Health effects of air pollution

Dra. Patricia Matus Correa

There is great evidence linking outdoor air pollution with mortality and morbidity in the
general population (1-7). The public health damage is consistent and shows its adverse
effects in urban areas both in developed and developing countries (7).The range of
adverse health effects is broad affecting both the respiratory and the cardiovascular
system, and young children and older adults were the most susceptible in the general
population (7). The risk increases with intensity of exposure. Little information supports
the presence of a threshold level for these effects. In fact, effects were found at low
levels not much higher than 3 to 5 g/m3 the U.S. background concentrations. The
adverse health effects of air pollution are observed in short-term exposures and also for
long time exposures (8-9).

The World Health Organization conducted a study of burden of disease caused by

environmental problems attributed to air pollution effects on respiratory diseases,
perinatal conditions and birth defects, cancer, cardiovascular diseases, bronchial
obstructive disease and asthma. Pruss-Ustun and Corvalan (2006) estimated that in
developing countries by 42% (95% CI 32-47) of all respiratory diseases are attributable
to air pollution.

Respiratory effects of air pollution have been described mainly for particulate matter
and ozone. However, other pollutants such as nitrogen oxides have also been associated
with respiratory diseases, mainly in children under 1 year (11). The mechanisms
involved in these effects are primarily irritation and inflammation of the airways (12).
Studies have shown that particles can trigger inflammation of small airways (diameter
<2 mm), which may cause exacerbation of asthma or obstructive bronchitis, airway
obstruction and decreased gas exchange (13). Air pollutants such as nitrogen oxides, can
also enhance the inflammatory reaction of the airway to allergens in asthmatics (14).
The particles can also interfere with the mechanisms of cleansing and destruction of
bacteria in lung tissue and this is a very important mechanism to link air pollution to
respiratory infections (15).

Pinkerton et al (16) studied the lungs of residents of Fresno (Central Valley) have
reported wall thickening and remodeling of the terminal bronchioles, associated with
increased collagen, inflammatory cells and interstitial macrophages loaded with
particulate matter. These changes were significantly more marked in the first generation
of the terminal bronchioles, suggesting that the accumulation of coal and mineral dust in
the lung, mainly affects the central acinar zone of the lung.

To live in area with high levels of particulate matter in air produces pulmonary retention
of a large numbers of particles, some of which appear to be products of combustion.
This was detected by comparing lungs of Mexico City residents with Vancouver
residents whose were exposed to an average of 66 and 14 g/m3 of PM10 in 3 years.
Moreover Churg and Brauer have reported that in lung tissue of autopsied human
particles is retained providing evidence on the role of PM2.5 (18).

Exposure to complex mixtures of air pollutants, mainly particulate matter and ozone
causes lung structural changes that are induced by sustained inflammation, leading to
vascular remodeling in the airways of the lung and impaired repair process. It has been
suggested that ozone can increase the toxicity of inhaled particles or vice versa, since
there were more lung damage in rats, both agents harmful to inhale a whole than
separately administered (19). This observation is supported by the study of Vincent et al
(20) who exposed rats for 4 hours by inhalation to 0.8 ppm ozone exposure by linking
this urban particulate matter. In this study, the effects of O3 (altered epithelial terminal
bronchioles and alveolar ducts and increased DNA synthesis) were clearly enhanced by
the co-exposure to urban particulate matter. Moreover, it is reported that both urban
particulate matter, like particles released from diesel and carbon black, are able to cause
mutagenesis by DNA damage in type II alveolar cells in culture (cell line A549) (21).

The mechanisms of damage induced by exposure to air pollutants have been the subject
of many studies in order to establish a criterion of biological plausibility, to offer
support and substantiate the need for measures to control pollution.
The inflammatory mechanism plays an important role in the exacerbation of respiratory
diseases promoted by exposure to respirable particles. It has been suggested that on the
surface of the particles produced a series of physical-chemical reactions that cause
intracellular oxidative stress. Due to the large contact area between particles and
pneumocytes (lungs cells) would be a release of inflammatory mediators in the lung,
which would trigger the recruitment of inflammatory cells with a heightened response
leading to functional and structural damage in the process of ventilation lung.

Mechanisms of lung injury have been proposed. The sequence of events would begin
with the activation of the cascade of inflammation, which may explain the molecular
events that lead to transcription of pro-inflammatory genes. The respirable particles
cause oxidative stress in cells with the generation of lipid peroxidation products such as
hydroxynonenal 4 and oxidized glutathione (GSSG). This change in intracellular redox
balance, would cause the acetylation of histones and DNA breakdown, encouraging the
promotion of mechanisms of gene transcription. Oxidative stress also directly induces
the production of NF-kB factor, allowing transcription of pro-inflammatory genes (TNF,
IL-8, IL-2, IL-6, GM-CSF, ICAM-1). Furthermore, oxidative stress and / or direct
interaction with the particles induce increased concentrations of calcium (Ca +2), which
in turn may stimulate the production of NF-kB, with subsequent increased release of
pro-inflammatory substances (22).

