Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling

Hollams, Elysia M., Deverell, Marie, Serralha, Michael, Suriyaarachchi, Devinda, Parsons, Faith, Zhang, Guicheng, de Klerk, Nicholas, Holt, Barbara J., Ladyman, Claire, Sadowska, Agata, Rowe, Julie, Loh, Richard, Sly, Peter D. and Holt, Patrick G. (2009) Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling. Journal of Allergy And Clinical Immunology, 124 3: 463-470. doi:10.1016/j.jaci.2009.06.019


Author Hollams, Elysia M.
Deverell, Marie
Serralha, Michael
Suriyaarachchi, Devinda
Parsons, Faith
Zhang, Guicheng
de Klerk, Nicholas
Holt, Barbara J.
Ladyman, Claire
Sadowska, Agata
Rowe, Julie
Loh, Richard
Sly, Peter D.
Holt, Patrick G.
Title Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
Journal name Journal of Allergy And Clinical Immunology   Check publisher's open access policy
ISSN 0091-6749
1085-8725
1097-6825
Publication date 2009-09-01
Sub-type Article (original research)
DOI 10.1016/j.jaci.2009.06.019
Volume 124
Issue 3
Start page 463
End page 470
Total pages 8
Place of publication Milwaukee, WI, United States
Publisher Mosby
Language eng
Abstract Background: Current treatment strategies for asthma in teenagers derive primarily from information on chronic disease in adults. More detailed understanding of risk factors related to teenage asthma might aid in the development of improved preventive and treatment strategies for this age group. Objective: We sought to identify biomarkers associated with asthma phenotypes in teenagers, particularly atopic asthma, and to identify markers that aid in discriminating between atopic subjects at high versus low risk of asthma. Methods: We studied 1380 unselected 14-year-olds and collected data on clinical history, allergic sensitization, and respiratory and immunoinflammatory function. The latter comprised measurements of circulating inflammatory markers and in vitro innate and adaptive immune functions, including house dust mite T-cell responses. We integrated the data into regression models to identify variables most strongly associated with asthma risk and severity among atopic subjects. Results: Eight hundred twenty-seven subjects were atopic, 140 subjects were asthmatic, and 81% of asthmatic subjects were also atopic. We identified asthma risk variables related to atopy intensity, including specific IgE and eosinophil levels, plus an additional series external to the TH2 cascade but that modified risk only in atopic subjects, including IFN-γ, IL-10, and IL-12 responses and neutrophil numbers in blood. Moreover, bronchial hyperresponsiveness was associated strongly with atopic but not nonatopic asthma, and the bronchial hyperresponsiveness risk profile was itself dominated by atopy-associated variables. Conclusions: Asthma in teenagers is predominantly driven by atopy acting in concert with a second tier of TH2-independent immunoinflammatory mechanisms, which contribute to pathogenesis only against the background of pre-existing inhalant allergy.
Keyword Asthma
atopy
bronchial hyperresponsiveness
IgE
eosinophils
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Health and Behavioural Sciences -- Publications
 
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Created: Wed, 17 Nov 2010, 21:30:17 EST