Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials

Abstract

Background Abnormal acid gastroesophageal reflux is common in idiopathic pulmonary fibrosis and is considered a risk factor for its development. Retrospective studies have suggested improved outcomes in patients treated with anti-acid therapy. The aim of this study was to determine the association between anti-acid therapy and disease progression in idiopathic pulmonary fibrosis. Methods Patients with IPF were identified from the placebo arms of the three IPFnet randomized clinical trials. Case report forms were designed to prospectively capture data regarding gastroesophageal reflux diagnosis and treatment. These data were analyzed to determine the relationship between use of anti-acid therapy (i.e. proton pump inhibitors and histamine-2 blockers) and change in forced vital capacity using a longitudinal repeated-measures model. Secondary outcomes analyzed included acute exacerbation, all-cause hospitalization, and all-cause mortality. Findings Two hundred and forty-two patients with idiopathic pulmonary fibrosis were randomized to receive placebo therapy. Fifty-one percent were taking anti-acid therapy upon enrollment. There were no significant differences in demographics and pulmonary physiology between patients taking and not taking anti-acid therapy. After adjustment for sex, baseline forced vital capacity %predicted, and baseline diffusing capacity for carbon monoxide %predicted, patients taking anti-acid therapy at baseline had a slower decline in forced vital capacity (estimated change over 30-weeks of -0.06 liters vs. -0.12 liters, p-value = 0.05). Patients taking anti-acid therapy at baseline had fewer acute exacerbations (no events versus nine events, p-value <0.01) during the study period. Interpretation The use of anti-acid therapy was associated with a slower decline in forced vital capacity over time and fewer acute exacerbations in patients with idiopathic pulmonary fibrosis. These findings support the hypothesis that abnormal acid gastroesophageal reflux contributes to disease progression and suggest that anti-acid therapy may be beneficial in patients with idiopathic pulmonary fibrosis.

Association of esophageal dilatation in chest CT scan with gastroesophageal reflux disease: A case control study

“…There was no significant difference between esophageal dilation and the grade of esophagitis by covariance analysis (Table s 3 and 4). pime pime pime pime p pi im me e EDITRICE Original Article pose the patient to the recurrent microaspiration and different respiratory complications including lung abscess, asthma and interstitial lung disease (ILD) [1,[20][21][22][23]. Secondly, ED might be correlated with the severity of lung disease or may be a clue for diagnosis of a serious underlying disorder.…”

Therapeutic advances in idiopathic pulmonary fibrosis

“…40 A retrospective analysis of the placebo arm of three IPF RCTs which compared patients on acid suppression with those who were not, found that the use of anti-acid therapy was associated with a slower decline in FVC over time and fewer acute exacerbations. 41 Interestingly, research studies have also shown that gastric contents that are not acidic are also capable of causing cellular injury in the lung. 40,41 To address the issue of reflux worsening disease, a clinical trial is currently being undertaken in the US comparing decline in FVC in IPF patients who have undergone fundoplication to those who have not (clinical trial number NCT01982968).…”

“…41 Interestingly, research studies have also shown that gastric contents that are not acidic are also capable of causing cellular injury in the lung. 40,41 To address the issue of reflux worsening disease, a clinical trial is currently being undertaken in the US comparing decline in FVC in IPF patients who have undergone fundoplication to those who have not (clinical trial number NCT01982968). The recent ATS guidelines conditionally recommend empirical treatment of gastro-oesophageal reflux in IPF patients but acknowledge that good-quality evidence is currently lacking.…”

Recommendations for the management of idiopathic pulmonary fibrosis in South Africa: a position statement of the South African Thoracic Society

“…It is known that IPF patients have significantly worse gastrooesophageal reflux than controls, and pepsin originating from the gastrointestinal tract has been isolated in BAL fluid in patients with acute exacerbations of IPF (4,26). Interestingly, the use of anti-acid therapy has been associated with a slower decline in FVC over time and fewer acute exacerbations (27). Current guidelines recommend empirical treatment of gastro-oesophageal reflux in IPF patients, but good quality evidence is lacking (3,4).…”