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INVITED REVIEW SERIES:
UNRAVELLING THE MANY FACES OF COPD TO OPTIMIZE
ITS CARE AND OUTCOMES
SERIES EDITORS: GREGORY G KING AND DON SIN
Contribution of air pollution to COPD and
small airway dysfunction
NORBERT BEREND
The George Institute for Global Health, Woolcock Institute for Medical Research, University of Sydney, Sydney; Australia
ABSTRACT
Although in many Western countries levels of ambient
air pollution have been improving with the setting of
upper limits and better urban planning, air pollution
in developing countries and particularly those with
rapid industrialization has become a major global
problem. Together with increased motor vehicle own-
ership and traffic congestion, there is a growing issue
with airborne particles of respirable size. These parti-
cles are thought responsible for respiratory and cardio-
vascular effects and have also been implicated in
cancer pathogenesis. The pathologic effects in the lung
are mediated via inflammatory pathways and involve
oxidative stress similar to cigarette smoking. These
effects are seen in the peripheral airways where the
smaller particle fractions are deposited and lead to
airway remodelling. However, emphysema and loss of
bronchioles seen with cigarette smoking have not been
described with ambient air pollution, and there are few
studies specifically looking at peripheral airway func-
tion. Definitive evidence of air pollution causing COPD
is lacking and a different study design is required to
link air pollution and COPD.
Key words: air pollution, chronic obstructive pulmonary
disease, peripheral airway, spirometry, study design.
Abbreviations: AQI, air quality indices; COPD, chronic obstruc-
tive pulmonary disease; CRP, C-reactive protein; DNA,
deoxyribonucleic acid; IL, interleukin; FEV1, forced expiratory
volume in 1 s; MBNT, multiple-breath nitrogen test; PM, particu-
late pollution; SBNT, single-breath nitrogen test; sCD62P, soluble
P-selectin; TNF-α, tumour necrosis factor alpha; FVC, forced vital
capacity; WHO, World Health Organization.
Correpondence: Norbert Berend, The George Institute for
Global Health, 321 Kent Street, Sydney, NSW 2000, Australia;
PO Box M201, Missenden Road, 2050, Australia. Email:
norbert.berend@sydney.edu.au
The Author: Norbert Berend is Head of Respiratory Research at
the George Institute for Global Health and affiliated with the Phy-
siology and Imaging Group at the Woolcock Institute for Medical
Research. His major interest is in the pathophysiology of COPD
and asthma, particularly in relation to small airway function.
Received 14 June 2015; invited to revise 6 and 27 July 2015;
revised 27 and 27 July 2015; accepted 27 July 2015.
Article first published online: 27 September 2015
© 2015 Asian Pacific Society of Respirology
INTRODUCTION
Air pollution became a public issue with the 1952
London smog which caused an estimated 12 000
deaths. It led to increased research into the effects of
air pollution and the setting of air quality standards.
The setting of upper limits for pollutants may imply
that there is a ‘safe’ threshold level which may not be
the case, especially for particulate pollution. The
World Health Organization (WHO) guidelines on air
quality state that ‘there is little evidence to suggest a
threshold below which no adverse health effects would
be anticipated’. Nevertheless, air quality guidelines for
particulate matter, ozone, nitrogen dioxide and
sulphur dioxide have been suggested,1 and the setting
of limits has resulted in a decrease in air pollution in
most Western countries. However, outdoor or ambient
air pollution remains a major global environmental
health problem. Only 12% of people in the world live in
cities which meet WHO air quality standards. Acute
effects of air pollution are reflected in respiratory
symptoms, cardiovascular events, hospitalizations
and mortality, while long-term effects include reduc-
tion in lung growth of children and adolescents,
reduced spirometric lung function in adults, cardio-
vascular disease and lung cancer. Ambient air pollu-
tion in both cities and rural areas was estimated to
cause 3.7 million premature deaths worldwide in
2012.2 This mortality is borne disproportionately by
low and middle-income countries in which 88% of the
excess deaths occur, with the greatest burden in WHO
Western Pacific and South-East Asia regions.
