Evidence shows that traffic-related air pollution is a contributory factor to a wide range of diseases
But the most harmful pollutants are currently unregulated
September 22nd 2017
The last few years has seen an increasing amount of research into the impact of traffic-related air pollution on human health. Much of the research has focused on the harmful impact of nitrogen dioxide (NO2) and particulate matter (PM), tiny particles that are emitted by diesel vehicles and other sources. In the UK, nitrogen dioxide emissions have exceeded the legal limit as set by the EU for the last seven years and have been the subject of a long-running legal dispute – see last month’s article ‘Air Pollution in the UK – Seven years of illegal NO2 emissions’. Nitrogen dioxide emissions are known to cause breathing difficulties and have been linked to respiratory symptoms and illnesses such as asthma and bronchitis, while PM particles have been found in the bloodstream, the lungs, and more recently in the brain, with research suggesting links with cardiovascular disease and neurological disorders such as Alzheimer’s disease.  In this article, we look at a cross-section of the most significant findings, including research on the impact of air pollution on children, research on the possible links between air pollution and a number of illnesses (such as diabetes, cardiovascular disease, and neurological disorders), and the implications of this research for measures to tackle traffic-related air pollution.
The impact of air pollution on London’s schoolchildren
Two years ago, researchers based at King’s College and Queen Mary College, University of London, published the results of a research project that set out to investigate the effects of air pollution on schoolchildren living within London’s Low Emission Zone. The research was funded by the National Institute for Health Research, NHS health trusts and other bodies. The study focused on 8-9 year-old children from schools located at various distances from a number of air pollution hotspots in the east London boroughs of Hackney and Tower Hamlets. The Low Emission Zone, set up in 2008, was predicted to have a significant effect on PM10 and NO2 concentrations, and the researchers hypothesized that “reduced exposure to traffic emissions would result in a reduction in the prevalence of respiratory/allergic symptoms associated with traffic-related pollutants.” 
Data was collected over three consecutive winters, November to March, 2008 to 2011. Respiratory and allergic symptoms were assessed using parent-completed questionnaires. These were collected at each visit, when health assessments were also carried out to examine lung function and collect biological samples. Around 1,800 children at 23 schools were invited to take part in the study, with around a thousand (56%) deciding to participate. Computer modelling techniques were used to gather data on air pollution exposure for the duration of the study (including measurements of NO2 and PM10 levels). Statistical analysis of the data “confirmed the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis,” and also identified a direct correlation between exposure to air pollution and a reduction in lung growth. Speaking to the Sunday Times, Ian Mudway, a respiratory toxicologist at King’s College London, said: “The data shows that traffic pollution stops children’s lungs growing properly. The evidence suggests that by 8-9 years of age, children from the most polluted areas have 5 to 10 per cent less lung capacity and they may never get that back.” 
“No evidence that Low Emission Zones can reduce pollution”
Additionally the researchers found that, in contrast to the predicted effect, the Low Emission Zone “did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied.” They conclude: “Importantly, the London Low Emission Zone has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.”  Professor Chris Griffiths, who coordinated the research, is a GP and Professor of Primary Care at Queen Mary College, University of London, and the Co-Director of the Asthma UK Centre for Applied Research. He said it was very disappointing that the Low Emission Zone, “which was specifically designed as a major public health intervention, has so far brought about no change. This raises questions over the government’s current consultation on air quality, which is based around the idea of creating similar low emission zones in up to 30 other polluted urban areas. There appears to be no evidence that these low emission zones can reduce pollution or improve health.”  In fact, these plans were dropped in the Government’s latest plans to tackle air pollution, as we explained in last month’s article, in favour of the long-term ambition of ending the sale of all new diesel vehicles by 2040, whilst in the shorter-term local authorities will be expected to come up with air quality plans.
The social inequalities of air pollution
The impact of air pollution on London’s schoolchildren was also the subject of a report commissioned by the Greater London Authority which was completed in 2013. Last year, however, the Guardian revealed that Boris Johnson, during his period of office as London’s Mayor, had prevented the full report from being published.  Speaking to the Guardian, the report’s author Katie King said that the Greater London Authority had publicly disclosed the positive conclusions in the report – namely, that the number of people exposed to illegal NO2 emissions would fall by 2020 – but had held back the negative findings. “The crux of the report was about understanding the inequalities of air pollution,” she said, “so they chose not to make public the findings regarding inequality. The information that they did take from the report was the positive, that exposure was predicted to fall in the future.” The positive findings were highlighted by the Mayor in a progress report on his air quality strategy, delivered in July 2015. These were the predictions that the number of Londoners exposed to illegal NO2 emissions would drop from 1 million in 2015 to around 300,000 in 2020 as a result of the Mayor’s policies on Low Emission Zones. The Mayor’s progress report also noted that deprived communities were more likely to be exposed to poor air quality, but the Guardian says that “it failed to mention the unpublished report’s revelation that in 2010, 433 of the city’s 1,777 primary schools were in areas where pollution breached the EU limits for NO2. Of those, 83% were considered deprived schools, with more than 40% of pupils on free school meals. Of the remaining schools located in areas below the pollution limit, less than a fifth were in deprived areas.” In response, Boris Johnson denied that there had been any cover-up, saying he had highlighted the problem of primary schools and poor air quality in areas of deprivation. However, the Guardian reports that his office did not deny he had stopped the full report from being released. And given the results of the NHS-funded research, mentioned above, the predictions on the impact of London’s Low Emission Zone may turn out to be unduly optimistic as regards the effects on human health.
