<p>Idiopathic pulmonary fibrosis and GERD: links and risks</p>

Abstract

Gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) are two pathological conditions often strictly related, even if a clear relationship of causality has not been demonstrated. GERD is a frequent comorbidity in IPF patients, as demonstrated using combined multichannel intraluminal impedance-pH, despite being mostly clinically silent. According to that, it has been hypothesized that microaspiration of gastric material may play a fundamental role in the fibrotic transformation of pulmonary parenchyma. In contrast, it cannot be excluded that IPF may favor GERD by increasing the negative intrathoracic pressure. Therefore, this relationship is uncertain as well as not univocal. Nevertheless, the latest international guidelines recommend the use of proton pump inhibitors (PPIs) in IPF based on several data showing that PPIs can stabilize lung function, reduce disease flares and hospitalizations. On the contrary, recent studies not only question the relevance of these results, but also associate the use of PPIs with an increased risk of lung infections and a negative prognostic outcome. The aim of this review is to analyze the possible links between GERD and IPF and their possible therapeutic implications, trying to translate this scientific evidence into useful information for clinical practice.

Diagnostic and Treatment Standards in Idiopathic Pulmonary Fibrosis in the Era of Antifibrotic Drugs in Poland: A Real-World Practice Survey

“…However, this recommendation carries very low confidence in effect estimates. On the contrary, recent studies not only question the relevance of the above mention retrospective findings but also associate the use of PPI with an increased risk of lung infections and a negative prognostic outcome [15]. Therefore, AAT prospective randomized trials in IPF are urgently needed.…”

“…PPI are used in the case of symptomatic GERD by 44% of the respondents and 12% use PPI regardless of GERD symptoms (43% and 11% in the previous survey, respectively). Although the potential role of gastroesophageal reflux (GER) in IPF pathogenesis and progression is not fully explained, it is suggested that AAT may decrease the risk for microaspiration-associated lung injury or damage, a mechanism that has been postulated to cause or worsen IPF [15]. Based on the encouraging retrospective clinical data, that PPI can stabilize lung function and reduce disease flares and hospitalizations, the international treatment guidelines recommend the use of AAT in IPF with the treatment indication being IPF and not GERD [4].…”

Epidemiology of Idiopathic Pulmonary Fibrosis

“…In animal models, the burden of proof is most substantial for GERD associated with IPF [67]. Chronic microaspiration insults may lead to pulmonary parenchyma damage attracting persistent inflammation resulting in fibrotic remodeling [68,69]. Tracheal pepsin is a predictable indicator of aspiration [70].…”

“…In a post-hoc data evaluation of the INPULSIS trials, IPF acute exacerbations frequently occurred on antacid therapy than those not on it [81]. PPI use results in alkaline gastric pH, which loses its bactericidal effect and increases respiratory infections on aspiration [69]. The clinical data available does not agree with a GERD and IPF relationship [82].…”

“…In most patients, refluxes are silent with the absence of any symptoms, and the best way to diagnose them is via esophageal MII-pH or high-resolution manometry. Alternatively, bronchoscopy with BAL presence of pepsin and bile salts can be used in IPF [69]. During meta-analysis, a lack of clarity with GERD diagnostic definitions was identified.…”