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

描述(申请人提供)：我们已经证明，呼吸道合胞病毒(RSV)感染在婴儿期是导致儿童喘息和哮喘的原因。目前，RSV免疫预防是唯一可用的针对严重RSV感染的药物预防策略，并且仅被许可用于高危婴儿。在婴儿期通过RSV免疫预防来预防RSV感染是否会降低随后发展为儿童喘息和哮喘的风险尚不清楚。具体目标：我们假设胎龄33至36 6/7周的健康早产儿在接受RSV免疫预防后，因RSV而来的医疗就诊次数将显著减少，这种减少随后将导致反复喘息和哮喘的风险降低。为了确定RSV预防是否降低了哮喘的风险，我们将1)证明如果健康的早产儿接受RSV免疫预防，他们的RSV可归因性医疗就诊次数显著减少；2)确定RSV免疫预防在降低婴儿期喘息、2至4岁儿童喘息和6岁儿童哮喘风险方面的效果。研究设计：我们将对在33至36 6/7周出生的婴儿进行一项回顾性出生队列研究，这些婴儿连续登记在已建立的出生队列PRIMA(预防呼吸道合胞病毒：对发病率和哮喘的影响)中。在目标1中，将分析婴儿时期毛细支气管炎就诊中RSV免疫预防的有效性，考虑到RSV免疫预防用药和毛细支气管炎就诊之间的时间关系。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。对于这两个目标，将使用倾向计分方法来调整指示(选择)偏差造成的混淆，并将进行各种敏感性分析，以测试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与喘息和哮喘相关的普遍和可改变的环境因素，喘息和哮喘是婴幼儿最常见和最重要的疾病。目前，没有一种预防策略被证明对这些疾病有效。Palivizumab是唯一可用的RSV致病预防策略，将失去专利，很快就会变得更负担得起。这项拟议研究的结果可能展示一种有效的预防终生疾病的策略，从而对临床和公共卫生产生重大影响。

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.