Department of Pathology, University of Michigan, Ann Arbor, Michigan, United States.
Department of Internal Medicine, Pulmonary, University of Michigan, Ann Arbor, Michigan, United States.
Am J Physiol Lung Cell Mol Physiol. 2024 Mar 1;326(3):L280-L291. doi: 10.1152/ajplung.00300.2023. Epub 2024 Jan 30.
Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life. These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function.
婴儿早期的呼吸道病毒感染与儿童哮喘的发展增强有关。特别是，大量呼吸道合胞病毒（RSV）住院婴儿会发展为肺部疾病。有人认为，婴儿早期的病毒感染可能导致肺部发育或修复的改变，从而对以后的肺功能产生负面影响。我们的数据表明，婴儿早期 RSV 感染会改变肺部结构，导致肺功能下降。在新生儿 RSV 感染后 5 周，基础肺功能测试（PFT）参数明显异常，肺功能下降以及肺泡空间增大。在生命早期 RSV 感染组中，肺功能变化持续到 3 月龄。先前已显示先前具有与持续 Th2 环境相关的免疫细胞积累减少的 小鼠中，早期 RSV 引起的改变的 PFT 和结构变化得到缓解。重要的是，在初始早期 RSV 感染后 3 个月进行二次 RSV 感染时，观察到长期影响，导致肺功能明显进一步受损，气道内有大量粘液沉积，并使肺泡空间融合。这些研究表明，婴儿早期呼吸道病毒感染会导致肺部结构/修复的改变，从而导致以后的肺功能下降。这些研究提出了一个新的发现，即婴儿早期呼吸道病毒感染可以长期改变肺部结构和功能。重要的是，数据还表明，炎症反应与随后的事件之间存在关键联系，这些事件在以后的生活中产生更严重的致病反应。这些发现提供了更多数据支持，表明肺部发育过程中的婴儿早期感染会改变气道功能的轨迹。
