Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children

Tamazoust Guiddir; Philippe Saint-Pierre; Elsa Purenne-Denis; Nathalie Lambert; Yacine Laoudi; Rémy Couderc; Rahelé Gouvis-Echraghi; Flore Amat; Jocelyne Just

doi:10.1016/j.jaip.2017.02.003

Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children

J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1351-1361.e2. doi: 10.1016/j.jaip.2017.02.003. Epub 2017 Mar 28.

Authors

Tamazoust Guiddir¹, Philippe Saint-Pierre², Elsa Purenne-Denis³, Nathalie Lambert¹, Yacine Laoudi³, Rémy Couderc⁴, Rahelé Gouvis-Echraghi³, Flore Amat¹, Jocelyne Just⁵

Affiliations

¹ Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France.
² Institute of Mathematics, Toulouse III Paul-Sabatier University, Toulouse, France.
³ Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁴ Biochemistry Laboratory, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁵ Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France. Electronic address: jocelyne.just@aphp.fr.

PMID: 28363401
DOI: 10.1016/j.jaip.2017.02.003

Abstract

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.

Keywords: Bacterial infection; Children; Gastroesophageal reflux; Multiple allergies; Severe asthma; Severe recurrent wheeze phenotypes.

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Asthma / drug therapy
Asthma / immunology*
Child
Child, Preschool
Cohort Studies
Disease Progression
Drug Resistance
Eosinophils / immunology*
Female
Humans
Infant
Male
Neutrophils / immunology*
Recurrence
Respiratory Sounds
Severity of Illness Index
Treatment Outcome

Substances

Adrenal Cortex Hormones