title: Capsaicin-evoked cough responses in asthmatic patients: Evidence for airway neuronal dysfunction.
abstract: BACKGROUND
  Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored.
  
  
  OBJECTIVE
  We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses.
  
  
  METHODS
  Capsaicin inhalational challenge was performed, and cough responses were analyzed by using nonlinear mixed-effects modeling to estimate the maximum cough response evoked by any concentration of capsaicin (Emax) and the capsaicin dose inducing half-maximal response (ED50).
  
  
  RESULTS
  Ninety-seven patients with stable asthma (median age, 23 years [interquartile range, 21-27 years]; 60% female) and 47 healthy volunteers (median age, 38 years [interquartile range, 29-47 years]; 64% female) were recruited. Asthmatic patients had higher Emaxand lower ED50values than healthy volunteers. Emaxvalues were 27% higher in female subjects (P = .006) and 46% higher in patients with nonatopic asthma (P = .003) compared with healthy volunteers. Also, patients with atopic asthma had a 21% lower Emaxvalue than nonatopic asthmatic patients (P = .04). The ED50value was 65% lower in female patients (P = .0001) and 71% lower in all asthmatic patients (P = .0008). ED50values were also influenced by asthma control and serum IgE levels, whereas Emaxvalues were related to 24-hour cough frequency. Age, body mass index, FEV1, PC20, fraction of exhaled nitric oxide, blood eosinophil counts, and inhaled steroid treatment did not influence cough parameters.
  
  
  CONCLUSIONS
  Patients with stable asthma exhibited exaggerated capsaicin-evoked cough responses consistent with neuronal dysfunction. Nonatopic asthmatic patients had the highest cough responses, suggesting this mechanism might be most important in type 2-low asthma phenotypes.
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; University Hospital of South Manchester, Manchester, United Kingdom.
authors.forename: Imran
authors.initials: I
authors.lastname: Satia
authors.affiliation: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tsamandouras
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Holt
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Huda
authors.initials: H
authors.lastname: Badri
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; Central Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodhead
authors.affiliation: Central Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Kayode
authors.initials: K
authors.lastname: Ogungbenro
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; University Hospital of South Manchester, Manchester, United Kingdom.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Felton
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fowler
authors.affiliation: Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; University Hospital of South Manchester, Manchester, United Kingdom. Electronic address: jacky.smith@manchester.ac.uk.
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Smith
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000294:innervation / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D055815:Young Adult
chemical_list: D002211:Capsaicin
keywords: Atopy; pharmacodynamic modeling; transient receptor potential vanilloid type 1; vagus