Discussion

CHAPTER SIX

Struggling to Breathe

‘Every parent who comes to me now is talking about [air pollution]’, Dr Ankit Parakh tells me in his consulting room. A pulmonologist in paediatric medicine at BLK Super Speciality Hospital, he is on the front line of Delhi’s smog epidemic. The BLK is one of several huge, privately owned hospitals that sprang up since the Indian economy liberalised in 1991 and, like so much in Delhi, the divide between the haves and the have-nots is stark. Beggars, traders and rickshaws crowd around the hospital entrance and spill out into the road. Inside, the paediatric wing is full of kids with shiny Nike trainers and concerned parents tapping impatiently on smartphones. Framed photos of happy (and exclusively white) child models adorn the walls. Most patients are here for breathing and respiratory disorders. Approximately one in three adults in Delhi, and two in three children, have respiratory symptoms due to poor air quality.

‘In India the main problem starts around September, October – it peaks in November, then there is a down phase from December to February, and again peaks around March, April and May,’ says Dr Parakh. As we speak it is currently the November peak. ‘Anywhere in these seasons sees a surge of asthma and wheezing patients.’ Wheezing is a technical term. Asthma tends not to be diagnosed until around the age of five, because the symptoms in young children can resemble a wide range of other respiratory problems. Asthma-like symptoms therefore tend to be called ‘pre-school wheeze’, which sometimes develops into asthma, sometimes not. ‘Children who are exposed to air pollution, even pregnant mothers … the risk of these children actually having wheezing or asthma is definitely there,’ says Dr Parakh. ‘It is also related to the birth weight of the child … underweight children will have more wheezing episodes, the episodes are more severe, they are more difficult to control. And now it has been shown [air pollution] is not just a trigger that increases an underlying asthma, it is also an inducer which actually can generate an asthma … And it is not just about respiratory issues, people have shown hypertension.’ He pauses, and says again, eyeing the queue waiting outside, ‘There is a lot of concern amongst parents.’

I don’t keep Dr Parakh long, aware that his consulting hours are short. When I leave, however, he insists on showing me the way to the Metro station. I expect him to point out the direction as we reach the main BLK entrance, but in fact he walks me out and onto the road, into the throng of people and traffic that seemed so distant in the sterility of his consulting room. Crossing the road, his stethoscope and brilliant white coat wrap around him like a protective layer. No one dares bother him. A girl of maybe eight or nine is begging nearby. She is covered in dust, her hair matted to the thickness of a door mat. Every minute of her work and life takes place on Delhi’s roads, breathing in some of the very worst air in the world. Dr Parakh shakes my hand and ushers me protectively towards the station’s barriers, and I soon step into the clean carriages of a Metro train.

It’s easy to take everything Dr Parakh said as a given, but the definitive link between modern air pollution and health has only been made relatively recently. It had long been suspected. In the 1950s epidemiologists in California such as John Goldsmith made the link between air pollution and heart attacks, but the causal link was elusive and other factors such as high smoking rates were hard to separate. The International Agency for Research on Cancer suspected that PM2.5 was carcinogenic to humans in 1988, but only definitively said so as recently as 2013. Professor Bert Brunekreef, chair of the European Respiratory Society Task Force on Air Pollution, admitted in 2016 that ‘when I started my career in environmental health some 35 years ago, air pollution in western Europe was not seen as much of a public health problem.’

By the 2000s and 2010s, however, studies began coming thick and fast, showing that common pollutants in the air affect our health at every stage of life, in the womb, continuing through childhood, adolescence and adulthood into old age. Professor Brunekreef describes this as the ‘life course’ of air pollution on human health. And it is this ‘life course’ that I’m going to take you through in this chapter, from conception through to your likely premature death. Sorry, this might not be the cheeriest chapter to read. But boy, is it full of counter-arguments to the statement that ‘air pollution never did me any harm’.

