The role of gastro-esophageal reflux (GER) in systemic sclerosis and lung fibrosis

Abstract

SummarySystemic sclerosis (SSc) is an autoimmune condition characterized by tissue fibrosis of the skin and internal organs. A significant subgroup of SSc patients develops progressive interstitial lung disease (ILD) leading to pulmonary fibrosis similar to IPF (idiopathic pulmonary fibrosis). Gastro-esophageal reflux (GER) has been suggested as a driving factor in the pathogenesis of both SSc-ILD and IPF. The esophagus is affected in 50-82% of patients with SSc. Gastric reflux may be liquid, gaseous, or particulate; acid or nonacid; distal (localized to the distal oesophagus) or proximal (reaching the proximal oesophagus and pharynx). Reflux to the proximal oesophagus, which is intuitively linked to microaspiration into the lungs, appears to be quite common in patients with ILD-SSc and IPF. Importantly, a significant proportion of GER reflux is asymptomatic. Concentration of pepsin and bile acids in bronchoalveolar lavage (BAL) and exhaled breath condensate (EBC) have been investigated as biomarkers of microaspiration in various respiratory diseases. The confirmation of a causative link of microaspiration in the genesis and progression of lung fibrosis would have a major impact in the management of ILD-SSc patients. It is likely that proteases such as pepsin, and not the acidity, are the primary target for future therapies. Potent inhibitors specific for proteases, e.g. pepstatin, are available and have been tested in phase-III clinical trials.