title: Human trachealis and main bronchi smooth muscle are normoresponsive in asthma.
abstract: BACKGROUND
  Airway smooth muscle (ASM) plays a key role in airway hyperresponsiveness (AHR) but it is unclear whether its contractility is intrinsically changed in asthma.
  
  
  OBJECTIVE
  To investigate whether key parameters of ASM contractility are altered in subjects with asthma.
  
  
  METHODS
  Human trachea and main bronchi were dissected free of epithelium and connective tissues and suspended in a force-length measurement set-up. After equilibration each tissue underwent a series of protocols to assess its methacholine dose-response relationship, shortening velocity, and response to length oscillations equivalent to tidal breathing and deep inspirations.
  
  
  RESULTS
  Main bronchi and tracheal ASM were significantly hyposensitive in subjects with asthma compared with control subjects. Trachea and main bronchi did not show significant differences in reactivity to methacholine and unloaded tissue shortening velocity (Vmax) compared with control subjects. There were no significant differences in responses to deep inspiration, with or without superimposed tidal breathing oscillations. No significant correlations were found between age, body mass index, or sex and sensitivity, reactivity, or Vmax.
  
  
  CONCLUSIONS
  Our data show that, in contrast to some animal models of AHR, human tracheal and main bronchial smooth muscle contractility is not increased in asthma. Specifically, our results indicate that it is highly unlikely that ASM half-maximum effective concentration (EC50) or Vmax contribute to AHR in asthma, but, because of high variability, we cannot conclude whether or not asthmatic ASM is hyperreactive.
authors.affiliation: 1 Meakins-Christie Laboratories.
authors.forename: Gijs
authors.initials: G
authors.lastname: Ijpma
authors.forename: Linda
authors.initials: L
authors.lastname: Kachmar
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Matusovsky
authors.forename: Jason H T
authors.initials: JH
authors.lastname: Bates
authors.forename: Andrea
authors.initials: A
authors.lastname: Benedetti
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lauzon
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D014132:Trachea / Q000502:physiology*; D055815:Young Adult
chemical_list: D016210:Methacholine Chloride
keywords: airway hyperresponsiveness; airway smooth muscle mechanics; asthma; shortening velocity; smooth muscle