In fact, it affects us before we are even conceived. The incidence of infertility has been creeping up in industrial countries from 7–8 per cent in 1960 to 20–35 per cent by the mid-2010s. During those 50 years, sperm concentration (the amount of sperm per millilitre of semen) almost halved. The sperm count in American males is decreasing by 1.5 per cent each year, and you don’t need to be a mathematician to work out that is unsustainable. Recent studies have started to suggest a strong link between ambient air pollution and this decline in fertility. Compounds of lead, cadmium, and mercury have long been known to damage the male reproductive system. Now smoke-derived PM2.5 and polycyclic aromatic hydrocarbons (PAHs) have been found to impair or disrupt sperm production too, even leading to DNA fragmentation in sperm. A long-term study in Taiwan of thousands of young adult males between 2001 and 2014, found that for every increment of 5mg/m3 of PM2.5 levels there was a decrease of 1.29 per cent in normal sperm morphology (the size and shape of sperm in a sample). An Italian study in 2003 found that tollgate workers – a cadre of society unusually exposed to traffic pollution – had significantly poorer sperm quality that other men from the same region.

If we do manage to conceive, then air pollution can damage the health of the foetus and lead to birth abnormalities. A study by Queen Mary University, London, in 2018, found that inhaled black carbon particles passed from pregnant women’s lungs to eventually cause small black spots in the placenta. A study in Ohio in 2017 of women living with high PM2.5 levels in the month prior to conception showed they had a higher chance of having a baby with birth defects – the most common being cleft lip/palate or abdominal wall defects –

compared to those that did not. In Wuhan, one of the most polluted cities in China, researchers also looked at all 105,988 births delivered in that city between 2011 and 2013. When these births were overlaid with the carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) readings, the risk of babies being born with congenital heart defects was higher among women with greater exposures. Previous studies in California and Australia also found a higher risk of artery and heart valve defects from increasing O3 exposure during the second month of pregnancy.

High air pollution exposure also increases the likelihood of having a premature birth. A team of researchers from Stockholm, London and Colorado concluded in 2017 that as many as 3.4 million premature births across 183 countries could be associated with PM2.5, with sub-Saharan Africa, North Africa and South and East Asia most affected. India alone accounted for about one million avoidable premature births. A US study in 2015 found that just over 3 per cent (or 15,808) of pre-term births nationally per year could be attributed to PM2.5.

Smoking has long been known to produce underweight babies, so it’s no big surprise that traffic smoke does much the same. A London study in 2017 found that among half a million newborns, high PM2.5 levels were associated with a 2–6 per cent increased risk of low birth weight.*

Even in Sweden, with its comparatively clean Arctic air, newborns with relatively high exposure to traffic-derived NOx were consistently found to have smaller foetal growth in late pregnancy: for every 10mg/m3 increment of NOx, birth weight reduced by 9 grams. Most worryingly, a 2017 US study using six years’ worth of data covering nearly a quarter of a million deliveries found ozone was associated with a significantly increased risk of stillbirth. Both long-term low-level and short-term high-level O3 exposure consistently increased the stillbirth risk, leading the researchers to estimate that approximately 8,000 stillbirths per year in the US could be the result of O3 exposure.

For those who have a successful birth, air pollution raises the risk of pneumonia among under-fives and lifelong lung conditions such as asthma. According to the WHO, 570,000 children under five die each year across the world from respiratory infections such as pneumonia, while up to 14 per cent of children aged over five currently report asthma symptoms, almost half of them related to air pollution.†

The Columbia Center for Children’s Environmental Health goes so far as to say that air pollution is the root cause of much of the ill health in childhood today. Young children breathe in more air than adults relative to body weight, meaning they are disproportionately affected by air pollutants compared to adults. Babies under the age of one tend to breathe 600 litres per kilo of body weight, per day. By the age of four, as we grow, it reduces to 450 litres; by age 12, it’s 300 litres; and by the age of 24 it plateaus at 200 litres per kilo per day and stays there for the rest of adulthood. When exposed to a polluted environment, children therefore suffer the ill effects three times more acutely than adults. Babies’ immune systems are also not fully developed and are more vulnerable to infections and almost defenceless against toxic exposure. Children are the first and worst victims of lead pollution too, because their body’s immaturity makes them most susceptible to neurological injury, leading to lowered IQs, reading and learning disabilities, impaired hearing and behavioural problems including ADHD.

