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Science & Society
The health toll of air pollution
Despite global efforts to clean up the air, outdoor and indoor air pollution still have a drastic negative
effect on public health
Philip Hunter*
N
ew findings that the global health toll
exacted by air pollution may have
overtaken the toll of smoking high-
light the need to further cut anthropomorphic
emissions. Epidemiological evidence rein-
forced by molecular analysis shows a grim
picture of how air pollutants, even at levels
within WHO guidelines, cause cardiovascular
damage and affect immunity and metabolic
conditions through sub-clinical inflamma-
tion. There has also been growing concern
about indoor air pollution, which can be
particularly significant in developing coun-
tries where smoking and wood burning are
still prevalent. But it is outdoor pollution that
has received the greatest attention, partly
because its toll on human health has contin-
ued to increase. This is even the case in
developed countries despite legislation to
improve air quality.
Meanwhile, the ongoing COVID-19 pande-
mic has further underlined the problem in
two ways. First through its likely contribu-
tion to severe pneumonia; and second, as the
abrupt drop in levels of some pollutants,
especially NO2, caused by global lockdowns
improved air quality in urban areas, which
provides a unique opportunity to obtain data
on health impacts.
A 2019 study estimated a mean loss of life
expectancy of 2.2 years and between 15 and
28% of total 1.85 million per year mortality
from cardiovascular disease in Europe attri-
butable to air pollution (Lelieveld et al,
2019). The same study argues that the exis-
tence of molecular pathways linking air
pollution to vascular impairment suggest that
the actual percentage may be closer to the
upper limit, higher than smoking. Similarly,
the 2019 State of Global Air Report (https://
Philip Hunter is a freelance journalist in London, UK
*Corresponding author. E-mail: ph@philiphunter.com
DOI 10.15252/embr.202051183 | EMBO Reports (2020) 21: e51183 | Published online 13 July 2020
ª 2020 The Author
www.stateofglobalair.org/sites/default/files/
soga_2019_report.pdf) from the non-profit
NGO Health Effects Institute stated that “air
pollution is now the third highest cause of
death among all health risks ranking just
above smoking in India”, and exceeded
malnutrition, alcohol misuse and lack of
exercise. The direct comparison between air
pollution and smoking remains contro-
versial though as it is hard to compare
them directly, in particular for indoor air
pollution.
......................................................
“. . . air pollution is now the
third highest cause of death
among all health risks ranking
just above smoking in
India. . .”
......................................................
Pollutants and exposure
The principal sources of outdoor pollution are
particulates, nitrogen oxides, SO2, ammonia
and ozone. Particulates are further divided by
diameter: PM10 up to 10 lm and PM2.5 up to
2.5 lm. Some authorities also recognize a
third category of PM1.0. These distinctions
reflect the fate of the particulates as they enter
the human respiratory system: the larger PM10
particles tend to be deposited in upper airways,
while the smaller ones are more likely to reach
the lung and have different health outcomes.
However, these categories gloss over varia-
tions in their constituents, as they include inor-
ganic, organic and biological compounds from
both natural and anthropogenic processes.
Particulates include dusts, soot, metals, salts,
polycyclic aromatic hydrocarbons, aromatic
amines, endotoxins and fungal spores which
makes analysis of their health outcomes more
challenging than for the distinct gaseous
compounds.
There are also variations in the relative
levels of the other components, with ozone
and NO2 more prevalent in urban areas, while
the concentration of ammonia from animal
waste and fertilisers is higher in rural places,
especially close to farms. Ammonia is corro-
sive when inhaled directly and can also form
PM2.5 particles through reaction with atmo-
spheric sulphuric and nitric acids. The case of
ammonia highlights another distinction
between primary pollutants generated by
human activities, such as NO2 from internal
combustion, and secondary pollutants result-
ing from chemical reactions in the air, such as
ground-level ozone. While ammonia itself is a
primary pollutant, those PM2.5 particles it can
form are secondary.
It also highlights the somewhat blurred
distinction between urban and rural pollution,
which varies significantly between countries
and regions. In most developed countries, air
quality is on average considerably better in
rural than urban areas, as was confirmed by
the CDC study of data collected by the coun-
try’s National Environmental Public Health
Tracking Network (Strosnider et al, 2017).
The CDC found that air quality correlated with
urban density on all three selected measures.
The total number of days when PM2.5 levels
were greater than the US EPA’s National
Ambient Air Quality Standards (NAAQS) for
24-hour average ranged from 11.21 days in
large central metropolitan counties to 0.95 in
so-called noncore rural counties. The mean
EMBO reports 21: e51183 | 2020 1 of 4

EMBO reports
annual average ambient concentrations of
PM2.5 ranged from 11.15 lg/m3 in large
central metropolitan counties to 8.87 lg/m3
in noncore counties and the total number of
days with maximum 8-hour average ozone
concentrations greater than the NAAQS dif-
fered more sharply: 47.54 days in large central
metropolitan counties compared with
3.81 days in noncore counties.