Chronic obstructive pulmonary disease (COPD) is
now the third most frequent cause of death in the
world and is largely attributable to cigarette smoking.
Indoor air pollution due to use of biomass fuels for
heating and cooking in developing countries is also
strongly implicated as a cause of COPD. Although
ambient air pollution has well-documented adverse
effects on patients with COPD, the evidence for air
pollution as a cause of COPD is not conclusive. Given
the magnitude of the problem of air pollution and
the high global burden of COPD, it is essential that
any links between air pollution and COPD be firmly
established.
Respirology (2016) 21, 237–244
doi: 10.1111/resp.12644
238
HIGH-POLLUTION COUNTRIES
The 10 most polluted countries and cities in the world
in terms of particulate pollution (PM) are listed in
Table 1. Half of the world’s 20 most polluted cities are
in India. Although China does not rank in the top 10,
it also has a major problem with air pollution. A recent
study across 16 cities in China showed a range parti-
cles of less than 10 um (PM10) of 52 ug/m3 to 156 ug/
m3. Although Beijing can have extremely high
readings of particles less than 2.5 um (PM2.5), there are
large seasonal and daily variations resulting in lower
mean levels than some other cities. It is unclear
whether chronic health effects are related to mean or
peak levels. In many countries, the air pollution read-
ings are available in real time on the web. However,
caution needs to be exercised in comparing the com-
posite air quality indices (AQI) across countries since
the AQI is not uniformly defined and may represent
different levels of pollutants.
THE IMPORTANT POLLUTANTS AND
BIOLOGICAL MECHANISMS
The important pollutants shown to have an effect on
respiratory and cardiovascular health are SO2, NO2, O3
and particulates. The particulates, especially PM2.5,
have been the focus of many recent studies because of
the documented mortality (3.2 million deaths per
year) attributable to ambient particulate pollution.3
Estimating the effects of individual pollutants on
health outcomes can be difficult as their effects can be
modulated by atmospheric conditions and there are
strong interactions between the different pollutants
in terms of common sources and interaction of
effects. The composition of particulates can be quite
heterogeneous including motor vehicle exhaust emis-
sions, wear of brakes and road particles, fungal spores
and pollens. Motor vehicle exhaust emissions also
vary depending on whether they emanate from petrol
or diesel engines with diesel engines producing far
greater numbers of particles. The nature of these par-
Table 1 Ranking of countries and cities in the world by
particulate pollution
Country PM 2.5 City PM
Pakistan Delhi
Qatar Karachi
Afghanistan Dakar
Bangladesh Dhaka
Iran Abu Dhabi
Egypt Doha
Mongolia Ulan Bator
United Arab Emirates Cairo
India Amman
Bahrain Beijing
Source: WHO, 2014—Ambient (outdoor) air pollution
database by ca5 and ci5. (www.who.int/phe/health_topics/
outdoorair/databases/cities/en/ accessed 05/08/2015).
Respirology (2016) 21, 237–244
N Berend
ticles depend on the type of diesel fuel, engine oper-
ating conditions and the efficiency of particle filters.