There remains, however, a question of causality around much health evidence regarding air pollution. By their very nature the studies are based on the epidemiology – i.e. health trends across a population. You can’t put 100 kids in a lab, expose them to pollutants, then cut them open to see what happened. So epidemiological evidence will always suffer from the kind of argument that goes, ‘just because 30 per cent of the population gets cancer and 30 per cent of the population eats cornflakes for breakfast, does not mean that cornflakes cause cancer’. When an epidemiology study is repeated in different places, and consistently comes up with the same results, however, it becomes very hard to ignore. And the epide­miological evidence for air pollution reducing the size of children’s lungs is, I would argue, the most compelling example.

The Californian Children’s Health Study is one of the most comprehensive investigations of the long-term consequences of air pollution that we have. Starting in 1993, more than 11,000 schoolchildren were selected from 16 communities, and their lung function measured annually while air pollution levels were measured continuously. The performance of the kids in forced expiratory volume or FEV tests (how much air a person can force out in one second) declined according to exposure to NO2 and PM2.5. The proportion of 18-year-olds with a low FEV was four times higher in the communities with the highest PM2.5 levels compared to the lowest. Their lung growth had actually been stunted. Living within half a kilometre of a freeway was associated with a 2 per cent deficit in forced vital capacity (the total amount of air in the lungs). International study after international study has since found the same, including in Mexico, Austria, Norway, Sweden, the UK, and the European Study Cohorts for Air Pollution Effects. A three-year study in China found that an increase of 10mg/m3 of PM2.5 was associated with a loss of 3.5ml in FEV capacity. In Delhi in 2012, one in three children in the city were found to have reduced lung function.

Professor Chris Griffiths, from the Centre for Primary Care and Public Health at St Barts Hospital and a working GP, was involved in a six-year children’s lung capacity study in London which concluded in the 2010s. The children living in areas with high levels of particulates and nitrogen dioxide had their lung capacity reduced by up to 10 per cent. I asked him if there remained a ‘causality problem’: ‘You’re not going to get a randomised clinical trial of air quality interventions, it doesn’t work like that,’ he argues. ‘You’ve got to reach a point where you say “Well how strong is the evidence? What’s the quality? What’s the causal inference?”’ Regarding his own lung study, he says ‘the mechanisms that underlie these observations are not clear, but that doesn’t mean that those associations aren’t there or aren’t important, just because we don’t quite know how air quality mechanistically reduces lung growth. But because the data is quite consistent wherever these studies have been done, Europe, Scandinavia, Boston, California and then most recently London, studies in different settings with different pollutants, yet they appear to be saying similar things about lung growth.’ The conclusion drawn by many, including the UK’s Royal College of Physicians, is that there is little reason to ‘doubt that air pollution adversely affects the normal growth of lung function during childhood, right up to the late teens’.

The ongoing Californian Children’s Health Study, led by William ‘Jim’ Gauderman, a professor of preventive medicine at Keck School of Medicine USC, also continues to add to the weight of evidence. While in 1993 Los Angeles had some of the worst atmospheric pollution in the world, by the 2010s it was still bad but much improved. His recent papers have been able to flip the arguments against epidemiology on their head. Cornflakes don’t cause cancer. But if you reduce the consumption of cornflakes‡

and the prevalence of cancer drops at precisely the same rate, then perhaps you do have to question what you’re putting in your bowl each morning. Comparing three cohorts of the Californian Children’s Health Study from 1994 to 2010, Gauderman and his team found that the mean four-year growth in FEV (volume of breath in one second) increased by 91ml for every decrease of 14ppb in NO2, and similarly for PM2.5:1 in other words, whenever the nitrogen dioxide and PM2.5 levels went down, the children’s lung function showed a marked improvement.

As our life course of air pollution moves from childhood and into adolescence, low FEV comes with an increased risk of cardiovascular disease – given that you’re missing 20 per cent of your possible lung capacity, you’re less able to exert yourself during exercise. Equally logical is the fact that asthma is both caused by high pollution and irritated by high pollution: ozone, nitrogen dioxide and PM2.5 all cause inflammation of the airways, and airway hyper-sensitivity is the defining characteristic of asthma. The UK Chief Medical Officer’s report suggests a link between diesel particles and the high asthma rate of 1 in 12 adults and 1 in 11 children in the UK. But respiratory conditions are only the most obvious ones affecting young adults. Our brain capacity may also be reduced upon entering adulthood. European studies have associated traffic pollution with lower cognitive development in junior school children followed by sustained attention deficit in adolescents. Studies in Mexico City have also revealed elevated levels of inflammation in the brains of children exposed to high air pollution, resulting in cognitive deficits.

