Toxic responses of the lung

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Toxic responses of the lung

• Environmental health and toxicology Lecture 7

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Lecture Objectives

• Understand the function of respiratory system
• State natural mechanisms against airborne hazards
• Be aware of occupational lung diseases
• Understand occupational airborne hazards
• Understand health effects linked to PM
• State mechanism involved in causing PM-related
  health effects

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Content

• Respiratory system
• Stages of lung toxic responses
• Workplace exposures
• Occupational lung diseases
• Air borne hazards
• Smoking
• Air pollution
• Particulate Matter

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Quiz

• What is the body's main method to remove dust,
  mucus, saliva, and other debris from the lungs?

• Coughing!
• But inability to cough can lead to infection.
  Deep breathing exercises may help keep finer
  structures of the lungs clear from particulate
  matter, etc.

Words mucus??, saliva??, debris??
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Respiratory System

• No oxygen -live only minutes
• Every cell needs constant supply of oxygen
• Lungs link to supply of life-giving oxygen

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Respiratory System

• Normal breathing online flash
  http//www.airinfonow.org/html/lungattack/lungplay
  .htm

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Lung anatomy
Words trachea??, cartilage??, pharynx?, larynx?
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Lung anatomy

• The blind sacs in the lung tissue, called
  alveoli, consist of several types of cells. Each
  alveolus has a network of capillaries that carry
  blood in the lungs.

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Lung anatomy
line the alveoli and secrete a substance called
"surfactant." Surfactant coats the alveoli and
provides pressure to keep them from collapsing.
Without surfactant the alveolar surfaces tend to
stick together which causes the alveoli to
collapse.
the largest, thin cells that form the walls, or
septa, of the alveoli.
II ???????
I ???????
?????
part of the connective tissue in the lungs.
????
???
scavenger cells that work to keep the lung free
of "foreign" materials.
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Development of the alveoli
Time of Development Structures that Develop
0-5 week old embryo major airways (trachea, bronchi) form
5-16 week old embryo bronchi branch and subdivide
16-26 week old embryo lung cells differentiate into different cell types
26 week old embryo - birth airways expand and grow
1-2 year old baby alveoli form by the formation of additional septa
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Lung volume
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???
????
???
????
?????
???
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Tidal breath

• Tidal breathing is the inhalation and exhalation
  method by which mammals breathe.
• It refers to the amount of air used when at rest
  and when breathing functions are automatic.
• It is measured by doctors trying to study or
  diagnose respiratory and other health problems.

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Natural mechanisms against airborne hazards

• Fine hairs in nose
• front-line barrier
• filter
• exercise/hard work
• Cough reflex clears trachea main bronchi
• Special cells destroy bacteria viruses
• Ciliary cells few hours to expect foreign
  material
• Innermost areas of lungs much longer to clear
  out

Words Cilia ??
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Respiratory System

• Lungs that receive prolonged /or repeated
  exposure to air contaminants eventually cannot
  keep up with the rate of deposition /or constant
  irritation.
• Result contaminants accumulate contributing to
  the development of Occupational Lung Diseases.

Diagram- black asbestos fibers- exposure
standards to be less than 1 fibre/cm3 for 8 hr
exposure.
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Stages of lung toxic responses

• Stage 1
• Exposure through inhalation
• Stage 2
• Action of agent on component of the cell
  starting with binding
• Stage 3
• Response of lung to loss of function
• Stage 4
• Transport of agents to other sites of action

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• Toxic actions are based on four factors
• Pattern of inhaled exposures
• Ability of the agent to bind to cellular
  components
• Capacity for cellular repair
• Capacity to detoxify the agent and excrete from
  the body.

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Disorders of the respiratory system

• Obstructive conditions?????
• Restrictive conditions (interstitial lung
  diseases)?????
• Vascular diseases ?????
• Infectious, environmental diseases ?????

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Obstructive conditions

• diseases of the lung where the airways (i.e.
  bronchi, bronchioles, alveoli) become reduced in
  volume or have free flow of gas impeded, making
  it more difficult to move air in and out of the
  lung.
• e.g., emphysema, bronchitis, asthma

Words emphysema???, bronchitis????, asthma??
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Restrictive conditions

• a loss of lung compliance, causing incomplete
  lung expansion and increased lung stiffness.
• e.g., fibrosis, sarcoidosis, alveolar damage,
  pleural effusion

Words fibrosis????, sarcoidosis????
alveolar damage ????, pleural effusion???
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Vascular diseases

• describes any condition that affects the blood
  circulation in the lungs.
• e.g., pulmonary edema, pulmonary embolism,
  pulmonary hypertension

Words pulmonary edema???, pulmonary embolism???
pulmonary hypertension???
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Infectious diseases

• communicable diseases, or contagious diseases
  comprise clinically evident illness resulting
  from the infection, presence and growth of
  pathogenic biological agents in an individual
  host organism.
• e.g., pneumonia, tuberculosis, asbestosis,
  particulate pollutants

Words pneumonia??, tuberculosis???,
asbestosis?????
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The Spectrum of Lung Disease
??
??
Restrictive lung disease
Chronic Obstructive Pulmonary Disease ????????
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Soreness of the throat
???
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Bronchitis
Chronic or acute inflammation of the mucous
membrane of the bronchial tubes.
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Emphysema

• A pathological condition of the lungs marked by
  an abnormal increase in the size of the air
  spaces, resulting in laboured breathing and an
  increased susceptibility to infection.

