Airway hyperresponsiveness in asthma: The role of the epithelium

Airway hyperresponsiveness (AHR) is a key clinical feature of asthma. The presence of AHR in people with asthma provides the substrate for bronchoconstriction in response to numerous diverse stimuli, contributing to airflow limitation and symptoms including breathlessness, wheeze, and chest tightnes...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2024-05, Vol.153 (5), p.1181-1193
Main Authors: Bradding, Peter, Porsbjerg, Celeste, Côté, Andréanne, Dahlén, Sven-Erik, Hallstrand, Teal S., Brightling, Christopher E.
Format: Article
Language:English
Subjects:
airway hyperresponsiveness
Asthma
bronchoconstriction
cytokines
epithelium
inflammation
mast cells
Medicin och hälsovetenskap
respiratory
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Summary:Airway hyperresponsiveness (AHR) is a key clinical feature of asthma. The presence of AHR in people with asthma provides the substrate for bronchoconstriction in response to numerous diverse stimuli, contributing to airflow limitation and symptoms including breathlessness, wheeze, and chest tightness. Dysfunctional airway smooth muscle significantly contributes to AHR and is displayed as increased sensitivity to direct pharmacologic bronchoconstrictor stimuli, such as inhaled histamine and methacholine (direct AHR), or to endogenous mediators released by activated airway cells such as mast cells (indirect AHR). Research in in vivo human models has shown that the disrupted airway epithelium plays an important role in driving inflammation that mediates indirect AHR in asthma through the release of cytokines such as thymic stromal lymphopoietin and IL-33. These cytokines upregulate type 2 cytokines promoting airway eosinophilia and induce the release of bronchoconstrictor mediators from mast cells such as histamine, prostaglandin D2, and cysteinyl leukotrienes. While bronchoconstriction is largely due to airway smooth muscle contraction, airway structural changes known as remodeling, likely mediated in part by epithelial-derived mediators, also lead to airflow obstruction and may enhance AHR. In this review, we outline the current knowledge of the role of the airway epithelium in AHR in asthma and its implications on the wider disease. Increased understanding of airway epithelial biology may contribute to better treatment options, particularly in precision medicine.
ISSN:0091-6749
1097-6825
1097-6825
DOI:10.1016/j.jaci.2024.02.011