Studies of gastro-oesophageal reflux treatment in interstitial pulmonary fibrosis
| First author [ref] Study type | n | Treatment | IPF symptoms | Exacerbations | FEV1 | Other outcomes |
| Medications | ||||||
| Bradford [169] Retrospective observational | 262 | Chronic 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/A | N/A | Unchanged | Increased risk of hospitalisation and respiratory hospitalisation in chronic anti-reflux medication users; no effect on mortality |
| Gribbin [170] Retrospective case–control | 920 | Anti-reflux medications (H2RA or PPI) | N/A | N/A | N/A | IPF diagnosis significantly associated with anti-reflux therapy (OR 2.20, 95% CI 1.88–2.58) |
| Lee [171] Retrospective observational | 204 | Anti-reflux medications (H2RA or PPI) | N/A | N/A | N/A | Anti-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 | 242 | Anti-reflux medications (H2RA or PPI) | N/A | N/A | Unchanged | Patients 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 | 18 | Anti-reflux medications (H2RA or PPI) undergoing oesophageal pH–impedance | N/A | N/A | N/A | Significant 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 | 215 | PPI therapy >12 months | N/A | N/A | N/A | Use 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 | 406 | Anti-reflux medications (H2RA or PPI) with and without nintedanib | N/A | N/A | N/A | Anti-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 | 786 | PPI any type (mean follow-up 2.6 years) | N/A | N/A | N/A | Patients 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 | 291 | Anti-reflux medications (H2RA or PPI) For 52 weeks follow-up | N/A | Overall and pulmonary infections higher in patients with advanced IPF treated with anti-reflux medications compared to those not treated | Unchanged | No difference in overall or IPF-related mortality between groups; no difference in hospitalisations between groups |
| Kreuter [178] Post hoc RCT analysis | 623 | Anti-reflux medications (H2RA or PPI) with and without pirfenidone | N/A | Severe pulmonary infections higher in patients treated with anti-reflux medications compared to those not treated; no difference in all-cause hospitalisation rate | Unchanged | No 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] RCT | 45 | PPI (omeprazole) | N/A | Small excess of lower respiratory tract infection in omeprazole-treated group | Small reduction in FEV1 in omeprazole-treated group | Non-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 |
| Surgery | ||||||
| Linden [180] Prospective observational | 19 | Nissen fundoplication (15-month follow-up) | N/A | N/A | Unchanged | Unchanged exercise capacity; stable oxygen requirements compared to IPF patients without fundoplication on transplant list |
| Raghu [181] Retrospective observational | 27 | Nissen fundoplication | N/A | N/A | Unchanged | Improvement 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] RCT | 58 | Nissen fundoplication | N/A | Non-significant reduction in exacerbations & respiratory hospitalisations in surgery-treated group | N/A | Non-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.