Original articleAsthma, lower airway diseasesWheeze phenotypes in young children have different courses during the preschool period
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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Whispers of change in preschool asthma phenotypes: Findings in the French ELFE cohort
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2021, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :Significant risk factors that are common across multiple cohort studies are atopic disease,4,36-39 viral infections, especially with RV,40-43 frequent wheeze,4,44,45 and decreased lung function.4,36,38,39,46 Furthermore, a cluster analysis of European preschool-age children described a severe, persistent asthma phenotype by the type and severity of allergic sensitization, severity of wheezing episodes and triggers for wheezing in the preschool years, and response to medication.47 Many children with recurrent wheeze develop atopic disease in early life (or vice versa), and atopic disease remains one of the most consistent risk factors for the development of asthma in later life.
Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children
2017, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :We thus believe that this recurrent severe wheeze phenotype is a particular phenotype that does not necessarily have a good prognosis. Nevertheless, children of cluster 2 will probably be at risk of persistent asthma during childhood due to the link of this cluster to atopy defined by the association with allergic sensitization.11 An earlier study by our group in asthmatic children showed a link between intra-alveolar eosinophilia and atopy.27
The recurrently wheezing preschool child - Benign or asthma in the making?
2015, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :As expected, early transient wheeze conferred a benign prognosis, with no respiratory sequelae by 18 years of age. In the 3 clusters described in the Trousseau Asthma Program cohort at 36 months of age, follow-up at 5 years of age found that patients with mild episodic viral wheeze became asymptomatic or continued to have mild episodic viral wheeze, whereas those with atopic multi-trigger wheeze continued with an atopic multi-trigger wheeze pattern and those with nonatopic uncontrolled wheeze developed severe uncontrolled wheeze in most cases.50 Atopic tendencies have consistently been associated with an augmented risk of asthma development.
Food allergy phenotypes
2015, Revue Francaise d'AllergologieAllergic phenotypes in children
2015, Revue Francaise d'Allergologie
Disclosures: Dr Gouvis-Echraghi received honoraria from Novartis and Alk Abello. The other authors have no disclosures.