Studies also suggest that immunological mechanisms may explain the effects of diesel
particulate emissions on asthma. The mechanisms of direct damage to the immune
system would include increased production of IgE and IgG immunoglobulin,
modulating the expression of cytokines with increased levels of interleukins and
chemokines. Phenomena that induce the migration of other cell types primarily of
eosinophils that are mediators of chronic bronchial inflammation, prolonged contraction
of peribronchial muscles, increased bronchial hyper responsiveness and bronchial
mucosal damage, clinically relevant aspects bronchial asthma (23).

Children are particularly vulnerable to respiratory problems because of their physical

characteristics and behaviour. At this stage of life the lung has not reached its full
development: there is less collateral ventilation and airway resistance of small accounts
for 50% of the total resistance to airflow (24). Most of the alveoli (80%) develop in the
postnatal period. This occurs because a smaller volume and lower pulmonary alveolar
surface, so that equal exposure to adults, enter higher dose to the body. The airways
continue to develop in childhood. This implies that peripheral airway (<2 mm diameter)
for 50% of the airflow resistance, while in adults only corresponds to less than 20%.
The absence of collateral ventilation, i.e. presence of pores of Kohn and channels of
Lambert, in children, aggravated obstruction of peripheral airways. Children breathe
more often and do more physical exercise than adults; this increases the effective dose
of air pollutants that captures the lung. In addition, children have less developed
respiratory muscles, and cough less effective in cleaning the central airways. Lung
defence mechanisms are not fully developed, causing greater difficulty in removing
particles reaching the airways. Finally, children spend more time outdoors than adults,
so that exposure to air pollutants is greatest. All this makes it more vulnerable to air
pollution than adults (25). So the burden of environmental pollution on respiratory
health of children is higher, especially in developing countries where coexist several
other insults such as indoor air pollution and malnutrition. Hence the importance of
establishing monitoring programs and special attention as are the strategies developed
within the framework of environmental pediatrics.

In children under 5 years has been estimated globally that acute lower respiratory
infections (pneumonia, bronchiolitis and bronchitis) are responsible for about 20% of
the 10.6 million deaths annually worldwide. About 90% of these deaths are due to
pneumonia (26).

In the last decade some studies also show that both particulate matter and ozone, are
increasing the risk of cardiovascular disease (Tsai S. et al, 2003; Kan H. et al, 2003;
Hong Y. et al, 2002; Tamagawa E. and Van Eaden, S., 2006 R. Maheswaran et al, 2005;
Henrotin J. et al, 2007). An analysis of daily mortality conducted in the 20 largest
counties in the United States within the period 1987-1994, showed that there is a 0.68%
increase in mortality due to cardiovascular and respiratory problems to an increase of 10
ug/m3 in the concentration of PM10 (Samet JM, 2000). A larger study conducted in 204
U.S. counties for 4 years and another study in the 5 largest cities in Europe indicate that
hospital admissions for cardiovascular disease are positively associated with increased
levels of air pollution (Dominici F, 2006 and von Kloto S, 2005).

The cardiovascular injury induced by air pollution results in significant changes in many
cardiovascular indexes. Some of the effects (changes in the heart rate, or heart rate
variability, blood pressure, vascular tone and blood coagulability) are developed in
response to increased levels of ambient particles. At the same time a chronic exposure
to increased concentration of particulate air pollutant accelerates the progression of
atherosclerosis (Simkhovich, 2008).The evidence suggests that stroke mortality and
hospital admissions should be higher in areas with elevated levels of outdoor air
pollution because of the combined acute and chronic effects of air pollution on stroke
risk (Maheswaran, 2005). A number of potential mechanisms could explain the
association between air pollution and stroke. Fine particles air pollution provokes
alveolar inflammation, causing the release of potential harmful cytokines, which results
in elevated coagulability (Seaton, 1995) and this condition increases thrombotic activity
in central and peripherical vascular system.
References

