Exhaled Biomarkers During Treatment of Rhinovirus

描述(由申请人提供)： 鼻病毒是公认的、流行病学上重要的下呼吸道疾病恶化的原因，包括哮喘、COPD和囊性纤维化。这种普通感冒病毒引起呼吸道生理变化的机制尚未得到很好的描述，部分原因是难以纵向评估下呼吸道生化和炎症。然而，随着高灵敏度分析的出现，现在可以安全地测量液体中包括细胞因子和白三烯在内的炎症介质，并且可以很容易地从呼气中凝结。此外，呼气中的化学成分可以很容易地分析出来，作为肺部氧化还原紊乱的证据。这项建议是一项精心设计的紫锥菊临床试验的辅助研究，该试验由美国国立卫生研究院资助，用于预防和治疗实验诱导的鼻腔鼻病毒感染。根据初步数据，我们假设在鼻病毒感染后，将通过呼出的呼吸冷凝物分析进行反复和安全的评估。此外，我们假设紫锥菊治疗的有益效果与这些化学和免疫变化的改善有关，并且可以通过呼出的生物标记物的分析来预测感冒症状的发展。我们将利用父母试验中描述良好的受试者来确定呼出的炎性细胞因子、白三烯、氢离子、氮氧化物和氧化还原成分(包括过氧化氢和脂质氧化产物)的基线和感染后水平。在实验性鼻病毒感染周围的一段时间内，168名受试者(40名安慰剂治疗组)每人将进行29次呼气冷凝液收集。对这些样本的分析将提供统计上强有力的数据，这些数据将极大地提高我们对鼻病毒对呼吸道化学和免疫影响的机械理解--这些影响与下呼吸道疾病的恶化高度相关。这项研究还将提供有关紫锥菊疗效的机制数据。该项目将在弗吉尼亚大学进行，该大学在普通感冒、呼吸道化学和呼出生物标记物的研究方面拥有广泛的专业知识。

DESCRIPTION (provided by applicant): Rhinovirus is a well-recognized, epidemiologically important cause of exacerbations of lower respiratory diseases including asthma, COPD, and cystic fibrosis. The mechanisms by which this common cold virus caused alteration in airway physiology are not well characterized in part because of the difficulty of assessing lower airway biochemistry and inflammation longitudinally. However, with the advent of high sensitivity assays, inflammatory mediators including cytokines and leukotrienes can now be measured in the fluid safely and easily condensed from exhaled breath. Additionally, chemical constituents of exhaled breath can be readily assayed for evidence of lung redox disturbances. This proposal is an ancillary study to a carefully designed NIH-funded clinical trial of Echinacea for the prophylaxis and treatment of experimentally induced nasal Rhinovirus infection. Based on preliminary data, we hypothesize that after Rhinovirus infection there will be repeatedly and safely assessed with exhaled breath condensate assays. Additionally we hypothesize that beneficial effects of Echinacea therapy correlate with amelioration of these chemical and immunologic alterations, and that development of cold symptoms can be predicted by assays of exhaled biomarkers. We will leverage the well-characterized subjects of the parent trial to identify baseline and post infection levels of exhaled inflammatory cytokines, leukotrienes, hydrogen ions, nitrogen oxides, and redox components including hydrogen peroxide and lipid oxidation products. Twenty-nine exhaled breath condensate collections will be performed by each of 168 subjects (40 placebo-treated) in a time period surrounding experimental Rhinovirus infection. Assays of these samples will provide statistically powerful data that will substantially improve our mechanistic understanding of airway chemical and immunologic effects of Rhinovirus-effects that are highly relevant to lower airway disease exacerbation. This study also will provide mechanistic data regarding efficacy of Echinacea. The project will be conducted at the University of Virginia, where expertise in the study of the common cold, airway chemistry, and exhaled biomarkers is extensive.