title: Assessment of peripheral airway function following chronic allergen challenge in a sheep model of asthma.
abstract: BACKGROUND
  There is increasing evidence that the small airways contribute significantly to the pathophysiology of asthma. However, due to the difficulty in accessing distal lung regions in clinical settings, functional changes in the peripheral airways are often overlooked in studies of asthmatic patients. The aim of the current study was to characterize progressive changes in small airway function in sheep repeatedly challenged with house dust mite (HDM) allergen.
  
  
  RESULTS
  Four spatially separate lung segments were utilized for HDM challenges. The right apical, right medial, right caudal and left caudal lung segments received 0, 8, 16 and 24 weekly challenges with HDM respectively. A wedged-bronchoscope technique was used to assess changes in peripheral resistance (R(p)) at rest, and in response to specific and non-specific stimuli throughout the trial. Allergen induced inflammatory cell infiltration into bronchoalveolar lavage and increases in R(p) in response to HDM and methacholine were localized to treated lung segments, with no changes observed in adjacent lung segments. The acute response to HDM was variable between sheep, and was significantly correlated to airway responsiveness to methacholine (r(s) = 0.095, P<0.01). There was no correlation between resting R(p) and the number of weeks of HDM exposure. Nor was there a correlation between the magnitude of early-phase airway response and the number of HDM-challenges.
  
  
  CONCLUSIONS
  Our findings indicate that airway responses to allergic and non-allergic stimuli are localized to specific treated areas of the lung. Furthermore, while there was a decline in peripheral airway function with HDM exposure, this decrease was not correlated with the length of allergen challenge.
authors.affiliation: Centre for Animal Biotechnology, Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Van der Velden
authors.forename: Donna
authors.initials: D
authors.lastname: Barker
authors.forename: Garry
authors.initials: G
authors.lastname: Barcham
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Koumoundouros
authors.forename: Kenneth
authors.initials: K
authors.lastname: Snibson
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002469:Cell Separation; D002908:Chronic Disease; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D016210:Methacholine Chloride / Q000494:pharmacology; D039981:Pyroglyphidae / Q000187:drug effects / Q000276:immunology*; D012756:Sheep / Q000276:immunology*
chemical_list: D000485:Allergens; D016210:Methacholine Chloride