1.OPS Evaluacin de los efectos de la contaminacin del aire en la salud de Amrica Latina y
el Caribe, ISBN 92 75 12598, 2005.
2.Dockery D, Pope A, Epidemiology of Acute Health Effects: Summary of Time-Series
Studies, En: Particles in our air Concentrations and Health Effects Ed, Wilson and
Spengler, Harvard University Press 1996:123-147.
3.Pope A, Dockery D, Epidemiology of Chronic Health Effects: Cross-Sectional Studies, En:
Particles in our air Concentrations and Health Effects Ed, Wilson and Spengler, Harvard
University Press 1996:149-167.
4.Nawrot T, Nemmar A, Nemery B Update in Environmental and Occupational Medicine
2005, Am J Respir Crit Care Med 2006; 173: 948-952.
5.Brunekreef B, Holgate ST Air pollution and health, Lancet 2002; 360:1233-42,
6.Mathieu-Nolf M Poisons in the air: a cause of chronic disease in children, J Clin Toxicol
2002; 40: 483-91.
7.EPA Air quality guidelines 1997.
8.World Health Organization (WHO) Air quality guidelines for Europe, World Health
Organization, Geneve, 2000.
9.World Health Organization (WHO) Air quality guidelines global update, Reporting on a
working group meeting, World Health Organization, Bonn, Germany 2005.
10. Prss-Ustun A, Corvaln C, Preventing disease through healthy environments towards
and estimate of the environmental burden of disease, WHO, ISBN 92 4 159382 2 2006.
11. Van Strien RT, Gent JF, Belanger K, Triche E, Bracken MB, Leaderer BP, Exposure to
NO2 and nitrous acid and respiratory symptoms in the first year of life, Epidemiology
2004; 15:471-8.
12. Ghio AJ, Devlin RB, Inflammatory lung injury after bronchial instillation of air pollution
particles, Am J Respir Crit Care Med 2001; 164:704-8.
13. Nell AE, Diaz-Sanchez D, Ng D, Hiura T, Saxon A, Enhancement of allergic
inflammation by the interaction between diesel exhaust particles and the immune system,
J Allergy Clin Immunol 1998;102:539-54.
14. Barck C, Lundahl J, Hallden G, Bylin G, Brief exposures to NO2 augment the allergic
inflammation in asthmatics, Environ Res 2005;97:58-66.
15. Harrods KS, Jaramillo RJ, Berger JA, Gigliotti AP, Seilkop SK, Reed MD, Inhaled diesel
engine emissions reduce bacterial clearance and exacerbate lung disease to pseudomonas
aeruginosa infection in vivo, Toxicol Sci 2005; 83:155-65.
16. Pinkerton KE, Green FHY, Saiki C, Vallyathan V, Plopper CG, Gopal V, Hung D,Bahne
EB, Lin SS, Menache MG, Schenker MB Distribution of particulate matter and tissue
remodelling in the human lung, Environ Health Perspect 2001,108:1063-1069.
17. Braur M, Avila-Casado C, Rortoul TL, Vedal S, Stevens B, Churg A Air Pollution and
retained particles un the lung, Environ Health Perspect 2001;109:1039-1043.
18. Churg A, Brauer M Human lung parenchyma retains PM 2,5 Am J Respir Crit Care Med
1997;155:2109-2111.
19. Kleinman MT, Bufalino C, Rasmussen R, Hyde D, Bhalla DK, Mautz WJ Toxicity of
chemical components of ambient fine particulate matter (PM 2,5) inhales by aged rats, J
Appl Toxicol 2000;20:357-364.
20. Vincent R, Bjarnason SG, Adamson IY, Hedgecock C, Kumarathasan P, Guenette J,
Potvin M, Goegan P, Bouthillier L Acute pulmonary toxicity of urban particulate matter
and ozone, Am J Pathol 1997;151:1563-1570.
21. Don Porto Carero A, Hoet PH, Verschaeve L, Schoeters G, Nemery B Genotoxic effect of
carbon black particles, diesel exhaust particles, and urban air particulates and their
extracts pn human alveolar epithelial cell line (A549) and a human monocytic cell line
(THP-1), Environ Mol Mutagen 2001;37:155-163.
22. Donaldson K, Stone V Current hypotheses on the mechanisms of toxicity of ultrafine
particles, Ann Ist Super Sanita 2003;39:405-410.
23. Pandya R, Solomon G, Kinner A, Balmes J Diesel exhaust and asthma: hypotheses and
molecular mechanisms, Environ Health Perspect 2002;110:103-112.
24. Murray JF Postnatal growth and development of the Lung, The Normal Lung, WB
Saunders Co, Philadelphia 1976 Chapter II, p: 21-53.
25. Oyarzn M, Pino P: Contaminacin atmosfrica y del aire intradomiciliario, En, Herrera
O y Quezada A, (eds,) Enfermedades Respiratorias en Pediatra, Editorial Mediterrneo
Ltda, Santiago de Chile (aceptado por los editores).
26. Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H, Global estimate of the incidence of
clinical pneumonia among children under five years of age, Bull World Health Organ
2004;82:895-903.