Killer air

The link between air pollution and mortality has been known for some time. But in 2020, a London coroner made headlines with a ruling that air pollution was a causal factor in the death of a nine-year-old girl. Maria Burke reports

Philip Barlow, the inner south London coroner, said Ella Kissi-Debrah’s death in February 2013 was caused by acute respiratory failure, severe asthma and exposure to nitrogen dioxide and particulate matter (PM) pollution in excess of World Health Organization (WHO) guidelines. Failure to reduce pollution levels to legal limits possibly contributed to Ella’s death, the coroner is reported as saying, as did the failure to provide her mother with information about the potential for air pollution – mainly from traffic emissions – to exacerbate asthma.

On the plus side, outdoor air quality in most high-income countries has improved significantly since the 1980s. Some air pollutants, such as SO₂ from coal and lead from petrol, have fallen dramatically. However, the latest UK government statistics in February 2023 show others have risen.[1]

The good news is that the UK has met domestic and international emission reduction commitments for SO₂ and NO_x thanks to declining coal use for energy generation and tighter fuel emissions standards; and for emissions of non-methane volatile organic compounds (NMVOCs) following stricter limits on industrial production of coatings. However, the bad news is that estimated emissions of particulate matter (PM_2.5 and PM₁₀) rose from 2020 to 2021 – probably due to the popularity of wood-burning stoves. Emissions from domestic combustion of wood increased by 124% between 2011 and 2021 and accounted for 21% of primary emissions of PM_2.5 and 12% of PM₁₀ in 2021.

When the UK Chief Medical Officer Chris Whitty chose to focus his 2022 Annual Report on air pollution[2], it was widely welcomed by health professionals. Recommendations included getting more electric vehicles on the roads, developing ways to reduce air pollution from non-exhaust sources such as tyres, more local urban planning and modifying farming practices, such as applying slurry directly to soil, to reduce ammonia pollution. Whitty also stressed that tackling indoor air pollution should be a priority now that people spend around 80% of their time indoors.

Mental health

Alongside physical health and premature deaths, meanwhile, there is growing evidence of concerns about the effects of air pollution on mental health. In 2022, the UK Committee on the Medical Effects of Air Pollution (COMEAP), reviewed nearly 70 epidemiological studies looking at possible links between air pollution and a decline in mental ability and dementia in older people.[3] It also considered studies investigating how air pollution might affect the brain. In its report, COMEAP concluded that it’s likely that air pollution does contribute to these effects, probably by interacting with the body’s circulation. It is known that air pollutants, particularly small particles, can affect the heart and blood vessels, including to the brain.

In February 2023, another study confirmed associations between air pollution and anxiety and depression in the UK.[4] It followed 389,000 individuals over 10 years, taking account of factors such as deprivation and employment status. The team, from the universities of Peking and Oxford and Imperial College London, found that air pollution concentrations where individuals lived when recruited into the study were associated with small increases in risk of subsequently developing clinical depression or anxiety. This was seen with combinations of air pollutants, as well as with specific components such as fine particulates and NO₂, where fossil fuel combustion – road transport – forms a major source.

‘This epidemiological study provides further evidence on potential impacts of air pollution on the brain,’ says Anna Hansell, Director of the Centre for Environmental Health and Sustainability at the University of Leicester, UK. ‘[Its] particular strength is that it followed up individuals over a long period of time. The findings suggest that reducing air pollution levels, even when low, potentially benefits mental health. It provides further evidence in support of reducing current UK air pollution levels.’

In another study also published in February 2023, a team from the Harvard T.H. Chan School of Public Health looked at long-term (11 years) exposure to air pollution and late-life depression in almost 9m adults older than 64 in the US.[5] It considered three pollutants – PM_2.5, NO₂ and O₃ – and found that exposure to all three is linked to statistically significant increases in the incidence of late-life depression. Long-term exposure to increased levels of O₃ was associated with the highest risk increase.