If you grew up in a rural oasis of clean air and avoided all the health problems thus far, then if you move to a city (or your village turns into a city, as several have in Asia in recent decades) at any point in adulthood, plenty of health problems still await. Sticking with the brain for the moment – and let’s face it, brain damage is one of our biggest fears – a Chinese study exposed lab mice to NO2 inhalation and found it caused deterioration of spatial learning and memory. The study authors memorably describe air pollution as ‘a multifaceted toxic chemical mixture capable of assaulting the central nervous system’. Outside of the mice fraternity, numerous epidemiological studies have linked NO2 pollution to an increased human risk of neurological disorders, including reduced cognitive and attention scores. One fascinatingly precise study of white matter loss among elderly women, made using MRI (magnetic resonance imaging) scans, suggested that for every 3mg/m3 increase in PM2.5, white matter loss increased by 1 per cent. Suicidal depression has even been suggested by more than one study to increase one to three days after a peak in PM2.5 and NO2.

For those who trust their gut more than their brain, a team from UCLA found that exposure to air pollution changes the composition of our gut bacteria. This leads to a whole range of health problems, including the circulation and build-up of cholesterol in the bloodstream. Other studies have found an association between air pollution and intestinal disease, appendicitis and even digestive tract cancers. There’s a direct link for the chunkier PM10 here too: while large enough to be ejected from our throat and lungs via mucociliary clearance (our respiratory system’s first line of defence, whereby a layer of fluid and mucus is constantly being propelled upwards for us to spit out), anything on the surface of the PM10 can be dissolved by saliva and find its way down into our gut. Depending on the chemical nasties on the surface of these coarse particles, this can lead to an imbalance in gut bacteria, or cause the chronic inflammation that leads to appendicitis or cancer.

Many airborne pollutants are known carcinogens. Polycyclic aromatic hydrocarbons (PAHs), for example, have toxic effects which can cause cell damage, leading to mutations and tumours. Long-term occupational studies of workers exposed to PAHs have shown an increased risk of skin, lung, bladder and gastrointestinal cancers. The PAH known as benzo[a]pyrene, emitted in high abundance by stubble burning, was named as a human carcinogen as early as the 1980s by both

the International Agency for Research on Cancer (IARC) and the US EPA. Since then the EPA has classified other PAH compounds as carcinogenic, all with confusingly complex names such as benz(a)anthracene, benzo(b)fluoranthene and indeno(1,2,3-cd)pyrene.

In summary, pick any major organ or body part and there will be a disease or defect related to air pollution. How about breast cancer? In Hong Kong, a 10ug/m3 increase annual PM2.5 exposure was found to increase the risk of breast cancer by an astonishing 80 per cent. Did someone say kidneys? Research from St Louis, Missouri, looked at more than eight years of data from nearly 2.5 million military veterans, and found that the veterans’ kidney function worsened over time according to the level of pollution they were exposed to. Higher PM concentrations were associated with an increased risk of end-stage renal disease, after which a person requires kidney dialysis to stay alive.

Air pollution can even change how our DNA behaves. Genes – the segment of DNA that tell the cells of the body what to do, and when – are controlled by a chemical switch known as a methyl group. These methyl groups can, in effect, switch a gene on or off. A 2014 study by the University of British Columbia put 16 volunteers into an enclosed booth for two hours, giving half the participants clean air to breathe while the other half breathed diesel fumes equivalent to a busy highway. The methyl groups changed at about 2,800 different points on the DNA of people who breathed in diesel fumes, affecting about 400 genes. No similar changes were seen among the group breathing clean air. Until that experiment, scientists mostly thought that DNA responded primarily to long-term exposures. A similar Chinese study in 2017 compared traffic police officers to office-based police officers and found that DNA damage was significantly increased among the traffic cops compared to the pen-pushers at City Hall.

