In vitro cellular assays for the identification of innovative drugs in respiratory pharmacology

Chronic respiratory diseases, such as COPD and idiopathic pulmonary fibrosis (IPF), pose significant clinical challenges due to persistent symptoms like chronic cough, mucus overproduction, and impaired epithelial repair, which lead to tissue remodeling, fibrosis, and a progressive decline in lung function. This thesis is divided into four parts, each addressing a crucial biological process involved in respiratory disease pathology. The first part focuses on the cough reflex and antitussive therapies, investigating the pharmacological profile of the NOP receptor and its potential role in developing new treatments for chronic cough. The second part explores mucin regulation and hypersecretion, specifically examining the mechanisms of driving mucus overproduction in respiratory diseases and evaluating the therapeutic potential of targeting key pathways, such as IL-13 and EGFR signaling. The third part examines epithelial repair and wound healing, with a particular focus on pro-fibrotic stimuli and therapeutic interventions that could mitigate fibrosis progression. The final part investigates epithelial-mesenchymal transition (EMT), a key factor in fibrosis development, assessing the impact of pharmacological inhibitors on this process in respiratory epithelial cells. Together, these four sections provide a comprehensive exploration of potential therapeutic targets and strategies for managing chronic respiratory diseases, laying the groundwork for the development of innovative treatments.