Sole Treatment of Acid Gastroesophageal Reflux in Idiopathic Pulmonary Fibrosis: A Case Series

doi:10.1378/chest.129.3.794

Chest

Volume 129, Issue 3, March 2006, Pages 794-800

https://doi.org/10.1378/chest.129.3.794 Get rights and content

Rationale

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease despite the available treatment regimes. Increased acid gastroesophageal reflux (GER) occurs in IPF patients.

Objectives

To follow the course of IPF in patients while being treated for acid GER alone.

Methods

A retrospective review of the clinical outcomes of four patients with newly diagnosed IPF and increased acid GER who chose to be treated solely with anti-acid GER therapy were followed up regularly with pulmonary function tests (PFTs) [measuring FVC and the diffusing capacity of the lung for carbon monoxide] over a period of 2 to 6 years. Anti-acid GER therapy was administered using proton-pump inhibitors and fundoplication, if needed. Adequate suppression of acid GER was ascertained by 24-h esophageal pH monitoring.

Main results

PFT results in all four patients stabilized or improved while their conditions were maintained with adequate treatment for acid GER. All patients were alive at the last follow-up, and none manifested an acute exacerbation of IPF or needed treatment for respiratory problems during this period. After maintaining 4 years of improved status (based on PFT and exercise testing findings) while adhering to treatment for acid GER, one patient’s deterioration correlated with poor compliance to daily treatment during the fifth year, although the PFT results at the sixth year showed stabilization compared to baseline values. The condition of another patient was stabilized by adhering to anti-acid GER treatment after an initial period of deterioration that was associated with nonadherence

Conclusions

Future clinical studies are indicated to clarify the role of acid GER in IPF and to determine whether adequate treatment for increased acid GER in part improves the outcome of patients with IPF.

Section snippets

Materials and Methods

A retrospective review of patients who met all of the following inclusion and exclusion criteria and had been managed for IPF at the University of Washington Medical Center (UWMC), Seattle, WA, were selected in this case series. The IPF patient database that is maintained in the Interstitial Lung Disease Clinic at the UWMC was reviewed for potential subject inclusion in this study. The clinical data were gathered in a retrospective manner and with the approval of the University of Washington

Discussion

The direct relationship between lung injury induced by acid and pulmonary fibrosis has been demonstrated in animals.18, 19, 20, 21²² We have demonstrated an increased acid GER in 87 to 91% of patients with IPF in two prospective studies.12, 23 In these studies, 25 to 47% of patients with IPF exhibited classic symptoms of GER such as heartburn or regurgitation despite having objective evidence of abnormal acid GER. Furthermore, treatment with standard doses of PPIs suppressed acid GER in only

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Cited by (182)

