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Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children
Tamazoust Guiddir1, Philippe Saint-Pierre2, Elsa Purenne-Denis3
1Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France.
Insights
Severe asthma in children involves distinct inflammatory pathways, with eosinophils implicated in older children and neutrophils in younger ones. Understanding these phenotypes can guide personalized treatment strategies for recurrent wheeze and asthma.
Area of Science:
- Pediatric Pulmonology
- Immunology
- Allergy
Background:
- Inflammatory pathways in severe recurrent wheeze (preschool children) and severe asthma (children) remain poorly understood.
- Characterizing these pathways is crucial for effective therapeutic interventions.
Purpose of the Study:
- To define phenotypes of severe recurrent wheeze and severe asthma in children.
- To investigate triggers, cellular involvement (eosinophils/neutrophils), and corticosteroid responsiveness.
- To identify distinct molecular phenotypes within the Severe Asthma Molecular Phenotype cohort.
Main Methods:
- Prospective enrollment of children with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze.
- Standardized clinical evaluations, blood work, and bronchoalveolar lavage (BAL).
- Cluster analysis applied to 350 children using 34 variables to identify distinct phenotypes.
Main Results:
- Three clusters identified: 1) Neutrophilic, steroid-refractory wheeze (n=138) with pneumonia/GERD history and high neutrophils. 2) Single aeroallergen sensitization (n=104), responsive to ICS. 3) Eosinophilic, steroid-refractory asthma (n=108) with allergies and high eosinophils.
- Cluster 1 showed uncontrolled asthma despite high-dose inhaled corticosteroids (ICS).
- Cluster 3 exhibited higher blood eosinophil and BAL eosinophil counts.
Conclusions:
- Asthma and recurrent wheeze inflammation pathways differ by age, involving eosinophils in older children and neutrophils in younger ones.
- Identification of distinct phenotypes aids in understanding disease mechanisms.
- Findings support the development of personalized treatment approaches for pediatric asthma and wheeze.
Background:
Little is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children.
Objectives:
The aim of the Severe Asthma Molecular Phenotype cohort was to characterize phenotypes of severe recurrent wheeze and severe asthma during childhood in terms of triggers (allergic or not), involved cells (eosinophil or neutrophil), and corticoid responsiveness.
Methods:
Children with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze were enrolled prospectively. They underwent standardized clinical and blood workup, and bronchoalveolar lavage (BAL) evaluation. Cluster analysis was applied to 350 children with 34 variables.
Results:
Three clusters were identified: cluster 1, Neutrophilic steroid-refractory recurrent wheeze phenotype, with 138 children uncontrolled despite high-dose inhaled corticosteroids (ICS) (92%, P < .001), with more history of pneumonia (31%, P < .001), more gastroesophageal reflux disease (37%, P < .001), and the highest blood neutrophil count (mean 4.524 cells/mm3, P = .05); cluster 2, Severe recurrent wheeze with sensitization to a single aeroallergen (12%, P = .002), with 104 children controlled with high-dose ICS (63%, P < .001); cluster 3, Eosinophilic steroid-refractory asthma phenotype, with 108 children uncontrolled despite high-dose ICS (76%, P < .001) with more allergic rhinitis, atopic dermatitis, and food allergies (82%, 40%, 31%, P < .001, respectively). They also had a higher blood eosinophil count and a higher percentage of BAL eosinophil (506/mm3, 2.6%, P < .001 respectively).
Conclusions:
Inflammation pathway of asthma and recurrent wheeze are related to eosinophil cells in older children and neutrophil cells in younger children. These results could improve personalized treatments.