title: Pulmonary edema measured by MRI correlates with late-phase response to allergen challenge.
abstract: OBJECTIVE
  Asthma is associated with reversible airway obstruction, leucocyte infiltration, airways hyperresponsiveness (AHR), and airways remodeling. Fluid accumulation causes pulmonary edema contributing to airways obstruction. We examined the temporal relationship between the late asthmatic response (LAR) following allergen challenge of sensitized guinea-pigs and pulmonary edema measured by magnetic resonance imaging (MRI).
  
  
  METHODS
  Ovalbumin (OVA) sensitized guinea-pigs received either a single OVA inhalation (acute) or nine OVA inhalations at 48 h intervals (chronic). Airways obstruction was measured as specific airways conductance (sG(aw)) by whole body plethysmography. AHR to inhaled histamine and bronchoalveolar lavage for leucocyte counts were measured 24 h after a single or the final chronic ovalbumin challenges. MRI was performed at intervals after OVA challenge and high-intensity edemic signals were quantified.
  
  
  RESULTS
  Ovalbumin caused early bronchoconstriction, followed at 7 h by an LAR and at 24 h AHR and leucocyte influx. The bright-intensity MRI edema signal, peaking at 7 h, was significantly (P < .05) greater after chronic (9.0 ± 0.7 × 10(3) mm(3)) than acute OVA (7.6 ± 0.2 × 10(3) mm(3)). Dexamethasone treatment before acute OVA abolished the AHR and LAR and significantly reduced eosinophils and the bright-intensity MRI edema from 9.1 ± 1.0 to 6.4 ± 0.3 × 10(3) mm(3).
  
  
  CONCLUSIONS
  We show a temporal relationship between edema and the LAR and their parallel reduction, along with eosinophils and AHR, by dexamethasone. This suggests a close causative association between pulmonary edema and impaired airways function.
authors.affiliation: 1Division of Pharmacology, Cardiff School of Pharmacy & Pharmaceutical Science, Cardiff University, Cardiff, United Kingdom.
authors.forename: Rhys L
authors.initials: RL
authors.lastname: Evans
authors.forename: Kumar K
authors.initials: KK
authors.lastname: Changani
authors.forename: Sarah
authors.initials: S
authors.lastname: Hotee
authors.forename: Kashmira
authors.initials: K
authors.lastname: Pindoria
authors.forename: Simon
authors.initials: S
authors.lastname: Campbell
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Nials
authors.forename: William R
authors.initials: WR
authors.lastname: Ford
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Broadley
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Kidd
mesh_terms: D000485:Allergens; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction; D002634:Chemotaxis, Leukocyte; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D010047:Ovalbumin; D011237:Predictive Value of Tests; D011654:Pulmonary Edema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D000485:Allergens; D018927:Anti-Asthmatic Agents; D003907:Dexamethasone; D010047:Ovalbumin
keywords: airways hyperresponsiveness; dexamethasone; edema; guinea-pig; magnetic resonance imaging (MRI); ovalbumin