title: The effect of airway remodelling on airway hyper-responsiveness in asthma.
abstract: BACKGROUND
  The mechanisms of airway hyper-responsiveness are only partially understood and the contribution of airway remodelling is unknown. Airway remodelling can be assessed by measuring airway distensibility, which is reduced in asthma, even when lung function is normal. We hypothesised that airway remodelling contributes to airway hyper-responsiveness in asthma, independent of steroid-responsive airway inflammation.
  
  
  OBJECTIVE
  To determine the relationship between airway distensibility and airway responsiveness at baseline and after 12 weeks of inhaled corticosteroid therapy in a group of asthmatics with airway hyper-responsiveness.
  
  
  METHODS
  Nineteen doctor-diagnosed asthmatics had airway distensibility measured as the slope of the relationship between conductance and lung volume by the forced oscillation technique. Lung function, exhaled nitric oxide and methacholine challenge were also measured. Subjects had inhaled corticosteroid therapy for 12 weeks after which all measurements were repeated.
  
  
  RESULTS
  At baseline, airway distensibility (mean, 95%CI) was 0.19(0.14-0.23) cm H(2)O(-1)s(-1), exhaled nitric oxide was 13.1(10.3-16.6)ppb and airway distensibility correlated with eNO (p=0.04) and disease duration (p=0.02) but not with airway responsiveness (p=0.46), FEV(1) (p=0.09) or age (p=0.23). After treatment, exhaled nitric oxide decreased (p=0.0002), FEV(1) improved (p=0.0001), airway responsiveness improved (p=0.0002), and there was a small improvement in airway distensibility but it did not normalise (p=0.05). Airway distensibility was not correlated with either exhaled nitric oxide (p=0.49) or airway responsiveness (p=0.20).
  
  
  CONCLUSIONS
  Uncontrolled airway inflammation causes a small decrease in the distensibility of the airways of asthmatics with airway hyper-responsiveness. The lack of association between airway responsiveness and airway distensibility, both before and after 12 weeks ICS treatment, suggests that airway remodelling does not contribute to airway hyper-responsiveness in asthma.
authors.affiliation: The Woolcock Institute of Medical Research, PO Box M77, Missenden Road, Glebe, NSW 2050, Australia. jesskermode@woolcock.org.au
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Kermode
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Kate M
authors.initials: KM
authors.lastname: Hardaker
authors.forename: Claude S
authors.initials: CS
authors.lastname: Farah
authors.forename: Norbert
authors.initials: N
authors.lastname: Berend
authors.forename: Gregory G
authors.initials: GG
authors.lastname: King
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Salome
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000187:drug effects*; D000403:Airway Resistance / Q000187:drug effects*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology*; D004338:Drug Combinations; D045853:Exhalation; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011795:Surveys and Questionnaires; D014109:Total Lung Capacity
chemical_list: D000730:Androstadienes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D009569:Nitric Oxide; D000420:Albuterol