哮喘联盟

   摘要
   研究背景：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）治疗是哮喘的最基本治疗，但是患者对于ICS的临床反应性不尽相同。
   目的：我们假设一组炎性生物标记物（例如，吸入一氧化氮分数[Feno]、痰中嗜酸性粒细胞计数、尿液中溴酪氨酸水平）可能预测激素的反应性。
   方法：本项研究分析包括两个阶段：纯激素治疗期（1期）和一个28天的吸入激素治疗期（2期），在这两个治疗期间，测量Feno值、痰中嗜酸性粒细胞计数、尿液中溴酪氨酸水平。ICSs反应性评估给予临床症状改善、FEV1增加12%以上、哮喘控制问卷评分降低0.5分以上、PC20AMP剂量增加。健康对照者在本项研究中同样评估这些生物标志物。
   结果：哮喘患者在纯激素治疗和ICS治疗后Feno值较正常升高，痰中嗜酸性粒细胞计数和尿中BrTyr水平升高。经过28周的ICSs治疗，哮喘患者Feno值减低82%，痰中嗜酸性粒细胞计数下降60%，尿中BrTyr水平降低58%。每一个生物标志物在纯激素治疗1期军显示出预测激素反应性的能力，但是高Feno值和高BrTyr水平联合应用对ICS治疗的好反应性具有最强的预测能力（13.3倍，P < .01)）。然而，生物标记物下降的程度与临床ICS治疗的反应性程度不相关。
   结论：应用无创性生物标记物可预测激素治疗哮喘患者的ICS临床反应性。
 

（林江涛 审校）
JAllergyClinImmunol.2014Dec6.pii:S0091-6749(14)01521-8.doi:10.1016/j.jaci.2014.10.026. [Epub ahead of print]

 

Biomarker-based asthma phenotypes of corticosteroid response.
 

Cowan DC1, Taylor DR1, Peterson LE2, Cowan JO1, Palmay R1, Williamson A1, Hammel J2, Erzurum SC3, Hazen SL4, Comhair SA5.
 

ABSTRACT
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: A noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy.
 

JAllergyClinImmunol.2014Dec6.pii:S0091-6749(14)01521-8.doi:10.1016/j.jaci.2014.10.026. [Epub ahead of print]