But it’s the effect on our cardiovascular system that is most fatal across the adult population. Yes, even more so than cancer or lung disease. Air pollution causes thinning arteries, blood clots, heart attacks and strokes. As fine nanoparticles enter the bloodstream through the walls of the lungs, they cause increased inflammation, resulting in changes in heart rate, heart rhythm and blood pressure. This is not just from chronic, long-term exposure, but also from short-term. In Beijing, data from daily cardiovascular emergency room visits were collected from ten large hospitals for the whole of 2013, the year of the now-infamous Airpocalypse. A 10mg/m3 increase in PM2.5 was associated with a 0.14 per cent increase in cardiovascular emergencies per day. That may not sound like much, but given the monthly high and low of PM2.5mg/m3 in Beijing can differ by as much as 300mg/m3, that could cause an increase in cardiovascular emergencies of 4 per cent, a significant burden on health services.

Years before David Newby’s gold nanoparticles study (see Chapter 3), his first exposure chamber study exposed volunteers to street levels of air pollution and found that blood vessels were more likely to clot compared to being exposed to clean air. ‘I like to call it a vascular stress test,’ he says, ‘What we do is put a little needle in the artery in the arm, and through that we infuse some agents to stimulate the blood vessels to relax and dilate. What we were able to show is when you are exposed to dilute [vehicular] exhaust, your blood vessels don’t relax as much … and that means blood flow might be slower. We also tested a protein that is released from some of these cells, called TPA, which stops clots forming within the blood vessel, so the blood continues to flow … It is a clever way the body is able to both continue blood flow but also prevent you from bleeding to death. What we found is the release of this TPA is lower when exposed to air pollution than if not. So, the defence mechanisms are hindered.’

Newby’s team took this research a stage further, taking blood from a human volunteer and passing it through an artificial coronary artery. Inside this ‘artery’ was a strip of pig aorta – one of the heart’s main pumps, at the top of the left ventricle – obtained from an abattoir. By cutting some of the surface off the pig aorta, it modelled what might happen when you have a heart attack and part of the artery bursts, exposing the deep layers of the artery.§

‘What we found was that when you expose people to dilute diesel exhaust, the amount of clot formed on that strip increased. And when we put a filter in and took the particles out and redid the test again, the amount of clot came down to normal levels. So, it does seem that the diesel exhaust exposure makes the blood thicker. So that’s three effects we’ve got: one, the blood vessels don’t relax as much; second, they don’t release as much of this clot-dissolving protein TPA; and when an artery is damaged, more clot forms. These are powerful mechanisms in the relationship between heart attacks and strokes.’ I ask if he also attempted this test with gas pollutants, without PM. ‘That’s right, we did some NO2 exposures, and also did it with ozone – just the gases on their own, no combustion-derived particles, and we didn’t see any effects. People have argued with us about that, they were expecting certainly NO2 to have an effect, but we didn’t see anything. Some people have argued that it is the combination of the NO2 with the particles that causes a problem, and that is possible.’ However, a team from University Hospital Jena, Germany, subsequently found a direct link with NO2 too. Their 2018 study of 693 heart attack patients found that a rise in NO2 of more than 20mg/m3 within 24 hours increased the risk of heart attack by up to 121 per cent, while a rapid hourly increase of NO2 of just 8mg/m3 increased the risk of heart attack by 73 per cent.

If we actually manage to reach old age, then air pollution severely undermines our quality of life. In a study of the elderly in the United States, PM2.5 and NO2 exposures were significantly associated with type 2 diabetes. Associations between air pollution and serum glucose, a measure used to assess diabetes status, have been reported even with short-term NO2 and PM2.5 exposure. The same mechanisms that affect the young developing brain also set to work on diminishing brain function towards the end of life. Experimental studies have shown that air pollutants cause neuro-inflammation, neuron damage and blood–brain barrier problems. One South Korean study of Parkinson’s disease hospital admissions from 2002 to 2013 found a ‘consistent and significant association’ between short-term exposure to air pollution (except for O3) and higher rates of Parkinson’s disease patients being admitted to hospital. The US Women’s Health Initiative Memory Study (WHIMS) also enrolled over a thousand older women with no previous signs of dementia between 1996 and 1998, and studied them over six to seven years with regular brain MRI scans. The women who lived in places with higher long-term levels of PM2.5 were found to have smaller brain volumes, not explained by demographic factors, socioeconomic status, lifestyle or other health characteristics. Frank Kelly’s research group at King’s even looked at 8 years worth of GP records of over 100,000 Londoners aged 50–79, and found that those living in areas with high NO2 and PM2.5 had a 40 per cent greater risk of developing dementia than those living with low pollution. The potential mechanism for this was suggested by work based in Lancaster, England (a relatively clean-air city, by UK standards). It found that local traffic pollution included 200 million metal nanoparticles per cubic metre, which it believed caused inflammation in the brain. I talked to Jim Mills, MD of Air Monitors, shortly after this study was released. ‘Can you imagine what the political change of opinion would be if that gets proven?’ he asked. ‘That all the problems we have with rising dementia in our population, which is one of the most scary things I think that we face at the moment, are actually down to our use or overuse of the internal combustion engine producing these tiny particles?’

