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

描述（由申请人提供）：高室内过敏原和污染物水平一再与哮喘发病率有关，特别是在美国哮喘发病率最高的城市儿童中。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，这种设计并不反映哮喘管理的推荐方法，其中包括ECS与控制药物的滴定。因此，目前尚不清楚 将ECS添加到控制药物滴定中导致改善的哮喘控制，并因此降低控制药物需求。另一个未回答的问题是，在控制性药物滴定中加入ECS是否比单独药物滴定更能减少过敏性炎症。ECS对过敏性炎症的作用可能大于控制药物，因为ECS通过减少促炎性环境暴露而靶向哮喘炎症途径的最上游点，而控制药物靶向该途径的下游点。令人惊讶的是，还不知道ECS试验中哮喘的改善是否是通过降低过敏原水平和/或降低污染物水平介导的。了解调节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率中的因果作用以及优化ECS设计以针对最具影响力的因素非常重要。因此，我们假设，在城市哮喘儿童中，在基于指南的控制药物滴定中添加个性化的、多方面的ECS将导致比单独的控制药物滴定更少的控制药物需求和过敏性炎症。我们将通过一项平行臂、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，该试验比较了ECS加控制药物滴定与单独控制药物滴定。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，和（2）确定颗粒物质（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在控制性药物治疗的背景下不能提供额外的获益，那么ECS在哮喘管理中的作用应该被降级。另一方面，如果ECS确实减少了控制药物的需求，应更加强调ECS在哮喘管理中的重要性，应进行研究以确定最佳ECS实践，并应改变政策以要求第三方支付ECS费用。

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.