Allergen Challenge Testing in Atopic Asthma Pharmaceutical Research: Past, Present, and Future Directions

Abstract

Over the years, various allergen inhalation challenge models have been developed to study the pathophysiology and pharmacology of allergen-induced asthma. Each allergen challenge method possesses unique benefits and disadvantages. The classic allergen challenge model is useful for assessing the efficacy of new treatments but does not reflect real-world repeated exposure and excludes approximately 50% of allergic asthmatics (i.e. those who do not exhibit a late asthmatic response). The early response model, while also artificial, is less time-consuming and allows for the generation of dose-response data but does not assess the late response or related sequelae. The repeated low-dose allergen model was developed with the purpose of mimicking natural exposure for induction of airway inflammation and airway hyperresponsiveness. However, this method does not consistently produce airway inflammation and is less practical to perform due to the number of study visits required. The segmental allergen model is the only one to allow direct sampling of airway secretions for airway inflammation studies, but it is highly invasive and requires special training and equipment. Attempts have been made to establish a repeated high-dose allergen model for the assessment of drug effects on symptoms and rescue medication use, but participant safety remains a concern and it is also less practical than the classic method. The most difficult allergen model to perform is the natural exposure method, for which standardisation may not be possible given the number of environmental factors that must be controlled or measured. Modifications to these allergen models could improve their clinical relevance and identify their specific, tailored applications in pharmaceutical research of allergic asthma.