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: 8966685
• 负责人: Elizabeth C. Matsui
• 金额: $ 66.57万
• 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/8966685
• 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; urban children

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已多次与哮喘发病率相关，尤其是城市儿童，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) 与无干预进行比较，这种设计并未反映推荐的哮喘管理方法，其中包括 ECS 与控制药物滴定相结合。因此，目前尚不清楚是否 在控制药物滴定中添加 ECS 可以改善哮喘控制，从而减少控制药物需求。另一个悬而未决的问题是，在控制药物滴定中添加 ECS 是否比单独药物滴定更能减少过敏性炎症。 ECS 可能比控制药物对过敏性炎症具有更大的影响，因为 ECS 通过减少促炎环境暴露来针对哮喘炎症途径的最上游点，而控制药物则针对该途径的下游点。令人惊讶的是，还不清楚 ECS 试验中哮喘的改善是否是通过降低过敏原水平和/或降低污染物水平来介导的。了解介导 ECS 对哮喘影响的因素对于反驳或支持室内过敏原和/或污染物在哮喘发病中的因果作用非常重要，对于优化 ECS 设计以针对最有影响力的因素也很重要。因此，我们假设，在城市哮喘儿童中，与单独的控制药物滴定相比，在基于指南的控制药物滴定中添加个性化、多方面的 ECS 将导致更少的控制药物需求和过敏性炎症。我们将通过 ECS 加控制药物滴定与单独控制药物滴定的平行随机对照试验来检验这一假设，并确定介导 ECS 临床效果的因素。我们的目标是：(1) 确定在控制药物滴定中添加 ECS 对控制药物需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 在控制药物治疗的背景下不能提供额外的益处，那么 ECS 在哮喘管理中的作用应该被降低。另一方面，如果 ECS 确实减少了控制药物需求，则应更加重视 ECS 在哮喘管理中的重要性，应进行研究以确定 ECS 最佳实践，并应更改政策以要求第三方付款人承担费用ECS 成本。