Indirect challenges cause the release of endogenous mediators that cause the airway
smooth muscle to contract and the airways to narrow. Airway sensitivity to indirect
challenges is reduced or even totally inhibited by treatment with inhaled corticosteroids
(ICS), so a positive response to an indirect stimulus is believed to reflect active airway
inflammation. The indirect challenges commonly used in pulmonary function laboratories
include exercise, eucapnic voluntary hyperpnea, hypertonic (4.5%) saline, and mannitol …