Particulate pollution may have deleterious effects
because of the size and/or chemical composition
of the particles as well as their association with
sulphates, nitrates, metals and hydrocarbons. The
particle retention in the lung depends on physical
properties such as the mass, volume, surface area and
number of particles, or on chemical processes such as
dissolution or leaching.4 Ultra-fine particles <100 nm
in diameter appear to have greater pulmonary reten-
tion with translocation to the pulmonary interstitium
and produce a greater degree of inflammation and
fibrosis (2). Ultrafine particles generate free radicals at
their surface with resultant oxidative stress and acti-
vation of transcription factors for pro-inflammatory
genes in macrophages and epithelial cells.5 The latter
effect may also be facilitated by the opening up of
calcium channels in macrophages.6 These effects can
occur very peripherally in the lungs.7 Particulate pol-
lution from different sources, for example, in ambient
air and in road tunnels may have different biological
effects which may be related to different composition
such as iron content of the particles.8
The presence of transition metals may determine
the toxic effects of PM10 through oxidative stress
which may be injurious as shown by an increase
in airspace epithelial permeability and may lead
to inflammation through the activation of transcrip-
tion factors for pro-inflammatory genes in both
macrophages and epithelial cells. Recently, it has
been shown that particulate air pollution may cause
further molecular events that enhance transcription
factor activation by causing acetylation of histones
leading to unwinding of deoxyribonucleic acid (DNA)
enhancing transcription factor DNA binding and
increasing transcription for pro-inflammatory genes.
A detailed review of the respiratory health effects of
diesel particulates has been recently published9.
The presence of oxidative stress can be assessed
in the blood or in breath condensates such as
8-isoprostane.10 Other biomarkers include nitric
oxide, nitrite/nitrate, malondialdehyde and F-2
isoprostanes.11 Changes in these biomarkers have
been identified in people exposed to high levels of air
pollution.12–14
There is evidence that short-term increase in par-
ticulates is associated with increased C-reactive
protein (CRP), fibrinogen, TNF-α and interleukin
10 (IL-1) in children15 and adults.16,17 In a natural experi-
ment, the effects of a 12-month stay in Antarctica on a
Japanese research vessel setting out from Tokyo dem-
onstrated a fall in leukocytes and IL-6 while in Antarc-
tica corresponding to falls in particulates in both
smokers and non-smokers.18
A series of important studies were conducted
before, during and after the Beijing Olympics to
look at the effects of the major reduction in air pollu-
tion levels (30–60%) achieved during the Olympics
by drastic measures to reduce motor vehicle traffic,
industrial activity and construction. Multiple
biomarkers of pulmonary and systemic inflamma-
tion, oxidative stress and thrombosis were measured
in young subjects who were non-smokers and free of
© 2015 Asian Pacific Society of Respirology
Air pollution and COPD
chronic disease including respiratory and cardiovas-
cular disease.12–14 The fractional exhaled nitric
oxide, exhaled breath condensation biomarkers (H+,
nitrite, nitrate and 8-isoprostane as well as urinary
8-hydroxy-2-deoxyguanosine) fell significantly by
4.5–72.5% during the Olympic period with subse-
quent rises during the post-Olympic period. The
latter were correlated with the rises in pollutants.
Similarly, changes were measured in CRP, fibrinogen,
von Willebrand Factor, soluble CD40ligand (sCD40L),
soluble P-selectin (sCD62P), white blood cell count,
heart rate and blood pressure. The sCD62P and von
Willebrand Factor levels fell significantly during the
Olympics with other decreases not reaching statistical
significance. Importantly, these studies provided evi-
dence that the air pollution in Beijing leads to
increased oxidative stress and systemic inflammation
in young, healthy people. Further studies are needed
to measure the particulates in more detail and iden-
tify the toxic constituents and their properties as well
as the consequences of exposure in terms of oxidative
stress and systemic inflammation as suggested by a
recent Editorial.19
However, no measures of lung function were
included in the above studies. It is the changes in lung
function that are ultimately responsible for the devel-
opment of respiratory symptoms and disability, and
the relationship of these oxidative and inflammatory
biomarkers to functional outcomes has not been
explored in pollution studies, in contrast to COPD
caused by cigarette smoking.
