Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma - 29/05/14
, Jin-Wen Y. Hsu, PhD a, Robert S. Zeiger, MD, PhD a, Wansu Chen, MS a, Alejandro Dorenbaum, MD b, Bradley E. Chipps, MD c, Tmirah Haselkorn, PhD bAbstract |
Background |
Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies.
Objective |
To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma.
Methods |
Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ2 analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy.
Results |
Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001).
Conclusion |
Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.
Le texte complet de cet article est disponible en PDF.Key words : TENOR, severe asthma, difficult-to-treat asthma, phenotype, demographics, atopy, cluster analysis
Abbreviations used : ATAQ, BMI, FVC, IgE, QoL, SARP, TENOR, VPC
Plan
| TENOR (The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens) was funded by Genentech Inc and Novartis Pharmaceuticals Corporation. This analysis was partially funded by the Department of Research and Evaluation within the Southern California Permanente Medical Group with funds from the Medical Group and the Kaiser Permanente Community Benefit Fund. Editorial support was provided by CircleScience, funded by Genentech Inc. |
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| Disclosure of potential conflict of interest: M. Schatz has received research support and provision of writing assistance from Genentech; has received consultancy fees from Amgen, GlaxoSmithKline, Merck, and Boston Scientific; and has received research support from Aerocrine, Merck, Genentech, GlaoxSmithKline, and MedImmune. R. S. Zeiger has received consultancy fees from Aercrine, AstraZeneca, Genentech, GlaxoSmithKline, MedImmune, Schering Plough, Sunovion, Novartis, and the National Heart, Lung, and Blood Institute/Penn State; and has received research support from Genentech, GlaxoSmithKline, Aerocrine, Merck, MedImmune, and Thermofisher. A. Dorenbaum is employed by and has stock in Genentech; and has an appointment at Stanford University in Allergy Immunology. B. E. Chipps has received consultancy fees from Genentech, AstraZeneca, GlaxoSmithKline, SRxA, Novartis, Sunovion, Merck-Schring, ISTA, and Dey; has received speakers’ bureau honoraria from Genetech, AstraZeneca, GlaxoSmithKline, Novartis, Sunovion, Merck-Schering, and ISTA; has received payment for the service on speakers’ bureaus for Genentech, AstraZeneca, GlaoxSmithKline, Novartis, Sunovion, Merck-Schering, and ISTA. T. Haselkorn has received consultancy fees for writing/reviewing the manuscript from Genentech. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 6
P. 1549-1556 - juin 2014 Retour au numéro
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