Protective Effect of Proton Pump Inhibitor for Survival in Patients with Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis

Abstract

Background/Aims The prevalence of gastroesophageal reflux disease (GERD) is high in patients with idiopathic pulmonary fibrosis (IPF). GERD may cause chronic microaspiration that leads to repeated subclinical lung injury, which leads to pulmonary fibrosis. Although some studies have suggested that proton pump inhibitors (PPI) were associated with a good prognosis in IPF, their effects remain unclear. Methods We retrospectively reviewed 786 consecutive adult patients with IPF at Seoul National University Bundang Hospital between April 2003 and March 2015. Results Mean duration of follow-up was 2.6 ± 2.8 years. Of the 786 patients with IPF, 107 (13.6%) were given diagnoses of GERD, and 103 (13.1%) died due to IPF-related pneumonia or respiratory failure. The prevalence of GERD and the cumulative incidence of de novo GERD increased depending on the period of follow-up in patients with IPF. Patients administered PPI for more than four months had a lower IPF-related mortality rate than patients on PPI less than 4 months (Log-rank P -value = 0.024 in Kaplan-Meier curve). In a univariate and multivariate Cox regression hazard model, younger age (hazard ratio [HR], 1.06; 95% CI, 1.03–1.10; P = 0.001), higher initial forced vital capacity (HR, 0.98; 95% CI, 0.96–0.99; P = 0.004), and longer duration of PPI use (HR, 0.97; 95% CI, 0.95–1.00; P = 0.022), but not a diagnosis of GERD, were significantly associated with lower IPF-related mortality. Conclusions In Korean patients with IPF, the prevalence of GERD was lower than in other countries. PPI use for at least 4 months may have a protective effect against IPF-related mortality.

Pathophysiological Studies Are Mandatory to Understand the Benefit of Proton Pump Inhibitors in Patients with Idiopathic Pulmonary Fibrosis

“…We read with great interest the paper by Lee et al 1 on the protective effect of proton pump inhibitors (PPIs) for survival in patients with gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF). The Authors reviewed a very large number of consecutive adult patients with IPF (n = 786) and concluded that the prevalence of GERD is lower in Korean patients than in other countries and that PPI use for at least 4 months may have a protective effect against IPF-related mortality.…”

Current and future perspectives in the management of gastroesophageal reflux disease

“…Lee et al . evaluated that patients with IPF who were treated for more than 4 months of PPI had a lower mortality rate . PPIs may directly inhibit the migration and interaction between inflammatory and endothelial cells.…”

“…100 Lee et al evaluated that patients with IPF who were treated for more than 4 months of PPI had a lower mortality rate. 111 PPIs may directly inhibit the migration and interaction between inflammatory and endothelial cells. Esomeprazole and lansoprazole suppress expression of inflammatory cytokines (tumor necrosis factor-␣, interleukin (IL)-1␤, IL-6, IL-8, adhesion molecules, fibronectin, and matrix metalloproteinase enzymes).…”

Gastroesophageal Reflux Disease in Idiopathic Pulmonary Fibrosis: Uncertainties and Controversies

“…The prevalence of hiatal hernia, which is associated with reflux and erosive esophagitis, was also increased in patients with IPF compared with healthy controls or patients with asthma or chronic obstructive pulmonary disease [20–22]. Studies reporting the prevalence of GERD and/or hiatal hernia are listed in Table 1 [10, 18, 19–39]. …”

“…The incidence of newly diagnosed GERD seems to be continuously increasing in patients with IPF [18]. A recent systematic review reported that 0–94% of patients with IPF suffer from GERD [7].…”