The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5 years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-β by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.

Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders

“…25 Salivary pepsin level can quickly distinguish true reflux with non-reflux diseases, and is important for the diagnosis of GERD patients with predominant respiratory symptoms. [14][15][16][17]26 In this study, the positive rate of detecting EES was 68.2%, which was consistent with the observation of a previous study, 24 suggesting that salivary pepsin is of certain diagnostic value for the diagnosis of EES. In addition, the salivary pepsin level and positive rate in the BE group were significantly higher than those in the HC group in the present study, suggesting that pepsin reflux does play a significant role in the process of BE formation.…”

Cryptotanshinone reverses the epithelial‐mesenchymal transformation process and attenuates bleomycin‐induced pulmonary fibrosis

“…IPF is one of the late outcomes of lung diseases, induced by a variety of causes, that is characterized by destruction of the alveolar histoarchitecture, excessive accumulation of extracellular matrix, infiltration of immunocytes, and irregular changes in fibroblasts (Martinez et al, 2017). As a chronic, progressive, fibrosing form of interstitial pneumonia, IPF reduced human survival, which has been historically approximately 50% with an average survival duration of fewer than 5 years (Bargagli et al, 2019; Lancet, 2015). Studies have suggested that the EMT (epithelial‐mesenchymal transformation) process, characterized by loss of epithelial markers and gain of mesenchymal markers, might account for the occurrence of fibrosis (Qian, Lin, Zhao, Wang, & Liu, 2018; Zhang et al, 2018).…”

Clinical significance of self-reported cough intensity and frequency in patients with interstitial lung disease: a cross-sectional study

“…A further study found no association between GORD and cough in patients with IPF [3]. Therefore, the impact and association of GORD with cough may be weaker in patients with IIPs than in those with CTD-ILD, even though GORD is thought to be involved in the pathogenesis of IIPs [32].…”