Persistent micro- and nanoplastics as triggers for interstitial lung disease
Lead Research Organisation:
Imperial College London
Department Name: School of Public Health
Abstract
Plastic is the third most abundant manmade material on Earth. It degrades and sheds particles or fibres too small to see with the naked eye, known as 'micro- and nanoplastic' (MNP). These particles are a newly recognised part of pollution in indoor and outdoor air and are of concern due to their potential to cross biological boundaries and enter living cells. This has alerted scientists, government, media and the public: the health effects of air pollution are well defined, but the additional impacts of breathing in plastic dust are poorly understood. This will become increasingly important for public health; plastic materials will continue to shed, even if there are efforts to reduce air
pollution from other sources.
In some plastic industries, workers exposed to high levels of fine plastic dust can develop lung disease leading to lung tissue scarring and compromised breathing. In this research, we seek to investigate this in greater detail, using a range of experimental (lung) models to determine the level of risk which exposure to environmental MNP air pollution presents, and the associated biological pathways leading to disease. We will do this by:
1. Quantifying exposure to past and present MNP by reanalysing old and analysing new air pollution samples for plastic.
2. Making different microplastic particles and fibres using milling, spinning and cutting techniques to ask controlled questions about the drivers of toxicity. The types of MNP materials will be based on those most commonly produced and found in the environment.
3. Evaluating the toxicity of inhaled MNP in the lung, using human relevant cell models and key markers of hazards posed by MNP to the lung.
4. Assess the longer term impacts of MNP inhalation on the development of lung tissue scarring in an animal model.
This novel and multidisciplinary research will advance understanding on whether there are impacts of inhaled MNP in the lung and why. This is an increasingly important knowledge gap. Rising plastic production will contribute to the plastic component of air pollution in the long term. In the short term, plastic materials shed and we have no knowledge of what the impact of inhaling this material might be. The findings will be important for national and international governments because they will allow them to assess the risks of inhaling microplastics. It will highlight whether any interventions are required to minimise exposure in the future. Medical professionals will benefit from being aware of the potential hazards when treating individuals with respiratory illness. The findings will also help industry develop safer alternatives to plastic materials.
pollution from other sources.
In some plastic industries, workers exposed to high levels of fine plastic dust can develop lung disease leading to lung tissue scarring and compromised breathing. In this research, we seek to investigate this in greater detail, using a range of experimental (lung) models to determine the level of risk which exposure to environmental MNP air pollution presents, and the associated biological pathways leading to disease. We will do this by:
1. Quantifying exposure to past and present MNP by reanalysing old and analysing new air pollution samples for plastic.
2. Making different microplastic particles and fibres using milling, spinning and cutting techniques to ask controlled questions about the drivers of toxicity. The types of MNP materials will be based on those most commonly produced and found in the environment.
3. Evaluating the toxicity of inhaled MNP in the lung, using human relevant cell models and key markers of hazards posed by MNP to the lung.
4. Assess the longer term impacts of MNP inhalation on the development of lung tissue scarring in an animal model.
This novel and multidisciplinary research will advance understanding on whether there are impacts of inhaled MNP in the lung and why. This is an increasingly important knowledge gap. Rising plastic production will contribute to the plastic component of air pollution in the long term. In the short term, plastic materials shed and we have no knowledge of what the impact of inhaling this material might be. The findings will be important for national and international governments because they will allow them to assess the risks of inhaling microplastics. It will highlight whether any interventions are required to minimise exposure in the future. Medical professionals will benefit from being aware of the potential hazards when treating individuals with respiratory illness. The findings will also help industry develop safer alternatives to plastic materials.
Technical Summary
Plastic is the third most abundant manmade material on Earth. It sheds micro- and nanoscopic particles or fibres known as micro-/nanoplastics (MNP), which form part of indoor and outdoor particulate air pollution (PM). Occupational and experimental observations suggest exposure to MNP can trigger fibrosis. In this proposal we seek to investigate this potential adverse outcome in greater mechanistic detail, across a range of experimental (lung) models (in vitro and in vivo) to establish whether inhalation of MNP contributes to an increased risk of restrictive lung disease, achieved through the following objectives ('obj.'): 1. Quantification of historic and contemporary MNP outdoor exposures in urban PM2.5 by analytical chemistry and spectromicroscopy methods, supporting data extrapolation in Obj. 3 and 4. 2. Generation of controlled MNP particles and fibres using cryomilling and electrospinning to support Obj. 3 and 4. Fibres will be cut to defined aspect ratios in a cryotome. The composition of these materials, informed by published environmental and industrial data, will be characterised in detail. 3. Evaluation of the toxicological response to inhaled MNP in the alveolar environment using an Adverse Outcome Pathway (AOP)-driven approach. The effects of MNP generated in Obj. 2 on key events in lung fibrosis (represented by AOP173) will be quantified using an advanced, physiologically relevant in vitro testing strategy. 4. In vivo challenges to assess the fibrogenic potential of inhaled MNP. Findings in Obj. 3 will be verified and the effects of MNP, generated in Obj. 2, on extracellular matrix remodelling assessed. The research will inform the WHO, EC and UK HSA, with application in risk assessment, and regulations to minimise MNP release and public exposure. It will stimulate innovations in low-shed, or fully biodegradable materials. We will engage our industry links, and exploit our connections to the EU CUSP cluster, COMEAP and UKHSA to disseminate findings.
