title: Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children.
abstract: BACKGROUND
  Little is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children.
  
  
  OBJECTIVE
  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.
authors.affiliation: Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France.
authors.forename: Tamazoust
authors.initials: T
authors.lastname: Guiddir
authors.affiliation: Institute of Mathematics, Toulouse III Paul-Sabatier University, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saint-Pierre
authors.affiliation: Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Purenne-Denis
authors.affiliation: Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambert
authors.affiliation: Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Laoudi
authors.affiliation: Biochemistry Laboratory, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Couderc
authors.affiliation: Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Rahelé
authors.initials: R
authors.lastname: Gouvis-Echraghi
authors.affiliation: Allergology Department, Armand Trousseau Children Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University Paris 06, Sorbonne University, Paris, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Amat
authors.affiliation: 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.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Just
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D004351:Drug Resistance; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D012008:Recurrence; D012135:Respiratory Sounds; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones
keywords: Bacterial infection; Children; Gastroesophageal reflux; Multiple allergies; Severe asthma; Severe recurrent wheeze phenotypes