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Getting to the heart of air pollution

The World Health Organization (WHO) estimates that air pollution is responsible for more than seven million premature deaths globally a year. Edinburgh researchers investigating the effects of air pollutants on cardiovascular health are helping to shape air quality guidelines.

The effects of air pollution on the lungs have been known for more than half a century, but the impact on cardiovascular health was uncovered more recently. In 2005, researchers at Edinburgh first started noticing that many early deaths linked to air pollution were not caused by lung disease, but heart attacks and stroke. Dr Mark Miller, Research Fellow in the University’s Centre for Cardiovascular Science, and Professor David Newby, British Health Foundation (BHF) Duke of Edinburgh Chair of Cardiology, wanted to understand why and how.

Professor Newby’s previous work had shown that smoking encourages the build-up of atherosclerotic plaques on the arteries by reducing the release of the clot dissolving factor tissue plasminogen activator (t-PA). “There are quite a few similarities between cigarette smoke and air pollution that comes from vehicle exhaust,” Dr Miller explains. “Some of the gases and chemicals on particles that are released by burning tobacco or fuel are the same.”

A volunteer cycling and reading during a dilute diesel exhaust exposure in the facilities at Umea University, Sweden
A volunteer cycling and reading during a dilute diesel exhaust exposure in the facilities at Umea University, Sweden, as part of the Edinburgh BHF research programme

The heart of the matter

Both clinical and epidemiological studies are helping to shed light on the effects of various air pollutants on the cardiovascular system.

In collaboration with scientists in the Netherlands and Sweden, Professor Newby examined the effects of controlled exposure to dilute petrodiesel and biodiesel exhaust on healthy volunteers. “A specialised chamber was used in which volunteers cycle intermittently to mimic the effects of cycling in heavy traffic for one-to-two hours,” Dr Miller says. Following exposure, they used different techniques to measure the health of the heart and blood vessels.

The results were astounding. “Exhaust exposure had lots of different effects on the heart, blood vessels and in the blood, all of which would increase the risk of developing a heart condition,” Dr Miller continues. Short-term exposure to diesel exhaust not only changed the rhythm of the heart and made the heart more susceptible to damage, it also made blood vessels stiffer and unresponsive, disrupting their ability to contract and relax to control blood flow around the body. It also thickened the blood, making it more likely to clot and reduced capacity to get rid of clots.

Can breathed in particles reach blood vessels and contribute to cardiovascular disease? Dr Miller and his team have been devising ways to study this. “Diesel exhaust particles are minute, they are smaller than coronaviruses, and they are found in tiny amounts in the blood, which makes them very difficult to measure,” he says. There is evidence from animal models that ultra-fine particles (less than 0.1μm) are able to cross the thin barrier between the lung and blood vessels in the lung and be carried to other organs. However, this has been very challenging to demonstrate in people.

A golden opportunity

“To determine whether inhaled particles can translocate into the bloodstream, we used gold nanoparticles that are similar in size to diesel exhaust particles,” Dr Miller explains. Gold nanoparticles are safe and can be accurately measured in very small concentrations. Fifteen minutes after exposure, Dr Miller was able to detect these breathed in particles in the blood of healthy volunteers. Moreover, when they carried out the experiment in patients with a history of stroke, they found the inhaled gold nanoparticles in surgical specimens of carotid artery disease. Similar work in a mouse model of atherosclerosis showed that the nanoparticles preferentially accumulated in diseased blood vessels. “Our discovery that breathed in particles get into your blood and build up in areas of disease, where they are likely to cause the most harm, made the headlines,” Dr Miller says.

Photos showing gold particle exposure research
Top row: Gold particle exposure equipment and a volunteer breathing in the particles through tubing to a facemask. Bottom left: a cluster of particles in the fatty cells of an atherosclerotic plaque within an artery. Bottom right: The use of Raman spectroscopy to identify gold particles (red and yellow) in a biopsy of vascular disease (grey) from a stroke patient

Campaigning for change

The results of this research meant that tackling air pollution soon became a top priority of the UK charity BHF. Their 2020 campaign Toxic Air: We’re Full of It has helped raise awareness of the damage that particulate matter (PM) has on cardiovascular health and led to nearly 10,000 people writing to their Member of Parliament to demand stricter air quality limits.

“The BHF has provided a platform so we can speak to people that matter,” Dr Miller says. “Although everyone knows air pollution is bad, they don’t necessarily know how bad.” Through attendance at events such as parliamentary receptions, Edinburgh researchers have helped to bring the science to life for decision-makers.

“We were very excited to see Mark Miller’s research feature in the UK Government’s 2019 Clean Air Strategy, which really captures how the narrative on air pollution has changed; Government are seeing the need to act on it as a health issue, rather than just as an environmental one,” says Rebecca Elliott, Prevention Policy Manager at BHF.

