The effectiveness of RSV immunoprophylaxis on the short- and long- term respiratory morbidity in children with Down syndrome

项目摘要 意义和背景：患有唐氏综合征（DS）的儿童，无论是否有其他危险因素， 呼吸道合胞病毒（RSV）感染的风险增加。全球范围内RSV是最常见的原因 下呼吸道感染（LRTI）的婴儿和幼儿。早期RSV LRTI进一步不利地 影响发育中的肺和免疫系统，并使患有DS的儿童患其他疾病的风险增加。 长期呼吸道疾病。因此，患有DS的儿童可能从RSV中获益 免疫预防是目前唯一可用的预防RSV LRTI的药理学策略。然而，在这方面， 数据不足限制了DS儿童常规使用RSV免疫预防， 无DS儿童的条件（早产< 29周，慢性肺病或血流动力学 严重先天性心脏病）。 目的、假设和具体目的：我们的总体假设是：1）在DS RSV儿童中 生命早期的LRTI增加了6岁以下呼吸道疾病的风险，2）RSV给药 免疫预防可降低RSV LRTI发病率和RSV LRTI早期引起的呼吸道发病率， 3）RSV免疫预防的管理抵消了RSV LRTI相关的费用 在生命的头2年住院治疗和6岁之前的呼吸道疾病。测试 假设，我们将：1）确定并量化生命最初2年内重度RSV LRTI的患病率 以及RSV LRTI与6岁以下呼吸道发病率的相关性; 2）描述收到， RSV免疫预防的安全性和依从性; 3）确定RSV的短期有效性 免疫预防对减少RSV LRTI医疗保健就诊和对儿童的长期有效性 呼吸系统结局，4）确定RSV免疫预防给药的成本效益， 降低DS儿童的RSV LRTI和随后的呼吸道发病率。 研究设计：我们将对4，063名出生时患有DS的儿童进行一项大型基于人群的出生队列研究。 1996年至2018年，参加田纳西州医疗补助计划或国防部军事医疗保健 系统，有史以来在这一人群中进行的最大队列。 影响：关于RSV感染负担和RSV有效性的知识差距 DS儿童免疫预防使决策者、临床医生和患者无法了解 临床决策这项拟议中的研究是有史以来规模最大的研究，是对 美国儿科学会呼吁进行足够有力的研究来回答这个问题并为政策提供信息 RSV免疫预防在该高危人群中的有效性。这项研究的结果将提供 为临床护理和政策提供信息，更重要的是可以改善儿童的人类健康 DS患者的治疗方法是现成的、安全的。

PROJECT SUMMARY Significance and Background: Children with Down syndrome (DS), irrespective of having other risk factors, are at increased risk for respiratory syncytial virus (RSV) infection. Worldwide RSV is the most common cause of lower respiratory tract infections (LRTI) in infants and young children. Early life RSV LRTI further adversely influences the developing lung and immune system, and sets up children with DS for an increased risk of other long term respiratory diseases. Children with DS may therefore potentially benefit from RSV immunoprophylaxis, the only currently available pharmacological strategy to prevent RSV LRTI. However, insufficient data limit routine use of RSV immunoprophylaxis in children with DS to the same qualifying conditions as children without DS (premature birth < 29 weeks, chronic lung disease, or hemodynamically significant congenital heart disease) per American Academy of Pediatrics guideline. Objectives, Hypothesis and Specific Aims: Our overarching hypotheses are: 1) In children with DS RSV LRTI early in life increases the risk of respiratory morbidity through age 6 years, 2) Administration of RSV immunoprophylaxis reduces RSV LRTI morbidity and later respiratory morbidity caused by RSV LRTI early in life, and 3) Administration of RSV immunoprophylaxis offsets the costs of both RSV LRTI related hospitalization during the first 2 years of life and respiratory morbidity through age 6 years. To test the hypotheses, we will: 1) Determine and quantify the prevalence of severe RSV LRTI in the first 2 years of life and the association of RSV LRTI with respiratory morbidity through age 6 years; 2) Characterize the receipt of, safety of, and adherence to RSV immunoprophylaxis; 3) Determine the short-term effectiveness of RSV immunoprophylaxis on reducing RSV LRTI healthcare visits and the long-term effectiveness on childhood respiratory outcomes, 4) Determine the cost-effectiveness of RSV immunoprophylaxis administration in reducing RSV LRTI and later respiratory morbidity in children with DS. Research Design: We will conduct a large population-based birth cohort study of 4,063 children with DS born 1996-2018 and enrolled in the Tennessee Medicaid Program or the Department of Defense military healthcare system, the largest cohort ever conducted in this population. Impact: The knowledge gaps about the burden of RSV infection and the effectiveness of RSV immunoprophylaxis in children with DS leave policy makers, clinicians and patients unable to make informed clinical decisions. The proposed research, the largest study ever conducted, is in direct response to the American Academy of Pediatrics call for adequately powered studies to answer the question and inform policy on effectiveness of RSV immunoprophylaxis in this high risk population. Results from this study will provide information in informing clinical care and policy, and more importantly may improve human health in children with DS with a readily available and safe therapy.