In COPD, systemic inflammation is present with
increased CRP, fibrinogen, leucocytes, TNF-α, IL-6
and IL-8.20–22 Donaldson et al.23 found that increased
plasma fibrinogen in patients with moderate to severe
COPD was associated with faster decline of the forced
expiratory volume in 1 s (FEV1). However, in another
study, even persistent systemic inflammation in
COPD (defined as the presence of two or more sys-
temic inflammatory biomarkers for 12 months),
which is seen in a minority of patients, although
associated with poor clinical outcomes including
increased exacerbations does not appear to be asso-
ciated with increased decline of the FEV1.22 The issue
remains highly controversial and there is no definitive
evidence of systemic inflammation being related to
decline of airway function.
EFFECTS OF AIR POLLUTION ON
PERIPHERAL AIRWAYS
Fine and ultra-fine particles are retained in the lung
periphery,24 and the peak deposition occurs in the
transition zone between the conducting airways and
the alveolar region.25 Peripheral airway remodelling in
the terminal and respiratory bronchioles, particularly
fibrosis and increase in airway smooth muscle, has
been demonstrated in the lungs of non-smokers
living in highly polluted Mexico City compared
to non-smokers in Vancouver.26 Furthermore, in
smoking subjects with normal FEV1 who already have
peripheral airways disease27 as defined by an abnor-
mal phase 3 on the single breath nitrogen test, even
© 2015 Asian Pacific Society of Respirology
239
greater deposition occurs in peripheral airways, sug-
gesting that a vicious cycle may occur with presence
of peripheral airways disease begetting even greater
deposition of particulates and raising the possibility
of synergistic effects of cigarette smoking and air
pollution on peripheral airway function. However,
studies of the effects of air pollution on peripheral
airway function have been limited to reduction of the
FEF25–75 in children28 or in patients with underlying
lung disease.29 Although it is generally true that flow
measurements made at the lower end of the flow
volume curve, that is at low lung volume, reflect the
function of more peripheral airways, there are a
number of problems with the FEF25–75 as a measure of
peripheral lung function. The FEF25–75, because of the
shape of the flow-volume curve, will always demon-
strate a greater percent change than the FEV1, and this
should not be interpreted as the test indicating a spe-
cific peripheral airway abnormality. In addition, the
predicted values for the FEV25–75 are much more vari-
able than those for the FEV1, and serial measurements
are highly dependent on an unchanged FVC. In many
longitudinal studies, there have been changes in the
FVC which makes comparisons of the FEF25–75 prob-
lematic. These issues with the FEF25–75 as a measure of
peripheral lung function have been summarized in an
American Thoracic Society statement.30 A study using
the single breath nitrogen test is further discussed
below.
ACUTE RESPIRATORY EFFECTS OF
AIR POLLUTION
There is evidence for acute effects of fine particulate
pollution and NO2 on patients with COPD or
asthma,31,32 patients with more severe disease being
at greater risk,33 as are individuals with airway
hyperresponsiveness and the obese.34,35 In the non-
obese and otherwise healthy individuals, the docu-
mented effects of pollution on lung function have
been found to be small36–38 or non-existent.38 The lack
of evidence for acute effects of pollution on respira-
tory function in normal individuals may be related to
the relatively poor sensitivity of spirometry to detect
subtle changes in the peripheral airways.
CHRONIC RESPIRATORY EFFECTS OF
AIR POLLUTION
In children and adolescents, chronic exposure to air
pollution is associated with a reduction in the age-
related increase of the FVC, interpreted as decreased
lung growth.39–41 In adults, the Swiss SAPALDIA study
found significant decrements in the FEV1 and FVC in
relation to SO2, NO2 and PM10 exposure,42 results
which mirror those obtained in relation to NO2 and
PM10 in England43 and Germany.44 On the other hand,
in a large multi-centre study of adults aged 20 to
44 years across the European Community with a 10
year follow-up, no significant adverse effects on
spirometric function were seen related to exposure to
PM2.5.45 Abbey et al.46 in a retrospective Californian
Respirology (2016) 21, 237–244
240
study found that an estimated exposure over 20 years
to elevated PM10 levels was associated with a 7.2%
decrement of predicted FEV1 in males with a family
history of asthma, bronchitis, emphysema or hay
fever.
