Relationship of Ambient Air Pollution Exposures with Vaso-Occlusive Pain Crises in Sickle Cell Disease

项目摘要 镰状细胞病（SCD）是最常见的遗传性疾病之一， 美国人，主要是非洲裔美国人，以及全球数百万人。尽管目前 预防/治疗方式，SCD发病率与过早死亡相关， 生活成本和生活质量。SCD的标志是血管闭塞性疼痛危象，一种复发性， 不可预测的，令人虚弱的事件人口统计学因素、基因型、社会心理因素、社会经济因素 社会经济地位（SES）和环境暴露与SCD疼痛危机有关。虽然精确的 血管闭塞性危象的病理生理学尚不完全清楚，确定的机制与 那些假定的心血管疾病发病率和死亡率与环境空气的良好关系 污染暴露。虽然从生物学上讲，暴露于环境空气污染可能与 随着镰状细胞疼痛危象风险的增加，流行病学研究非常有限。该研究建议采取 现有的全州医院管理数据集的优势;复杂，创新的时空 为以前资助的研究开发的颗粒物（PM）和成分暴露模型; 美国环保署开发的分层贝叶斯臭氧暴露模型;以及案例交叉研究 设计我们将检查血管闭塞性疼痛的住院和急诊就诊是否 SCD患者的危机与短期暴露于环境空气污染物有关。拟议 据我们所知，这项研究将首次全面评估臭氧、PM2.5、 和生物学相关的交通相关的PM组件对SCD血管闭塞性疼痛危机之间的全州 报告SCD相关死亡率较高的人群。我们的研究结果可以推进 了解在经历衰弱的人群中对空气污染的病理生理反应 和代价高昂的不良后果。

Project Summary Sickle cell disease (SCD), one of the most common inherited disorders, effects an estimated 100,000 Americans, mostly of African-American descent, as well as millions globally. Despite current preventative/treatment modalities, SCD morbidity is associated with premature mortality and substantial financial and quality of life costs. A hallmark of SCD is the vaso-occlusive pain crisis, a recurrent, unpredictable, and debilitating event. Demographic factors, genotype, psychosocial factors, socioeconomic status (SES) and environmental exposures have been linked with SCD pain crises. Although the precise pathophysiology of vaso-occlusive crises is not fully understood, identified mechanisms are markedly similar to those postulated for the well-established associations of cardiovascular morbidity and mortality with ambient air pollution exposures. While it is biologically plausible that exposure to ambient air pollution could be associated with increased risk of sickle cell pain crises, epidemiologic research is very limited. The proposed study takes advantage of an existing statewide hospital administrative dataset; complex, innovative spatio-temporal particulate matter (PM) and component exposure models developed for previously funded research; hierarchical Bayesian ozone exposure models developed by the US EPA; and the case crossover study design. We will examine whether hospitalizations and emergency department visits for vaso-occlusive pain crises among SCD patients are associated with short-term exposures to ambient air pollutants. The proposed study will, to the best of our knowledge, be the first to evaluate comprehensively the effects of ozone, PM2.5, and biologically relevant traffic-related PM components on SCD vaso-occlusive pain crises among a statewide population with a high rate of reported SCD-related mortality. The results of our study could advance understanding of pathophysiological responses to air pollution among a population experiencing debilitating and costly adverse outcomes.