‘The patterns are similar across all three pollutants, which provides increased confidence in the findings,’ says Oliver Robinson, Professor of neuroscience and mental health at University College London, UK. ‘The authors adjust for many relevant confounders [such as socioeconomic status, poverty and psychosocial stress] and also show that the effects are greater in those who are more vulnerable due to being older, having other comorbid illnesses, or being socioeconomically disadvantaged.’

Significantly, Robinson points out that average levels of pollution in the US study may be much lower than in the UK. Areas like Tower Hamlets in London, for example, have more than double the median NO₂ exposure in the study. This would mean there is ‘a substantially greater exposure and risk’ in London. However, he adds: ‘There is a complex relationship between individual vulnerability and resilience, and environmental exposure, so it is not that everyone who is exposed to these pollutants will go on to develop depression.’

Potential pathways

The Harvard researchers discuss the various mechanisms by which air pollutants impact mental health. Previous animal studies, for example, have shown that air pollutants may pass to the central nervous system through nasal linings and capillaries in the lungs, causing inflammation in nerve cells and autoimmune responses. They note there are various potential pathways including raised levels of oxidative stress in the brain and increased release of stress hormones, which are linked to several cognitive and mental outcomes. What’s more, older adults are at higher risk of depression related to hazardous environmental pollutants exposure because their lungs and nerve cells are more vulnerable to inflammatory triggers.[6]

Inflammation has been shown to play a role in various psychiatric disorders. A 2009 study, for example, found that patients with major depression had increased blood inflammatory biomarkers, including inflammatory cytokines – proteins that act as chemical messengers for the immune system.[7] These have been shown to access the brain and interact with virtually every function known to be involved in depression, including neurotransmitter metabolism, neuroendocrine function, and neural plasticity. Researchers think that when inflammatory pathways are activated in the brain, support for neurons by proteins called neurotrophic factors is reduced and release of the neurotransmitter glutamate is affected.

Other clinical studies have suggested that long-term exposure to increased levels of atmospheric particles is linked with altered brain structure, smaller total cerebral brain volume, reduced white matter, as well as leaky capillaries, all of which may trigger psychiatric illness.[8]

Foetal development

If air pollutants can alter brain structure, then a big concern is whether particulates like PM_2.5 are damaging the brains of babies as they develop in the womb. A group from Taiwan studied almost 18,000 Taiwanese children, along with data from 71 air pollution monitoring stations across the country.[9] They adjusted for factors such as maternal education, smoking, age and household income. All the monitoring was outdoors where construction, industry vehicles and road traffic are the main sources of particles.

The team found that exposure to higher levels of PM_2.5 during the second trimester of pregnancy was associated with babies taking longer to reach both fine motor neurodevelopmental milestones, such as grasping objects and following objects with their eyes and head, and gross motor milestones, such as head raising, crawling and walking. Personal and social skills were also more likely to be delayed if they had been exposed to higher levels of PM_2.5 during pregnancy. All three observations were unrelated to postnatal PM_2.5 exposure.

‘PM_2.5 can cross the placenta and have been shown to adversely affect developing brain cells,’ says Andrew Whitelaw, Emeritus Professor of neonatal medicine, University of Bristol, UK. ‘It is alarming that the average level of particle air pollution in Taiwan was … more than three times the safe limit of 10μg/m₃ defined by the WHO. This level of particle air pollution would be possible but unusual in the UK. [However] it underlines the importance of public awareness of the many serious effects of air pollution on health and the importance of widespread monitoring so that efforts will be made to reduce air pollution inside and outside the home.’

PM_2.5 can cross the placenta and have been shown to adversely affect developing brain cells. It is alarming that the average level of particle air pollution in Taiwan was … more than three times the safe limit of 10μg/m3 defined by the WHO.
Andrew Whitelaw Emeritus Professor of neonatal medicine, University of Bristol, UK

Cardiology

Increasingly, research is focusing on the risk of fine particulates. A US team recently reported a retrospective study of 3.7m adults in California followed for up to 10 years.[10] They found that long-term PM_2.5 exposure was associated with an increased risk of heart attack, as well as deaths from cardiovascular disease (CVD) and ischemic heart disease (IHD), and these associations were more pronounced in low socioeconomic status communities. Moderate concentrations of PM_2.5 below the current US regulatory standard of 12μg/m₃ were also found to have associations. The study is one of the biggest to include information on participants’ addresses, allowing the researchers to construct individual one-year mean PM_2.5 exposures.