Underlying this dementia research, and almost all the health problems throughout the life course of air pollution, is oxidative stress. Oxidation is happening all the time, within our bodies and throughout the natural world. Highly reactive compounds search for electrons to steal from others, which sets off a chain reaction as compounds either lose an electron or try to replace one. The easiest example to picture is rust. When iron meets oxygen it creates iron oxide, or rust – oxygen steals electrons from iron, which forms a new, weaker compound. This flow of electrons is necessary for life to exist, driving photosynthesis by oxidising water (H2O), which releases electrons to turn carbon dioxide (CO2) into carbohydrates and oxygen (O2). It’s literally why we breathe: oxygen comes in and reacts with big hydrocarbon molecules like sugar to break them down and give us energy. Almost everything eventually oxides down to CO2 or H2O, which we breathe out and pee out, and the process continues ad infinitum. So, oxidation equals good, right? Not completely. Oxidation is both caused by and causes free radicals, such hydroxyl (OH), those atmospheric firecrackers that for the milliseconds of their existence are desperately looking for a fight. Again, free radicals are natural and necessary, and form part of our immune system. It’s just that we don’t want to encounter an unnatural number of them. If we do, it causes more oxidation than our bodies can deal with: this is known as oxidative stress.

Professor Frank Kelly, chair of the Committee on the Medical Effects of Air Pollutants, took up his first lectureship in the late 1980s looking at the effect of the free radical OH on premature babies. ‘Because their lungs are under-developed they have to get extra oxygen in incubators to keep them alive and their brains functioning. But in giving their bodies more than the 21 per cent oxygen which we breathe normally – some of these kids require 90–100 per cent oxygen – it actually ends up damaging the tissue and they have a whole range of conditions that develop in their eyes, brains and lungs, because of this high oxygen concentration. And the reason this happens is because of free radicals.’ Kelly’s work in this then brand-new field of research found that while the lung tissue is protected from free radicals by the natural antioxidants in the body, if OH enters in high enough concentrations and for long enough, then the natural defences are overwhelmed – the atmospheric guard dog is unleashed, if you will, desperately snapping at soft body tissue and causing inflammation.‖

Our body is under constant oxidative stress, even without pollutants getting involved. It causes damage to cells, proteins, DNA, and may even be the whole reason why we age. ‘It’s a bit like if you leave butter out too long it goes rancid and oxidises,’ says David Newby. ‘There is a [theory] that atherosclerosis, this fatty deposit in your arteries and the underlying cause of heart attacks and strokes … gets oxidised [by pollutants], and it’s this oxidisation that causes [heart disease].’ The bad news is that NO2, pumped into every town and city in the world by car engines and boilers, happens to be a highly reactive free radical. Ozone, while not a free radical, is highly reactive and has an abundance of oxygen atoms, so tends to get into a fight with free radicals wherever it appears. PM and black carbon are coated in toxic material full of potential free radical stimulants. Our bodies’ defences are therefore overwhelmed by this multi-pronged attack. ‘Certainly when you look at the oxidative potential of [air pollution] particles, you really get a huge signal,’ says Newby. ‘In one of the studies I was telling you about – [blood vessels] not relaxing as much – part of the reason that we think they don’t relax is that the oxidative stress consumes the mediator which makes the arteries relax … before it can have an effect on the blood vessels.’

