Antacid therapy in idiopathic pulmonary fibrosis: more questions than answers?

Gastroesophageal Reflux Disease in Idiopathic Pulmonary Fibrosis: Uncertainties and Controversies

“…It is unclear whether various GERD phenotypes (acid or nonacid and symptomatic or asymptomatic) differently affect the pathogenesis, progression, and exacerbations of IPF or the response to or benefit from antireflux/antacid therapy. Interestingly, genetic predisposition is supposed to underlie GERD-related injury in patients with IPF [12]. …”

“…The current hypothesis is that gastric contents are microaspirated, which is facilitated by weakened lower esophageal sphincter (LES), to the pharyngeal region and subsequently aspirated into the lower respiratory tract. Some previous studies have supported this hypothesis by reporting the detection of gastric contents (acids and pepsin) in the bronchoalveolar lavage fluid (BALF) of patients with IPF [9, 10]; such microaspiration may stimulate the fibroproliferative responses of the lung at molecular and cellular levels [11, 12]. Furthermore, some studies found that both antacid drugs and antireflux surgery were potentially beneficial to patients with IPF [1, 2, 13], although some other studies do not agree with this claim [14, 15].…”

Gastro-oesophageal reflux and idiopathic pulmonary fibrosis: the heart burn in patients with IPF can no longer be silent

“…However, post hoc and exploratory analyses from the two groups from three clinical trials on pirfenidone in IPF did not reveal differences in the rate of decrease of lung function or mortality when comparing AAT users versus non-users at baseline [11,12]. Several questions regarding the association of GORD and IPF and management of GORD in patients with IPF need to be addressed in much needed prospective studies [6].…”

“…Based on the increased prevalence, it has been hypothesised that GOR-associated microaspirations may have a pathogenic role in IPF. This stimulated further research, including in animal models, which suggested that aspiration of acid refluxate causes the parenchymal damage associated with pneumonitis and increased epithelial permeability with the consequence of stimulated fibrotic proliferation and perhaps of acute exacerbations (summarised in [6]). Therefore, an early dream was that supressing microaspiration may alter the course of IPF, namely by allowing greater symptom management, disease stabilisation and perhaps improved survival [7].…”

“…Such trials need also to assess potential risks in this specific patient population, especially the potential concern of pneumonia and respiratory infections with pre-specified criteria (including theoretical effects of changes to the gut and thus lung microbiome). Furthermore, a potential effect of AAT on the on the absorption, bioavailability and efficacy of concomitant antifibrotic therapies must be studied [6].…”