‘This study has significant improvements over the previous ones on ambient PM_2.5 and CVD risk, as it utilised individual-level data instead of ecological data used in previous studies,’ says Peter Ka Hung Chan, an epidemiologist from the University of Oxford, UK. ‘What the authors have done is a state-of-the-art approach, and we should take actual personal exposure into account in future studies.’ However, he cautions that this one study alone does not provide enough evidence to ‘quantitatively judge’ how much harm PM_2.5 is causing at a low level or whether the regulatory standard is sufficient. ‘This is not to say PM_2.5 at low levels is not harmful,’ he adds.

Meanwhile, several epidemiological studies have reported increased blood pressure and more hospital visits due to high blood pressure (hypertension) following short-term exposures to several air pollutants including PM_2.5 as well as PM₁₀, SO₂, O₃ and NO₂. They also observed significant high blood pressure risks for long-term exposures to PM_2.5, PM₁₀, NO₂, and SO₂. However, little is known about the effects on adolescents. This is important because raised blood pressure in adolescence is associated with hypertension and poor cardiovascular health in adulthood. Also, this age group is more vulnerable to air pollution as they spend more time outdoors. A team from the UK and Brazil analysed previous studies including 15,000 adolescents from China, Europe and the US.[11] They concluded that ambient air pollution was linked to higher adolescent blood pressure. The team observed significantly raised systolic and diastolic blood pressure (SBP and DBP) following long-term exposure to higher PM_2.5 concentrations and raised DBP with long-term exposure to NO₂. However, they did note limitations in some of the studies reviewed and called for more and better research. 

‘Some of the limitations stem from the fact that all the studies that were reviewed were observational,’ says Kevin McConway, a statistician at The Open University, UK. ‘Despite the uncertainties, I’d be very surprised if it turned out that there was no involvement at all of air pollution in adolescents’ blood pressure levels.’

Most studies of associations between air pollution and different aspects of health are observational, so each one on its own has some difficulty in establishing cause and effect, McConway notes. But he concludes that ‘associations have been found, generally in a consistent way, with many different aspects of health’.

References
1 Emissions of air pollutants in the UK – Summary, DEFRA, gov.uk/government/statistics/emissions-of-air-pollutants/emissions-of-air-pollutants-in-the-uk-summary.
2 Chief Medical Officer’s annual report 2022: air pollution, DHSC, gov.uk/government/publications/chief-medical-officers-annual-report-2022-air-pollution.
3 Air pollution: cognitive decline and dementia, UK Health Security Agency, gov.uk/government/publications/air-pollution-cognitive-decline-and-dementia.
4 T. Yang et al, JAMA Psychiatry, doi: 10.1001/jamapsychiatry.2022.4812.
5 X. Qiu et al, JAMA Netw Open., doi: 10.1001/jamanetworkopen. 2022.53668.
6 Q. Liu et al, Environ. Sci. Pollut. Res. Int., doi: 10.1007/s11356-021-12357-3 https://www.ncbi.nlm.nih.gov/pubmed/33481201.
7 A.H. Miller et al, Biol. Psychiatry, doi:10.1016/j.biopsych.2008.11.029.
8 D. Cserbik et al, Environ. Int., doi: 10.1016/j.envint.2020.105933.
9 P. Shih et al, Dev. Med. & Child Neurology, doi: 10.1111/dmcn.15430.
10 S.E. Alexeeff et al, JAMA Network Open, doi: 10.1001/jamanetworkopen.2023.0561.
11 S. Tandon et al, doi: 10.1016/j.cpcardiol.2022.101460.