美国婴儿期呼吸道合胞病毒感染与儿童期支气管哮喘（INSPIRE）研究：一项基于人群的前瞻性出生队列研究
2023/05/25
摘要
背景：早期严重呼吸道合胞病毒（RSV）感染与儿童期喘息性疾病的发病有关。然而，婴儿期呼吸道合胞病毒感染与儿童期支气管哮喘（哮喘）发生发展的关系尚不明确。本研究旨在评估婴儿期呼吸道合胞病毒感染与儿童期哮喘之间的关系。
方法：INSPIRE是一个基于人群的大型出生队列，由2012年6月至12月或2013年6月至12月之间足月出生的非低出生体重健康婴儿组成，从美国田纳西州中部的11家儿科诊所招募。本研究通过分子学和血清学技术联合病毒识别的被动和主动监测，确定受试婴儿出生第一年呼吸道合胞病毒的感染状况（无感染与感染）。之后对受试儿童进行前瞻性随访，以了解5年期哮喘的主要转归，本研究对所有完成5年随访的受试者进行了分析。根据儿童的性别、种族和民族、是否母乳喂养、婴儿期日常护理情况、子宫内或婴儿早期接触二手烟情况，以及母亲是否罹患哮喘，调整已有数据儿童的统计模型。
结果：本研究共纳入1946名符合条件的儿童，其中1741名（89%）有可用数据用以评估出生第一年呼吸道合胞病毒的感染状况。在1741名受试儿童中，婴儿期呼吸道合胞病毒感染者有944人（54%；95%CI 52%-57%）。婴儿期未感染呼吸道合胞病毒的儿童5年内罹患哮喘的比例（91/587，16%）低于婴儿期感染呼吸道合病毒的儿童（139/670，21%；p=0.016）。与婴儿期感染呼吸道合胞病毒的儿童相比，婴儿期未感染呼吸道合病毒可降低26% 5年内哮喘风险（调整后RR为0.74，95%CI 0.58-0.94，p=0.014）。通过避免婴儿期呼吸道合胞病毒感染，预计可预防5年内哮喘病例比例为15%（95%CI 2.2-26.8）。
结论：在足月出生的健康儿童中，出生第一年无呼吸道合胞病毒感染可显著降低儿童哮喘发病的风险。本研究结果表明，婴儿期呼吸道合胞病毒感染与儿童期哮喘之间存在年龄依赖性关联。但为确定因果关系，需进一步研究预防、延迟或降低儿童哮喘初始呼吸道合胞病毒感染严重程度的干预措施的效果。
Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population-based, prospective birth cohort study.
Rosas-Salazar C, Chirkova T, Gebretsadik T, Chappell JD, Peebles RS Jr, Dupont WD, Jadhao SJ, Gergen PJ, Anderson LJ, Hartert TV
Abstract
BACKGROUND:Early-life severe respiratory syncytial virus (RSV) infection has been associated with the onset of childhood wheezing illnesses. However, the relationship between RSV infection during infancy and the development of childhood asthma is unclear. We aimed to assess the association between RSV infection during infancy and childhood asthma.
METHODS:INSPIRE is a large, population-based, birth cohort of healthy infants with non-low birthweight born at term between June and December, 2012, or between June and December, 2013. Infants were recruited from 11 paediatric practices across middle Tennessee, USA. We ascertained RSV infection status (no infection vs infection) in the first year of life using a combination of passive and active surveillance with viral identification through molecular and serological techniques. Children were then followed up prospectively for the primary outcome of 5-year current asthma, which we analysed in all participants who completed 5-year follow-up. Statistical models, which were done for children with available data, were adjusted for child's sex, race and ethnicity, any breastfeeding, day-care attendance during infancy, exposure to second-hand smoke in utero or during early infancy, and maternal asthma.
RESULTS:Of 1946 eligible children who were enrolled in the study, 1741 (89%) had available data to assess RSV infection status in the first year of life. The proportion of children with RSV infection during infancy was 944 (54%; 95% CI 52-57) of 1741 children. The proportion of children with 5-year current asthma was lower among those without RSV infection during infancy (91 [16%] of 587) than those with RSV infection during infancy (139 [21%] of 670; p=0·016). Not being infected with RSV during infancy was associated with a 26% lower risk of 5-year current asthma than being infected with RSV during infancy (adjusted RR 0·74, 95% CI 0·58-0·94, p=0·014). The estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection during infancy was 15% (95% CI 2·2-26·8).
CONCLUSIONS:Among healthy children born at term, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. Our findings show an age-dependent association between RSV infection during infancy and childhood asthma. However, to definitively establish causality, the effect of interventions that prevent, delay, or decrease the severity of the initial RSV infection on childhood asthma will need to be studied.
