title: The role of the small airways in the clinical expression of asthma in adults.
abstract: BACKGROUND
  The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown.
  
  
  OBJECTIVE
  We sought to determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment.
  
  
  METHODS
  Adult subjects with asthma had lung function and asthma control (5-item Asthma Control Questionnaire [ACQ-5 score] ≥1.5 = poorly controlled, ACQ-5 score ≤0.75 = well controlled) measured at baseline. A subgroup with AHR had repeat measurements after 3 months of high-dose ICS treatment. The indices of ventilation heterogeneity in the regions of the lung where gas transport occurs predominantly through convection (ventilation heterogeneity in convection-dependent airways [Scond]) and through diffusion (ventilation heterogeneity in diffusion-dependent airways [Sacin]) were derived by using the multiple-breath nitrogen washout technique.
  
  
  RESULTS
  At baseline (n = 105), subjects with poorly controlled asthma had worse FEV(1), fraction of exhaled nitric oxide measured at 200 mL/s (Feno), Scond, and Sacin values. In the treatment group (n = 50) spirometric, Feno, residual volume (RV)/total lung capacity (TLC), AHR, and Scond values significantly improved. Asthma control also improved (mean ACQ-5 score, 1.3-0.7; P < .0001). The change in ACQ-5 score correlated with changes in Feno (r(s) = 0.31, P = .03), Sacin (r(s) = 0.32, P = .02), and Scond (r(s) = 0.41, P = .003) values. The independent predictors of a change in asthma control were changes in Scond and Sacin values (model r(2) = 0.20, P = .005).
  
  
  CONCLUSIONS
  Current asthma control is associated with markers of small-airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small-airway function might be useful in monitoring the response to therapy in asthmatic subjects.
authors.affiliation: Woolcock Institute of Medical Research, Glebe, Australia. cfarah@med.usyd.edu.au
authors.forename: Claude S
authors.initials: CS
authors.lastname: Farah
authors.forename: Gregory G
authors.initials: GG
authors.lastname: King
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Sue R
authors.initials: SR
authors.lastname: Downie
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Kermode
authors.forename: Kate M
authors.initials: KM
authors.lastname: Hardaker
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Peters
authors.forename: Norbert
authors.initials: N
authors.lastname: Berend
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Salome
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001507:Beclomethasone / Q000031:analogs & derivatives / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010991:Plethysmography; D012882:Skin Tests; D013147:Spirometry
chemical_list: D018927:Anti-Asthmatic Agents; D009569:Nitric Oxide; D001507:Beclomethasone