Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unclear origin, associated with a median survival of 3–5 years from the time of diagnosis.1 At present, two IPF-specific pharmacological therapies are available that slow disease progression, but to date there is no known cure.2, 3 Patients with IPF have frequent comorbid conditions, including a high reported prevalence of gastro-oesophageal reflux (GER) and gastro-oesophageal reflux disease (GERD).4, 5, 6 The potential role of GER in the pathogenesis or progression of disease has been an important focus of research, in an effort to find effective therapeutic approaches to patient management. GER and consequent microaspirations have been proposed as pathogenic in IPF and there are data to suggest that treatment with antacid therapy might be of clinical benefit in terms of slowing chronic disease progression, and possibly even survival.7, 8, 9 Conversely, other reports10, 11 question the efficacy of antacid therapy in IPF and have suggested that possible harm cannot be excluded.
The most recent international guideline statement on the treatment of IPF12 attempted to address the role for antacid therapy in the management of IPF, with the non-conflicted voting members of the committee making a conditional recommendation for the use of antacid therapy in the treatment of patients with IPF. From the outset, this recommendation has been controversial in light of the absence of data generated from any placebo-controlled trial. We believe that there is equipoise regarding the pathogenic role of GER in IPF,13 and it is unclear whether the guideline recommendation should be interpreted to suggest that the majority of patients with IPF with no symptoms of GER might reasonably be offered regular antacid therapy, in the hope of slowing disease progression. In this perspective, we have summarised the evidence addressing the association between GER and IPF, and have sought to contextualise the current conditional guideline recommendation for practitioners caring for these patients.
In December, 2015, a working group of 48 international interstitial lung disease (ILD) experts assembled at the Ettore Majorana Foundation and Centre for Scientific Culture in Erice, Italy, to discuss priority clinical and research issues in ILD. Participants represented 17 countries from Europe and North America. Among the topics of discussion was the current conditional guideline recommendation for antacid therapy in IPF. In pro–con debates and round-table discussions, the evidence supporting this recommendation was presented for consideration. Given the current controversies, this Position Paper was prepared by the primary participants (authors) who discussed this issue while incorporating input from all other participants of the Erice ILD Working Group (appendix).
In recent literature on IPF, symptomatic GER has been termed GERD. However, in the current perspective, we discuss the hypothesis that asymptomatic reflux might be pathogenic in IPF and is, for that reason, a form of GERD. Therefore, to avoid confusion, we have adopted the following two concepts. First, when appropriate, GER (referring to acid or non-acid reflux) will be subdivided into asymptomatic and symptomatic GER, with symptoms categorised as oesophageal or non-oesophageal. Second, for reflux of gastric contents (acid or non-acid) into the airways (excluding aspiration pneumonia) causing pulmonary symptoms or complications we use the term microaspiration, which could be symptomatic or asymptomatic.
Key messages
- •
Gastro-oesophageal reflux (GER) is proposed as pathogenic in the development or progression of idiopathic pulmonary fibrosis (IPF)
- •
To date, international guidelines conditionally recommend the use of antacid therapy for patients with IPF
- •
There is a paucity of high-quality data supporting a pathogenic role of GER in IPF, or a benefit of antacid therapy in patients with IPF
- •
Given the clinical equipoise, we have aimed to contextualise the guideline recommendation for practitioners caring for patients with IPF
- •
Moving forward, consistent terminology must be adopted and prospective randomised trials of antireflux therapy must be completed to meaningfully address the question of antacid therapy use for patients with IPF