HIPTox – Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology: A single-centre double-blind human exposure trial protocol

Thomas Faherty, Huda Badri, Dawei Hu, Aristeidis Voliotis, Franics D. Pope, Ian Mudway, Jacky Smith, Gordon McFiggans
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Abstract

Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-center investigation on the cognitive functioning of healthy human volunteers aged 50 and above, with a familial predisposition to dementia. Participants will all undertake five sequential controlled exposures. The sources of the air pollution exposures are wood smoke, diesel exhaust, cleaning products, and cooking emissions, with clean air serving as the control. Pre- and post-exposure spirometry, nasal lavage, blood sampling, and cognitive assessments will be performed. Repeated testing pre- and post-exposure to controlled levels of pollutants will allow for the identification of acute changes in functioning as well as the detection of peripheral markers of neuroinflammation and neuronal toxicity. This comprehensive approach enables the identification of the most hazardous components in indoor and outdoor air pollutants and further understanding of the pathways contributing to neurodegenerative diseases. The results of this project have the potential to facilitate greater refinement in policy, emphasizing health-relevant pollutants and providing details to aid mitigation against pollutant-associated health risks.
HIPTox - 通过机理毒理学评估室内外空气污染物暴露对健康影响的危害识别平台:单中心双盲人体暴露试验方案
在过去十年中,我们对空气污染对短期和长期人口健康影响的认识有了长足的进步,主要集中在对心血管和呼吸系统的不利影响上。然而,越来越多的证据表明,暴露于空气污染会影响认知功能,尤其是易感人群。我们的研究旨在通过对 50 岁及以上有痴呆症家族倾向的健康志愿者的认知功能进行单中心调查,评估普遍存在的室内和室外污染物对认知功能的影响,并对其危害进行排序。所有参与者都将进行五次连续的受控暴露。空气污染暴露的来源是木烟、柴油废气、清洁产品和烹饪排放物,清洁空气作为对照。暴露前后将进行肺活量测定、鼻腔灌洗、血液采样和认知评估。在暴露于受控水平的污染物之前和之后进行重复测试,可以确定功能的急性变化,并检测神经炎症和神经元毒性的外周标志物。这种综合方法能够识别室内和室外空气污染物中最有害的成分,并进一步了解导致神经退行性疾病的途径。该项目的成果有可能促进政策的进一步完善,强调与健康相关的污染物,并提供详细信息,帮助减轻与污染物相关的健康风险。
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