The BREATHE project: A study of air pollution and child development
Further evidence of the impact of traffic-related air pollution on child development has come from Spain, where a number of research institutions collaborated on a project called BREATHE (also known as ‘Brain Development and Air Pollution Ultra-fine Particles in Schoolchildren’), which was funded by the European Research Council.  The research was based in Barcelona and set out to evaluate the impact of air pollution exposure on cognitive development in primary schoolchildren. The researchers say that air pollution concentrations in Barcelona are among the highest in Europe, partly attributed to high traffic density with a large proportion of diesel-powered vehicles (around 50%), relatively low precipitation, high population density, and an urban landscape characterized by high-storey buildings and narrow streets, which reduces the dispersion of pollutants. Of the 416 schools in Barcelona, 40 schools were selected to obtain the greatest contrast in traffic-related air pollution levels, as measured by NO2 concentrations. Of the 40 schools, 39 accepted the invitation to participate and about 2,700 schoolchildren took part in the project. 
Air pollution increases the risk of developing myopia
Data gathered from the BREATHE project and published in April this year showed a link between exposure to traffic-related air pollution and myopia in schoolchildren aged 7 to 10 years of age, as measured by the use of spectacles. In their introduction to the study, the authors state:
“Exposure to traffic-related air pollution is associated with a wide range of adverse health outcomes, with the lungs being one of the most commonly affected organs, mainly because of their constant direct exposure to air pollutants. Similarly, the eyes are directly exposed to air pollution, making them a prime target organ for the adverse effects of such an exposure. In addition to the short-term effects of air pollution on the eye, such as irritation of the ocular surface and its accompanying symptoms and complaints, chronic exposure to air pollution has been associated with long-lasting ocular conditions such as dry eye disease and cataract. Although air pollution could induce myopia through systemic inflammation and oxidative stress, to date no studies have reported on the potential effect of air pollution on the development of myopia.” 
In this case, data was collected over a three-year period from 2012 to 2015. Air pollution was calculated by monitoring exposure to NO2 and black carbon particles at school, and by the predictive modelling of exposure to NO2 and PM particles (PM2.5) at home. As a result of their analysis, the researchers conclude that exposure to traffic-related air pollution increases the risk of developing myopia, as indicated by the number of children using spectacles.
Air pollution affects cognitive development
More results from the BREATHE project were published in March 2015. This investigation set out to assess whether exposure to traffic-related air pollution has an impact on children’s cognitive development.  As in the previous investigation, around 2,700 schoolchildren aged 7 to 10 years from 39 schools in Barcelona participated. The schools were located in both high and low polluted areas, as measured by traffic-related NO2 concentrations. The children were assessed using computerized tests every three months over four week-long visits in a 12-month period from January 2012 to March 2013. During each visit, air pollution was monitored for levels of NO2, elemental carbon and ultra-fine particles with a dimension of 10–700 nm (i.e. 10 to 700 nanometres), both outside and inside the classroom. Analysis showed that those schools that were closest to major roads had the highest concentrations of pollutants in their classrooms. The children’s cognitive development was assessed through their performance in the tests and an analysis of the long-term changes in working memory and attentiveness. Statistical analyses of the data indicated that children from highly polluted schools had a smaller increase in cognitive development over time compared to children from lowly polluted schools. Children with attention deficit / hyperactivity disorder were even more vulnerable to pollution levels. The researchers conclude: “Importantly, these findings do not prove that traffic-related air pollution causes impairment of cognitive development. Rather, they suggest that the developing brain may be vulnerable to traffic-related air pollution well into middle childhood, a conclusion that has implications for the design of air pollution regulations and for the location of new schools.”
Evidence of slower brain growth in schoolchildren
Further news of these findings was reported in Horizon: the EU Research and Innovation Magazine in July this year.  The report mentions some findings that were not reported in the 2015 publication. Anthony King reports the finding that even one high-pollution day before a test could effect a child’s performance. Additionally, he says that the researchers used magnetic resonance imaging (MRI) to examine 350 children, which showed that “high pollution was linked to slower growth in the front of the brain, in an area believed to be important in decision-making, social behaviour and complex thinking.” Professor Jordi Sunyer is a senior researcher at the Barcelona Institute for Global Health and a lead scientist on the BREATHE project. He says that the harmful effects detected in the research are due to ultra-fine PM particles, mainly emitted by diesel vehicles. Ultra-fine PM particles refers to particulate matter that has an aerodynamic diameter smaller than 0.1 micrometres (< 0.1µg/m3 or < 100 nm); these are far smaller than the fine PM particles (PM2.5) which have an aerodynamic diameter smaller than 2.5µg/m3. These ultra-fine particles are tiny particles of carbon that are breathed into the lungs, cross into the bloodstream and travel to the brain, he said: they "stimulate immune cells and produce an inflammatory effect at various levels of the brain." On the implications of the research for the building of new schools, he said: "If you move traffic 50 metres from a school, ultra-fine particle amounts drop by more than half. At 200 metres, you get 10 times less." As well as reducing the number of diesel vehicles in Europe, Professor Sunyer recommends that local authorities take short-term measures to alleviate the problem by creating barriers between air pollution and citizens, including natural barriers such as trees, hedges and 'green walls'.
Links with diabetes
Air pollution may also contribute to the development of diabetes, affecting children in particular. Research published by the American Diabetes Association in 2016 suggests a link between long-term exposure to air pollution (PM10 and NO2) and insulin resistance in the general population, “mainly attributable to pre-diabetic individuals” (i.e. individuals whose blood sugar is abnormally high, a condition that increases the risk of contracting diabetes and cardiovascular disease).  The American Diabetes Association has also published evidence which suggests that exposure to elevated concentrations of NO2 and PM2.5 may contribute to the development of type 2 diabetes “through direct effects on insulin sensitivity and β-cell function”. This latter research, published in January this year, studied children aged 8 to 15 years who were classed as overweight or obese and were followed over a three-year period. 
