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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN85634746 ### Funding Statement This research was funded through a multicentre consortium grant awarded by the Natural Environment Research Council, grant number NE/W002213/1. I.M. is part funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, a partnership between Public Health England and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NIHR, Public Health England or the Department of Health and Social Care ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The University of Manchester Research Ethics Committee (UREC) of The University of Manchester gave ethical approval for this work (ID 2022-14762-25491). The Health Research Authority (HRA) Integrated Research Application System (IRAS) gave ethical approval of this work (ID 314890). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes There are currently no plans to share participant-level datasets. * eCRF : electronic case report form ERT : Expression Recognition Task FIT : Face Identification Task GCP : good clinical practice GPCog : general practitioner assessment of cognition hCRF : hard-copy case report form HRA : Health Research Authority ICF : informed consent form IRAS : Integrated Research Application System MAC : Manchester Aerosol Chamber MCRF : Manchester Clinical Research Facility nl : nasal lavage PI : principal investigator PIS : participant information sheet PM : particulate matter less than 2.5 micrometres in diameter PPIE : Patient and Public Involvement and Engagement PPT : Purdue Pegboard Test PVT : Psychomotor Vigilance Task RT : response time SAE : serious adverse event SDF : source data file SNB : Spatial n-back Task SOA : secondary organic aerosol sp : spirometry UREC : University of Manchester Research Ethics Committee vs : vital signs