Studies of gastro-oesophageal reflux treatment in interstitial pulmonary fibrosis

First author [ref]
Study type
nTreatmentIPF symptomsExacerbationsFEV1Other outcomes
 Bradford [169]
Retrospective observational
262Chronic anti-reflux medications (>6 months non-p.r.n. use of any antacid, sucralfate, H2RA or PPI) versus non-users (<6 months of use or none)N/AN/AUnchangedIncreased risk of hospitalisation and respiratory hospitalisation in chronic anti-reflux medication users;
no effect on mortality
 Gribbin [170]
Retrospective case–control
920Anti-reflux medications (H2RA or PPI)N/AN/AN/AIPF diagnosis significantly associated with anti-reflux therapy (OR 2.20, 95% CI 1.88–2.58)
 Lee [171]
Retrospective observational
204Anti-reflux medications (H2RA or PPI)N/AN/AN/AAnti-reflux medications were an independent predictor of longer survival time;
anti-reflux medications were associated with a lower radiological fibrosis score
 Lee [172]
Retrospective observational
242Anti-reflux medications (H2RA or PPI)N/AN/AUnchangedPatients taking anti-reflux medications at baseline had a smaller decrease in FVC at 30 weeks (−0.06 L, 95% CI −0.11 to −0.01) compared to those not taking anti-reflux medications (−0.12 L, 95% CI −0.17 to −0.08; difference 0.07 L, 95% CI 0–0.14; p=0.05).
No change in all-cause mortality
 Kilduff [173]
Prospective observational
18Anti-reflux medications (H2RA or PPI) undergoing oesophageal pH–impedanceN/AN/AN/ASignificant decrease in the number of acid reflux events (p=0.02), but an increase in the number of non-acid reflux events (p=0.01); no change in cough frequency (p=0.70)
 Ghebremariam [174]
Prospective observational
215PPI therapy >12 monthsN/AN/AN/AUse of PPIs was associated with a significant reduction in the number of patients with lung transplantation or death (p=0.025) and a 1.4-year increase in longevity (median survival of 3.4 versus 2 years; p<0.001)
 Raghu [181]
Prospective observational
406Anti-reflux medications (H2RA or PPI) with and without nintedanibN/AN/AN/AAnti-reflux medication use at baseline did not influence the treatment effect of nintedanib on reducing decline in FVC in patients with IPF
 Lee [176]
Retrospective observational
786PPI any type (mean follow-up 2.6 years)N/AN/AN/APatients administered PPI >4 months had a lower IPF-related mortality rate than patients on PPI <4 months;
younger age, higher initial FVC and longer duration of PPI use, but not a diagnosis of GORD, were significantly associated with lower IPF-related mortality
 Kreuter [177]
Pooled analysis
291Anti-reflux medications (H2RA or PPI)
For 52 weeks follow-up
N/AOverall and pulmonary infections higher in patients with advanced IPF treated with anti-reflux medications compared to those not treatedUnchangedNo difference in overall or IPF-related mortality between groups;
no difference in hospitalisations between groups
 Kreuter [178]
Post hoc RCT analysis
623Anti-reflux medications (H2RA or PPI) with and without pirfenidoneN/ASevere pulmonary infections higher in patients treated with anti-reflux medications compared to those not treated; no difference in all-cause hospitalisation rateUnchangedNo significant differences in disease progression, all-cause mortality rate IPF-related mortality rate or mean change in percent FVC between groups; severe gastrointestinal adverse events were more frequent with anti-reflux medications
 Dutta [179]
45PPI (omeprazole)N/ASmall excess of lower respiratory tract infection in omeprazole-treated groupSmall reduction in FEV1 in omeprazole-treated groupNon-significant reduction in geometric mean cough frequency at the end of treatment, adjusted for baseline in the omeprazole group compared with placebo;
omeprazole was well tolerated and adverse event profiles were similar in both groups;
non-significant reduction in FVC associated with omeprazole
 Linden [180]
Prospective observational
19Nissen fundoplication (15-month follow-up)N/AN/AUnchangedUnchanged exercise capacity;
stable oxygen requirements compared to IPF patients without fundoplication on transplant list
 Raghu [181]
Retrospective observational
27Nissen fundoplicationN/AN/AUnchangedImprovement in mean DeMeester scores from 42 to 4 (p<0.01); trend toward stabilisation in observed FVC
No 90-day deaths
 Raghu (WRAP-IPF trial) [34]
58Nissen fundoplicationN/ANon-significant reduction in exacerbations & respiratory hospitalisations in surgery-treated groupN/ANon-significant reduction in rate of change of FVC (p=0.28) and mortality over 48 weeks

Abbreviations: IPF: interstitial pulmonary fibrosis; FEV1: forced expiratory volume in 1 s; H2RA: histamine-2 receptor antagonist; PPI: proton pump inhibitor; FVC: forced vital capacity; GORD: gastro-oesophageal reflux; RCT: randomised controlled trial.