Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation

Abstract

Background-Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Objective-Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Methods-Data from five clinical trials of 1,708 children age 12-71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Results-Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 ("minimal sensitization"), 0.93 ± 0.10 for class 2 ("sensitization with indoor pet exposure"), 0.60 ± 0.07 for class 3 ("sensitization with tobacco smoke exposure"), and 0.81 ± 0.10 for class 4 ("multiple sensitization and eczema") (p < 0.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Conclusion-Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.

Extract and component‐specific sensitization patterns in Canadian moderate‐to‐severe preschool asthmatics

“…subgroups: (a) a food and environmentally sensitized group, representative of the classical progression of the atopic march; (b) an environmentally sensitized group; and (c) a nonsensitized group (Figure 2). These data are consistent with reports that the nonsensitized group tends to be less responsive to standard corticosteroid asthma medications 8. Specifically, these reports are from the high-risk CAPS and MACS studies from Australia and the population-based LISAplus study from Germany 6,7.…”

“…These data are consistent with reports that the nonsensitized group tends to be less responsive to standard corticosteroid asthma medications. 8 In conclusion, we provide data describing a potentially highrisk preschool asthma cohort in Canada using a comprehensive approach capturing sensitization to allergens of paramount importance. By applying both allergen extracts and components, we identified that peanut and animal allergens from cat and dog were major allergen sources in this North American cohort of preschool asthmatics.…”

“…interesting studies have however shown, by microarray analyses, an upregulation of both IL-1β expression and IL-6 expression in spontaneous urticarial wheals as compared to unaffected skin 7,8. In the present study, we confirm this upregulation, and moreover, we demonstrate, for the first time, that IL6 and IL1β mRNA expression is significantly increased in positive autologous serum skin tests (ASST).We compared IL6 and IL1β mRNA expression in skin biopsies of negative ASST versus positive ASST, as well as in spontaneous urticarial wheals compared to uninvolved skin.…”

EAACI Guidelines on Allergen Immunotherapy: House dust mite‐driven allergic asthma

“…However, decreased symptoms and medication use can be considered as a surrogate for asthma control . The decrease in specific AHR might lead to less allergen‐driven asthma exacerbations . Of note, the number of studies that demonstrated a significant effect on the early and, most importantly, the late phase of allergen‐induced bronchial reaction is very limited. There is limited evidence on potential direct or indirect cost‐saving effect by adding HDM SCIT to regular asthma treatment. Asthma control and lung function should be assessed regularly (preferably before each SCIT injection); a minimum 30 minutes of observation after therapy at the office is recommended; SCIT should be administered by healthcare professionals (HCPs) with proper training in AIT, under proper conditions to manage severe bronchospasm or a systemic anaphylactic reaction.…”

One step forward, 2 steps back: The enigma of preschool wheeze

“…Second, although several studies, such as that by Oksel et al, 3 have focused only on lung function variables, others have also included other observable clinical features, such as symptoms and allergic sensitization variables in the phenotype identification models. 6,7 There is currently no consensus on which approach is best for the purpose of personalized care delivery. Indeed, some have argued that a phenotype might or might not be associated with an underlying disease mechanism but provides an opportunity for application of personalized therapy (eg, a patient with persistently low lung function despite therapy attempts).…”