Novel severe wheezy young children phenotypes: boys atopic multiple-trigger and girls nonatopic uncontrolled wheeze

J Allergy Clin Immunol. 2012 Jul;130(1):103-10.e8. doi: 10.1016/j.jaci.2012.02.041. Epub 2012 Apr 13.


Background: Recurrent wheezing during infancy is a heterogeneous disorder that has been associated with early-onset asthma.

Objective: To identify phenotypes of severe recurrent wheezing and therapeutic approaches.

Methods: We performed cluster analysis with 20 variables of 551 children with active asthma, younger than 36 months old, and enrolled in the Trousseau Asthma Program.

Results: We identified 3 independent clusters of children with wheezing. Cluster 1, mild episodic viral wheeze (n= 327), consisted of children with wheezing related only to colds (71%), mild disease (76%), and mainly normal chest x-ray results. Cluster 2, nonatopic uncontrolled wheeze (n = 157), was characterized by moderate to severe disease (91%), uncontrolled wheezing despite high doses of inhaled corticosteroids (55%), parents with asthma, and increased levels of ferritine. Cluster 3, atopic multiple-trigger wheeze (n = 67), included more children with multiple-trigger wheeze (68%) than did clusters 1 or 2; eczema (75%); a positive result from the Phadiatop Infant test (90%); increased levels of IgE, IgA, and IgG; and abnormal results from chest x-rays. In separate analysis, 1 parameter for boys (increased total level of IgE) and 2 parameters for girls (wheezing severity and increased total level of IgE) properly classified 90% of boys and 83% of girls in the appropriate cluster. Significant associations were found between overcrowding, molds and cockroaches at home, and atopic multiple-trigger wheeze and between day-care attendance and nonatopic uncontrolled wheeze in other parts.

Conclusion: We identified different phenotypes of recurrent wheezing in young children by using cluster analysis with usual variables. These phenotypes require confirmation in longer, follow-up studies.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Age of Onset
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / etiology
  • Asthma / physiopathology*
  • Child, Preschool
  • Cluster Analysis
  • Female
  • Humans
  • Hypersensitivity, Immediate / etiology
  • Hypersensitivity, Immediate / physiopathology*
  • Immunoglobulin E / blood
  • Infant
  • Male
  • Phenotype
  • Respiratory Sounds / physiopathology*
  • Risk Factors
  • Severity of Illness Index*


  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Immunoglobulin E