A number of studies have found that the effects of
air pollution (SO2, NO2 and PM10) on reducing lung
function and lung growth in children is attenuated
with reduction of pollution or moving to a less pol-
luted environment.47,48 An improvement in the
decline in spirometric lung function with reduced
exposure to PM10 has also been shown for adults49
suggesting that the effects of pollution may be similar
to what has been shown in cigarette smokers.50,51
STUDIES LOOKING AT AIR POLLUTION
AS A CAUSE OF COPD
Despite chronic exposure to air pollution causing
only modest changes in spirometric lung function,
there have been a large number of studies addressing
the question of whether air pollution causes COPD.
However, the studies have varied in terms of the
quality and nature of pollution data collected and
estimates of exposure to air pollution. Most studies
have attempted to establish associations between air
pollution and incidence or prevalence of COPD or
chronic bronchitis. Usually lung function was rec-
orded using spirometry, although there were many
studies assessing only clinical features. The majority
of studies were cross-sectional case-control studies
and a number of studies included subjects with
underlying chronic lung diseases. This variability in
the studies makes the drawing of conclusions some-
what uncertain. The multitude of studies has led to a
number of meta-analyses, systematic and other
reviews all of which have highlighted the deficiencies
in the data. These reviews have been either inconclu-
sive,52 have shown insufficient evidence to prove
a causal relationship between air pollution and
COPD45,53 or at best have been suggestive of a causal
association.54 A recent meta-analysis of five cohorts in
Europe (ESCAPE) found decrements of FEV1 and FVC
in relation to levels of NO2 and PM10 but no significant
effects on longitudinal changes in lung function.35
Furthermore, the majority of studies were undertaken
in areas with much lower pollution levels than are
currently seen in developing countries.
A longitudinal study looking at the rate of decline of
FEV1, which is an appropriate study design, was the
UCLA Population Study of CORD.55 Subjects over
the age of 7 years and up to the age of 59 years living
in three cities of Southern California with varying
degrees and types of air pollution were followed for a
period of 5–6 years, and the annual rate of decline of
FEV1 was calculated. In never-smoking males and
females, a stepwise increase in the rate of decline was
demonstrated between the subjects in the least to
those in the more polluted cities. When comparing
the rates of decline between the least and most pol-
luted areas, the ‘excessive’ loss of FEV1 attributable
to pollution was 23.6 mL/yr. This excessive rate of
decline is similar to that seen in smokers with early
Respirology (2016) 21, 237–244
N Berend
COPD.56 In another report from this study popula-
tion,57 the significance of the difference in lung func-
tion over the 5 years was greater for the slope of phase
3 of the single-breath nitrogen test (SBNT) than for
the FEV1, and since the SBNT is indicative of small
airway function the authors speculated that the earli-
est pathological changes may occur in the peripheral,
small airways.
The weaknesses of the study were the measure-
ments of the pollutants using only one measuring
station per city, the frequency of the lung function
measurements (once at the beginning and once at the
end of the 5-year period) as well as the follow-up
achieved in only ∼50% of subjects.
EFFECTS OF INDOOR AIR POLLUTION
Indoor air pollution due to combustion of unpro-
cessed biomass fuel in the form of wood, dung, coal
and crop residues for cooking heating and lighting is
common in developing countries. It has been esti-
mated that in these countries up to three billion
people and 90% of rural households are exposed to
open fires or poorly functioning and unflued stoves
and heaters.58
There is now extensive evidence that biomass
smoke exposure causes serious respiratory illness,
particularly in the form of acute lower respiratory
infection in children,59,60 and possibly of COPD. One of
the first associations of wood and crop residue smoke
with COPD was reported by Woolcock et al. in New
Guinea.61 Since then, many reports of this association
have emerged from different parts of the developing
world62–69 and even from European countries.70 The
evidence points towards women being at particularly
high risk because of longer periods of exposure in the
home.65,67,71 One study in China has demonstrated a
greater prevalence of COPD in rural women exposed
to biomass smoke than in city women who were ciga-
rette smokers.67 In China, the prevalence of COPD in
men is 8.2%, whereas in women it is 5.1%.69 However,
about 65% of Chinese men smoke while only about
4% of women smoke. Therefore, the main cause of
COPD in women in China appears to be biomass
smoke exposure, although it is possible that passive
smoking in the home and elsewhere will contaminate
these figures. However, throughout the Asia Pacific
region and in other developing parts of the world,
cigarette smoking is much more prevalent in men
than in women, and most of the COPD in women
appears to be caused by biomass smoke exposure.