Effects on the unborn child?
Research has also investigated the effects of air pollution exposure on children at the foetal stage. A longitudinal study was published two years ago by the American Medical Association in its journal JAMA Psychiatry.  The participants included a sample of 40 urban youth who were followed up prospectively from the foetal stage up to the ages of 7 to 9 years. The research in this case focused on the effect of polycyclic aromatic hydrocarbons, described as ubiquitous and toxic environmental pollutants. The researchers detected a “close-response relationship” between exposure to these pollutants and reductions in the white matter of the brain in later childhood. These reductions “were confined almost exclusively to the left hemisphere of the brain and involved almost its entire surface.” The reduced white matter in the left hemisphere was closely associated with a slower speed in processing information during intelligence tests and more severe behavioural problems, including symptoms of attention deficit / hyperactivity disorder. The authors of the study also suggest that postnatal exposure contributes to additional disturbances in the development of white matter in later childhood, a finding that shares similarities with the slower brain growth detected in the BREATHE project, as mentioned above.
Links with cardiovascular disease, strokes and heart failure
There is a growing body of research that has demonstrated a link between particulate air pollution and the development of cardiovascular disease, such as furring of the arteries.  For those people already suffering from heart disease, air pollution can worsen their condition. A study published in the British Medical Journal shows that short-term exposure to air pollution increases the risk of a stroke, with a risk of hospitalisation or death from heart failure in the following week,  while a study published in the American Heart Association journal Circulation shows that short-term exposure to high levels of air pollution can trigger a heart attack (“myocardial infarction”).  The British Heart Foundation (BHF) says air pollution “is a particular problem for the 570,000 people in the UK living with heart failure.”  At the British Heart Foundation’s Centre for Cardiovascular Science based at the University of Edinburgh, a team of researchers have analysed data from twelve countries covering more than four million people living with heart failure “and found they had an increased risk of hospitalisation and death where pollution levels were high.” Lead researcher Professor David Newby said: “People with heart failure are a vulnerable group and, when the air quality falls, more of them are admitted to hospital.”
Research at the BHF Centre for Cardiovascular Science
Recent research at the Centre for Cardiovascular Science has been particularly concerned about “nanosized particulate matter in air pollution, such as that derived from vehicle exhaust.”  This nanosized particulate matter refers to the ultra-fine particles of air pollution that were featured in the research findings described above. The teams working at the Centre for Cardiovascular Science have published research demonstrating “that acute exposure to diesel exhaust causes vascular dysfunction, thrombosis, and myocardial ischaemia in healthy individuals and in patients with coronary heart disease” (‘myocardial ischaemia’ is a blockage or a hardening of the coronary arteries, resulting in a reduction of the blood flow to the heart muscle).  However, while research has demonstrated the links between exposure to particulate air pollution and the development of numerous vascular ailments, the mechanisms through which inhalation could trigger acute cardiovascular events, such as strokes and heart attacks, are only beginning to be understood, and there is a major area of uncertainty surrounding the question of how precisely inhaled particles influence the progression of systemic cardiovascular disease, particularly whether inhaled particles are transported from the lungs, enter the bloodstream and make a direct contribution to cardiovascular disorders.
This was the question that researchers set out to answer in a study that was published by the American Chemical Society in April this year and was carried out by scientists from the UK and the Netherlands. The scientists were based at the BHF Centre for Cardiovascular Science, the Medical Research Council Centre for Inflammation Research (also based at the University of Edinburgh), the University of Edinburgh School of Chemistry, the National Institute for Public Health and the Environment (Netherlands), and Utrecht University and VU University (both in the Netherlands). This particular research was motivated by the growth in engineered nanomaterials and concerns over the potential for human exposure. In their introduction, the scientists say that engineered nanoparticles have “potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality.” These environmental nanoparticles are the ultra-fine particles whose dimension is far smaller than the so-called fine particles (PM2.5), as mentioned above. Consequently, the research has implications for our understanding of how precisely air pollution may contribute to the development and progression of cardiovascular disease.
The fate of ultra-fine particles
To find an answer to this question, the researchers recruited 14 volunteers who were exposed to biologically inert, and hence harmless, gold nanoparticles of varying sizes. The volunteers were all male, non-smokers, and aged 18 to 35. Prior to exposure, none of the volunteers had gold detectable in the bloodstream, but gold was detectable in the bloodstream as early as 15mins after exposure in some subjects and was present in the majority at 24 hours. Further research was carried out using 12 volunteers who were suffering from a “cerebrovascular accident,” the medical term for a stroke, and were waiting to undergo surgery. As a result of this research, the scientists were able to conclude that inhaled nanoparticles are transported from the lung into the bloodstream, “where they accumulate at sites of vascular inflammation” (‘vascular inflammation’ is a condition characterised by the build-up of a fatty plaque on the walls of the arteries). The smaller particles were more likely to accumulate, indicating that the ultra-fine particles of air pollution, such as the tiny carbon particles emitted by diesel vehicles, are the most harmful to human health.
