Abstract
Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either “direct” or “indirect,” referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.
Highlights
Airway hyperresponsiveness (AHR) is one of the hallmark features of asthma
The chronic inflammation is associated with AHR that leads to recurrent episodes of wheezing, chest tightness, and coughing [Global Initiative for Asthma (GINA), 2007]
Symptoms often do not reflect the degree of airway inflammation and AHR, the two key features attenuated by the mainstay therapy for asthma, inhaled corticosteroids (ICS; Sont et al, 1996)
Summary
Airway hyperresponsiveness (AHR) is one of the hallmark features of asthma. Bronchial provocation tests (BPTs) are used to assess the presence of AHR to assist in making a clinical diagnosis of asthma in individuals with symptoms and signs that suggest asthma. Bronchial provocation tests are useful in a clinical setting if spirometry is normal and a reversibility test using a standard dose of β2-agonist does not demonstrate significant reversibility or bronchodilatation. They may be useful if a past history of asthma has not been substantiated by objective measures of lung function documenting reversible airflow obstruction, as well as in the evaluation of atypical symptoms such as chronic cough (Irwin, 2006). Where possible we will demonstrate the differences and www.frontiersin.org
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