Biomarker-based asthma phenotypes of corticosteroid response.
Biomarker-based asthma phenotypes of corticosteroid response.
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DOI：
10.1016/j.jaci.2014.10.026
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发表时间：
2015-04
影响因子：
14.2
通讯作者：
Comhair, Suzy A. A.
中科院分区：
文献类型：
--
作者：
Cowan, Douglas C.;Taylor, D. Robin;Peterson, Laura E.;Cowan, Jan O.;Palmay, Rochelle;Williamson, Avis;Hammel, Jef;Erzurum, Serpil C.;Hazen, Stanley L.;Comhair, Suzy A. A.
关键词：
哮喘是一种具有不同表型的异质性疾病。吸入性皮质类固醇（ICS）治疗是哮喘的主要治疗方法，但临床反应是可变的。我们假设一组炎症生物标志物，即FENO、痰嗜酸性粒细胞和尿溴酪氨酸（BrTyr）可能预测类固醇反应性。本分析所源自的原始研究包括2个阶段：类固醇初治阶段1和ICS 28天试验（阶段2），在此期间测量FENO、痰嗜酸性粒细胞和尿BrTyr。ICS的应答基于临床改善，包括：FEV 1增加≥12%;哮喘控制问卷减少≥0.5分; 5′-单磷酸腺苷激发浓度增加≥2倍剂量，导致FEV 1下降20%（PC 20 AMP）。在这项研究中还评估了健康对照，以比较哮喘患者的生物标志物。哮喘患者在激素初治期和ICS后FENO、痰嗜酸性粒细胞和尿BrTyr均高于正常人。ICS治疗28天后，82%的哮喘患者FENO下降，60%的患者痰嗜酸性粒细胞下降，58%的患者尿BrTyr下降。类固醇初治期的每种生物标志物都可用于预测类固醇反应性，但高FENO和高尿BrTyr的组合具有预测对ICS的有利反应的最佳功效（13.3倍; p<0.01）。然而，生物标志物的降低幅度与ICS的临床应答幅度无关。类固醇初治哮喘患者的一组非侵入性生物标志物可预测ICS的临床反应性
Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma but the clinical response to ICS is variable. We hypothesized that a panel of inflammatory biomarkers i.e. FENO, sputum eosinophils and urinary BromoTyrosine (BrTyr) might predict steroid responsiveness. The original study, from which this analysis originates, comprised 2 phases: a steroid naïve phase 1 and a 28-day trial of ICS (phase 2) during which times, FENO, sputum eosinophils, and urinary BrTyr were measured. Response to ICS was based on clinical improvements including: ≥12% increase in FEV1; ≥0.5 point decrease in Asthma Control Questionnaire; and ≥2 doubling dose increase in provocation concentration of adenosine 5′-monophosphate causing a 20% fall in FEV1 (PC20 AMP). Healthy controls were also evaluated in this study for comparison of biomarkers to asthmatics. Asthmatics had higher than normal FENO, sputum eosinophils and urinary BrTyr at steroid naïve phase and after ICS. After 28-day trial of ICS, FENO decreased in 82% of asthmatics, sputum eosinophils decreased in 60% and urinary BrTyr decreased in 58%. Each of the biomarkers at steroid naïve phase had utility for predicting steroid- responsiveness, but the combination of high FENO and high urinary BrTyr had the best power (13.3 fold; p<0.01) to predict a favorable response to ICS. However, the magnitude of decrease of biomarkers was unrelated to the magnitude of clinical response to ICS. A noninvasive panel of biomarkers in steroid naïve asthmatics predicts clinical responsiveness to ICS.
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影响因子：
9.6
作者：
Bacci, E;Cianchetti, S;Paggiaro, P
通讯作者：
Paggiaro, P
影响因子：
10
作者：
Fleming, Louise;Wilson, Nicola;Bush, Andrew
通讯作者：
Bush, Andrew
DOI：
10.1056/nejmoa0808991
发表时间：
2009-03-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haldar P;Brightling CE;Hargadon B;Gupta S;Monteiro W;Sousa A;Marshall RP;Bradding P;Green RH;Wardlaw AJ;Pavord ID
通讯作者：
Pavord ID
DOI：
10.1164/ajrccm.161.1.9809100
发表时间：
2000-01-01
影响因子：
24.7
作者：
Jatakanon, A;Lim, S;Barnes, PJ
通讯作者：
Barnes, PJ
DOI：
10.1164/ajrccm.164.5.2012125
发表时间：
2001-09-01
影响因子：
24.7
作者：
Jones, SL;Kittelson, J;Taylor, DR
通讯作者：
Taylor, DR