News of these findings was reported in the New Scientist in April this year by Michael Le Page, who says that the gold nanoparticles could still be found in blood and urine samples three months after inhalation.  Mark Miller, who led the research at the Centre, says that the team was “really surprised that levels were so high three months afterwards.” He described the health implications of the research as follows. When nanoparticles get into the body, he said, they accumulate in the fatty plaques that can grow inside arteries, causing heart attacks and strokes, and the reactive compounds found in air pollution could have all sorts of harmful effects, from impairing the contraction of blood vessels to promoting clotting. The New Scientist also quotes a statement from Frank Kelly, Professor of Environmental Health at King’s College London, who said the study goes a long way towards explaining how air pollution causes vascular injury and disease. “If these findings with gold particles reflect the movement of exhaust-generated carbon particles, then the increased production of very small particles by modern engines is a cause for further concern,” he said.
“Efforts to regulate air pollution are focusing on the wrong particles”
The research also has significant implications for the monitoring of air pollution. The technological devices that are widely used to measure air pollution at the roadside are able to measure the total mass of PM particles in a cubic metre of air, but they are unable to measure the number of such particles. And legal limits for PM emissions, as set by the EU, are based on these measures of total mass. However, thousands of ultra-fine particles can weigh much less in total than a small number of larger-sized particles, and it is the ultra-fine particles that are the most dangerous. This has led Professor David Newby to comment that current efforts to regulate air pollution are focusing on the wrong particles. “We are potentially looking in the wrong place,” he said. And Mark Miller says: “Ideally, we would measure numbers, but the technology is not there.”  A further problem is that, while EU legislation sets limits for particulate matter smaller than 2.5µg/m3 (PM2.5), there is no separate regulation for these far smaller ultra-fine particles.
Professor Newby also thinks that the number of ultra-fine particles has risen in the past decade over Europe as a result of diesel emissions, which means that the risk to human health has increased. This is in contrast to those who claim that air pollution has improved over the last few decades because the mass of PM2.5 particles has fallen in most of Europe, as measured by the widely used technology. According to a recent EU assessment of its Ambient Air Quality Directive, PM2.5 levels exceeded the legal limit in just six member states in 2014: the Czech Republic, Poland, Bulgaria, France, Hungary and Italy.  And, although the UK has broken the legal limit for NO2 emissions over the last seven years, the EU assessment records that in 2013 the UK was within the legal limit for both PM10 and PM2.5 particles. The EU legal limits that are intended to regulate air pollution mean therefore that the UK Government is under less pressure to tackle the problem of ultra-fine particles. 
Legal limits are not safety limits
There is also a further problem here in the disparity between the EU’s definition of legal limits and what the World Health Organization (WHO) regards as safety limits. The WHO guideline values for particulate matter are 20μg/m3 for PM10 and 10μg/m3 for PM2.5, whereas the EU legal limits are 40μg/m3 for PM10 and 25μg/m3 for PM2.5, taken as the average over a twelve-month period. In short, the WHO sets higher standards for safety limits. The WHO published a database in May last year of air pollution statistics from urban areas across the globe. These figures show that the UK breached what the WHO describes as safety limits for PM10 and PM2.5 particles in towns and cities across the UK. Safety limits for PM10 were breached in ten towns and cities. These were: London, Glasgow, Leeds, Nottingham, Southampton, Oxford, Scunthorpe, Port Talbot, Eastbourne, and Stanford-Le-Hope in Essex. Safety limits for PM2.5 were breached in 39 towns and cities. These include the ten already mentioned and Middlesbrough, Carlisle, York, Hull, Manchester, Liverpool, Stoke-on-Trent, Birmingham, Bristol, Newport, Cardiff, Swansea, Plymouth, Portsmouth, Brighton, Southend, and Norwich. If we add to this the problem of measuring and regulating the currently unregulated ultra-fine particles, which scientists now regard as the most harmful to human health, it becomes obvious that current regulatory mechanisms are inadequate to tackle the problem of air pollution. 
Pathways to the brain
Returning to recent research, we mentioned above that scientists working on the BREATHE project have said that ultra-fine particles are breathed into the lungs, cross into the bloodstream and travel to the brain, with an MRI scan showing an association between a high level of air pollution and a slower development of a child’s brain.  However, other researchers have found that airborne pollutants can enter the brain through an alternative pathway: namely, directly through the nose and the olfactory nerve. Further, the finding that PM particles can enter the brain has led some to suggest there may be a link between air pollution and neurological diseases such as Alzheimer’s disease and Parkinson’s disease.
A significant discovery which made national news was published in September last year in the journal PNAS: Proceedings of the National Academy of Sciences of the USA.  The research was carried out by scientists from the UK, Mexico, and the USA, and led by Professor Barbara Maher at the University of Lancaster. The scientists analysed samples of brain tissue from 37 people. Some of the samples came from 29 people who had lived and died in Mexico City and whose ages ranged from 3 to 85. The rest of the samples came from 8 people from Manchester whose ages ranged from 62 to 92 and included some who had suffered from severe to moderate forms of Alzheimer’s disease. The scientists found tiny particles of iron oxide, also known as magnetite, in all of the 37 samples. Small quantities of magnetite can occur naturally in the brain, and in the PNAS paper the authors point out that “biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over twenty years ago.” However, in their research the scientists “used magnetic analyses and electron microscopy to identify the abundant presence in the human brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source.” Further, these magnetite nanoparticles matched precisely “the high-temperature magnetite nanospheres, formed by combustion and/or friction-derived heating, which are prolific in urban, airborne particulate matter.”