Influencing policy

Dr Miller currently sits in the UK government advisory group COMEAP (Committee on the Medical Effects of Air Pollutants) which provides independent advice to the Department of Health on the health risks of air pollution and a group that is helping the Department for Environment, Food & Rural Affairs draw up new guidelines on what the limits of air pollution should be.

The new UK Environment Act, which became law in November 2021, will introduce a legally-binding duty on the UK government to reduce the annual average level of fine PM (PM2.5, less than 2.5μm) in ambient air by October 2022. The target has not yet been set but will take into consideration the WHO’s annual mean guideline level for PM2.5.

As Dr Miller points out, many vehicle exhaust emissions are smaller than PM2.5, but because they are so difficult to measure there are currently no emissions reduction targets set on ultra-fine PM. “Although we are moving in the right direction, we need to speed things up; more needs to be done to reduce air pollution, especially from vehicles,” he says. “Using public transport and encouraging active travel could help reduce ultra-fine particles in the air and lead to a huge improvements in cardiovascular health.”

Funding for active travel and introducing low emission zones in urban areas are some of the actions set out in the Scottish Government’s new air quality strategy Cleaner Air for Scotland 2 – Towards a Better Place for Everyone. For Andrew G Taylor, Air Quality Policy Manager in the Scottish Government, Dr Miller and Professor Newby’s research has been vital in introducing changes for the better: “This work has provided a valuable contribution to the evidence base on human health impacts of air pollution in Scotland, helping to inform the health-based actions to deliver air quality improvements over the next five years.”

Vehicles and a cyclist in central Edinburgh
Vehicles and a cyclist in central Edinburgh

What about other air pollutants?

In addition to PM, there are gaseous components, chiefly sulphur dioxide, nitrogen dioxide, ozone and carbon monoxide, which contribute to air pollution. As part of his research in the Centre for Cardiovascular Science, Dr Ken Lee, Clinical Research Fellow and Cardiology Registrar at the Royal Infirmary of Edinburgh, investigated the association between daily increases in these gaseous pollutants and particulate matter (PM2.5 and PM10), and admission to hospital for stroke or mortality from stroke.

In 2015, he completed a large systematic review of observational studies and found a close association between exposure to air pollutants and adverse stroke outcomes, especially in low- and middle-income countries (LMICs). Not long after, the WHO commissioned him and a small team of researchers to assess the evidence of the effects of carbon monoxide on myocardial infarction (MI).

“We worked closely with WHO methodologists to establish a list of criteria against which to assess the certainty of the evidence,” Dr Lee explains. When they pulled all the relevant studies together, they found that for every 1mg/m3 increase in ambient carbon monoxide concentration, the risk of MI (defined as hospitalisation or death due to MI) increases by five per cent “This might seem like a small number but everyone is exposed to air pollution, so on a population level this is quite a large effect,” Dr Lee says.

The WHO used these findings to set carbon monoxide targets in their latest guidelines for global air quality published in September 2021. “In addition to setting lower levels for key air pollutants, these guidelines also set interim targets to help steer implementation,” says Dr Lee. He is cautiously optimistic about the impact they will have in the next few years.

Flames ignited to heat water as seen through a gas boiler's viewing window
Flames ignited to heat water as seen through a gas boiler's viewing window

Taking it indoors

Another of Dr Lee’s key findings is that household air pollution, which disproportionately affects LMICs where people rely on polluting fuels and technologies for domestic cooking and heating, increases not only the risk of cardiovascular disease but also that of a whole range of illnesses.

“Indoor air pollution is a huge problem in the developing world and one that the WHO is keen to tackle,” he says. “In 2017, we estimated that indoor air pollution was associated with 1.8 million deaths around the world.”

Since 2000, mortality associated with household air pollution has reduced by 36 per cent, but the greatest reductions have been recorded in higher-income nations. Urgent health and energy strategies are needed to reduce the adverse impact of household air pollution on health in LMICs. “Solutions will require local government action, but our work has helped to raise awareness of the problem and, hopefully, created momentum to drive change,” Dr Lee explains.

Bringing research into policy is not easy; it takes time and commitment. Yet, as Dr Lee and Dr Miller’s achievements to date demonstrate, these efforts are vital for realising the real-world benefits of their work and addressing one of the most important environmental and public health issues the world is facing. Understanding which pollutants are having the most harmful effects helps third sector organisations like the BHF target their policy asks and make recommendations for action that will get to the root of the problem.

By Monica Hoyos-Flight, Science Writer.

Photos courtesy of Dr Mark Miller, Sam Sills and georgeclerk/Getty.

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