Optimizing the Measurement of Therapeutic Targets for Treatment of Asthma Induced by Allergen Inhalation Challenge in Mild Allergic Asthma

This study will measure lung function tests examine biological samples collected before and after inhaled allergen challenges and diluent (control) challenges in participants with mild allergic asthma. Each inhaled challenge will consist of 3 consecutive days (triads) where participants will inhale either allergen extract or saline diluent (control) and airway function will be measured, and biological samples will be obtained. Inhaled allergen challenges will be controlled, with diluent inhalation challenge in a randomized crossover design. Each participant will be required to attend the research lab on at least three consecutive days for an inhaled challenge triad. On triad Day 1, study staff will provide an overview of the study purpose and procedure and answer any questions the participant may have. The individual will then provide informed consent if they wish to participate (i.e. sign the consent form), and safety labs will be collected for blood chemistry and hematology, urinalysis. Skin prick testing will be conducted to determine relevant allergen sensitivities and to determine which allergen extract will be used for the skin test titration and inhalation. A pre-allergen challenge methacholine test is conducted, followed by sputum induction, blood draw and nasal brushing. On Day 2 of the triad, the participant will inhale a dose of allergen that is 3 doubling doses lower than that estimated (using methacholine test and skin titration) to give a 20% fall in forced expiratory volume in 1 second. The participant will continue inhaling doubling doses of allergen extract until a 20% fall in forced expiratory volume in 1 second has been reached. Spirometry will be performed for 7 hours. At 7h post-inhalation a bronchodilator will be administered, and a sputum sample will be collected. Participants will be sent home with bronchodilator to use if needed. On Day 3 of the triad, participants will return at approximately 24h post-allergen challenge for a methacholine test, sputum induction, blood draw and nasal brushing.

Participants will also undergo a Triad 2 (Days 1-3) for an inhaled challenge with 0.9% saline. The intervention (allergen or diluent) will be randomized to Triad 1 or Triad 2. A four-week washout is required between allergen inhalation and a subsequent diluent inhalation. A one-week washout is required between diluent inhalation and a subsequent allergen inhalation.