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.