Idiopathic pulmonary fibrosis and GERD: links and risks

Figures & data

Figure 1 Mechanisms behind GERD. The imbalance between triggering and defensive factors causes GERD.⁶–13

Abbreviations: GERD, gastroesophageal reflux disease; GER, gastroesophageal reflux.

Figure 2 Mutual mechanisms behind GERD and IPF.

Abbreviations: GERD, gastroesophageal reflux disease; IPF, idiopathic pulmonary fibrosis.

Table 1 Data from studies investigating the role of PPIs or antireflux surgery in IPF

Authors	Years	Type of study	Population size (n patients)	Results
Cantu et al^Citation75	2004	Retrospective cohort study	457	Post-operative reflux incidence was 76% (127 of 167 patients). In 14 patients with early fundoplication, survival was 100% at 1 and 3 years compared with those with reflux and no intervention (92% ±3.3, 76% ±5.8; p<0.02). Patients underwent early fundoplication had less BOS 1 and 3 years (100%, 100%) compared with patients with reflux that does not underwent fundoplication (96% ±2.5, 60% ±7.5; p<0.01)
Raghu et al^Citation67	2006	Case series	4	Stabilization or improvement of pulmonary function tests (FVC and DLCO) with antisecretory therapy. Poor adherence to therapy seems correlate with transient deterioration of pulmonary function tests
Linden et al^Citation72	2006	Retrospective cohort study	45	No perioperative complications and no decrease in lung function over 15-month follow-up. Patients who underwent fundoplication had stable oxygen requirement, whereas controls had a statistically significant deterioration in oxygen requirement.
Lee et al^Citation49	2011	Retrospective cohort study	204	Prolonged median survival time (1967 vs 896 days) and lower radiologic fibrotic score (14% vs 19%) for PPI/H2RA vs controls
Fisichella et al^Citation74	2011	Prospective study	39	Comparing pepsin levels in BALF, transplant patients with GERD had more pepsin than both patients without it and who underwent LARS (p=0.029). Patients with more pepsin had quicker progression to BOS and more acute rejection episodes.
Raghu et al^Citation73	2013	Retrospective cohort study	14	FVC evaluated before and after LARS showed increase of mean FVC (+0.08L) after surgery
Lee et al^Citation68	2013	Post hoc analysis of RCTs	242	Lower loss in FVC at 30 or 52 weeks and fewer acute exacerbations (0vs9)
Noth et al^Citation29	2012	Retrospective cohort study	74	IPF patients with hiatal hernia in antisecretory therapy had better DLCO (p<0.03) and improved composite physiologic index (CPI) scores (p<0.04) than controls
Ghebremariam et al^Citation41	2015	Retrospective analysis (data from two ILD databases)	215	IPF patients on PPIs had prolonged transplant-free survival over controls (median survival of 3.4 vs 2 years). No differences in predicted FVC% or DLCO% in the 12 months following the initial pulmonary function
Kreuter et al^Citation42	2016	Post hoc analysis of three RCTs	624	No significant difference for disease progression, all-cause and IPF-related mortality, FVC, 6MWD, hospital admission rate. Adverse events were similar in these two groups. Overall infections (p=0.0174) and pulmonary infections (p=0.0214) were higher in patients with advanced IPF (FVC <70%) who were treated with antisecretory than not treated with it
Lee et al^Citation28	2016	Retrospective cohort study	786	Patients treated with PPI for over 4 months had a lower IPF-related mortality than patients on PPI for <4 months (HR 0.97; 95% CI 0.95–1.00). PPIs use (p=0.024) but not a diagnosis of GERD, were significantly associated with lower IPF-related mortality
Raghu et al^Citation77	2018	Prospective randomized controlled study	58	LARS was associated with lower decline of FVC (–0.05 vs –0.13 L), longer time to FVC decline or death, fewer clinical events and deaths. Most common adverse events after surgery were transient dysphagia and abdominal distention
Costabel et al^Citation71	2018	Post hoc analysis of RCTs	406	Considering both nintedanib/placebo treated patients there were similar annual decrease rate of FVC in both antisecretory treated/non-treated patients. Antisecretory medication at baseline was not associated with a more favorable course of disease and did not impact the treatment effect of nintedanib

Abbreviations: BOS, bronchiolitis obliterans syndrome; DL_CO, diffusing lung capacity for carbon monoxide; PPI, proton pump inhibitor; H₂RA, H-2 receptor antagonist; BALF, Bronchoalveolar lavage fluid; GERD, gastro-esophageal reflux disease; LARS, laparoscopic anti-reflux surgery; RCT, randomised controlled trial.

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