Original article
Asthma, lower airway diseases
Wheeze phenotypes in young children have different courses during the preschool period

https://doi.org/10.1016/j.anai.2013.07.002Get rights and content

Abstract

Background

Rules for predicting the course of asthma in wheezy infants have low specificity.

Objective

To determine if the novel phenotypes—mild early viral wheeze (EVW), atopic multiple-trigger wheeze (MTW), and nonatopic uncontrolled wheeze (NAUW)—have different courses during the preschool period.

Methods

Part of the prospectively followed Trousseau Asthma Program cohort was phenotyped using cluster analysis with 12 parameters (sex, asthma severity and control with inhaled corticosteroid [ICS], parental asthma, allergic rhinitis, eczema, food allergy, EVW or MTW, and allergen exposure trigger). Wheezing trajectories were assessed by crossing the original phenotypes with the phenotypes obtained at 5 years.

Results

Four clusters were identified at 5 years of age: asymptomatic children (n = 47) with no wheezing (98%), children with mild EVW (n = 40, 87% with EVW, 50% with EVW controlled with low-dose ICS), those with atopic MTW (n = 30, 100% with MTW, only 17% with MTW controlled with low-dose ICS, more significant for pollen asthmatic trigger), and those with atopic severe UW (n = 33, 63% with UW uncontrolled despite high doses of ICS, more significant for allergic rhinitis and dust as asthmatic trigger). Those with mild EVW became asymptomatic or remained with mild EVW. Those with atopic MTW remained with atopic MTW and those with NAUW developed severe UW in most cases.

Conclusion

These results show that remission is most frequently observed in mild EVW and that no remission is observed in atopic MTW.

Introduction

Wheezing in the young child is not classified as asthma because the wheeze can resolve spontaneously during childhood.1 This particular course of recurrent early wheezing suggests that wheezing is not related to the chronic inflammation that characterizes asthma. Conversely, it is well known that asthma with early onset during infancy has a poor prognosis. Identifying those children who will develop asthma at a young age will help in the prognosis of respiratory symptoms and could guide treatment and prevention strategies.2

Wheezing phenotypes are frequently defined retrospectively in birth cohorts; thus, the development of asthma is difficult to predict in clinical practice. Nevertheless, it has been reported in the literature that the natural course of wheezing disorders changes according to the age of onset and depending on the association of atopic features or severe viral exacerbations and disease severity. All studies on this subject have shown that IgE-related diseases confer asthma severity,[3], [4] especially for acute exacerbations, and a more severe decrease in lung function during childhood and throughout adulthood.5

Several prediction rules have been developed to predict whether preschool children will have asthma at school age: the stringent and loose forms of the Asthma Predictive Index6 and the Prevention and Incidence of Asthma and Mite Allergy risk score7 have been externally validated. However, these are difficult to apply in clinical practice because of their generally low positive predictive value.

In 2008, a European Respiratory Society Task Force8 defined 2 novel phenotypes in preschool children: episodic (viral) wheeze (EVW; wheezing only during colds and asymptomatic between episodes) and multiple-trigger wheeze (MTW; wheezing during colds and symptomatic between episodes with other triggers such as house dust, grass, pets, tobacco smoke, exercise, or cold air). MTW also has been associated with a distinct endophenotype with a thicker reticular basement membrane and greater mucosal eosinophilic inflammation than that found in children with EW.9

In a cross-sectional study using a clustering approach, the authors' group previously defined 3 phenotypes of recurrent wheezers in children younger than 3 years old by taking into account the previously identified phenotypes and atopic features: those with mild EVW, those with atopic MTW, and those with nonatopic uncontrolled wheeze (NAUW).10

The aim of the present study was to confirm the hypothesis that these prospectively defined phenotypes could have different courses during childhood.

Section snippets

Study Design

All wheezy infants who were part of the Trousseau Asthma Program study10 and prospectively followed to 5 years of age were considered for inclusion.

Clinical parameters were assessed over the telephone by questions from the International Study of Asthma and Allergies in Childhood.11 The other parameters were mostly the same as in the previous study10:

  • 1.

    Maternal and paternal history of asthma.

  • 2.

    Allergic rhinitis (AR), eczema, and food allergy were assessed mainly by questions from the International

Results

Of the 300 children who were 5 years old at the time of follow-up, 150 could be assessed for all the parameters listed above. The initial characteristics of the 150 children who could not be recontacted did not differ from those of the final sample (Table 1) and were the same as those in the initial 3 clusters (eTable 1). Moreover, the studied population of the 150 children had similar characteristics to the 3 initial clusters previously described,10 especially concerning sex, clinical and

Discussion

There were 3 main results of this study: (1) the prognosis is good for children classified with mild EVW at 3 years old because 69% remained in the least severe phenotypes (asymptomatic or mild EVW) at 5 years old; (2) the prognosis of the initially severe phenotypes is poor: none of the children with the atopic MTW phenotype became asymptomatic (ie, cluster 1) at 5 years and 61% with atopic MTW and 59% with NAUW were classified as having atopic MTW or atopic UW; and (3) the changes observed in

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    Disclosures: Dr Gouvis-Echraghi received honoraria from Novartis and Alk Abello. The other authors have no disclosures.

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