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

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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.

Section snippets

Methods

Patients were part of the 3-year (2008-2010) Trousseau Asthma Program of the Centre de l'Asthme et des Allergies at the Hôpital Trousseau in Paris; the study included children with recurrent wheezing. All the children had been referred to the center by a primary care physician for persistent, recurrent wheezing; 67% were outpatients from Paris and the surrounding area, and the remaining 33% were from all regions of France. Data were collected from the children by using questionnaires and

Description of the population

We studied 551 consecutive pediatric outpatients with recurrent wheezing. There were 384 boys (69.7%), and the average age of participants was 19 ± 8.8 months. Most children had uncontrolled or partially controlled wheezing and were receiving ICS (51% were receiving high doses and 29% were receiving low doses).

Asthma phenotypes, based on cluster analysis

We used the cluster approach to generate a dendrogram that revealed 3 clusters of children with shared phenotypes (see Fig E1 in this article's Online Repository at www.jacionline.org).

Discussion

We identified 2 novel phenotypes of severe wheezing, which we called atopic MTW and nonatopic uncontrolled wheeze, compared with a phenotype of milder, recurrent wheeze, which we called mild EVW.

Previously reported phenotypes of wheezing preschool children, but not infants, were classified as EVW and MTW, based on expert recommendations for treatment.4 Sonnappa et al17 associated MTW with significant abnormalities in pulmonary function, independent of atopy or wheezing status. Our analysis of

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    Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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