Proton pump inhibitors in IPF: beyond mere suppression of gastric acidity

Proton pump inhibitors (PPIs) are structurally composed of benzimidazole core; a pharmacologically common scaffold that makes up nearly one quarter of the hundred most selling drugs including anticancer, opioid, antihistaminic and antihelmintic drugs. In medicinal chemistry, benzimidazoles are coined as privileged scaffolds due to their ability to recognize and bind diverse biological targets. In this regard, PPIs have been linked to other extra-intestinal functions including direct modulation of airway epithelial, vascular endothelial and immune cells. PPIs have been reported to improve outcomes in idiopathic pulmonary fibrosis (IPF) including slowing the decline in measures of lung function, reducing episodes of acute exacerbations and prolonging transplant-free survival. Recently, the evidence-based guidelines for IPF treatment conditionally recommended the use of PPIs in IPF. However, no prospective clinical trial has been conducted to empirically evaluate the safety and efficacy of PPIs in IPF. Here, we discuss emerging anti-inflammatory and antifibrotic activity of PPIs in the context of IPF. We also discuss possible molecular mechanisms by which PPIs may unleash their beneficial effect in IPF.