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Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
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Release of Airway Alarmins IL-33 and TSLP in Paediatric Acute Severe Asthma: A Case-Control Study

M Ramphul1, I C Scott2, H Killick2

  • 1Department of Paediatric Respiratory Medicine, Leicester Children's Hospital. Leicester Royal Infirmary, Leicester, UK.

Acta Paediatrica (Oslo, Norway : 1992)
|December 12, 2025
PubMed

Insights

Interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) alarmins are significantly elevated during childhood asthma attacks. These findings suggest potential therapeutic targets for preventing severe asthma exacerbations in children.

Area of Science:

  • Pediatric Allergy and Immunology
  • Respiratory Medicine
  • Cytokine Biology

Background:

  • Childhood-onset asthma is linked to airway alarmins Interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP).
  • Understanding alarmin levels during asthma exacerbations is crucial for targeted therapies.

Purpose of the Study:

  • To quantify IL-33 and TSLP levels in the airways of children and young people (CYP) experiencing asthma attacks.
  • To compare alarmin-cytokine concentrations between acute asthma, stable asthma, and non-asthmatic control groups.

Main Methods:

  • A prospective, observational, case-control feasibility study design.
  • High-sensitivity immunoassays were employed to measure IL-33 and TSLP concentrations in sputum.
  • Participants included CYP with acute asthma attacks, stable asthma, and healthy controls.

Main Results:

  • Sputum IL-33 and TSLP levels were 3.4 and 17.7 times higher, respectively, in acute asthmatics compared to stable asthmatics.
  • No significant difference in sputum IL-33 and TSLP was observed between stable asthmatics and non-asthmatic controls.
  • Elevated alarmin levels were specific to acute asthma exacerbations in children.

Conclusions:

  • IL-33 and TSLP are significantly increased during acute severe asthma attacks in children.
  • These elevated alarmins may contribute to ongoing airway inflammation and remodeling during pediatric asthma exacerbations.
  • Findings support clinical investigation of anti-TSLP and anti-IL-33 biologics for managing childhood asthma attacks.
Abstract

Keywords:
IL‐33TSLPairway epitheliumalarminasthmabiomarkerexacerbationpaediatricphenotyping

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