George Paul E, Kalmus Grace, Lipscomb Joseph, Howard David H, Kopp Benjamin, Lam Wilbur A, Ebelt Stefanie
Emory University, Rollins School of Public Health, Atlanta, Georgia, USA.
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta (CHOA), Georgia, USA.
JCI Insight. 2025 Jun 9;10(11). doi: 10.1172/jci.insight.190648.
Sickle cell disease (SCD) causes severe morbidity and early mortality, yet it varies phenotypically. Both air pollution and SCD affect the cardiorespiratory, inflammatory, and endothelial systems; however, limited evidence exists on the effect of long-term air pollution exposure in SCD. We hypothesized that annual ambient (outdoor) concentrations of fine particulate matter (PM2.5), particles with a diameter of 2.5 μm or less, at a child's home would be significantly associated with worse clinical, laboratory, and stroke-risk imaging outcomes. Patient data for this retrospective study were obtained from a cohort of children with SCD (from 2010 to 2019). Annual PM2.5 exposure was estimated using remote-sensing air pollution datasets. Statistical analyses employed fixed effects multivariable models, offering a robust approach to isolate the effect of PM2.5 exposure. The final cohort included 1,089 children with SCD. Higher annual PM2.5 concentrations were significantly associated with more annual hospital days, higher likelihood of hospitalization and abnormal stroke-risk screening, and elevated inflammatory markers. Of note, hydroxyurea use mitigated the inflammatory response to PM2.5 but did not mitigate the effect of PM2.5 on clinical outcomes. Importantly, the elevated stroke risk associated with PM2.5 exposure persisted, even among children receiving hydroxyurea therapy, highlighting a critical concern in pediatric SCD management. These results underscore the clinical importance of addressing environmental factors for comprehensive SCD care.
镰状细胞病（SCD）会导致严重的发病和早期死亡，但其表型存在差异。空气污染和SCD都会影响心肺、炎症和内皮系统；然而，关于长期暴露于空气污染对SCD影响的证据有限。我们假设，儿童家中空气中细颗粒物（PM2.5，直径为2.5μm或更小的颗粒物）的年度环境（室外）浓度会与更差的临床、实验室和中风风险成像结果显著相关。这项回顾性研究的患者数据来自一组患有SCD的儿童（2010年至2019年）。使用遥感空气污染数据集估算年度PM2.5暴露量。统计分析采用固定效应多变量模型，这是一种用于分离PM2.5暴露影响的稳健方法。最终队列包括1089名患有SCD的儿童。较高的年度PM2.5浓度与更多的年度住院天数、更高的住院可能性和异常中风风险筛查以及炎症标志物升高显著相关。值得注意的是，使用羟基脲可减轻对PM2.5的炎症反应，但不能减轻PM2.5对临床结果的影响。重要的是，即使在接受羟基脲治疗的儿童中，与PM2.5暴露相关的中风风险升高仍然存在，这凸显了儿童SCD管理中的一个关键问题。这些结果强调了在全面的SCD护理中解决环境因素的临床重要性。