The authors say that, because many of the airborne magnetite pollution particles are so small, they can enter the brain directly through the olfactory nerves (i.e. the cranial nerves supplying the smell receptors to the nose) and by crossing the damaged olfactory unit. The importance of this discovery is that nano-scale magnetite can respond to external magnetic fields and is toxic to the brain. Nano-scale magnetite is implicated in oxidative cell damage which has a causal link to neurodegenerative illnesses such as Alzheimer’s disease; hence, the authors argue, “exposure to such airborne PM-derived magnetite nanoparticles might need to be examined as a possible hazard to human health.”
Millions of nanoparticles in a single gram of brain tissue
Speaking to BBC News, lead researcher Professor Barbara Maher said she had previously identified magnetite particles in air samples gathered next to a busy road in Lancaster and outside a power station, and she suspected that similar particles might be found in the brain samples.  Her suspicions were confirmed by the results which she described as shocking, as a magnetic extraction showed there were a million of these particles in a single gram of brain tissue. It was the shape of the nanoparticles detected in the microscopy that gave a clue as to their origins. Naturally occurring particles of magnetite have a jagged shape, but the majority of the millions of particles found in the tissue samples were smooth and rounded, and displayed features that Professor Maher said could only be created in the high temperatures of a vehicle engine or braking system. “They are spherical shapes and they have little crystallites around their surfaces, and they occur with other metals like platinum which comes from catalytic converters,” she said. These particles were 100 times more numerous than the naturally occurring particles. Professor Maher said it was the first time such particles had been found in the human brain and the discovery opened up a new area of investigation: namely, the question of whether “these magnetite particles are causing or accelerating neurodegenerative disease.”
Links with neurodegenerative disease?
David Allsop is a Professor of Neuroscience at Lancaster University who specialises in neurological diseases and is a co-author of the PNAS paper. Speaking to BBC News, he said that pollution particles could be an important risk factor for conditions such as Alzheimer’s and Parkinson’s disease. “There is no absolutely proven link at the moment but there are lots of suggestive observations,” he said. “Other people have found these pollution particles in the middle of the plaques that accumulate in the brain in Alzheimer’s disease so they could well be a contributor to plaque formation. These particles are made out of iron and iron is very reactive so it’s almost certainly going to do some damage to the brain. It’s involved in producing very reactive molecules called reaction oxygen species which produce oxidative damage and that’s very well defined. We already know oxidative damage contributes to brain damage in Alzheimer’s patients so if you’ve got iron in the brain it’s very likely to do some damage. It can’t be benign.” 
However, Dr Clare Walton, Research Communications Manager at the Alzheimer’s Society, said there was no strong evidence that magnetite causes Alzheimer’s disease or makes it worse. “This study offers convincing evidence that magnetite from air pollution can get into the brain,” she said, “but it doesn’t tell us what effect this has on brain health or conditions such as Alzheimer’s disease. The causes of dementia are complex and so far there hasn’t been enough research to say whether living in cities and polluted areas raises the risk of dementia. Further work in this area is important, but until we have more information people should not be unduly worried.” 
The search for evidence
In the last twelve months there have been a number of studies that have investigated possible links between air pollution and neurodegenerative illnesses such as Alzheimer’s and Parkinson’s disease . A recent study was published in the journal Environmental Health Perspectives last month.  The aim of the research was to examine whether exposure to PM air pollution is related to the risk of contracting Parkinson’s disease. In their introduction, the authors state: “Toxins in air pollution have been shown to promote inflammation and oxidative stress, both of which are thought to contribute to Parkinson’s disease.” The researchers, based at a number of institutions in the USA, followed over 50,000 men in the Health Professionals Follow-up Study, a large cohort of men in the USA which included 550 cases of Parkinson’s disease. They estimated the cumulative average exposure to various sizes of PM up to two years before the onset of Parkinson’s by linking each participant’s place of residence throughout the study with location-specific PM models. Statistical analysis of the results did not show any significant associations between PM exposure and the risk of contracting the disease. They conclude: “In this study we found no evidence that exposure to air pollution is a risk factor for Parkinson’s disease in men.”
Other researchers however have found associations between air pollution exposure and the development of Parkinson’s disease. A review of the available literature on the subject was published in the journal Reviews on Environmental Health in July this year.  The review focused on a broad range of studies that investigated possible links between a number of pollutants (including PM particles of various sizes, NO2, and airborne metals) and the development of Parkinson’s disease. The author states: “Air pollution exposure is linked to numerous adverse effects on human health, including brain inflammation and oxidative stress, processes that are believed to contribute to the development and progression of Parkinson’s Disease.” The review produced mixed results: some showed a strong association; some showed a moderate association, and some showed none at all. The author found that the studies that looked at air pollution exposure over a longer time span were more likely to find a positive association. The types of pollutants that were investigated in the studies include PM particles (PM2.5 and PM10), traffic-related NO2 emissions, airborne metals, and second-hand smoking.
The problem of size
In the main, research on the impact of air pollution on human health has tended to focus on the impact of NO2 and PM pollution and, because existing data is more readily available, and because new data can be gathered more easily, on PM2.5 and PM10 particles in particular. There has been far less research on the impact of the smaller ultra-fine particles that have featured in the BREATHE project and the PNAS paper. A nanometre is one billionth of a metre, and the nanoparticles (or ‘nanospheres’) in the PNAS study are less than 200 nanometres in diameter. Writing for BBC News, David Shukman draws a comparison with a human hair, which is at least 50,000 nanometres thick. As the size of the particles decreases, the number of pathways increases, together with the potential to do harm. “While large particles of pollution such as soot can be trapped inside the nose,” he says, “smaller types can enter the lungs and even smaller ones can cross into the bloodstream. But nanoscale particles of magnetite are believed to be small enough to pass from the nose into the olfactory bulb and then via the nervous system into the frontal cortex of the brain.”  Airborne particles of a smaller size, such as the ultra-fine particles of carbon emitted by diesel vehicles, would find it just as easy to follow this pathway to the brain. In the search for links between air pollution and neurodegenerative disease, it may be the case therefore, as Professor David Newby suggested above, that researchers have been focusing on the wrong particles.
