Individualized therapy for persistent asthma in young children

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• 作者：Anne M. Fitzpatrick ; PhD^a ; ^&lowast ; ; Daniel J. Jackson ; MD^b ; ^&lowast ; ; David T. Mauger ; PhD^c ; Susan J. Boehmer ; MA^c ; Wanda Phipatanakul ; MD ; MS^d ; William J. Sheehan ; MD^d ; James N. Moy ; MD^e ; Ian M. Paul ; MD ; MSc^f ; Leonard B. Bacharier ; MD^g ; Michael D. Cabana ; MD^h ; Ronina Covar ; MD^p ; Fernando Holguin ; MDⁱ ; Robert F. Lemanske Jr. ; MD^j ; Fernando D. Martinez ; MD^k ; Jacqueline A. Pongracic ; MD^l ; Avraham Beigelman ; MD^g ; Sachin N. Baxi ; MD^d ; Mindy Benson ; MSN ; PNP^m ; Kathryn Blake ; PharmDⁿ ; James F. Chmiel ; MD^o ; Cori L. Daines ; MD^k ; Michael O. Daines ; MD^k ; Jonathan M. Gaffin ; MD^q ; Deborah Ann Gentile ; MD^r ; W. Adam Gower ; MD^s ; Elliot Israel ; MD^t ; Harsha Vardhan Kumar ; MD^u ; Jason E. Lang ; MD ; MPH^v ; Stephen C. Lazarus ; MD^h ; John J. Lima ; PharmDⁿ ; Ngoc Ly ; MD^w ; Jyothi Marbin ; MD^x ; Wayne Morgan ; MD^k ; Ross E. Myers ; MD^y ; J. Tod Olin ; MD^p ; Stephen P. Peters ; MD ; PhD^s ; Hengameh H. Raissy ; PharmD^z ; Rachel G. Robison ; MD^l ; Kristie Ross ; MD^o ; Christine A. Sorkness ; PharmD^aa ; Shannon M. Thyne ; MD^bb ; Stanley J. Szefler ; MD^cc ; ^{Stanley.Szefler@childrenscolorado.org} ; for the National Institutes of Health/National Heart ; Lung ; Blood Institute AsthmaNet^&Dagger ;
• 关键词：Asthma ; asthma treatment ; asthma biomarkers ; asthma phenotype ; inhaled corticosteroid ; leukotriene receptor antagonist ; personalized medicine ; treatment response
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：138
• 期：6
• 页码：1608-1618.e12
• 全文大小：3130 K
• 卷排序：138

文摘

Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications.MethodsThe Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response.ResultsSeventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/μL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments.ConclusionsIn young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.