Gastro-esophageal Reflux and Idiopathic Pulmonary Fibrosis—New Evidences of a Causal Relationship

Introduction

Interstitial lung disease (ILD) represents an heterogeneous group of both acute and chronic parenchymal lung diseases (Figure 1) and idiopathic pulmonary fibrosis (IPF) is considered by various authors as the prototype of ILD.1 IPF is becoming an increasingly important respiratory disease with approximately 4000 new cases diagnosed each year in the UK and 18,000 in USA, respectively.1 It is characterized by diffuse pulmonary infiltrates, exertional dyspnea, restrictive lung defects with decreased diffusing capacity of carbon monoxide (DL), and histologic evidence of varying degrees of pulmonary inflammation and fibrosis.1 These abnormalities lead to a decrease in lung volumes and gas transfer across the alveolo-capillary barrier, determining ventilatory failure, secondary pulmonary hypertension, and cor pulmonale. ILD is recognized to be associated with increased morbidity and mortality, with a median survival from diagnosis ranging from 3 to 5 years, especially when significant secondary pulmonary hypertension arises as a consequence of the disease process.1, 2 Currently, no cure is available and treatment strategies show limited effect on this progressive and fatal disease.3 The mechanisms leading to IPF are unknown, although recent studies evaluating the pathogenesis of ILD have evolved our understanding on parenchymal inflammation and fibrosis. Several proinflammatory and profibrotic cytokines, cellular and molecular mechanisms have been implicated as contributory factors.4 There is evidence that both cell-mediated and humoral immunity (eg, proinflammatory and profibrotic cytokines) may play a role in the pathogenesis of ILD.5–7 A causative relationship between ILD and other factors, notably genetic, environmental, and occupational parameters has further been proposed.8, 9 Reported risk factors include cigarette smoking10 and exposure to metal and wood dust.11

Abstract

Idiopathic pulmonary fibrosis (IPF) is a relentless and progressive lung disease of unknown etiology with no effective cure available. Recent data support the concept that chronic silent microaspiration (ie, aspiration of gastric acid, food, bile salts, and trypsin in forms of small droplets) could be involved in the pathogenesis, development, and progression of IPF. However, limited data are present on this direction and the precise relationship between chronic microaspiration and IPF remains poorly understood. It has been demonstrated that gastro-esophageal reflux (GER) plays an important role in causing extra-esophageal symptoms, including chronic bronchitis, bronchiectasis, diffuse panbronchiolitis, recurrent pneumonia, chronic cough, hoarseness, and asthma. Moreover, it is considered a presumed risk factor for microaspiration. Recent studies evidenced that it is strongly associated with IPF with an estimated prevalence of up to 90%. This review aims to explore the relationship between GER and pulmonary fibrosis by highlighting the pathophysiologic mechanisms, the role of diagnostic testing, as well as the therapeutic options for this important group of patients. Furthermore, the gaps in our current understanding of the diagnosis and treatment of chronic microaspiration in patients with IPF will be highlighted. Clarifying the role of chronic microaspiration in IPF is essential because it could potentially have a widespread clinical impact on the progression of this fatal disease.

Keywords

pulmonary fibrosis, impedance pH-metry, acid and nonacid reflux, reflux disease, asthma, interstitial lung disease, microaspiration