Using massive, multi-regional EHR data to estimate the impacts of climate change on fungal disease epidemiology in the U.S.

摘要 在过去的40年里，真菌疾病已经成为一个紧迫的健康问题，因为发病率 显著增加，新的病原体出现，对抗真菌药物的耐药性上升和流行 免疫抑制的情况有所增加。气候变化可能通过以下方式加剧真菌疾病的风险 改变病原体适宜的环境栖息地，延长孢子传播季节， 增加极端气候事件的发生频率，从而调动孢子，进一步削弱适应能力 易受伤害的人群。对气候影响的机械的、定量的和因果的理解 真菌疾病的分布和严重程度将是保护中国高危人群健康的关键 未来几十年，并解决导致社会脆弱性各轴心之间健康差距的因素。至 迄今为止，美国对真菌疾病的流行病学研究仅限于时空范围和 样本量，排除了气候和极端事件对真菌疾病的影响的可靠特征 风险。虽然作为研究真菌疾病的资源在很大程度上尚未开发，但电子健康记录(EHR)和 传染病监测系统生成可用于评估风险的海量健康数据集 真菌感染的因素，包括念珠菌病、隐球菌病、曲霉病、芽孢菌病、组织胞浆菌病、 球孢子菌病和皮霉病。通过与Cerner(密苏里州堪萨斯城)的合作，我们将分析 确定了超过9600万名患者、14亿次就诊和47亿个临床事件的电子病历数据。属性的子集 数据库提供患者3位数字邮政编码的地理位置。我们还将分析监控 2000年以来加利福尼亚州所有报告的球孢子菌病病例(&gt；95,000例)的数据，地理位置为患者 地址。在解决了电子病历中的错误分类、选择和缺失数据偏向之后，我们的团队将 估计美国真菌疾病的发病率、住院率和死亡率的地区趋势。我们将 应用现代时间序列方法来了解气候变化的影响，包括温度变化， 降水和湿度对真菌病发病率和地理出苗率的影响。我们将调查 热浪、沙尘暴、热带气旋和洪水等极端事件对发病率和 考察对基础设施的投资是否可以减轻影响。我们将确定是否暴露于- 气候和真菌感染之间的反应关系受到社会经济地位和种族的影响， 并确定调节社会劣势之间关系的个人和社区层面的因素 以及真菌感染和严重后果，如先前存在的合并症和住房质量。我们会 应用我们估计的暴露-疾病关系来量化真菌疾病发病率的比例 2000年可归因于人为气候变化，并预计本世纪中叶和结束时 重点疾病分布和负担情况。该项目将产生对气候流行病学的深入了解。 美国的主要真菌病，以及社会劣势和韧性在缓解未来影响方面的作用。

ABSTRACT In the past 40 years, fungal diseases have emerged as a pressing health concern, as incidence rates have increased markedly, novel pathogens have emerged, resistance to antifungal drugs has risen and prevalence of immunosuppressive conditions has increased. Changes in climate may exacerbate fungal disease risks by shifting the suitable environmental habitat for pathogens, lengthening the transmission season of spores, increasing the frequency of extreme climate events that mobilize spores and further straining adaptive capacity of vulnerable populations. A mechanistic, quantitative, and causal understanding of the effects of climate on the distribution and severity of fungal diseases will be critical to protecting the health of high-risk groups in the coming decades, and to addressing factors leading to health disparities across axes of social vulnerability. To date, epidemiologic studies of fungal diseases in the U.S. have been limited in spatiotemporal scope and sample size, precluding robust characterization of the impact of climate and extreme events on fungal disease risk. While largely untapped as a resource for investigating fungal disease, electronic health record (EHR) and infectious disease surveillance systems generate massive health datasets that can be used to estimate risk factors for fungal infections, including candidiasis, cryptococcosis, aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis and dermatomycosis. Via partnership with Cerner (Kansas City, MO), we will analyze de- identified EHR data for over 96 million patients, 1.4 billion visits, and 4.7 billion clinical events. A subset of the databases is available with geographic locations of patient 3-digit zip codes. We will also analyze surveillance data on all reported cases (>95,000) of coccidioidomycosis in California since 2000, geolocated to patient address. After addressing misclassification, selection, and missing data biases in the EHR, our team will estimate regional trends in incidence, hospitalization and mortality rates for fungal diseases in the U.S. We will apply modern time series approaches to understand the effects of climate variability, including in temperature, precipitation, and humidity, on fungal disease incidence and geographic emergence. We will investigate the impacts of extreme events such as heat waves, dust storms, tropical cyclones and flooding on incidence and examine whether investment in infrastructure can mitigate effects. We will determine whether exposure- response relationships between climate and fungal infection are modified by socio-economic status and race, and identify individual- and community-level factors that mediate the relationship between social disadvantage and fungal infections and severe outcomes, such as preexisting comorbidities and housing quality. We will apply our estimated exposure-disease relationships to quantify the proportion of fungal disease incidence since 2000 that is attributable to anthropogenic climate change, and project mid- and end-of-century estimates of the distribution and burden of key diseases. The project will yield robust understanding of the climate epidemiology of major mycoses in the U.S., and the role of social disadvantage and resilience in moderating future impacts.