title: Site of allergic airway narrowing and the influence of exogenous surfactant in the Brown Norway rat.
abstract: BACKGROUND
  The parameters R(N) (newtonian resistance), G (tissue damping), and H (tissue elastance) of the constant phase model of respiratory mechanics provide information concerning the site of altered mechanical properties of the lung. The aims of this study were to compare the site of allergic airway narrowing implied from respiratory mechanics to a direct assessment by morphometry and to evaluate the effects of exogenous surfactant administration on the site and magnitude of airway narrowing.
  
  
  METHODS
  We induced airway narrowing by ovalbumin sensitization and challenge and we tested the effects of a natural surfactant lacking surfactant proteins A and D (Infasurf®) on airway responses. Sensitized, mechanically ventilated Brown Norway rats underwent an aerosol challenge with 5% ovalbumin or vehicle. Other animals received nebulized surfactant prior to challenge. Three or 20 minutes after ovalbumin challenge, airway luminal areas were assessed on snap-frozen lungs by morphometry.
  
  
  RESULTS
  At 3 minutes, R(N) and G detected large airway narrowing whereas at 20 minutes G and H detected small airway narrowing. Surfactant inhibited R(N) at the peak of the early allergic response and ovalbumin-induced increase in bronchoalveolar lavage fluid cysteinyl leukotrienes and amphiregulin but not IgE-induced mast cell activation in vitro.
  
  
  CONCLUSIONS
  Allergen challenge triggers the rapid onset of large airway narrowing, detected by R(N) and G, and subsequent peripheral airway narrowing detected by G and H. Surfactant inhibits airway narrowing and reduces mast cell-derived mediators.
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, and the Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Sana
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Kimitake
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Paul-André
authors.initials: PA
authors.lastname: Risse
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Bullimore
authors.forename: Andrea
authors.initials: A
authors.lastname: Benedetti
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D066258:Amphiregulin; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects*; D002118:Calcium; D002460:Cell Line; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D012701:Serotonin / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D066258:Amphiregulin; C587850:Areg protein, rat; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D015289:Leukotrienes; D013501:Surface-Active Agents; D012701:Serotonin; D010047:Ovalbumin; D002118:Calcium