......................................................
“In most developed countries,
air quality is on average
considerably better in rural
than urban areas. . .”
......................................................
On the other hand, a recent study in India
indicates that air pollution is just as great a
health threat in rural as in urban communi-
ties (Karambelas et al, 2018). Air pollution
in rural and urban areas each caused on
average 5.4 premature deaths per 10,000
people annually in Northern India. Because
more people live outside cities in that
region, this actually equated to 383,600
deaths in rural areas and 117,200 in urban
areas. It mainly reflects the toll in rural
communities exacted by fine particulates
and carbon monoxide from incomplete
combustion of wood and other biomass in
cooking and heating.
The Indian case also underlines dif-
ferences over air quality standards. Most
developed nations underwent a first round
of air quality legislation in the mid-20th
century, driven chiefly by the rising health
toll from soot as a result of coal burning.
Most influential were the UK Clean Air Act
of 1956, the US Clean Air Act of 1963 and
Japan’s Air Pollution Control Act of 1968.
The major developing nations have followed
suit but are still unwilling to close the gap
completely because they fear it would
dampen economic growth.
Increasingly stringent guidelines
These earlier Clean Air acts achieved
remarkable benefits, according to Sara Adar
from the Department of Epidemiology at the
University of Michigan, USA. “From a policy
perspective, I think that one of the most
compelling papers that I have seen in recent
years is one by Dr. Arden Pope and his
colleagues that documented measurable
improvements in life expectancy with reduc-
tions in air pollution in the United States
2 of 4 EMBO reports 21: e51183 | 2020
that were observed after the Clean Air Act”,
she said (Pope et al, 2009). The main
finding of that paper was that for a reduction
of 10 lg per cubic metre of fine particulate
matter, there was an average increase in life
expectancy of 7 months. Some of those
gains have since been reversed by rising
pollution—mainly NO2, diesel particulates
and ground-level ozone—from different
sources, primarily vehicular traffic.
At the same time, more stringent recom-
mendations have come into force across the
developed world, underpinned by guidelines
from the WHO. WHO recommends keeping
PM2.5 below 10 lg/m3 as an annual mean
and 25 lg/m3 as a maximum 24-hour mean.
For coarse particulates, the limits are 20 lg/
m3 annual mean and 50 lg/m3 as a maxi-
mum 24-hour mean. For NO2, the limits are
40 lg/m3 annual mean and 200 lg/m3 maxi-
mum 1-hour mean. For SO2, they are 20 lg/
m3 maximum 24-hour mean and 500 lg/m3
maximum 10-min mean, reflecting greater
tolerance and also potential exposure over
short periods in that case. Finally, recom-
mended maximum ozone levels are 100 lg/
m3 maximum 8-hour mean. These levels
have rarely been achieved so far in develop-
ing countries. For example, 670 million
Indian people were exposed to PM2.5 levels
that failed to meet even the country’s own
standard of 40 lg/m3. Less than 1% enjoyed
air quality that met WHO’s more exacting
10 lg/m3 (Purohit et al, 2019).
China has also been lagging behind WHO
guidelines. The first major initiative to clean up
the air was announced in September 2013 with
a 4-year plan to reduce PM2.5 levels from
89.5 lg/m3 to 60 by 2017 in Beijing mainly by
closing coal-fired power stations and banning
combustion of coal for heat in the city and
surrounding areas. This enabled the annual
average PM2.5 level of 58 lg/m3, a fall of 35%
over 4 years (https://www.chinadialogue.net/
article/show/single/en/10711-China-releases-2-
2-action-plan-for-air-pollution). China followed
up by publishing a new plan in 2018, but
merely to extend those targets to other cities
by 2020, so is still well behind the WHO
guidelines.
Even low levels hurt
Meanwhile, those WHO guidelines could be
tightened further in light of evidence that
even low levels of air pollution cause signifi-
cant health problems. A 2019 study of air
pollution in 652 cities around the world
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Philip Hunter
found that exposure over time even to lower
levels than those recommended by the WHO
result in a noticeable rise in mortality in
some areas (Liu et al, 2019). It also found
that significant short-term exposure to
particulate matter over 1–2 days correlated
with a small, but detectable, increase in
deaths. This was one of the most compre-
hensive studies of global air pollution
impacts conducted so far and presents a
compelling case to further reduce exposure,
commented Stefan Reis at the UK Centre for
Ecology & Hydrology’s Atmospheric Chem-
istry and Effects, in Edinburgh. Reis agreed
this raised a difficult question of whether
efforts should focus on reducing concentra-
tions below current limit values at monitor-
ing sites, or instead aim to reduce exposure
of the overall population. Whatever the
case, it was now clear that current limits
should be replaced by lower ones.