The chronic airflow obstructive disorder caused by
biomass smoke fulfils the definition of COPD in being
characterized by chronic airflow obstruction not
completely reversed by bronchodilator and is there-
fore broadly similar to cigarette smoke-induced
COPD. However, some important differences may
define this particular phenotype of COPD. The rate of
decline of the FEV1 in subjects exposed to biomass
smoke appears to be less than in cigarette smokers.72
Chronic bronchitis is a common clinical feature in
biomass induced COPD.63,73 Imaging studies demon-
strate the presence of emphysema as well as evidence
© 2015 Asian Pacific Society of Respirology
Air pollution and COPD
of parenchymal fibrosis.61,74,75 Another study suggest-
ing a different COPD phenotype in biomass smoke-
exposed women versus cigarette-exposed individuals
found less emphysema but more airway wall thicken-
ing due to biomass exposure.76 A detailed study com-
paring lung morphology in cigarette smoke and
biomass smoke-induced COPD revealed that airway
inflammation was similar in these groups. However,
women with biomass-induced COPD had less severe
emphysema, more severe airway fibrosis, more fibro-
sis in the lung parenchyma and more right heart
abnormalities.77 Indeed, the fibrotic features of this
phenotype may be suggestive of pneumoconiosis.78
The cardiac abnormalities are consistent with the
suggestion that biomass-induced COPD may be asso-
ciated with more severe pulmonary artery hyperten-
sion and cor pulmonale.75 Despite these pathological
differences, the quality of life and survival in women
with biomass-induced COPD quality of life and mor-
tality appears to be similar to cigarette-induced
COPD.79
In summary, biomass smoke may be a major cause
of COPD. Women appear to be at particular risk of this
form of COPD in the developing world, and this may
be aggravated by passive inhalation of tobacco
smoke. There are no specific treatment guidelines
for biomass-induced COPD which is lumped with
cigarette-smoke induced COPD in the Global Initia-
tive for Chronic Obstructive Lung Disease and other
guidelines.
AN APPROACH TO ESTABLISHING AIR
POLLUTION AS A RISK FACTOR
FOR COPD
Despite data showing that the chronic effects of air
pollution on spirometric lung function are modest,
this does not rule out that there may be a subset of the
population more susceptible to its effects, at risk of
developing COPD. The cross-sectional and case-
control studies performed previously may not have
detected such an at-risk population. A different study
design may be more appropriate, based on similar-
ities to COPD caused by cigarette smoking. Clearly,
the current data suggest that pathological and func-
tional changes due to air pollution can occur in
peripheral airways, similar to the effects of cigarette
smoking. However, evidence for emphysema contrib-
uting to decline in FEV180,81 or loss of bronchioles82
which has been demonstrated in early COPD in
smokers is lacking for air pollution. Similarities
between the known effects of smoking and air pollu-
tion are summarized in Table 2.
