title: Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome.
abstract: BACKGROUND
  Cough hypersensitivity may be related to the pathogenesis of upper airway cough syndrome (UACS). The purpose of the study was to investigate the role of capsaicin-sensitive cough receptors on the laryngopharynx and lower airway in the cough hypersensitivity of patients with UACS.
  
  
  METHODS
  59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39 healthy volunteers were recruited for the study. Cough threshold C5, defined as the lowest concentration of capsaicin required for the induction of ≥ 5 coughs upon exposure to capsaicin, were determined at baseline and after laryngopharngeal anesthesia with lidocaine in all the subjects. After induced sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by ELISA. In 15 patients with UACS, sputum cytology and measurement of the above mediators were repeated after successful therapy.
  
  
  RESULTS
  C5 response to capsaicin was significantly lower in the UACS group than in the rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) µmol/L vs. 7.8 (3.9, 93.75) µmol/L vs. 31.2 (15.6, 62.5) µmol/L, H=40.12, P=0.000]. Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin in the subjects of all 3 groups by a similar degree, but the increase in the UACS group was still the lowest, with an increased level of histamine, PGE2, and CGRP in the induced sputum. When cough resolved with the treatment of cetirizine alone or in combination with erythromycin, the levels of CGRP and histamine in the induced sputum decreased significantly in 15 patients with UACS, with no obvious change in cell differential or concentration of PGE2 in the induced sputum.
  
  
  CONCLUSIONS
  Laryngeal TRPV1 plays an important role in cough sensitivity, but sensitization of capsaicin-sensitive cough receptors in the lower airway may be more responsible for the cough hypersensitivity in patients with UACS.
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Xianghuai
authors.initials: X
authors.lastname: Xu
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Yang
authors.forename: Hanjing
authors.initials: H
authors.lastname: Lü
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology; D002211:Capsaicin / Q000009:adverse effects* / Q000378:metabolism; D016022:Case-Control Studies; D003371:Cough / Q000209:etiology*; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000150:complications* / Q000378:metabolism; D007013:Hypopharynx / Q000187:drug effects / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013183:Sputum / Q000166:cytology / Q000378:metabolism; D018709:Statistics, Nonparametric; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D018015:Receptors, Calcitonin Gene-Related Peptide; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D006632:Histamine; D008012:Lidocaine; D015232:Dinoprostone; D002211:Capsaicin