Airway Hyperresponsiveness in Allergic Asthma

Airway hyperresponsiveness (AHR) is a cardinal feature of allergic asthma, manifesting as an exaggerated narrowing of the bronchial passages in response to stimuli that would be innocuous in healthy individuals. This phenomenon arises from a complex interplay between airway smooth muscle (ASM) contraction, inflammatory cell activation and structural alterations of the airway wall. In allergic asthma, exposure to allergens triggers epithelial release of cytokines such as thymic stromal lymphopoietin and interleukin-33, which in turn drive type 2 inflammation characterised by eosinophil infiltration and mast cell degranulation. These inflammatory mediators promote both direct responsiveness of ASM to pharmacological agonists and indirect reactivity via endogenous bronchoconstrictors. Over time, persistent inflammation leads to airway remodelling, including subepithelial fibrosis and increased smooth muscle mass, further enhancing sensitivity to constrictive stimuli. Clinically, AHR underpins symptoms of wheeze, breathlessness and chest tightness and forms the basis for bronchial challenge tests that assess disease severity and guide personalised therapy.

Research from Nature Portfolio

Recent in vivo imaging studies in murine models have employed ultra-high-resolution computed tomography to visualise the dynamic airway and parenchymal changes that accompany allergic challenge. In the acute phase, allergen inhalation induced peribronchial ground-glass opacities, transient proximal airway dilatation and regional air-trapping despite measurable bronchoconstriction. Over the ensuing hours, recurrent episodes of paradoxical airway dilation alongside peripheral atelectasis were observed, correlating with functional assessments of AHR. These findings illuminate the structural substrates of airflow limitation and may inform optimisation of targeted drug delivery to regions of maximal reactivity.

Airway Hyperresponsiveness in Allergic Asthma publication trend

The graph below shows the total number of articles in airway hyperresponsiveness in allergic asthma across all publications each year (not limited to Nature Index journals).

Technical terms

Airway hyperresponsiveness (AHR): Exaggerated bronchoconstrictive response of the airways to physical or chemical stimuli.

Direct AHR: Sensitivity of airway smooth muscle to inhaled pharmacological agonists such as histamine or methacholine.

Indirect AHR: Bronchoconstriction mediated by endogenous inflammatory mediators released from airway cells.

Airway remodelling: Structural changes in the bronchial wall, including smooth muscle hypertrophy and subepithelial fibrosis.

Bronchial challenge test: Controlled inhalation of a provoking agent to assess degree of airway responsiveness.

References

1. Airway hyperresponsiveness in asthma: The role of the epithelium. Journal of Allergy and Clinical Immunology (2024).
2. Ultra-high-resolution computed tomography shows changes in the lungs related with airway hyperresponsiveness in a murine asthma model. Scientific Reports (2021).
3. Effects of dupilumab on mannitol airway hyperresponsiveness in uncontrolled severe asthma. Journal of Allergy and Clinical Immunology (2024).
4. Plasma proteome changes linked to late phase response after inhaled allergen challenge in asthmatics. Respiratory Research (2022).