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
Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
J Allergy Clin Immunol. 2015 Apr;135(4):877-883.e1. doi: 10.1016/j.jaci.2014.10.026. Epub 2014 Dec 6.
Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.
We hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.
The original study from which this analysis originates comprised 2 phases: a steroid-naive phase 1 and a 28-day trial of ICSs (phase 2) during which Feno values, sputum eosinophil counts, and urinary BrTyr levels were measured. The response to ICSs was based on clinical improvements, including a 12% or greater increase in FEV1, a 0.5-point or greater decrease in Asthma Control Questionnaire score, and 2 doubling dose or greater increase in provocative concentration of adenosine 5'-monophosphate causing a 20% decrease in FEV1 (PC20AMP). Healthy control subjects were also evaluated in this study for comparison of biomarkers with those seen in asthmatic patients.
Asthmatic patients had higher than normal Feno values, sputum eosinophil counts, and urinary BrTyr levels during the steroid-naive phase and after ICS therapy. After 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power (13.3-fold, P < .01) to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.
A noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy.
哮喘是一种具有不同表型的异质性疾病。吸入性糖皮质激素（ICS）治疗是哮喘治疗的主要手段，但临床对ICS的反应存在差异。
我们假设一组炎症生物标志物（即呼出气一氧化氮分数[Feno]、痰液嗜酸性粒细胞计数和尿溴酪氨酸[BrTyr]水平）可能预测类固醇反应性。
本分析所源自的原始研究包括两个阶段：未使用类固醇的第1阶段和为期28天的ICS试验（第2阶段），在此期间测量Feno值、痰液嗜酸性粒细胞计数和尿BrTyr水平。对ICS的反应基于临床改善情况，包括第1秒用力呼气容积（FEV1）增加12%或更多、哮喘控制问卷评分降低0.5分或更多，以及使FEV1降低20%的腺苷5'-单磷酸激发浓度（PC20AMP）增加2倍剂量或更多。本研究还评估了健康对照受试者，以比较生物标志物与哮喘患者的生物标志物。
哮喘患者在未使用类固醇阶段和ICS治疗后，Feno值、痰液嗜酸性粒细胞计数和尿BrTyr水平均高于正常。经过28天的ICS试验后，82%的哮喘患者Feno值下降，60%的患者痰液嗜酸性粒细胞计数下降，58%的患者尿BrTyr水平下降。在未使用类固醇阶段，每种生物标志物都有助于预测类固醇反应性，但高Feno值和高尿BrTyr水平的组合预测对ICS治疗有良好反应的能力最强（13.3倍，P <.01）。然而，生物标志物水平下降的幅度与对ICS治疗的临床反应幅度无关。
未使用类固醇的哮喘患者的一组非侵入性生物标志物可预测对ICS治疗的临床反应性。
