How Atmospheric Particulate Affects Lung Health

Abstract

Air pollution is a major health threat, estimated to lead to 6.7 million deaths annually. In addition to contributing to premature mortality, air pollution adversely affects quality of life by increasing the risk of asthma, cardiovascular disease, impaired lung development in children, neurocognitive decline and cancer. There is a clear need for more detailed assessments in studies examining the relationship between air pollution and human health, beyond solely considering PM2.5 mass concentrations. For epidemiological studies, patient records from the Greater Manchester Care Records, all first COVID-19 cases diagnosed between March 1, 2020 and May 31, 2022 were followed until COVID-19 related hospitalization or death within 28 days. Long-term exposure was estimated using mean annual concentrations of particulate matter with diameter ≤2.5 μm (PM2.5), ≤10 μm (PM10), nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2) and benzene (C6H6) in 2019 using a validated air pollution model developed by the Department for Environment, Food and Rural Affairs (DEFRA). Residential greenspace availability was assessed using the Normalized Difference Vegetation Index. The association of long-term exposure to air pollution or residential greenspace with COVID-19 hospitalization and mortality were estimated using multivariate logistic regression models after adjusting for potential individual, temporal and spatial confounders. For toxicological studies, cytotoxicity, oxidative stress and DNA damage assays were performed on A549 human alveolar lung cells with tyre additives or brake-wear particles (BWP). In epidemiological studies, significant positive associations were observed between most pollutants and COVID-19 hospital admissions and mortality. Significant negative associations were observed between greenspace availability and COVID-19 hospitalization and mortality. Individuals who were older, overweight or obese, current smokers, or had underlying comorbidities showed greater associations between all pollutants of interest and hospital admission, compared to the corresponding groups. Individuals in most deprived groups showed weaker associations between residential greenspace and COVID-19 hospital admissions and mortality. In toxicological studies, tyre-additives and BWP caused glutathione (GSH) depletion and induced DNA strand breaks after 24 h exposure in a concentration-dependent manner. The presence of N-acetyl-L-cysteine (NAC), a GSH precursor, mitigated DNA damage. This thesis explores how particle composition and source influence COVID-19 severity and DNA damage outcomes. It also highlights the importance of addressing environmental health disparities by examining the disproportionate impacts of air pollution on disadvantaged populations.

Date of Award	12 Dec 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	David Topping (Main Supervisor)