In 2017, another team from Edinburgh Napier University looked at the release of defence proteins and peptides, which effectively march out to defend the body at the first sign of trouble. One such peptide, known as LL-37, present in saliva, tears and lung fluids, has many immune system functions including guiding inflammatory cells to a wound or infection. The Napier team examined the effect of black carbon particles of 14nm (within the range of particles able to enter the bloodstream) on LL-37. Even with relatively low concen­trations of nanoparticles, the presence of LL-37 seemed to reduce; at high concentrations, it disappeared. On further investigation, it was found that the black carbon particles had grown in size. They had, like a cartoon snowball rolling down a hill, simply stuck the peptides onto their own surface, and in doing so rendered them powerless. The bundles of carbon particles and LL-37 no longer had any effect on the bacteria present in the test.2

To make matters worse, according to Frank Kelly, activated inflammatory cells also generate and release large quantities of free radicals themselves as a form of defence. In the absence of any invading organisms to kill, these free radicals can turn on their host and start attacking local cell tissue components. Many of these reactions happen first in the lung lining fluid, the first line of defence the pollutants encounter when we breathe them in. Chemical chaos ensues, and an inundated immune system resorts to calling the body’s last line of defence: a tank battalion of inflammatory cells. That chain of events precedes anything from an asthma attack to the early formation of tumours. Presumably, then, taking antioxidant supplements could counter this effect? ‘If you look at trials that give antioxidant vitamins, they have absolutely no benefit whatsoever,’ says David Newby, disappointingly. ‘It doesn’t matter how many antioxidants are flowing around in your bloodstream … that local burst is very difficult to prevent.’

The heart is particularly susceptible to oxidative stress, as it is an extremely active organ with a high metabolic rate and high energy demand. It’s not exposed to the air, so can’t oxidise and spoil in the same way as a lump of butter, but nanoparticles entering into the bloodstream can carry oxidative molecules on their surface. According to Newby’s gold study, once inhaled, nanoparticles of 30 nanometres (83.3 times smaller than PM2.5, most coming from car engines) can travel anywhere the blood goes, which is basically our entire body. They are reactive and toxic due to their large surface areas (remember it’s golf balls versus the footballs?), leading to oxidative stress and inflammation. The European ‘Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air’ study investigated the health effects of nanoparticles in coronary heart disease patients. It observed that the risk of developing ischemia – when blood flow to your heart is reduced, preventing it from receiving enough oxygen – was significantly greater two days after exposure to increased outdoor levels of nanoparticles. A US report on nanoparticles similarly concluded that they have ‘greater oxidant potential and were much more prone to introducing cellular injury compared with PM10 and PM2.5’.

Ken Donaldson, a recently retired particle toxicologist from the University of Edinburgh’s MRC Centre for Inflammation Research, spent the latter half of his career studying the toxicological impact of nanoparticles. I ask him if, in general, nanoparticles from combustion sources are more toxic than those from non-combustion sources. ‘Yes’, is the simple answer: ‘combustion-derived particles are the big hazard [because they] have more than just a larger surface area, they have metals and organics. Both of these can undergo redox cycling¶

to produce oxidative stress.’

Add all these health effects up, and what do you get? According to the WHO, the answer is 4.2 million premature deaths a year (or 7.4 per cent of all deaths) from outdoor air pollution. The WHO even provides exact figures for each country. In the Philippines in 2012, for example, the WHO attributes 28,696 deaths to ambient air pollution. But unlike during the great smogs of London and Donora, these aren’t numbers that represent people suddenly dropping down dead from air pollution. So how do we end up with such precise figures?

Frank Kelly, chair of COMEAP (Committee on the Medical Effects of Air Pollutants), tells me these figures are calculations based on the total years of life lost: in the UK, air pollution is shortening life expectancies by three to seven months on average, amounting to 340,000 years lost across the total population. Divide this by the average lifespan, and you get to a figure of around 40,000 ‘deaths’. Kelly even uses the word ‘guesstimation’. Given that almost every article on air pollution leads with these annual death figures, isn’t that a bit problematic? Numbers of deaths, says Kelly, is something that the public can easily understand, whereas ‘they don’t understand and don’t worry about losing three months off our lives. But even that is a generalisation – some people are losing a day and some are losing ten years … My response is, we talk about 89,000 premature deaths from smoking [in the UK] each year – Department of Health, official figures – that uses the same terminology, the same approach. It just helps to put it in terms of the risks we face in society. Breathing poor air in cities [kills more people than] drinking, more than obesity, way more than road accidents. But don’t take [the numbers of deaths] as being 100 per cent accurate, because we haven’t got that precision.’

