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

描述（由申请人提供）：我们已经证明婴儿期呼吸道合胞病毒（RSV）感染是儿童喘息和哮喘发生的因果途径。目前，RSV免疫预防是严重RSV感染的唯一可用的药物预防策略，并且仅被许可用于高危婴儿。通过RSV免疫预防在婴儿期预防RSV感染是否会降低随后发生儿童喘息和哮喘的风险尚不清楚。具体目标：我们假设，胎龄为33至36 6/7周的健康早产儿在RSV免疫预防给药后，RSV相关的医疗访视将出现可测量的减少，这种减少随后将导致喘息和哮喘复发的风险降低。为了确定RSV预防是否可降低哮喘风险，我们将1）证明如果健康早产儿接受RSV免疫预防，其RSV相关的医疗访视可显著减少; 2）确定RSV免疫预防对降低婴儿期喘息、2 - 4岁儿童期喘息和6岁儿童期哮喘风险的影响。研究设计：我们将对妊娠33至36 6/7周出生的婴儿进行一项回顾性出生队列研究，这些婴儿连续入组已建立的出生队列PRIMA（预防RSV：对发病和哮喘的影响）。在目的1中，将分析RSV免疫预防对婴儿期毛细支气管炎医疗保健访视的有效性，说明RSV免疫预防给药与毛细支气管炎医疗保健访视之间的时间关系。在目标2中，我们将确定RSV免疫预防对降低婴儿期RSV发病率以及对1岁婴儿喘息、2 - 4岁儿童喘息和6岁儿童哮喘发展的影响。对于这两个目的，将应用倾向评分方法调整适应症（选择）偏倚的混杂，并将进行各种敏感性分析，以检验效应估计值的准确性和稳健性。影响：婴儿RSV感染代表与喘息和哮喘相关的普遍存在且可改变的环境因素，喘息和哮喘是婴儿期和儿童期最常见和最重要的疾病。目前，没有任何预防策略被证明对这些疾病有效。帕利珠单抗，唯一可用的预防策略，可归因于RSV的发病率，将关闭专利和更负担得起的很快。拟议研究的结果可能证明一种有效的终身疾病预防策略，因此具有重大的临床和公共卫生影响。

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.