Effect of continuous allergen challenge on clinical symptoms and mediator release in dust‐mite‐allergic patients

Abstract

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).

Levocetirizine better protects than desloratadine in a nasal provocation with allergen

“…43,44 An increase in IL-5, IL-8, eotaxin, and ECP levels was generally reported. 43,[45][46][47][48][49] A few studies only indicated an inhibition of IL-8 secretion by astemizole in a nasal challenge with allergen and of ECP and eosinophil influx by cetirizine, loratadine, or azelastine in seasonal trials. [50][51][52][53] In this single-dose trial, we could not demonstrate any effect of either levocetirizine or desloratadine at 5 mg on cytokine levels (IL-4 and IL-5), on chemokine levels (IL-8 and eotaxin), or on ECP secretion.…”

Conjunctival allergen challenge: Models in the investigation of ocular allergy

“…Implications of this study were twofold: it showed that tryptase is a good indicator of mast-cell degranulation, and it showed that conjunctival challenges can be used to induce mast-cell degranulation. Studies in which the conjunctiva was challenged with allergen have shown increases in histamine, kinins, prostaglandins, albumin, and TAME-esterase (toluene-sulfo-trypsin-arginine methyl ester) [11]; leukotrienes B4, C4, D4, and E4 [12]; eosinophil cationic protein (ECP) [13]; and histaminase [14]. An understanding of the release of histaminase, the enzyme that breaks down the released histamine, following a conjunctival challenge is especially important in understanding the time course of signs and symptoms.…”

Sublingual house dust mite immunotherapy has no impact on decrease of circulating erythrocytes upon airway allergen challenge in allergic rhinitis

“…objective symptom-medication scores, subjective visual analogue scores, and percutaneous, conjunctival and respiratory allergen challenges are the current state of the art methods to determine the effects of allergen immunotherapy. Of those, allergen provocations in allergen challenge chambers represent the gold standard 16–18 . An environmental allergen challenge chamber was recently used to prove the clinical efficacy of a HDM sublingual tablet 15 .…”