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，估计影响10万人 美国人，主要是非裔美国人后裔，以及全球数百万人。尽管目前 预防/治疗方式，SCD发病率与过早死亡和大量 财务和生活质量成本。SCD的一个特点是血管闭塞性疼痛危机，一种反复发作的， 不可预测的、令人衰弱的事件。人口因素、基因、社会心理因素、社会经济因素 状态(SES)和环境暴露与SCD疼痛危机有关。尽管准确地说 血管闭塞危象的病理生理学机制尚不完全清楚，已确定的机制明显类似于 心血管疾病发病率和死亡率与环境空气密切相关的假设 暴露在污染中。虽然从生物学上讲暴露在环境空气污染中可能与 随着镰状细胞疼痛危机风险的增加，流行病学研究非常有限。拟议的研究采取了 现有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； 美国环保局开发的层次化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科就诊情况 SCD患者的危机与短期暴露于环境空气污染物有关。建议数 据我们所知，这项研究将是第一个全面评估臭氧、PM2.5、 和生物相关的交通相关PM成分在全州范围内的SCD血管闭塞性疼痛危机中的作用 报告的SCD相关死亡率较高的人群。我们的研究结果可能会推动 衰弱人群对空气污染的病理生理反应的了解 以及代价高昂的不利后果。

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.