背景：早期严重呼吸道合胞病毒（RSV）感染与儿童期喘息性疾病的发病有关。然而，婴儿期呼吸道合胞病毒感染与儿童期支气管哮喘（哮喘）发生发展的关系尚不明确。本研究旨在评估婴儿期呼吸道合胞病毒感染与儿童期哮喘之间的关系。
方法：INSPIRE是一个基于人群的大型出生队列，由2012年6月至12月或2013年6月至12月之间足月出生的非低出生体重健康婴儿组成，从美国田纳西州中部的11家儿科诊所招募。本研究通过分子学和血清学技术联合病毒识别的被动和主动监测，确定受试婴儿出生第一年呼吸道合胞病毒的感染状况（无感染与感染）。之后对受试儿童进行前瞻性随访，以了解5年期哮喘的主要转归，本研究对所有完成5年随访的受试者进行了分析。根据儿童的性别、种族和民族、是否母乳喂养、婴儿期日常护理情况、子宫内或婴儿早期接触二手烟情况，以及母亲是否罹患哮喘，调整已有数据儿童的统计模型。
结果：本研究共纳入1946名符合条件的儿童，其中1741名（89%）有可用数据用以评估出生第一年呼吸道合胞病毒的感染状况。在1741名受试儿童中，婴儿期呼吸道合胞病毒感染者有944人（54%；95%CI 52%-57%）。婴儿期未感染呼吸道合胞病毒的儿童5年内罹患哮喘的比例（91/587，16%）低于婴儿期感染呼吸道合病毒的儿童（139/670，21%；p=0.016）。与婴儿期感染呼吸道合胞病毒的儿童相比，婴儿期未感染呼吸道合病毒可降低26% 5年内哮喘风险（调整后RR为0.74，95%CI 0.58-0.94，p=0.014）。通过避免婴儿期呼吸道合胞病毒感染，预计可预防5年内哮喘病例比例为15%（95%CI 2.2-26.8）。
结论：在足月出生的健康儿童中，出生第一年无呼吸道合胞病毒感染可显著降低儿童哮喘发病的风险。本研究结果表明，婴儿期呼吸道合胞病毒感染与儿童期哮喘之间存在年龄依赖性关联。但为确定因果关系，需进一步研究预防、延迟或降低儿童哮喘初始呼吸道合胞病毒感染严重程度的干预措施的效果。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Lancet. 2023 Apr 19:S0140-6736(23)00811-5. doi: 10.1016/S0140-6736(23)00811-5.)
(Lancet. 2023 Apr 19:S0140-6736(23)00811-5. doi: 10.1016/S0140-6736(23)00811-5.)
Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population-based, prospective birth cohort study.
Rosas-Salazar C, Chirkova T, Gebretsadik T, Chappell JD, Peebles RS Jr, Dupont WD, Jadhao SJ, Gergen PJ, Anderson LJ, Hartert TV
Abstract
BACKGROUND:Early-life severe respiratory syncytial virus (RSV) infection has been associated with the onset of childhood wheezing illnesses. However, the relationship between RSV infection during infancy and the development of childhood asthma is unclear. We aimed to assess the association between RSV infection during infancy and childhood asthma.
METHODS:INSPIRE is a large, population-based, birth cohort of healthy infants with non-low birthweight born at term between June and December, 2012, or between June and December, 2013. Infants were recruited from 11 paediatric practices across middle Tennessee, USA. We ascertained RSV infection status (no infection vs infection) in the first year of life using a combination of passive and active surveillance with viral identification through molecular and serological techniques. Children were then followed up prospectively for the primary outcome of 5-year current asthma, which we analysed in all participants who completed 5-year follow-up. Statistical models, which were done for children with available data, were adjusted for child's sex, race and ethnicity, any breastfeeding, day-care attendance during infancy, exposure to second-hand smoke in utero or during early infancy, and maternal asthma.
RESULTS:Of 1946 eligible children who were enrolled in the study, 1741 (89%) had available data to assess RSV infection status in the first year of life. The proportion of children with RSV infection during infancy was 944 (54%; 95% CI 52-57) of 1741 children. The proportion of children with 5-year current asthma was lower among those without RSV infection during infancy (91 [16%] of 587) than those with RSV infection during infancy (139 [21%] of 670; p=0·016). Not being infected with RSV during infancy was associated with a 26% lower risk of 5-year current asthma than being infected with RSV during infancy (adjusted RR 0·74, 95% CI 0·58-0·94, p=0·014). The estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection during infancy was 15% (95% CI 2·2-26·8).
CONCLUSIONS:Among healthy children born at term, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. Our findings show an age-dependent association between RSV infection during infancy and childhood asthma. However, to definitively establish causality, the effect of interventions that prevent, delay, or decrease the severity of the initial RSV infection on childhood asthma will need to be studied.
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