title: Components of airway hyperresponsiveness and their associations with inflammation and remodeling in mice.
abstract: BACKGROUND
  Pathologic changes, including inflammation and remodeling, occur in the asthmatic airway. However, their relative contribution to the components of airway hyperresponsiveness (AHR) remains unclear.
  
  
  OBJECTIVE
  Attempting to delineate AHR into discrete immune-mediated and structural remodeling components, we performed a detailed time course of the development, progression, and persistence of maximal respiratory system resistance, airway reactivity, and airway sensitivity.
  
  
  METHODS
  Mice exposed to increasing durations of persistent allergen were assessed for airway function, morphometry, and inflammation.
  
  
  RESULTS
  Allergen exposure resulted in increases for all indices of AHR that persisted for at least 4 weeks after chronic allergen exposure (P < .01 for all values). Early increases in AHR were associated with increases in immune-mediated events, including airway eosinophils (P < .01), whereas sustained AHR was associated with structural remodeling events. Increased maximal respiratory system resistance, evident by 6 weeks postallergen and persisting for at least 4 weeks after 8 weeks of chronic exposure, was associated with an increase in collagen deposition (P < .01). Increased airway reactivity and sensitivity, each evident by 1 week after allergen and persisting for at least 4 weeks after 8 weeks of chronic exposure, were associated with an increase in airway smooth muscle area (P < .01).
  
  
  CONCLUSIONS
  Our novel observation of distinct temporal relationships in the development, progression, and persistence of the individual indices of AHR supports our hypothesis that multiple underlying factors contribute to airway dysfunction.
  
  
  CONCLUSIONS
  These findings illustrate the importance of clearly addressing specific components of airway dysfunction to provide greater insight into specific pathophysiologic mechanisms in airway disease.
authors.affiliation: Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Southam
authors.forename: Russ
authors.initials: R
authors.lastname: Ellis
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wattie
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers