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

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. (J Allergy Clin Immunol 2012;130:103-10.)