Effect of nedocromil sodium pretreatment on the immediate and late responses of the airway to segmental antigen challenge.
In many patients with asthma, exposure to allergen results in worsening symptoms, pulmonary dysfunction, and increased airway inflammation. In this study, segmental allergen challenge and bronchoalveolar lavage were used to evaluate the airway responses at 5 minutes and 48 hours and to study the extent of inhibition of the response by pretreatment with nedocromil sodium in eight subjects with allergic asthma in a double-blind, placebo-controlled trial. At 5 minutes after challenge, nedocromil sodium pretreatment significantly reduced histamine concentrations, with a trend toward a concomitant reduction in tryptase levels. Nedocromil sodium did not affect the increase in total protein, total cell counts, or cell concentrations that occurred 48 hours after challenge, but it did significantly reduce eosinophil recruitment. Eosinophil activation, assessed as release of granule proteins, was unaffected. A significant positive correlation was shown between the degree of histamine reduction at 5 minutes and the degree of reduction of eosinophil influx at 48 hours, raising the possibility that eosinophil influx into the airway may depend on mediators or cytokines released during the immediate response to allergen.
Calhoun
W J
WJ
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, PA 15261, USA.
Jarjour
N N
NN
Gleich
G J
GJ
Schwartz
L B
LB
Busse
W W
WW
D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000941:Antigens / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053818:Chymases; D004311:Double-Blind Method; D006636:Histamine Release; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D017835:Nedocromil / Q000627:therapeutic use*; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D000941:Antigens; D018836:Inflammation Mediators; D017835:Nedocromil; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases