who did not (median of 1967 days vs 896 days [P < .01]). Nissen fundoplication prolonged survival similarly. After adjustment for potentially confounding factors, the only predictor of prolonged survival apart from lung function was GERD therapy.
Viewpoint
The prognosis of IPF is as dire as that of lung cancer, with a median survival between 2 and 3 years. Its cause and pathophysiology are unclear, and current therapies provide limited benefit. Thus, a treatment that may prolong survival, especially one that is already available and the safety of which is known, is of considerable interest. Lee and colleagues' study goes some of the distance to fulfilling that need. The results suggest that any of the currently available GERD treatments can prolong median survival by almost 3 years, namely by a factor of more than 2.
But the study has some limitations. First, it was an observational study rather than a prospective, randomized treatment study. The 2 groups, those who received GERD treatment and those who did not, seemed to be reasonably well-balanced; however, the decision to treat GERD may not have been uniformly applied. There may also be other unknown confounding factors. Second, it would have been interesting to know whether GERD medications only benefited patients who had symptoms or a diagnosis of GERD, but that analysis was not reported. The study also doesn’t explore whether a patient with IPF must have a diagnosis of GERD to benefit from GERD therapy. Third, the observation that patients who had symptoms or a diagnosis of GERD had longer survival than those who did not seems to contradict the hypothesis that GERD contributes to IPF progression.
Despite these limitations, the potential ability to prolong survival of patients with this aggressive disease, the need for IPF treatments, and the safety and general availability of oral treatments for GERD all argue in favor of their greater use in IPF. The substantial prolongation of life in this study speaks for itself. Clearly, a prospective trial with a randomized, double-blind treatment assignment would be needed to confirm the benefit but may pose ethical concerns.
Abstract
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