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 5 clinical trials of 1708 children aged 12 to 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 <.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Conclusions: 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 915-924.e7 |
| Journal | Journal of Allergy and Clinical Immunology: In Practice |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2019 |
Funding
Conflicts of interest: L. B. Bacharier reports personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, Sanofi/Regeneron, Vectura, Circassia, and AstraZeneca, outside the submitted work. T. W. Guilbert reports personal fees from American Board of Pediatrics; Pediatric Pulmonary Subboard, GSK, Regeneron Pharmaceuticals, Merck, Novartis/Regeneron, Aviragen, GlaxoSmithKline/Regeneron; grants and personal fees from Sanofi/Regeneron; grants from NIH, and other from UpToDate, outside the submitted work. D. J. Jackson reports personal fees from Vectura Group, Boehringer Ingelheim, and GlaxoSmithKline; and consulting fees from Novartis, outside the submitted work. S. J. Szefler reports consultancy fees from Merck, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Aerocrine, Novartis, Astra Zeneca, Daiichi Sankyo, Roche, and Teva; and grants from GlaxoSmithKline, outside the submitted work. M. D. Cabana reports personal fees from Merck, ThemoFisher, Genentech, and Novartis, outside the submitted work. Ronina Covar reports grants from Roche and Astra Zeneca; nonfinancial support from GlaxoSmithKline, outside the submitted work. R. F. Lemanske Jr reports grants from Pharmaxis; personal fees from Elsevier and UpToDate, outside the submitted work. F. D. Martinez reports grants from National Institutes of Health/Office of the Director and Johnson & Johnson; and personal fees from Copeval and Commense, Inc, outside the submitted work. W. Morgan reports grants from the Cystic Fibrosis Foundation; and personal fees from Cystic Fibrosis Foundation, Genentech, American Thoracic Society, American College of Chest Physicians, outside the submitted work. J. A. Pongracic reports grants from Northwestern University, during the conduct of the study; other from Boehringer Ingelheim, GlaxoSmithKline, Teva Pharmaceuticals, and Merck, outside the submitted work. R. S. Zeiger reports grants from National Heart, Lung, and Blood Institute, during the conduct of the study; grants from Aerocrine, Genentech, MedImmune/AstraZeneca, Merck, GlaxoSmithKline, ALK Pharma; and personal fees from AstraZeneca, Genentech, Novartis, Teva Pharmaceuticals, GlaxoSmithKline, Theravance BioPharma, Regeneron Pharmaceuticals, and Patara Pharma, outside the submitted work. D. T. Mauger reports nonfinancial support from Merck, Boehringer Ingelheim, GlaxoSmithKline, Teva Pharmaceuticals, and Vifor, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. The analysis is supported by Children\u2019s Healthcare of Atlanta Pediatric Research Alliance , Center for Clinical Outcomes Research and Public Health ; The National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002378 ; and The AsthmaNet Data Coordinating Center U10 HL098115 .
Keywords
- Asthma exacerbation
- Asthma in children
- Inhaled corticosteroid
- Latent class analysis
- Phenotype
- Preschool child
- Sensitization
- Type 2 inflammation
- Wheeze
ASJC Scopus subject areas
- Immunology and Allergy