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

RSV 免疫预防对唐氏综合症儿童短期和长期呼吸道疾病发病率的有效性

• 批准号: 10398259
• 负责人: PINGSHENG WU
• 金额: $ 45.25万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-12 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10398259
• 关键词: 6 year old; Academy; Adaptive Immune System; Adherence; Adverse event; American; Anatomy; Asthma; Birth; Child; Childhood; Chromosome 21; Chronic lung disease; Clinical; Cohort Studies; Congenital chromosomal disease; Cost-Benefit Analysis; Data; Department of Defense; Disease; Down Syndrome; Effectiveness; Eligibility Determination; Enrollment; Guidelines; Health; Health Care Visit; Healthcare Systems; Hospitalization; Human; Immune system; Infant; Infection; Knowledge; Lead; Life; Lower Respiratory Tract Infection; Lung; Medicaid; Military Personnel; Morbidity - disease rate; Observational Study; Outcome; Patients; Pediatrics; Pharmacology; Physiological; Policies; Policy Maker; Population; Premature Birth; Prevalence; Preventive therapy; Qualifying; Randomized Clinical Trials; Research; Research Design; Respiratory Disease; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Risk; Risk Factors; Safety; Socioeconomic Factors; Tennessee; Testing; Variant; Viral; Vulnerable Populations; Wheezing; clinical care; cohort; congenital heart disorder; cost; cost effectiveness; demographics; hemodynamics; high risk population; immunoprophylaxis; improved; infancy; mortality; population based; post-market; prevent; programs; respiratory; respiratory morbidity; response

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.

项目概要 意义和背景：患有唐氏综合症（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 RSV 是最常见的原因 婴儿和幼儿下呼吸道感染（LRTI）的风险。早期生活 RSV LRTI 进一步不利 影响肺部和免疫系统的发育，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 的儿童可能会从 RSV 中受益 免疫预防是目前唯一可用的预防 RSV LRTI 的药理学策略。然而， 数据不足限制了 DS 儿童常规使用 RSV 免疫预防的资格 没有 DS 的儿童的情况（早产 < 29 周、慢性肺部疾病或血流动力学异常） 严重先天性心脏病）根据美国儿科学会指南。 目的、假设和具体目标：我们的总体假设是：1) 患有 DS RSV 的儿童 生命早期的 LRTI 会增加 6 岁时患呼吸道疾病的风险，2) 施用 RSV 免疫预防可降低 RSV LRTI 发病率以及早期由 RSV LRTI 引起的呼吸道疾病发病率 生命，以及 3) RSV 免疫预防的施用抵消了 RSV LRTI 相关的费用 出生后 2 年内住院，以及 6 岁时出现呼吸道疾病。测试 假设，我们将： 1) 确定并量化出生后 2 年内严重 RSV LRTI 的患病率 以及 RSV LRTI 与 6 岁以下呼吸道疾病发病率的关系； 2) 描述收到的情况， RSV 免疫预防的安全性和依从性； 3) 确定RSV的短期有效性 免疫预防减少 RSV LRTI 医疗就诊次数及其对儿童的长期有效性 呼吸系统结果，4) 确定 RSV 免疫预防给药的成本效益 减少 DS 儿童的 RSV LRTI 和后来的呼吸道疾病发病率。 研究设计：我们将对 4,063 名患有 DS 的儿童进行一项大规模的出生队列研究 1996-2018年并参加田纳西州医疗补助计划或国防部军事医疗保健 系统，这是迄今为止在该人群中进行的最大的队列研究。 影响：关于 RSV 感染负担和 RSV 有效性的知识差距 DS 儿童的免疫预防使政策制定者、临床医生和患者无法了解情况 临床决策。拟议的研究是迄今为止进行的最大规模的研究，是对 美国儿科学会呼吁进行充分有力的研究来回答这个问题并为政策提供信息 RSV 免疫预防在这一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 患者可采用现成且安全的治疗方法。