title: The role of nitrosative stress in the pathogenesis of unexplained chronic cough with cough hypersensitivity.
abstract: BACKGROUND
  Unexplained chronic cough is a common condition without specific causes. A hyperreactivity of the cough reflex has been suggested as a mechanism for inducing chronic cough. We hypothesized that nitrosative stress in the upper airway might play a role in cough  hypersensitivity by causing neurochemical abnormalities.
  
  
  METHODS
  Fifty-one patients with unexplained chronic cough and 27 controls were enrolled. A capsaicin cough provocation test was performed to determine cough sensitivity. Nitrosative stress in the upper airway was  assessed by quantifying 3-nitrotyrosine (3-NT) immunostaining in nasal epithelial cells (NECs) and measuring nasal nitric oxide (nNO). The effect of NO on airway epithelium was investigated by measuring the levels of substance P (SP) in nasal lavage fluid and evaluating SP expression in airway  epithelial cells.
  
  
  RESULTS
  Based on the results of the capsaicin test, patients were divided into two groups: a cough hypersensitivity (CHS) group and a normal cough sensitivity (NCS) group. The levels of 3-NT immunoreactivity in NECs were significantly higher in CHS (49  ± 2.9%) than in NCS (27 ± 3.3%) and controls (12 ± 1.6%), a pattern that was also reflected in the values of nNO (350 ± 43, 215 ± 23, and 138 ± 23 ppb in CHS, NCS, and controls, respectively). SP concentration was also elevated in nasal lavage fluids  from CHS (746 ± 28 pg/mL) compared with that from NCS (624 ± 40 pg/mL) and controls (526 ± 41 pg/mL). SP expression in airway epithelial cells was greatly enhanced by exposure to NO donor, which was attenuated by pretreatment with either NO scavenger or NO synthase inhibitor.
  
  
  CONCLUSIONS
  Increased nitrosative stress in the upper airway may play a role in the pathogenesis of unexplained chronic cough with CHS through enhanced secretion of SP.
authors.affiliation: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Bae
authors.forename: Keun Ai
authors.initials: KA
authors.lastname: Moon
authors.forename: Tae-Bum
authors.initials: TB
authors.lastname: Kim
authors.forename: Yong Ju
authors.initials: YJ
authors.lastname: Jang
authors.forename: Yoon Su
authors.initials: YS
authors.lastname: Lee
authors.forename: Chan Sun
authors.initials: CS
authors.lastname: Park
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Hee-Bom
authors.initials: HB
authors.lastname: Moon
authors.forename: You Sook
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003371:Cough / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009299:Nasal Provocation Tests; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015538:Nitrosation; D013312:Stress, Physiological; D013373:Substance P / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D013373:Substance P; D019001:Nitric Oxide Synthase