COMEAP has regularly stressed that air pollution is shortening the lives of many more people than just those 40,000 a year in the UK. We will all die. But air pollution is likely to make you and me die sooner than we would have done otherwise. And, as it is related to many chronic, debilitating diseases, it is likely to make some of the years that we live much more painful than they would have been otherwise. The UK Chief Medical Officer’s annual report recommends ‘not just focusing on mortality, but using data that capture the full health consequence of pollution on morbidity, mental health impacts, and impacts on quality of life … Life-years (or quality-adjusted life years) are more appropriate for analysing policies than numbers of deaths, as it is when people die rather than whether they die that matters.’

Professor Chris Griffiths at St Barts Hospital believes the annual death figures aren’t entirely helpful: ‘there are other important ways of expressing the adverse health effects … I think the lung growth data is a little bit easier for people to get their head around, by saying “These children’s lungs aren’t as big as they should be [because of air pollution]”.’ I ask him if the focus should shift to quality of life. ‘Yes, yes. You’ve got more people with asthma, people with asthma having more asthma attacks, more pneumonia, more hospital admissions, more strokes, heart attacks, premature births, small birthweights, these are all statistically significant adverse health effects and they all add up, as you say, to impaired quality of life. I think we are getting stuck on the issue of mortality and air quality … the truth is if people’s lives leading up to that point of death are miserable because their lungs are destroyed … then air quality is important.’

Our life expectancy, then, is being reduced on average in Europe by 8.6 months to a year by PM2.5 pollution and in India by 1.1 to 3.4 years (or as much as 6.3 years in Delhi). But take away the source of the PM, and we see health dramatically improve. Frank Kelly writes of ‘consistent evidence that a reduction in the level of particulate pollution following a sustained intervention (mainly regulatory actions) is associated with improvements in public health’. The WHO argues that ‘health improvements can be expected to start almost immediately after a reduction in air pollution’. The deaths of many people every year are undoubtedly being caused by air pollution, although we’ll never have an exact number. But all of our lives are being shortened, or worsened, by air pollution. If we want it to stop, we have to fight back.

Notes

* The reasons include placental inflammation, impaired oxygen transport across the placenta, unstable blood pressure and even inflammation of the foetal lungs.

† The WHO also suggests that warming temperatures and ever-rising carbon dioxide levels may increase pollen levels, making asthma rates even worse.

‡ Other breakfast cereal analogies are available.

§ Of all the scientists I spoke to, or read about, for this book, I felt that David Newby pushed the boundaries more than most in the quest for the causal link to air pollution. I was surprised when, in early 2018, a scandal broke in Germany following the revelation that VW had taken part in an NO2 exposure test on 25 human volunteers. It led news bulletins not just nationally but internationally. Chancellor Angela Merkel called it ‘wrong and no way ethically justified’. Newby had been conducting similar studies for years. The German newspaper Tageszeitung probably put it best in saying that ‘human volunteers only had to inhale exhaust fumes for a few hours, people [in cities] … have been breathing in levels of nitrogen oxide far higher than EU limits for years’. Quite.

‖ Many animals are affected in the same way, too. Studies have found that European house sparrows, blue tits and great tits from areas with higher vehicle pollution had increased levels of oxidative stress compared to birds in less polluted areas, while street dogs culled in Mexico City were found to have far greater lung and brain inflammation than rural dogs.

¶ Redox is a portmanteau word combining ‘reduction’ and ‘oxidation’. As one molecule loses an electron (thanks to a scrap with a free radical) it is oxidised, while the molecule gaining an electron is reduced. I know, it sounds like it’s the wrong way round. Thanks scientists. The other way to think of it is the oxidation state of a molecule is either increased (oxidised) or decreased (reduction) – and so on, in an endless cycle.