Immune system in the pathogenesis of chronic cough

WAO-ARIA consensus on chronic cough – Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways

“… 21 , 51 , 52 Similar modulation of cough can also be induced by IL-17-mediated infiltration of neutrophils whose probable role in neurogenic inflammation is generation of reactive oxygen species and sensitization of cough neuronal pathway. The same effect can result from bradykinin-induced secretion of PGs 43 which are potent tussigens. 12 Data also suggest an important role of mast cells in chronic cough patients.…”

“…HCR is best described as a hyperexcitable neuroinflammation of the cough-triggering vagal neuronal pathway. This can occur centrally, 42 peripherally or both, 37 , 43 and is mediated by increased neuronal expression of TRP ion channels. 44 Triggers, which in otherwise normal individuals do not necessarily exacerbate cough, can cause prolonged coughing in patients with HCR ( Fig.…”

“… 19 The intricate regulatory role of the immune system in HCR is deciphered by experimental in-vivo and in-vitro models comparing different cough phenotypes to each other or to healthy individuals. Based on specimen findings from broncho-alveolar lavage fluid, induced sputum and lung biopsies of patients with different cough phenotypes, 43 studies suggest inflammatory cells such as eosinophils, neutrophils and mast cells are involved in the pathogenesis of cough. In fact, there is a considerable similarity in biochemical profile among patients with HCR (see below).…”

“…A detailed description of immune cascade pathways in HCR is comprehensively described elsewhere. 43 , 49 , 50 Importantly, in vivo and in vitro data from these reviews address the immune modulatory role of cough in a variety of lower airway clinical phenotypes of chronic cough but unfortunately most patient populations included in these studies are small in size. Neurokinins such as substance P, CGRP, and interleukins (IL)-4 and IL-5 stimulate eosinophils to release effector molecules such as major basic proteins, cysteinyl leukotrienes, and eosinophil granule-derived cationic proteins with resultant stimulation of cough sensory and muscarinic nerves.…”

“…Neurokinins such as substance P, CGRP, and interleukins (IL)-4 and IL-5 stimulate eosinophils to release effector molecules such as major basic proteins, cysteinyl leukotrienes, and eosinophil granule-derived cationic proteins with resultant stimulation of cough sensory and muscarinic nerves. 12 , 43 Nerve growth factor (NGF), whose main source in humans is eosinophils, increases expression of TRP channels (TRPV1, TRPA1) on sensory nerves with inflammation, thus highlighting the role of allergic airway inflammation in chronic cough. 21 , 51 , 52 Similar modulation of cough can also be induced by IL-17-mediated infiltration of neutrophils whose probable role in neurogenic inflammation is generation of reactive oxygen species and sensitization of cough neuronal pathway.…”