title: Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation.
abstract: BACKGROUND
  Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship.
  
  
  METHODS
  Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate.
  
  
  RESULTS
  At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001).
  
  
  CONCLUSIONS
  Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.
authors.affiliation: Woolcock Institute of Medical Research, Camperdown, NSW 2050, Australia. sued@woolcock.org.au
authors.forename: Sue R
authors.initials: SR
authors.lastname: Downie
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Salome
authors.forename: Sylvia
authors.initials: S
authors.lastname: Verbanck
authors.forename: Bruce
authors.initials: B
authors.lastname: Thompson
authors.forename: Norbert
authors.initials: N
authors.lastname: Berend
authors.forename: Gregory G
authors.initials: GG
authors.lastname: King
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology*; D001991:Bronchitis / Q000503:physiopathology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012119:Respiration
chemical_list: D000305:Adrenal Cortex Hormones