PM particles classified as carcinogenic by the World Health Organization
The Department for the Environment, Food and Rural Affairs (Defra) says: “Generally, if you are young and in a good state of health, moderate air pollution levels are unlikely to have any serious short-term effects.” However, it continues, elevated levels or long-term exposure to air pollution can affect the respiratory system and “can also lead to more serious conditions such as heart disease and cancer.”  The link with cancer was given an authoritative status in October 2013 when the International Agency for Research on Cancer (IARC), an agency of the World Health Organization, issued a press release in which it announced that it had classified outdoor air pollution as carcinogenic to humans (Group 1).  This followed a press release issued in June 2012, in which IARC declared diesel engine exhaust to be carcinogenic to humans (Group 1), “based on sufficient evidence that exposure is associated with an increased risk for lung cancer.”  The press release on outdoor air pollution, issued in 2013, said:
“After thoroughly reviewing the latest available scientific literature, the world’s leading experts convened by the IARC Monographs Programme concluded that there is sufficient evidence that exposure to outdoor air pollution causes lung cancer (Group 1). They also noted a positive association with an increased risk of bladder cancer. Particulate matter, a major component of outdoor air pollution, was evaluated separately and was also classified as carcinogenic to humans (Group 1). The IARC evaluation showed an increasing risk of lung cancer with increasing levels of exposure to particulate matter and air pollution. Although the composition of air pollution and levels of exposure can vary dramatically between locations, the conclusions of the Working Group apply to all regions of the world.” 
What do we know?
The World Health Organization estimated in 2014 that, globally, around 7m premature deaths a year can be attributed to air pollution, while an assessment published in the journal Nature in September 2015 estimates that air pollution contributes to more than 3m premature deaths a year worldwide, “predominantly in Asia.”  As regards the UK, a report published in 2016 by the Royal College of Physicians says that each year in the UK, “around 40,000 deaths are attributable to exposure to outdoor air pollution.”  And as regards specific outcomes, the World Health Organization has said that evidence published in 2013 “strengthened the causal link between fine particles (PM2.5) and cardiovascular and respiratory ill health. It also showed that long-term exposure to PM2.5 can trigger a range of problems, such as atherosclerosis, adverse birth outcomes and childhood respiratory diseases, and suggested possible links with neurological development, cognitive function and diabetes.” 
However, evidence of an association between two phenomena does not mean that one is a cause of the other. Research has shown that traffic-related air pollution can trigger asthma attacks in those suffering from severe forms of asthma, but there is no definitive proof that air pollution is one of the causes of asthma. In the case of diabetes, there is evidence that air pollution increases the risk of contracting the disease in certain individuals, but again there is no scientific evidence of causation. In the case of cardiovascular problems and heart disease, research has shown that air pollution can trigger a stroke and is a significant contributory factor in the development of heart disease, with a growing body of evidence that acute exposure to diesel exhaust does indeed cause a number of cardiovascular problems (see the research at the BHF Centre for Cardiovascular Science, above). But in the case of dementia and other neurological illnesses, the evidence for an association with air pollution is contradictory. What we do know however is that PM particles of different sizes can enter the lungs, the bloodstream and the brain, and have a significant impact on young adults; we don’t know whether this increases the risk of contracting a neurodegenerative disease in later life. The links with respiratory illnesses, lung cancer and cardiovascular disease are more certain. And research has shown that air pollution has a significant impact on children, with consequences for their mental capacity, their physical and cognitive development, and their physical health.
The Call for Action
Four years ago, following the announcement that IARC had classified outdoor air pollution and PM particles as carcinogenic to humans, the World Health Organization said the evidence “reveals the urgent need to take action at the local, regional and global levels to reduce the health threat posed by outdoor air pollution.”  It repeated an earlier call to all countries “to develop policies and implement measures to improve air quality to meet WHO guidelines” and “to implement the European Union (EU) legislation on air quality in full, with stricter values for air pollution limits.” The UK Government’s response, as discussed in last month’s article, has been inadequate to say the least, and its actions have been motivated less by the need to take urgent action to reduce a health threat and more by economic concerns, in particular by the need to avoid fines from the EU. Whilst the UK Government’s actions have been ineffective, the World Health Organization said in 2016 that there were signs of hope. The good news was that “awareness is rising and more cities are monitoring their air quality,” according to the WHO’s Director of Public Health, Dr Maria Neira.  The research discussed in this article suggests that more needs to be done as regard monitoring, particularly with the methods and the technology used to measure ultra-fine particles, now viewed as the most dangerous for human health. More investment in the research and technology in this area would obviously help. That, together with rectifying the lack of regulation in this area, and resolving the disparity between EU legal limits and WHO safety limits, might create some extra signs of hope.
 The UK Government’s Department for the Environment, Food and Rural Affairs says nitrogen dioxide (NO2) irritates the airways of the lungs, increasing the symptoms of those suffering from lung diseases, while fine particles (PM) can be carried deep into the lungs where they can cause inflammation and a worsening of heart and lung diseases. “People with lung or heart conditions may be more susceptible to the effects of air pollution,” it says. See ‘Effects of air pollution’ at https://uk-air.defra.gov.uk/air-pollution/effects. As well as causing breathing difficulties, high levels of NO2 can trigger asthma attacks for those who suffer from a severe form of the condition. See the Asthma UK website at https://www.asthma.org.uk/advice/triggers/pollution/.
