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，婴儿时期呼吸道合胞病毒（RSV）感染是儿童喘息和哮喘发展的因果途径。目前，RSV免疫预防是唯一可用于严重RSV感染的药物预防策略，并且仅被许可用于高危婴儿。通过RSV免疫预防预防婴儿期RSV感染是否会降低儿童喘息和哮喘后续发展的风险尚不清楚。具体目的：我们假设胎龄为33至36 6/7周的健康早产儿在给予RSV免疫预防治疗后，RSV引起的医疗保健就诊次数会明显减少，这种减少随后会导致复发性喘息和哮喘的风险降低。为了确定预防RSV是否会降低哮喘的风险，我们将1)证明健康的早产儿如果接受RSV免疫预防，可显著减少RSV导致的医疗保健就诊次数；2)确定呼吸道合胞病毒免疫预防对降低婴儿期喘息、2 ~ 4岁儿童喘息和6岁儿童哮喘风险的作用。研究设计：我们将对妊娠33至36 6/7周出生的婴儿进行回顾性出生队列研究，并连续纳入已建立的出生队列PRIMA（预防RSV：对发病率和哮喘的影响）。在Aim 1中，考虑到RSV免疫预防给药与毛细支气管炎保健就诊之间的时间关系，将分析RSV免疫预防在婴儿期毛细支气管炎保健就诊中的有效性。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，以及对1岁时婴儿喘息、2至4岁儿童喘息和6岁儿童哮喘发展的影响。为了实现这两个目标，倾向评分方法将被应用于调整适应症（选择）偏差的混淆，并将进行各种敏感性分析以检验效果估计的准确性和稳健性。影响：婴儿呼吸道合胞病毒感染是一种普遍存在且可改变的与喘息和哮喘相关的环境因素，这是婴儿期和儿童期最常见和重要的疾病。目前没有任何预防策略被证明对这些疾病有效。Palivizumab是唯一可用的预防rsv发病率的策略，很快就会失效，价格也会更便宜。这项研究的结果可能证明了一种有效的终身疾病预防策略，从而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.