Abstract

Indirect challenges to assess bronchial hyperresponsiveness are being increasingly used both for research and for assessment in the routine pulmonary function laboratory. “Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract with or without inducing microvascular leakage. Because the responses to these challenges are modified or completely inhibited by inhaled steroids, the airway response to the challenges may be a closer reflection of active airway inflammation” (fig. 1) [1]. In contrast, the direct tests, inhaled aerosols of histamine and methacholine act directly on receptors on the bronchial smooth muscle to cause contraction. While sensitive for detecting bronchial hyperresponsiveness a positive response to these agents is not specific for identifying asthma particularly at the higher concentrations. The best known of the indirect challenges is exercise. Other indirect challenges include eucapnic voluntary hyperpnoea, mannitol, adenosine monophosphate and hyperosmolar saline. All these indirect challenges are associated with release of mediators of bronchoconstriction. For this reason they have the potential to be used to identify presence of inflammatory cells particularly mast cells [2]. Figure 1 The events that lead to airway narrowing and a reduction in forced expiratory volume in 1 s in response to different indirect challenge tests. While hyperpnoea, mannitol and 4.5% saline all act to increase osmolarity that causes mediators to be released, adenosine acts to release mast cell mediators through a specific receptor on the mast cell. ASL: airway surface liquid; FEV1: forced expiratory volume in 1 s. Modified from [2] with permission from the publisher. ### Usefulness Exercise testing is used to diagnose exercise-induced bronchoconstriction (EIB). The term EIB describes the transient increase in airways resistance that follows vigorous exercise. EIB is thought to result from transient dehydration of the airway surface in response to conditioning the inspired …

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