 Wood, H., et al. (2015) Effects of Air Pollution and the Introduction of the London Low Emission Zone on the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East London: A Sequential Cross-Sectional Study. PLoS ONE 10(8): e0109121. https://doi.org/10.1371/journal.pone.0109121. Retrieved from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109121.
 Quoted by Laura Donnelly in ‘Air pollution stunting children’s lungs, study finds’, The Telegraph, 25/10/2015. Retrieved from: http://www.telegraph.co.uk/journalists/laura-donnelly/11953613/Air-pollution-stunting-childrens-lungs-study-finds.html.
 Ibid: see .
 Ibid: see .
 Adam Vaughan and Esther Addley, ‘Boris Johnson “held back” negative findings of air pollution report’, The Guardian, 17/05/2016. Retrieved from: https://www.theguardian.com/environment/2016/may/17/boris-johnson-held-back-negative-findings-of-air-pollution-report. The report’s author Katie King is Director of the environmental consultancy Aether, based in Oxford.
 See the BREATHE Project website at http://www.creal.cat/projectebreathe/.
 Dadvand, P., et al. (2017) Traffic-related air pollution and spectacles use in schoolchildren. PLoS ONE 12(4): e0167046. https://doi.org/10.1371 /journal.pone.0167046. Retrieved from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167046.
 Ibid: see .
 Sunyer, J., et al. (2015) Association between Traffic-Related Air Pollution in Schools and Cognitive Development in Primary School Children: A Prospective Cohort Study. PLoS Med 12(3): e1001792. https://doi.org/10.1371/journal.pmed.1001792. Retrieved from: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001792.
 Anthony King, ‘Traffic pollution prevents children’s brains from reaching their full potential’, Horizon, 17/07/2017. Retrieved from: https://phys.org/news/2017-07-traffic-pollution-children-brains-full.html.
 Wolf, K., et al. (2016) Association Between Long-Term Exposure to Air Pollution and Biomarkers Related to Insulin Resistance, Subclinical Inflammation and Adipokines. Diabetes, 65(8): db151567. https://doi.org/10.2337/db15-1567. Retrieved from: http://diabetes.diabetesjournals.org/content/early/2016/08/16/db15-1567.
 Alderete, T., et al. (2017). Longitudinal Associations Between Ambient Air Pollution with Insulin Sensitivity, β-Cell Function, and Adiposity in Los Angeles Latino Children. Diabetes, 66(1): db161416. https://doi.org/10.2337/db16-1416. Retrieved from: http://diabetes.diabetesjournals.org/content/early/2017/01/27/db16-1416.long.
 Peterson, B., et al. (2015). Effects of Prenatal Exposure to Air Pollutants (Polycyclic Aromatic Hydrocarbons) on the Development of Brain White Matter, Cognition, and Behavior in Later Childhood. JAMA Psychiatry, 72(6), 531−540. https://doi.org/10.1001/jamapsychiatry.2015.57. Retrieved from: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2205842.
 Brook, R., et al. (2010). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation, 121, 2331−2378. https://doi.org/10.1161/CIR.0b013e3181dbece1. Retrieved from: http://circ.ahajournals.org/content/121/21/2331.
 Shah, A., et al. (2015). Short term exposure to air pollution and stroke: systematic review and metaanalysis. British Medical Journal, 350: h1295. Retrieved from: http://www.bmj.com/content/350/bmj.h1295.
 Peters, A., et al. (2001). Increased particulate air pollution and the triggering of myocardial infarction. Circulation, 103, 2810−2815. https://doi.org/10.1161/01.CIR.103.23.2810. Retrieved from: http://circ.ahajournals.org/content/103/23/2810.
 ‘Research that shows how air pollution can affect our hearts’, British Heart Foundation. Retrieved from the BHF website at:
 Miller, M. et al. (2017). Inhaled Nanoparticles Accumulate at Sites of Vascular Disease. ACS Nano, 11(5), 4542–4552. https://doi.org/10.1021/acsnano.6b08551. Retrieved from: http://pubs.acs.org/doi/abs/10.1021/acsnano.6b08551.
 Ibid: see . The relevant research was published in the European Heart Journal and Circulation as follows:
(a) Lucking, A., et al. (2008). Diesel exhaust inhalation increases thrombus formation in man. European Heart Journal, 29, 3043−3051.
(b) Mills, N., et al. (2005). Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation, 112, 3930−3936.
 Michael Le Page, ‘Pollution nanoparticles may enter your blood and cause disease’, New Scientist, 26/04/2017. Retrieved from: https://www.newscientist.com/article/2128923-pollution-nanoparticles-may-enter-your-blood-and-cause-disease/.
 Ibid: see .
 Implementation of the Air Quality Directive. A study for the European Parliament’s Committee on Environment, Public Health and Food Safety. Nagl, C., Schneider, J., and Thielen, P. April 2016. Retrieved from: http://www.europarl.europa.eu/RegData/etudes/STUD/2016/578986/IPOL_STU(2016)578986_EN.pdf.
 In stark contrast to the EU’s assessment, the authors of the study on London’s Low Emission Zone, published in 2015, state: “Levels of traffic-related air pollution in London are among the worst in Europe, with European Union (EU) limit values for particulate matter with an aerodynamic diameter of < 10μm (PM10) and nitrogen dioxide (NO2) regularly exceeded in many areas of the city" (ibid: see ). The Environmental Research Group at King's College London provides real-time data on London's air pollution levels via the London Air Quality Network. The network consist of a number of monitoring stations spanning London and the South-East, funded by local authorities and other bodies, and complemented by modelling techniques that can 'fill in the gaps' to provide the missing data between the stations. For further info, see http://www.londonair.org.uk/LondonAir/General/about.aspx.
