Environmental Exposures, NOS Genes, and Exhaled Nitric Oxide in Pediatric Asthma

描述(申请人提供)：哮喘是儿童时期最常见的慢性致残性疾病。在哮喘儿童的医疗管理中，没有简单的、非侵入性的呼吸道炎症措施来帮助指导医生。呼出的一氧化氮(ENO)是一种随着呼吸道炎症而增加的指标，已被提议作为一种治疗儿童哮喘的工具；然而，在将其用作哮喘治疗的临床工具之前，必须填补我们对ENO的认识空白。这项研究将探索环境暴露和一氧化氮合酶基因多态性如何影响哮喘儿童的eNO水平。此外，我们还将研究eNO水平与哮喘加重次数、报告的医疗保健利用率以及有效的生活质量指数(哮喘儿童健康调查)的关系。这项建议的二次分析使用了辛辛那提哮喘预防(CAP)研究(R01-HL65731-01)的数据，这是一项由NHLBI资助的HEPA-CPZ空气净化器的纵向试验。CAP研究涉及225名6至12岁的儿童，他们被医生诊断为哮喘，并暴露在环境烟草烟雾(ETS)中。在长达一年的研究期间，收集了许多关于环境暴露(例如，稳定的室内过敏原、ETS暴露的生物标记物和空气尼古丁水平)和哮喘严重程度的指标。这项应用的目的是评估环境和遗传因素对eNO水平的纵向影响，并检查eNO与哮喘严重程度的关系。为了实现我们的目标，我们将完成以下目标：目标1：在12个月的研究期间，确定环境暴露(致敏和室内过敏原暴露)与eNO水平的纵向关系。目的：评估在12个月的研究期间，一氧化氮合酶基因的多态性是否与eNO水平相关，以及环境暴露是否改变了这种关系。目的3：确定12个月内ENO水平与哮喘严重程度的关系。这一分析是创新的，因为据我们所知，还没有研究使用纵向研究设计来检验多重环境暴露和基因多态与哮喘儿童eNO的关系。这项拟议的探索性研究具有重要意义，因为它提供了一个独特的机会，将有关ENO的流行病学数据从研究领域转化为临床实践。如果这项研究和其他研究证明了ENO的效用，它将增强我们管理疾病的能力，并改善患有儿童期最致残疾病的儿童的生活质量。

DESCRIPTION (provided by applicant): Asthma is the most common chronic and disabling disease of childhood. There are no simple, noninvasive measures of airway inflammation to help guide physicians in the medical management of children with asthma. Exhaled nitric oxide (eNO), a measure that increases with airway inflammation, has been proposed as such a tool to manage childhood asthma; however, there are gaps in our knowledge about eNO that must be filled before it can be used as a clinical tool in asthma management. This study will explore how environmental exposures and polymorphisms in nitric oxide synthase genes may affect eNO levels in children with asthma. In addition, we will examine the relationship of eNO levels with number of asthma exacerbations, reported healthcare utilization, and a validated quality of life index (Child Health Survey for Asthma). This proposed secondary analysis uses data from the Cincinnati Asthma Prevention (CAP) study (R01-HL65731-01), a longitudinal, NHLBI-funded trial of HEPA-CPZ air cleaners. The CAP study involved 225 children, 6 to 12 years of age, who had doctor diagnosed asthma and were exposed to environmental tobacco smoke (ETS). Numerous measures of environmental exposure (e.g. settled indoor allergens, biomarkers of ETS exposure, and air nicotine levels) and asthma severity were collected during the year long study period. The objectives of this application are to evaluate the longitudinal effects of environmental and genetic factors on eNO levels and to examine the association of eNO with asthma severity. To achieve our objectives we will complete the following aims: Aim 1: To determine the longitudinal relationship of environmental exposures (sensitization and exposure to indoor allergens) with eNO levels over the 12 month study period. Aim 2: To evaluate whether polymorphisms in NOS genes are associated with eNO levels as measured over the twelve month study period and whether environmental exposures modify this relationship. Aim 3: To determine the relationship of eNO levels and asthma severity over a 12 month period. This analysis is innovative because to our knowledge no studies have examined the relationship of multiple environmental exposures and genetic polymorphisms with eNO in asthmatic children using a longitudinal study design. This proposed exploratory study is relevant because it offers a unique opportunity to translate epidemiologic data about eNO from the research arena to clinical practice. If this and other studies demonstrate the utility of eNO, it would enhance our ability to manage disease and improve the quality of life for children who have the most disabling disease of childhood.