Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in...

Area of Science:

• Allergy and Immunology
• Pulmonary Medicine
• Pharmacology

Background:

• APC 366, a selective mast cell tryptase inhibitor, previously demonstrated efficacy in a sheep model of allergic asthma.
• It inhibited antigen-induced early asthmatic response (EAR), late asthmatic response (LAR), and bronchial hyperresponsiveness (BHR).

Purpose of the Study:

• To evaluate the effects of APC 366 on antigen-induced EAR, LAR, and BHR.
• To investigate these effects in mild atopic asthmatics not receiving anti-inflammatory therapy.

Main Methods:

• A randomized, double-blinded, crossover study involving 16 mild atopic asthmatics.
• Participants received aerosolized APC 366 (5 mg) or placebo three times daily for four days.
• Allergen challenge was performed on day 4, followed by histamine challenge the next morning.

Main Results:

• APC 366 significantly reduced the area under the curve for the LAR compared to placebo (P =.012).
• A significant reduction in the mean maximum fall in FEV(1) for the LAR was observed with APC 366 (P =.007).
• No significant effects on BHR were found; EAR reduction was not statistically significant.

Conclusions:

• Short-term, repeated administration of APC 366 effectively reduced antigen-induced LAR in atopic asthmatics.
• These findings highlight the role of mast cell tryptase in the late-phase allergic asthma response.