Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen

Abstract

Background: The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. Objective: We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. Methods: Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. Results: Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. Conclusions: Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.

Endotype of allergic asthma with airway obstruction in urban children

“…41,42 These genes have been previously shown to be upregulated by prolonged allergen exposure in an environmental exposure chamber model. 43 At the cellular and molecular level, MUC5AC is expressed in the upper airways, trachea, and bronchi 44 where, uniquely, it is tethered to secreting club cells 45 and its viscosity is increased in the presence of oxidative stress. 46 These properties likely link overexpression of MUC5AC to airway obstruction and hyperresponsiveness.…”

Allergic rhinitis

“…Allergen exposure, either topically intranasally or in an exposure chamber 37 , can be used to study nasal allergic reactions, monitor symptoms and collect nasal secretions and serum for mediator measurements in response to the allergen 38 or nasal scrapings or biopsy from patients [39][40][41] . In addition, blood cells (such as basophils and antigen-specific T cells) and nasal mucosa tissue can be studied ex vivo 42 using different stimuli and interventions.…”

Allergen exposure chambers: implementation in clinical trials in allergen immunotherapy

“…However, the conclusion drawn from the most recent review [ 30 ] that CPT works in 3 out of 4 studies may be a result of the fact that extracted instead of natural crude allergenic materials must be used for topical allergen provocation tests not always reflecting the individual sensitization profile of the patient and the natural environmental exposure conditions, respectively. The same seems to be true for nasal provocation tests with highly heterogenic evidence in the literature regarding NPT as assessment tool for clinical reactivity in general [ 31 ] or correlation with reactivity in allergen challenge chamber exposure [ 32 ]. These results suggest that sensitization profiles of patients are as diverse as allergenic materials used for testing and until today a distinctive (clinical and non-clinical) parameter as relevant endpoint in reflecting clinical efficacy in AIT trials has not been established.…”