Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients.
This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).
Horak
F
F
ENT University Clinic Vienna, Austria.
Toth
J
J
Hirschwehr
R
R
Marks
B
B
Stübner
U P
UP
Jäger
S
S
Berger
U
U
Schleinzer
K
K
Günczler
P
P
D000328:Adult; D039741:Antigens, Dermatophagoides; D001798:Blood Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D001985:Bronchial Provocation Tests / Q000009:adverse effects / Q000379:methods*; D053818:Chymases; D018592:Cross-Over Studies; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D005128:Eye Diseases / Q000175:diagnosis / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage* / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D017997:Leukotriene C4 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D017336:Loratadine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000276:immunology; D010865:Pilot Projects; D015230:Prostaglandin D2 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D011852:Radioallergosorbent Test; D012130:Respiratory Hypersensitivity / Q000175:diagnosis / Q000276:immunology*; D012220:Rhinitis / Q000175:diagnosis / Q000276:immunology; D012260:Ribonucleases; D012697:Serine Endopeptidases / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D012882:Skin Tests; D053802:Tryptases
D039741:Antigens, Dermatophagoides; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D006023:Glycoproteins; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; D017997:Leukotriene C4; D017336:Loratadine; D012260:Ribonucleases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D015230:Prostaglandin D2