......................................................
“. . . the findings about short-
term exposure would require
reducing peak exposures to
have a positive effect on public
health.”
......................................................
“These limit values are not typically
representing ‘safe levels’ in any case, but are
often the result of assessments over what
concentration targets are technically and
politically ‘feasible’ in a given time scale,
and therefore represent intermediate objec-
tives that are ‘achievable’, rather than ulti-
mate goals to reach”, Reis explained. “In the
scientific community, a lot of debate is ongo-
ing about what the best targets are in the
meantime, where air quality limit value
compliance is usually legislated to be
achieved at existing air quality monitoring
locations. Alternative ways to assess
improvements would be to estimate the
overall reduction in population exposure,
perhaps by substantially increasing monitor-
ing, as current air quality monitoring sites
are sparsely distributed and not representa-
tive of the whole population in many areas”.
Reis also suggested that the findings
about short-term exposure would require
reducing peak exposures to have a positive
effect on public health. “And for vulnerable
individuals, attaining limit values every-
where is going to reduce for example acute
symptoms like triggering asthma episodes or
worsening other health conditions”, he said.
ª 2020 The Author

Philip Hunter
“At the population level, reducing air pollu-
tion irrespective of the starting point is, as
far as we currently know, going to improve
public health overall, even in areas where
current levels are already at or below air
quality limit or guideline values”.
......................................................
“The COVID-19 pandemic has
presented an unexpected
opportunity to study the health
impacts of short-term changes
in air pollution”
......................................................
An opportunity to study ozone
The COVID-19 pandemic has presented an
unexpected opportunity to study the health
impacts of short-term changes in air pollu-
tion. Levels of many air pollutants, espe-
cially NO2 and diesel particulate matter from
vehicle emissions, fell during lockdowns,
while ozone levels in urban areas often rose.
Some of the ozone close to ground, as
opposed to stratospheric ozone, is produced
by reactions between NO, NO2 and volatile
organic compounds under the action of
sunlight. The chemistry is quite complex,
but the main point is NO2 and NO increases
the production of O3, while an increased
NO/NO2 ratio reduces ozone concentration
(Melkonyan & Kuttler, 2012). During the
COVID-19 crisis overall levels of NOx have
fallen, but the NO/NO2 ratio seems to have
increased. As Reis pointed out, reduction of
NOx to very low levels would ultimately cut
ozone as well, “[b]ut we are currently in a
‘pollution climate’ where ozone is reduced
by high concentrations of NO2, which occur
typically in and around cities and other
major source areas”. Yet, more consensus
was needed to determine just what impact
reduced pollution levels would be likely to
have on health, according to Jonathan Grigg,
a leading UK paediatrician specialized on air
pollution at the Blizard Institute at the
London School of Medicine and Dentistry.
Although ozone’s contribution to ill
health can be separated out more readily,
other pollutants tend to rise and fall in
concentration together under changing emis-
sion conditions. One of the big challenges is
therefore to separate the individual contribu-
tions of each to negative health outcomes
and the extent to which they are cumulative.
“In general for health effects it has proved
ª 2020 The Author
really very difficult to separate out the
impacts of particulate matter and NO2
epidemiologically”, Grigg said. He noted that
many of these are therefore lumped together
as traffic-associated pollutants, but there is a
real need to assess how they operate
together: “The general feeling is that they do
contribute independently of each other, but
probably interact as well”.
It is also important to separate out the
contributions of different sources, such as traf-
fic and secondary agricultural pollutants from
farming practices. Ozone is the best known
and most widely studied secondary pollutant,
but other key ones include peroxyacyl nitrates
(PANs), nitric acid and ammonia. PANs are
produced primarily by combustion of organic
fuels, nitric acid from industrial processes and
ammonia from agricultural activities. As Grigg
pointed out, the contribution of these pollu-
tants varies not just with their potential to
cause health damage but also their source,
because this relates to the degree of exposure.
Traffic pollutants for instance likely impose a
particularly heavy burden in cities.
......................................................
“While being indoors offers
some protection against
outdoor pollution, it increases
exposure to pollutants arising
from cooking and domestic
cleaning. . .”
......................................................
Indoor pollution
The global lockdowns have also highlighted
the impact of domestic sources of pollution.
While being indoors offers some protection
against outdoor pollution, it increases expo-
sure to pollutants arising from cooking and
domestic cleaning, as well as general house-
hold particulates. “Indoor air pollution is
still a big issue, another black box coming
into the frame”, Grigg noted. “For example,
gas cooking without adequate ventilation
can lead to high levels of NO2”. He added
that some allergic conditions, especially
asthma, can be triggered by even small
amounts of indoor pollution.