The spirometric definition of COPD is a post-
bronchodilator FEV1 < 80% predicted with an FEV1/
FVC ratio of <0.7. In order to reach these figures,
typically at an age of >40 years, there is usually a rate
of decline of the FEV1 in excess of the age-related pre-
dicted decline. In smokers, this rate is highly variable
ranging from the normal ∼25 mL/yr to 150 mL/yr
with only a proportion of smokers developing
COPD.56,83 In a recently published study of current and
ex-smokers, Lange et al.84 found that only 7% of sub-
© 2015 Asian Pacific Society of Respirology
241
Table 2 Comparison of effects of cigarette smoking and
air pollution in adults
Cigarette Air
Effect smoking pollution
Peripheral airway remodelling Yes Yes
Loss of bronchioles Yes ?
Emphysema Yes ?
Peripheral airway dysfunction Yes Yes
COPD† Yes ?
Chronic bronchitis Yes Yes
†
As defined by spirometry. COPD, chronic obstructive pulmo-
nary disease.
jects with a normal FEV1 at the age of 40 years devel-
oped COPD after 22 years of follow-up. By contrast,
26% of subjects with an abnormal FEV1 at baseline
developed COPD. The former group had a signifi-
cantly increased rate of decline of the FEV1. Indeed,
the number of subjects with >40 mL per year decline
in this group was 2–3× higher than in the subjects who
already had an abnormal FEV1 at baseline. The situa-
tion may be different with air pollution. The concern
that people growing up in polluted environments are
at greater risk of developing COPD because they
already have a low or low-normal FEV1 is mitigated by
the fact that in this population the FVC is also low.
Indeed, during the period of lung growth, the effects
of air pollution on the FVC tend to be greater than on
the FEV1. In order to develop COPD with both a low
FEV1 and a low FEV1/FVC ratio, they need develop a
greater than normal rate of decline of the FEV1 in
excess of the effects on FVC.
Establishing an accelerated decline of the FEV1 in
an individual and hence demonstrating that the
person is at risk of developing COPD is difficult and
requires many measurements over several years.
Given the variability and repeatability of the test, the
FEV1 performed twice over 12 months would need to
show a change of 15% to be certain that there is exces-
sive decline.30,85,86 This can be reduced by extending
the period of observation and performing more
measurements. Thus, identifying at-risk individuals
in clinical practice is impractical. What is needed is a
biomarker which predicts accelerated loss of lung
function when the patient is first seen. A study is
needed, looking at a population exposed to air pollu-
tion, to establish whether there is a risk of developing
COPD by demonstrating an accelerated rate of
decline of the FEV1 at least in a proportion of subjects
and to look for a functional biomarker, as well as pos-
sible biomarkers of airway or systemic inflammation
and oxidative stress which may be useful in identify-
ing individuals who are at risk of developing COPD.
For smokers, the SBNT may predict a rate of decline
of the FEV1.87–89 and development of COPD before the
FEV1 becomes abnormal. It is unknown whether
peripheral airway pathology as demonstrated by
changes in peripheral airway function similarly pre-
dicts loss of FEV1 with exposure to air pollution. The
multiple-breath nitrogen test (MBNT) may have
some advantages over the SBNT. The MBNT can
Respirology (2016) 21, 237–244
242
demonstrate abnormalities in the conducting as well
as the acinar zones of the lung by the nitrogen slope
derived indices of Scond and Sacin, respectively.
These indices have been shown to be abnormal in
COPD90 and precede abnormality in the FEV1 in ciga-
rette smokers.91 Theoretical modelling suggest these
tests are sensitive to abnormalities at the acinar
entrance, and this is where deposition of respirable
particles occurs and subsequent pathology is
found.
CONCLUSION
Air pollution is known to be associated with excess
hospitalizations, respiratory and cardiovascular mor-
tality as well as lung cancer. It has been associated
with reduced lung growth in children and adoles-
cents, effects which appear to be at least partially
reversible with decline in pollution. In adults, current
evidence suggests that air pollution can lead to a
modest reduction in lung function, but studies are
lacking to see if there is a proportion of the exposed
population at risk of developing COPD. Such studies
are important as the air pollution, especially particu-
late pollution, is rising in developing countries due to
increased motor vehicle traffic and industrialization.
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