 The World Health Organization database, including notes on measurements and safety limits, is available as a spreadsheet from the WHO website at: http://www.who.int/phe/health_topics/outdoorair/databases/cities/en/. The full list of the 39 towns and cities in breach of the WHO’s safety limits for PM2.5 in 2016 is: Armagh, Belfast, Londonderry, Prestonpans, Middlesbrough, Carlisle, York, Hull, Manchester, Salford, Warrington, Wigan, Liverpool, Birkenhead, Stoke-on-Trent, Birmingham, Leamington Spa, Bristol, Chepstow, Newport, Cardiff, Swansea, Plymouth, Saltash, Portsmouth, Brighton, Southend, Thurrock, and Norwich. For a summary of the WHO’s findings and reactions to the figures, see: Ian Johnston, ‘Air pollution in UK “wreaking havoc on human health,” WHO warns’, The Independent, 12/05/2016. Retrieved from: http://www.independent.co.uk/environment/dozens-of-british-cities-are-breaching-air-pollution-limits-in-public-health-crisis-a7025401.html. The WHO database was updated in April 2017, with more towns and cities added to the list. For the EU legal limits, see: ‘Air Quality Standards’, European Commission, last updated 22/09/2017. Accessed from: http://ec.europa.eu/environment/air/quality/standards.htm.
 Ibid; see .
 Maher, B., et al. (2016). Magnetite pollution nanoparticles in the human brain. PNAS: Proceedings of the National Academy of Sciences of the USA, 113(39), 10797−10801, 27/09/2016. https://doi.org/10.1073/pnas.1605941113. Retrieved from: http://www.pnas.org/content/113/39/10797.
 David Shukman, ‘Pollution particles “get into brain”‘, BBC News, 05/09/2016. Retrieved from: http://www.bbc.co.uk/news/science-environment-37276219.
 Ibid: see .
 Ibid: see .
 Palacios, N., et al. (2017). Air Pollution and Risk of Parkinson’s Disease in a Large Prospective Study of Men. Environmental Health Perspectives, 125(8): 087011, 18/08/2017. https://doi.org/10.1289/EHP259. Retrieved from: https://ehp.niehs.nih.gov/ehp259/.
 Palacios, N. (2017). Air pollution and Parkinson’s disease – evidence and future directions. Reviews on Environmental Health, 21/07/2017. https://doi.org/10.1515/reveh-2017-0009. Retrieved from: https://www.degruyter.com/view/j/reveh.ahead-of-print/reveh-2017-0009/reveh-2017-0009.xml.
 Ibid: see . In June this year, the journal Current Environmental Health Reports published a review of the literature on the ways in which air pollutants can find a pathway to the brain. The authors state: “Accumulating research indicates that ambient outdoor air pollution impacts the brain and may affect neurodegenerative diseases, yet the potential underlying mechanisms are poorly understood.” They conclude that, to exert effects on the central nervous system, “multiple direct and indirect pathways in response to air pollution exposure likely interact in concert.” See: Jayaraj, R., et al. (2017). Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the Neuroinflammation Hypothesis, Current Environmental Health Reports, 4(2), 166−179. https://doi.org/10.1007/s40572-017-0142-3. Retrieved from: https://link.springer.com/article/10.1007%2Fs40572-017-0142-3.
 Ibid: see .
 ‘Outdoor air pollution a leading environmental cause of cancer deaths’, IARC Press Release No. 221, 17/10/2013. Retrieved from: http://www.iarc.fr/en/media-centre/iarcnews/pdf/pr221_E.pdf. IARC categories (1, 2a, 2b and 3) are based on an evaluation of the evidence, Group 1 indicating “there is sufficient evidence of carcinogenicity in humans”.
’DIESEL ENGINE EXHAUST CARCINOGENIC’, IARC Press Release No. 213, 12/06/2012. Retrieved from: http://www.iarc.fr/en/media-centre/pr/2012/pdfs/pr213_E.pdf.
 Ibid: see .
 Lelieveld, J., et al. (2015). The contribution of outdoor air pollution sources to premature mortality on a global scale. Nature, 525, 367−371. https://doi.org/10.1038/nature15371. Retrieved from: https://www.nature.com/nature/journal/v525/n7569/full/nature15371.html. For the World Health Organization estimate, see: ‘7 million premature deaths annually linked to air pollution’, WHO News Release, 25/03/2014. Retrieved from: http://www.who.int/mediacentre/news/releases/2014/air-pollution/en/.
 Every breath we take: the lifelong impact of air pollution, Royal College of Physicians, February 2016. Available as a PDF from: https://www.rcplondon.ac.uk/projects/outputs/every-breath-we-take-lifelong-impact-air-pollution.
 ‘Outdoor air pollution a leading environmental cause of cancer deaths’, World Health Organization News, 17/10/2013. Retrieved from: http://www.euro.who.int/en/health-topics/environment-and-health/air-quality/news/news/2013/10/outdoor-air-pollution-a-leading-environmental-cause-of-cancer-deaths.
 Ibid: see .
 Quoted by Ian Johnston in ‘Air pollution in UK “wreaking havoc on human health,” WHO warns’, The Independent, 12/05/2016. Retrieved from: http://www.independent.co.uk/environment/dozens-of-british-cities-are-breaching-air-pollution-limits-in-public-health-crisis-a7025401.html.