Idiopathic Pulmonary Fibrosis-Treatment and Management
2021, Encyclopedia of Respiratory Medicine, Second Edition
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Currently, two antifibrotic medications have been shown to reduce the rate of decline in lung function over time among IPF patients and are mainstays of IPF treatment. Patients meeting the criteria for consideration of lung transplantation must be referred to a lung transplant program in a timely manner. Other areas of treatment include management of symptoms and comorbid conditions including abnormal acid gastroesophageal reflux, obstructive sleep apnea, pulmonary hypertension, as well as participation in clinical trials, patient education, pulmonary rehabilitation and judicial use of supplemental oxygen. This article summarizes the current approach to treatment of IPF.
Meta-analysis of Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis
2019, Chest
The relationship between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) is controversial. Current guidelines recommend that clinicians use regular antacid treatment, while two recent meta-analyses of antacid therapy in IPF were inconclusive. The objective of this study was to examine the evidence regarding the association between GERD and IPF through a systematic review and a meta-analysis, with special reference to the methodologic quality of the observational studies.
The MEDLINE, EMBASE, Ovid, and Web of Science (1966-May 2018) databases were searched for original articles published in any language, and we then systematically reviewed the bibliographies of the retrieved articles. Observational studies (cohort and case-control studies) were selected if they allowed the calculation of a measure of association relating GERD to IPF.
Eighteen case-control studies including 3,206 patients with IPF and 9,368 control subjects met the inclusion criteria of the meta-analysis. The meta-analysis indicated that GERD is associated with IPF (OR, 2.94 [95% CI, 1.95-4.42]; P homogeneity < .0001). Overall, the results remained consistent whatever the data source (clinical studies vs databases) or the type of control subject (healthy volunteers, patients with respiratory diseases other than interstitial lung disease, or patients with non-IPF interstitial lung disease). In a meta-regression, after controlling for smoking, GERD and IPF were not related.
GERD and IPF may be related, but this association is most likely confounded, especially by smoking. Our confidence in the estimate of association is low because it is exclusively from case-control studies.
PROSPERO; No.: CRD42016053728; URL: http://www.crd.york.ac.uk/PROSPERO
Comorbidities of IPF: How do they impact on prognosis
2018, Pulmonary Pharmacology and Therapeutics
Idiopathic Pulmonary Fibrosis (IPF) is a severe parenchymal lung disease characterized by an intense deposition of collagen in the interstitial spaces. The introduction of anti-fibrotic drugs increased patients' life expectancy highlighting the role of comorbidities in patients' management and prognosis. IPF is frequently associated with other diseases mainly because of its onset during middle age and sometimes because of the presence of common pathogenic pathways such as in the case of lung cancer. Comorbidities may differently influence prognosis of IPF patients. However, except for major impacting ones as LC, PH and cardiovascular diseases, data exploring their impact on prognosis are still few and sometimes conflicting highlighting the need of new large and targeted studies. In this review we discuss the current knowledge on the most common comorbidities associated with IPF (cardiovascular diseases, pulmonary hypertension, lung cancer, emphysema, gastro-oesophageal reflux and depression), focusing on their prognostic role.
Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial
2018, The Lancet Respiratory Medicine
Citation Excerpt :
Evidence to date is mixed regarding the clinical impact of abnormal acid GER and treatment of GER on the progression of IPF.4,5 Several retrospective cohort studies have described the prevalence of abnormal acid GER in patients with IPF6–9 and assessed the association of anti-acid therapies for GER (H2-receptor antagonists and proton-pump inhibitors) with clinical outcomes in IPF.10,11 Two large secondary analyses12,13 of data from clinical trials reached different conclusions; one reported a significant reduction in rate of physiological decline and acute exacerbation with anti-acid therapies,12 the other reported no effect.13
Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to determine whether treatment of abnormal acid GER with laparoscopic anti-reflux surgery reduces the rate of disease progression.
The WRAP-IPF trial was a randomised controlled trial of laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER recruited from six academic centres in the USA. We enrolled patients with IPF, abnormal acid GER (DeMeester score of ≥14·7; measured by 24-h pH monitoring) and preserved forced vital capacity (FVC). We excluded patients with a FVC below 50% predicted, a FEV₁/FVC ratio of less than 0·65, a history of acute respiratory illness in the past 12 weeks, a body-mass index greater than 35, and known severe pulmonary hypertension. Concomitant therapy with nintedanib and pirfenidone was allowed. The primary endpoint was change in FVC from randomisation to week 48, in the intention-to-treat population with mixed-effects models for repeated measures. This trial is registered with ClinicalTrials.gov, number NCT01982968.
Between June 1, 2014, and Sept 30, 2016, we screened 72 patients and randomly assigned 58 patients to receive surgery (n=29) or no surgery (n=29). 27 patients in the surgery group and 20 patients in the no surgery group had an FVC measurement at 48 weeks (p=0·041). Intention-to-treat analysis adjusted for baseline anti-fibrotic use demonstrated the adjusted rate of change in FVC over 48 weeks was −0·05 L (95% CI −0·15 to 0·05) in the surgery group and −0·13 L (−0·23 to −0·02) in the non-surgery group (p=0·28). Acute exacerbation, respiratory-related hospitalisation, and death was less common in the surgery group without statistical significance. Dysphagia (eight [29%] of 28) and abdominal distention (four [14%] of 28) were the most common adverse events after surgery. There was one death in the surgery group and four deaths in the non-surgery group.
Laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER is safe and well tolerated. A larger, well powered, randomised controlled study of anti-reflux surgery is needed in this population.
US National Institutes of Health National Heart, Lung and Blood Institute.
Treatment of Gastroesophageal Reflux in Patients With Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis
2018, Chest
Gastroesophageal reflux (GER) is common in patients with idiopathic pulmonary fibrosis (IPF) and has been proposed as a potential contributor to disease progression and exacerbation. Whether treatment of GER improves health outcomes in patients with IPF is controversial. Our objective was to review the efficacy and safety of GER treatments in IPF.
We performed a systematic review and meta-analysis, using MEDLINE, Embase, Central (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov. These databases were searched from their inception, and Google Scholar and conference abstracts were searched until September 2017 without language restrictions for randomized and observational studies evaluating the effects of pharmacologic or nonpharmacologic treatment. Primary outcomes were IPF-related mortality and all-cause mortality. Evidence was evaluated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The study was registered with PROSPERO (#CRD42017076257).
Thirteen observational studies were identified through the search strategy, and eight were included in the meta-analysis. Pharmacologic treatment of GER was associated with a significant reduction in IPF-related mortality as compared with no GER treatment (unadjusted risk: HR, 0.60; 95% CI, 0.38-0.97; P = .04; I² = 0%; three studies; N = 2,033; adjusted risk: HR, 0.45; 95% CI, 0.24-0.84; P = .01; I² = 0%; three studies; N = 2,033) but not all-cause mortality (unadjusted: HR, 0.73; 95% CI, 0.45-1.2; P = .22; I² = 46%; three studies; N = 1,316; adjusted: HR, 0.76; 95% CI, 0.31-1.84; P = .54; I² = 89%; four studies; N = 1,585). The quality of evidence for these outcomes was low.
Low-quality evidence suggests pharmacologic treatment of GER is associated with a reduction in IPF-related mortality but not overall mortality. Randomized trials of antacid therapy in IPF are needed.
Evaluation of Comorbidity Burden on Disease Progression and Mortality in Patients with Interstitial Pneumonia with Autoimmune Features: a Retrospective Cohort Study
2023, Research Square

