RSV immunoprophylaxis impact on RSV morbidity & asthma in healthy preterm infants

RSV 免疫预防对 RSV 发病率的影响

基本信息

批准号：
8757597
负责人：
PINGSHENG WU
金额：
$ 13.14万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8757597
关键词：
4 year old 6 year old Accounting Address Age Asthma Birth Bronchiolitis Childhood Childhood Asthma Clinical Cohort Studies Development Disease Effectiveness Enrollment Environmental Risk Factor Generic Drugs Gestational Age Goals Health Care Visit Hospitalization Infant Infant Development Legal patent Licensing Measurable Medicaid Morbidity - disease rate Outcome Palivizumab Passive Immunotherapy Pathway interactions Population Pregnancy Premature Infant Prevention Prevention strategy Primary Prevention Public Health Publishing Randomized Clinical Trials Recurrence Research Research Design Research Infrastructure Respiratory Syncytial Virus Infections Respiratory Syncytial Virus Vaccines Respiratory syncytial virus Risk Risk Reduction Scoring Method Selection Bias System Testing Time Vaccines Wheezing asthma prevention cohort cost effective therapy experience health care delivery health care service utilization high risk high risk infant immunoprophylaxis infancy infant morbidity interest population based prevent prophylactic public health relevance

项目摘要

DESCRIPTION (provided by applicant): We have demonstrated that respiratory syncytial virus (RSV) infection during infancy is in the causal pathway of the development of childhood wheezing and asthma. Currently, RSV immunoprophylaxis is the only available pharmacologic preventive strategy for severe RSV infection, and is licensed for use only in high-risk infants. Whether prevention of RSV infection during infancy through RSV immunoprophylaxis will reduce the risk of subsequent development of childhood wheezing and asthma is unknown. Specific Aims: We hypothesize that healthy preterm infants with a gestational age of 33 to 36 6/7 weeks will experience a measureable reduction in RSV-attributable healthcare visits after RSV immunoprophylaxis administration, and this reduction will subsequently result in a reduced risk of recurrent wheeze and asthma. To determine whether RSV prevention reduces the risk of asthma, we will 1) demonstrate that healthy preterm infants experience a measurable reduction in RSV-attributable healthcare visits if they receive RSV immunoprophylaxis; 2) determine the effect of RSV immunoprophylaxis on reducing the risk of wheezing in infancy, childhood wheezing between age 2 to 4 years, and childhood asthma by age 6 years. Research Design: We will conduct a retrospective birth cohort study of infants who were born at 33 to 36 6/7 weeks of gestation and were continuously enrolled in an established birth cohort, PRIMA (Prevention of RSV: Impact on Morbidity and Asthma). In Aim 1, the effectiveness of RSV immunoprophylaxis on bronchiolitis healthcare visits during infancy will be analyzed accounting for the temporal relationship between RSV immunoprophylaxis administration and bronchiolitis healthcare visits. In Aim 2, we will determine the effect of RSV immunoprophylaxis on reducing RSV morbidity during infancy and on the development of infant wheezing at 1-year, childhood wheezing between age 2 to 4 years, and childhood asthma by age 6 years. For both aims, propensity score methods will be applied to adjust for confounding by indication (selection) bias, and various sensitivity analyses will be conducted to test the accuracy and the robustness of the effect estimates. Impact: Infant RSV infection represents a ubiquitous and modifiable environmental factor associated with wheezing and asthma, the most common and significant diseases of infancy and childhood. Currently no prevention strategy has been proven effective for these diseases. Palivizumab, the only available prevention strategy for RSV-attributable morbidity, will be off patent and be more affordable soon. The results of the proposed study may demonstrate an effective preventive strategy of a lifelong disease, and thus have significant clinical and public health impact.

描述（由申请人提供）：我们已经证明，婴儿期间的呼吸道合胞病毒（RSV）感染是儿童期喘息和哮喘发育的因果途径。目前，RSV免疫预防是严重RSV感染的唯一可用的药理学预防策略，仅在高危婴儿中使用许可。婴儿期间通过RSV免疫预防在婴儿期预防RSV感染是否会降低随后喘息和哮喘的随后发展的风险。具体目的：我们假设，胎龄为33至36 6/7周的健康早产儿将经历RSV免疫促par剂量后的RSV效力可降低可衡量的RSV-Attributable Healthcare访问，随后，这种降低将导致降低的呼吸和呼吸和呼吸量的风险降低。为了确定预防RSV是否会降低哮喘的风险，我们将1）证明健康的早产儿经历了可衡量的RSV促进性医疗访问，如果他们接受RSV免疫预防； 2）确定RSV免疫预防对降低婴儿期喘息的风险，2至4岁之间的儿童喘息以及童年哮喘的影响。研究设计：我们将对出生于33至36 6/7周的婴儿进行回顾性出生队列研究，并不断入选已建立的出生队列Prima（预防RSV：对发病率和哮喘的影响）。在AIM 1中，将分析RSV免疫预防对婴儿炎治疗期间细支气管炎医疗探访的有效性，以说明RSV免疫预防施用与支气管炎医疗访问之间的时间关系。在AIM 2中，我们将确定RSV免疫预防对降低婴儿期RSV发病率的影响以及1年时婴儿喘息的发展，儿童期在2至4岁之间喘息，以及童年时期的儿童哮喘，到6岁。对于这两个目的，倾向得分方法都将应用于通过指示（选择）偏置混淆的调整，并将进行各种灵敏度分析以测试效应估计值的准确性和鲁棒性。影响：婴儿RSV感染代表着与喘息和哮喘有关的无处不在且可修改的环境因素，这是婴儿期和儿童期最常见和最重要的疾病。目前尚未证明预防策略对这些疾病有效。 Palivizumab是唯一可用的RSV侵略发病率的预防策略，它将不再是专利的，并且很快就会实惠。拟议研究的结果可能证明了终身疾病的有效预防策略，因此具有重大的临床和公共卫生影响。