Chest
Volume 138, Issue 2, Supplement, August 2010, Pages 4S-10S
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Airway Hyperresponsiveness in Asthma: Its Measurement and Clinical Significance
The Relationship of Airway Hyperresponsiveness and Airway Inflammation: Airway Hyperresponsiveness in Asthma: Its Measurement and Clinical Significance

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Airway hyperresponsiveness (AHR) is a clinical feature of asthma and is often in proportion to the underlying severity of the disease. To understand AHR and the mechanisms that contribute to these processes, it is helpful to divide the airway components that affect this feature of asthma into “persistent” and “variable” categories. The persistent component of AHR represents structural changes in the airway, whereas the variable feature relates to inflammatory events. Insight into how these interrelated components of AHR can contribute to asthma is gained by studying treatment effects and models of asthma provocation.

Section snippets

What Are the Components of AHR?

In studying, discussing, and understanding the components that comprise AHR, it is helpful, and possibly informative, to divide the factors that contribute to AHR into two categories: persistent and variable2, 3 (Fig 2). Under this concept, which may be an oversimplification of this feature of asthma, the persistent aspects of AHR have been largely attributed to structural changes in the airway, which can include subendothelial thickening, subbasement membrane thickening, smooth muscle

Detection of AHR

It is important to indicate that detection of AHR can also be arbitrarily divided into two stimuli: direct and indirect (Fig 4). Direct stimulation of the airway to measure AHR is seen principally with methacholine or histamine, both of which act directly on airway smooth muscle to evoke a contractual response.1, 2, 3 Because the degree of the airway contractual, or closure, response is enhanced in asthma, smaller concentrations of agonists are needed to decrease the FEV1 by 20% and thus lead

What Lessons Have Been Learned About AHR From Treatment of Asthma?

In 1999, Sont and colleagues4 reported on the effects of a treatment strategy directed toward reducing AHR vs guideline-directed care alone on clinical outcomes of asthma and also the underlying features of airway inflammation and histopathology in these patients. All enrolled subjects had AHR as defined by a PC20 to methacholine < 8 mg/mL. The enrolled patients were divided into two groups: reference treatment (the level of step care was based on guideline recommendations) and an AHR strategy

The Effect of an Inhaled Allergen Bronchial Provocation on AHR

Interleukin (IL)-5 is increased in lumen secretions following allergen challenge and correlates with the presence of eosinophils recruited to the lung.6 To dissect these processes (ie, mediator vs cellular aspects), Shi and colleagues7 had patients with asthma inhale IL-5 and evaluated its effects on AHR and recruitment of eosinophils. Twenty-four hours after inhaling IL-5, eosinophils markedly increased in the sputum and paralleled a significant enhancement in responsiveness with methacholine.

Conclusions

Defining the contribution of airway inflammation to AHR depends on many aspects. First, it depends on the component of AHR that is measured, persistent vs variable. Although this is an arbitrary division, it does allow for evaluation of structural changes vs the variable level (ie, inflammation). Second, the measurement of AHR is influenced by the methods used to detect it, whether it is methacholine causing a direct constriction of airway muscle or other substances that are indirect activators

Acknowledgments

Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

References (13)

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Funding/Support: This work was supported by the National Institutes of Health, National Heart, Lung and Blood Institute [Grant R01 HL069116] and the National Institute of Allergy and Infectious Diseases [N01-AI-25496].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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