One of the most comprehensive studies
of indoor air pollution and its impacts on
children, published in January 2020 by the
UK Royal College of Paediatrics and Child
Health (https://www.rcpch.ac.uk/sites/defa
ult/files/2020-01/the-inside-story-report_ja
14693178, 2020, 8, Downloaded from https://www.embopress.org/doi/10.15252/embr.202051183, Wiley Online Library on [10/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
EMBO reports
nuary-2020.pdf), found not surprisingly that
problems were most acute in older build-
ings. Its main recommendations were better
ventilation, legislation and building regula-
tions, perhaps with retrospective application
to older constructions. The report also noted
that indoor pollution had become more
important because children were spending
more and more time inside.
......................................................
“Wherever the pollution comes
from, health impacts ripple
around many systems of the
body and increase the risk of
cardiovascular diseases,
cognitive and behavioural
impacts or cancer”
......................................................
One point is that although building regu-
lations have improved health in some
respects, reducing energy consumption
through air-tight insulation have actually
worsened indoor pollution, commented
Linda Birnbaum, former Director of the US
National Institute of Environmental Health
Sciences. “Indoor air is usually much more
contaminated than our ambient air, but
indoor air is not regulated, except somewhat
for radon”, she said. “Not only do outdoor
pollutants come in, but in our attempts to
reduce energy usage, we have sealed many
of our buildings, so things generated indoors
cannot escape. Use of many kinds of house-
hold and personal care products inside,
including ways of heating and cooking,
generate lots of air pollutants. Mould can
also be a problem if there is dampness
indoors”.
Biological effects
Wherever the pollution comes from, health
impacts ripple around many systems of the
body and increase the risk of cardiovascular
diseases, cognitive and behavioural impacts or
cancer. One of the challenges has therefore
been connecting the epidemiological findings
with the underlying molecular mechanisms.
This has led to the field known as molecular
epidemiology to establish quantifiable relation-
ships or causal chains, by linking external
exposure and measurable biomarkers of
disease risk. One such biomarker related to
cancer is the level of genotoxic compounds
covalently bound to DNA. In turn, this can
EMBO reports 21: e51183 | 2020 3 of 4

EMBO reports
provide extra evidence that levels of exposure
to air pollutants were indeed responsible for
elevated rates of certain cancers. Fragmenta-
tion of DNA in mature sperm is another
biomarker for risk of infertility. The presence
of chromosomal aberrations in peripheral
lymphocytes is another, internationally recog-
nized, biomarker indicative of increased risk of
cancer.
......................................................
“There is also mounting
evidence that at least some of
the adverse health impacts are
mediated by epigenetic
changes which may influence
inflammation and disease
development”
......................................................
Although these markers still do not show
direct causal associations between disease
and air pollution, progress has been made
on associations between particulates and
disease, even though these comprise a vari-
ety of different compounds. A recent study
found that mechanisms of carcinogenicity
induced by particulates involve different
cellular responses, with synergies and antag-
onisms between components. Testing a
carcinogen with multiple components and
multiple effects is therefore more complex
for particulates than the other air pollutants
(Santibáñez-Andrade et al, 2020).
At a broad level, particulates operate by
disrupting processes related to survival of
tumour cells, including apoptosis, autop-
hagy and crosstalk between mitochondria
and the cell nucleus. There is also mounting
evidence that at least some of the adverse
health impacts are mediated by epigenetic
4 of 4 EMBO reports 21: e51183 | 2020
changes which may influence inflammation
and disease development (Rider & Carlsten,
2019). The authors concede that it is still
unclear exactly how air pollutants change
DNA methylation and to what extent
systemic effects are mediated by particulate
matter translocating from the lungs into the
blood. There is now consensus though that
reactive oxygen species is pivotal and
perhaps may reduce expression of methion-
ine adenosyltransferase, which is crucial for
maintenance of DNA methylation.
Indeed, studies of mice and rats exposed
to air pollutants have identified DNA methy-
lation of male gametes and concomitant
significant decrease in the daily production
of spermatozoa, in parallel with an increase
in the proportion of abnormal sperm shapes,
with the effect strongest for diesel exhaust
(Ferrari et al, 2019). The same review high-
lights evidence that some negative impacts
of air pollution could even be heritable via
epigenetically altered sperm.
Although more work is needed to eluci-
date many of these connections in more
detail, there is already sufficient evidence to
persuade governments that air pollution
should be further reduced, both in urban
and rural areas, outdoors and indoors.
Meanwhile, developing countries should
give higher priority to bringing levels of
pollution down towards current WHO guide-
lines.
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