Heterogeneity of severe asthma in childhood: Confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program - 10/08/11
, W. Gerald Teague, MD b, Deborah A. Meyers, PhD c, Stephen P. Peters, MD, PhD c, Xingnan Li, PhD c, Huashi Li, MS c, Sally E. Wenzel, MD d, Shean Aujla, MD d, Mario Castro, MD e, Leonard B. Bacharier, MD e, Benjamin M. Gaston, MD b, Eugene R. Bleecker, MD c, Wendy C. Moore, MD cNational Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program
Reprint requests: Anne M. Fitzpatrick, PhD, 2015 Uppergate Drive, Atlanta, GA 30322.Abstract |
Background |
Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities.
Objectives |
This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity.
Methods |
Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program.
Results |
Four clusters of asthma were identified. Children in cluster 1 (n = 48) had relatively normal lung function and less atopy. Children in cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication use. Cluster 3 (n = 32) had greater comorbidity, increased bronchial responsiveness, and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication use. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines.
Conclusion |
Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting.
Le texte complet de cet article est disponible en PDF.Key words : Allergic sensitization, asthma, severe asthma, asthma guidelines, children, cluster analysis, lung function, phenotype
Abbreviations used : ATS, GINA, ICS, LABA, NAEPP, NHLBI, SARP
Plan
| Supported by National Institutes of Health grants RO1 HL069170, RO1 HL069167, RO1 HL069174, RO1 HL69149, and RO1 HL091762 and in part by the Center for Developmental Lung Biology, Children’s Healthcare of Atlanta, and PHS grants UL1 RR025008, KL2 RR025009, TL1 RR025010, and UL1 RR024992 from the Clinical and Translational Science Award Program, National Institutes of Health, National Center for Research Resources. |
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| Disclosure of potential conflict of interest: A. M. Fitzpatrick has received research support from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. W. G. Teague is a speaker for Merck, has received research support from the National Institutes of Health and the American Lung Association, and is a volunteer for Not One More Life. D. A. Meyers has received research support from the National Institutes of Health. S. P. Peters has received research support from the National Institutes of Health, National Heart, Lung, and Blood Institute Severe Asthma Research Program. M. Castro is a consultant for Electrocore, NKTT, Schering, Asthmatx, and Cephalon; is on the advisory board for Genentech; is a speaker for AstraZeneca, Boehringer-Ingelheim, Pfizer, Merck, and GlaxoSmithKline; has received grants from Asthmatx, Amgen, Ception, Genentech, Medimmune, Merck, Novartis, the National Institutes of Health, and GlaxoSmithKline; and has received royalties from Elsevier. L. B. Bacharier has received honoraria from AstraZeneca and has received honoraria from and is on the advisory board for Genentech, Glaxo-SmithKline, Merck, Schering-Plough, and Aerocrine. B. M. Gaston has received research support from the National Institutes of Health and has served as an expert witness on the topic of exhaled nitric oxide for Apieron. E. R. Bleecker is an advisor and consultant for Aerovance, AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer, and Wyeth and has received research support from Aerovance, Amgen, AstraZeneca, Boehringer-Ingelheim, Centocor, Ception, Genentech, GlaxoSmithKline, the National Institutes of Health, Novartis, Pfizer, and Wyeth. The rest of the authors have declared that they have no conflict of interest. |
Vol 127 - N° 2
P. 382 - février 2011 Retour au numéro
Article précédent
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