The Perils and Pitfalls of Esophageal Dysmotility in Idiopathic Pulmonary Fibrosis

Abstract

Introduction: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF).Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of anti-reflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux -a prerequisite of aspiration), and pulmonary function in IPF patients. Methods:We prospectively recruited 35 IPF patients (aged 53-75yrs; 27 male) who underwent highresolution impedance manometry and 24-hr pH-impedance, together with pulmonary function assessment.Results: Twenty-two (63%) patients exhibited dysmotility, 16(73%) ineffective esophageal motility (IEM) and 6(27%) esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (%FVC:p=0.032) and more proximal reflux (p=0.074) than patients with normal motility. In patients with IEM, intra-thoracic pressure inversely correlated with the number of proximal events (r=-0.429;p=0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r=0.583;p=0.018), whilst in patients with normal motility it inversely correlated with the bolus exposure time (r=-0.478;p=0.098) and number of proximal events (r=-0.542;p=0.056). %FVC in IEM patients inversely correlated with the percentage of reflux events reaching the proximal esophagus (r=-0.520;p=0.039) and inspiratory LESP (r=-0.477;p=0.062), and positively correlated with intrathoracic pressure (r=0.633;p=0.008). Conclusions:We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intra-thoracic pressures and higher LESPs.

Towards a more precise classification of esophageal motility disorders in patients with systemic sclerosis

“…As to the relationship between motility alterations leading to GER and the potential development of idiopathic pulmonary fibrosis (IPF), Gao et al 44 found that patients with this complication presented with lower LES and UES, higher prevalence of hypotensive LES and hiatal hernia (HH), and combined impedance showed that 46.4% of them had weak peristalsis and the bolus transit was impaired. A recent study 45 using this sophisticated HRIM has shown a significantly higher rate of IEM in IPF patients than in controls and this motor abnormality was associated with more proximal reflux and worse pulmonary function tests in the former population, thus corroborating the pathogenetic role of esophageal dysmotility in this group of ILD patients, similar to what may occur in SSc patients.…”

“…As to the relationship between motility alterations leading to GER and the potential development of idiopathic pulmonary fibrosis (IPF), Gao et al 44 found that patients with this complication presented with lower LES and UES, higher prevalence of hypotensive LES and hiatal hernia (HH), and combined impedance showed that 46.4% of them had weak peristalsis and the bolus transit was impaired. A recent study 45…”

The causal relationship between gastro-esophageal reflux disease and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study

“…[38] Reflux events generally occur during inspiration and are inversely correlated with inspiratory thoracic pressures. [9] [10] Other mechanical factors that might contribute to GERD secondary to IPF are reduced esophageal body motility, lower basal lower esophageal sphincter pressure, and delayed gastric emptying. [36] We therefore investigated the possibility of causality in both directions using a bidirectional MR approach, but we found no evidence of a causal effect of IPF on GERD risk.…”

“…[8] This is plausible given that reduced lung compliance in IPF can lead to more negative intrathoracic pressures and reflux events are inversely correlated with inspiratory thoracic pressures. [9,10] Unlike observational associations, genetic associations are not affected by classical confounding or reverse causation, as genes are randomly allocated at conception. A Mendelian randomisation (MR) approach that uses genetic variants known to affect GERD as its proxies (instrumental variables) can therefore provide indirect evidence for a causal effect of GERD on the risk of IPF, if its underlying assumptions hold.…”

“…[8] This is plausible given that reduced lung compliance in IPF can lead to more negative intrathoracic pressures and reflux events are inversely correlated with inspiratory thoracic pressures. [9, 10]…”