Childhood asthma clusters and response to therapy in clinical trials.
Childhood asthma clusters and response to therapy in clinical trials.
复制标题
DOI：
10.1016/j.jaci.2013.09.002
复制
发表时间：
2014-02
影响因子：
14.2
通讯作者：
Jackson, Daniel J.
中科院分区：
文献类型：
--
作者：
Chang, Timothy S.;Lemanske, Robert F., Jr.;Mauger, David T.;Fitzpatrick, Anne M.;Sorkness, Christine A.;Szefler, Stanley J.;Gangnon, Ronald E.;Page, C. David;Jackson, Daniel J.
儿童哮喘簇，或子类，已开发的计算方法，没有评估的临床效用。复制并确定先前在重度哮喘研究计划（SARP）中通过计算确定的儿童哮喘簇是否与儿童哮喘研究和教育（CARE）网络临床试验中的治疗反应相关。使用SARP参与者数据确定聚类分配模型。来自三项CARE试验的611名6-18岁的参与者被分配到SARP儿科集群。在每项试验中，主要和次要结局均按聚类进行分析。CARE参与者被分配到SARP集群具有很高的准确性。同一组SARP和CARE儿童的基线特征相似。CARE试验中的治疗应答在各组间基本相似。然而，由于样本量较小，早发性/严重肺功能组的儿童对氟替卡松/沙美特罗的反应最好（64%对比BADGER试验中2.5倍氟替卡松和13%氟替卡松/孟鲁司特，p=0.011），早发性/合并症组对治疗的临床疗效最低（例如，CLIC试验中FEV 1变化为-0.076%）。在这项研究中，我们使用一个独立的大型临床试验网络复制了SARP儿童哮喘集群。早发性/严重肺功能和早发性/合并症簇分别与对治疗的差异和有限反应相关。进一步的前瞻性研究治疗反应的集群可以提供新的见解儿童哮喘治疗。
Childhood asthma clusters, or subclass, have been developed by computational methods without evaluation of clinical utility. To replicate and determine if childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) network clinical trials. A cluster assignment model was determined using SARP participant data. 611 participants 6-18 years old from three CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between the SARP and CARE children of the same cluster. Treatment response in the CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% versus 23% 2.5x fluticasone and 13% fluticasone/montelukast in the BADGER trial, p=0.011) and the early-onset/comorbidity cluster had the least clinical efficacy to treatments (e.g. −0.076% change in FEV1 in the CLIC trial). In this study, we replicated the SARP pediatric asthma clusters using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment.
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DOI：
10.1164/rccm.200711-1754oc
发表时间：
2008-08-01
影响因子：
24.7
作者：
Haldar P;Pavord ID;Shaw DE;Berry MA;Thomas M;Brightling CE;Wardlaw AJ;Green RH
通讯作者：
Green RH
DOI：
10.1016/j.jaci.2010.11.015
发表时间：
2011-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Fitzpatrick AM;Teague WG;Meyers DA;Peters SP;Li X;Li H;Wenzel SE;Aujla S;Castro M;Bacharier LB;Gaston BM;Bleecker ER;Moore WC;National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program
通讯作者：
National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program
影响因子：
6.1
作者：
Sekigawa, T.;Tajima, A.;Inoue, I.
通讯作者：
Inoue, I.
影响因子：
5.8
作者：
Halekoh, U;Hojsgaard, S;Yan, J
通讯作者：
Yan, J
影响因子：
14.2
作者：
Lotvall, Jan;Akdis, Cezmi A.;Greenberger, Paul A.
通讯作者：
Greenberger, Paul A.