Environmental Control as Add-on Therapy in Urban Children with Asthma

环境控制作为城市哮喘儿童的附加治疗

• 批准号: 8791315
• 负责人: Elizabeth C. Matsui
• 金额: $ 67.39万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-13 至 2018-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8791315
• 关键词: Address; Adrenal Cortex Hormones; Allergens; Allergic; Allergic inflammation; Asthma; Biological Markers; Breathing; Canis familiaris; Child; Dictyoptera; Dose; Environmental Exposure; Felis catus; Guidelines; Health; Home environment; IgE; Indoor pollutant; Inflammatory; Influentials; Intervention; Intervention Trial; Link; Measures; Mediating; Morbidity - disease rate; Mus; Outcome; Participant; Particulate Matter; Pathway interactions; Pharmaceutical Preparations; Policies; Randomized Controlled Trials; Role; Serum; Skin Test End-Point Titration; Stratification; Symptoms; Testing; Third-Party Payer; Titrations; Treatment Step; arm; asthmatic; base; clinical effect; cost; design; disease natural history; environmental intervention; eosinophil; improved; indoor allergen; inner city; mast cell; novel; peripheral blood; pollutant; pyroglyphid

DESCRIPTION (provided by applicant): High indoor allergen and pollutant levels have repeatedly been linked to asthma morbidity, especially among urban children, who have among the highest asthma morbidity in the US. However, environmental intervention trials for asthma have typically compared an environmental control strategy (ECS) to no intervention, a design that does not reflect the recommended approach to asthma management, which includes ECSs in conjunction with titration of controller medication. As a result, it remains unknown whether the addition of an ECS to controller medication titration results in improved asthma control, and therefore a reduced controller medication requirement. Another unanswered question is whether the addition of an ECS to controller medication titration results in greater reduction of allergic inflammation than medication titration alone. ECSs may have a greater effect on allergic inflammation than controller medications because ECSs target the most upstream point of the asthma inflammatory pathway by reducing pro-inflammatory environmental exposures, while controller medications target a downstream point of this pathway. Surprisingly, it is also unknown whether the improvement in asthma in ECS trials is mediated by reductions in allergen levels and/or reduction in pollutant levels. Understanding the factors that mediate the effects of an ECS on asthma is important for refuting, or supporting, a causal role for indoor allergens and/or pollutants in asthma morbidity, and also for optimizing the design of ECSs to target the most influential factors. We therefore hypothesize that the addition of an individually-tailored, multi-faceted ECS to guidelines-based controller medication titration will result in less controlle medication requirement and allergic inflammation than controller medication titration alone among urban asthmatic children. We will test this hypothesis and identify the factors that mediate the clinical effects of the ECS with a parallel-arm, randomized controlled trial of ECS plus controller medication titration vs. controller medication titration alone. Our aims are: (1) T determine the effect of the addition of ECS to controller medication titration on controller medication requirements and allergic inflammatory biomarkers, and (2) To determine whether reductions in particulate matter (PM) and/or indoor allergens mediate the effects of an ECS on asthma. This proposed trial will answer a pivotal question because if ECSs do not provide additional benefit in the context of treatment with controller medication, the role of ECS in asthma management should be downgraded. On the other hand, if ECSs do indeed reduce controller medication requirements, greater emphasis should be placed on the importance of ECSs in asthma management, studies should be conducted to identify best ECS practices, and policies should be changed to require third party payers to cover ECS costs.

描述(由申请人提供)：室内过敏原和污染物水平高一再与哮喘发病率有关，特别是在城市儿童中，他们是美国哮喘发病率最高的人群之一。然而，哮喘的环境干预试验通常将环境控制策略(ECS)与不干预进行比较，这种设计没有反映推荐的哮喘管理方法，其中包括ECS和控制剂药物的滴定。因此，目前还不清楚 在控释剂药物滴定中加入ECS可改善哮喘控制，从而减少控释剂用药需求。另一个悬而未决的问题是，在控制性药物滴定中添加ECS是否比单独使用药物滴定更能减少过敏性炎症。ECSS对过敏性炎症的影响可能比对照药物更大，因为ECSS通过减少促炎环境暴露而针对哮喘炎症途径的最上游点，而控制器药物针对这一途径的下游点。令人惊讶的是，ECS试验中哮喘的改善是否由过敏原水平的降低和/或污染物水平的降低所调节，也是未知的。了解ECS对哮喘影响的中介因素，对于驳斥或支持室内过敏原和/或污染物在哮喘发病中的因果作用，以及优化ECS的设计，以针对最具影响的因素，具有重要意义。因此，我们假设，在城市哮喘儿童中，在基于指南的控制性药物滴定中加入个性化定制的多方面ECS将导致较少的控制性用药需求和过敏性炎症。我们将通过ECS加控制剂药物滴定与单独控制剂药物滴定的平行对照随机对照试验来检验这一假设，并确定影响ECS临床效果的因素。我们的目标是：(1)确定在控制器药物滴定中添加ECS对控制器用药要求和过敏性炎症生物标志物的影响，以及(2)确定颗粒物(PM)和/或室内过敏原的减少是否介导了ECS对哮喘的影响。这项拟议的试验将回答一个关键问题，因为如果ECS在控制性药物治疗的背景下不能提供额外的好处，ECS在哮喘管理中的作用应该被降低。另一方面，如果ECS确实减少了控制者的用药要求，则应更加强调ECS在哮喘管理中的重要性，应进行研究以确定ECS的最佳做法，并应改变政策，要求第三方付款人支付ECS费用。