title: Effect of a topical corticosteroid on airway hyperresponsiveness and eosinophilic inflammation induced by trimellitic anhydride exposure in sensitized guinea pigs.
abstract: BACKGROUND
  Topical corticosteroids are effective in the treatment of asthma by improving bronchial hyperresponsiveness and reducing airway inflammation.
  
  
  METHODS
  We assessed the effect of a nebulized corticosteroid, budesonide, on airway hyperresponsiveness and inflammatory response provoked by inhalation of trimellitic anhydride (TMA) dust, a known cause of occupational asthma in human beings, in guinea pigs sensitized to the free hapten. Male Dunkin-Hartley guinea pigs (n = 24) were injected intradermally with 0.1 ml of 0.3% TMA in corn oil, followed by exposure 21 to 28 days later to five consecutive doses of budesonide aerosol (0.5 mg/ml) or saline solution, administered for 10 minutes every 12 hours. They were then exposed (noses only) to TMA dust (8 mg/m3) or air for 1 hour (four groups, n = 6 in each). Airway responsiveness to acetylcholine, defined as the concentration needed to cause a 200% increase in lung resistance (PC200), was measured 8 hours later.
  
  
  RESULTS
  In saline-treated guinea pigs exposed to TMA, mean PC200 was 0.094 mmol/L (geometric SEM, 1.4 mmol/L) compared with 0.31 mmol/L (geometric SEM, 1.3 mmol/L, p < 0.05) in those guinea pigs pretreated with budesonide. In sham-exposed sensitized guinea pigs, PC200 was 0.35 mmol/L (geometric SEM, 1.2 mmol/L), which was not significantly different from the budesonide-treated group (0.36 mmol/L; geometric SEM, 1.3 mmol/L). There was a significant increase in the number of eosinophils in the subepithelium of guinea pigs further exposed to TMA dust (71.5 +/- 6.8 cells/unit area [mean +/- SEM]) compared with those exposed to air (22.7 +/- 6.7, p < 0.01). Budesonide did not inhibit the number of subepithelial eosinophils of guinea pigs exposed to TMA dust (54.0 +/- 3.7 cells/unit area) or in those exposed to air (24.3 +/- 6.7 cells/unit area) and did not affect the increase in eosinophils found in bronchoalveolar fluid.
  
  
  CONCLUSIONS
  Budesonide significantly inhibited the increase in airway responsiveness but not the eosinophilic inflammation induced by exposure to TMA dust in sensitized guinea pigs.
authors.affiliation: Department of Thoracic Medicine, National Heart & Lung Institute, London, England.
authors.forename: J P
authors.initials: JP
authors.lastname: Hayes
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: A J
authors.initials: AJ
authors.lastname: Taylor
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000287:Administration, Topical; D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide; D005938:Glucocorticoids; D006168:Guinea Pigs; D008297:Male; D010796:Phthalic Anhydrides / Q000276:immunology; D011282:Pregnenediones / Q000008:administration & dosage / Q000627:therapeutic use*; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000336:Aerosols; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D010796:Phthalic Anhydrides; D011282:Pregnenediones; D019819:Budesonide; C015559:trimellitic anhydride