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Chest

Selected ReportsSole Treatment of Acid Gastroesophageal Reflux in Idiopathic Pulmonary Fibrosis: A Case Series

Rationale

Objectives

Methods

Main results

Conclusions

Section snippets

Materials and Methods

Discussion

Chest

Lancet

Determinants of survival in idiopathic pulmonary fibrosis

Am J Respir Crit Care Med

Idiopathic pulmonary fibrosis: predicting response to therapy and survival

Am J Respir Crit Care Med

Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis

Am J Respir Crit Care Med

Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model

Am J Respir Crit Care Med

Cryptogenic fibrosing alveolitis: clinical features and their influence on survival

Thorax

Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification

Am J Repir Crit Care Med

American Thoracic Society.. Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement

Am J Respir Crit Care Med

Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis

Am J Respir Crit Care Med

Interstitial lung disease and gastroesophageal reflux

Am J Med

Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis

Am J Respir Crit Care Med

American Thoracic Society.. Lung function testing: selection of reference values and interpretive strategies

Am Rev Respir Dis

Ambulatory 24-hour esophageal pH monitoring: why, when, and what to do

J Clin Gastroenterol

American Thoracic Society.. Standardization of spirometry

Am J Respir Crit Care Med

Selected Reports
Sole Treatment of Acid Gastroesophageal Reflux in Idiopathic Pulmonary Fibrosis: A Case Series