• It can be caused by irreversible expansion of the
  alveoli or by the destruction of alveolar walls.

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Asthma

• A chronic respiratory disease, often arising from
  allergies, that is characterised by sudden
  recurring attacks of laboured breathing, chest
  constriction, and coughing.

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Pulmonary Edema

• Pulmonary Edema is Abnormal fluid accumulation
  within the alveoli and the interstitial tissues
  of the lungs.

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Occupational health trends

• Occupational lung diseases
• workplace exposure to irritating or toxic
  substances- may cause acute or chronic
  respiratory ailments.

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Occupational lung diseases

• Occupational Asthma
• Reactive Airways Dysfunction Syndrome (RADS)
  ????????????(asthma-like syndrome developing
  after a single exposure to high levels of an
  irritating vapour, fume, or smoke. )
• Emphysema
• Chronic Bronchitis (repeated infections and/or
  exposure to irritants such as fumes/dusts, oil
  aerosols, gases, smoke)

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Occupational lung diseases

• Pneumoconiosis (PM 5µm)
• Hypersensitivity Pneumonitis (organic
  dusts-fungi, animal proteins, vegetable proteins)
• Granulomatous Disease (TB, toxins-Berylliosis
  best known occupational example)

Words Pneumoconiosis???, Hypersensitivity
Pneumonitis????? Granulomatous
Disease????, Berylliosis???
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Occupational lung diseases

• Pneumonia toxic process or more commonly
  infections (health care, child care animal care
  workers) fungi, bacteria, viruses, other
  microorganisms
• Occupational Lung Cancer smoking, coal tar,
  pitch volatiles, mustard gas, arsenic, asbestos,
  radium, petroleum, chromates, uranium

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Pneumoconiosis

• Depending upon the type of dust, the disease is
  given different names
• black lung coal, carbon
• Asbestosis asbestos
• Silicosis silica
• Bauxite fibrosis bauxite
• Berylliosis beryllium
• Siderosis iron
• Byssinosis cotton
• Silicosiderosis mixed dust containing silica
  and iron

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Acute respiratory irritation

• It results from the inhalation of chemicals
• Ammonia, chlorine, nitrogen oxide in the form of
  gases, aerosols
• If such irritants reach the lower airways it
  damage the alveolis pulmonary edema may occur
• Although the effect of irritants are usually
  short lived, some may cause chronic alveolar
  damage or airway obstruction.

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Occupational lung hazards

• Classification of work hazards
• Physical
• Mechanical
• Chemical
• Biological
• Psychosocial

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Hazard and Risk

• Hazard
• potentially harmful
• Risk
• probability of harm
• (quantifiable as risk assessment)

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Airborne hazards

• Mineral dust
• Organic dust
• Chemical dust
• Fumes
• Mists sprays
• Vapours
• Radiation
• Biological hazards

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Airborne hazards Mineral dust

• Dusts mineral fibres from stones, rocks, ores
• Sources
• Mining, quarrying, tunnelling, blasting,
  smelting, grinding, milling, processing,
  drilling, abrading
• Industries
• mines, quarries, foundries
• Lung effects
• pneumoconiosis (asbestosis, silicosis, black
  lung) chronic bronchitis, emphysema, fibrosis,
  cancer

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Airborne hazards Organic dust

• Dusts formed from living materials-micro-organisms
  , plants, animals natural products like wood
  leather.
• Sources
• Wood, cereal grains (planting, harvesting,
  storing, transporting, processing), animal
  husbandry (droppings, dander, feathers)
• Industries
• Agriculture, manufacturers (furniture/ drugs),
  millers, bakers, chemists
• Lung effects
• Hypersensitivity reactions-occupational asthma or
  hypersensitivity pneumonitis-permanent
  obstructive disease, diffuse lung fibrosis. Wood
  dusts -cancer

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Airborne hazards Chemical dust

• Synthetic chemicals (powder form), such as
  pesticides, pharmaceuticals, dyes, bleaching
  agents, detergents, paints
• Sources
• Any contact from making, packaging, applying,
  weathering
• Industries
• aircraft building, pulp mills, chemical,
  breweries, foundries, hairdressing, health care,
  labs, manufacturing (paints), paint sprayers
• Lung effects
• Depends on toxic properties of specific
  chemicals-irritants, allergens, cancer

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Airborne hazards Fumes

• Very small solid particles formed when hot
  vapours cool rapidly condense
• Can give off hazardous gases
• Act like very fine mineral dust in lungs
• Sources
• High heat processes
• Industries
• Smelting, arc-welding, furnace work
• Lung effects
• Difficult to assess effects of separate materials
  since several hazards present at same time. Can
  lead to emphysema lung cancer.

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Airborne hazards Mists sprays

• Liquid droplets suspended in air or other
  propellant gas.
• Sources
• Cleaning products, pesticides, paints, cosmetic
  products, rust removers
• Industries
• Cutting, grind, spraying and pickling
  operations, electroplating
• Lung effects
• The finer the spray, the deeper into the lungs it
  goes. Effect depends on material, concentration
  and temperature.

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Airborne hazards Vapours

• Vapours hang out with parent liquid
• Sources
• Inorganic-high boiling points, dont vaporise at
  room temperature-arent usually associate with
  lung disease
• Organic-many vaporise at room temperature-used as
  solvents (ketones, alcohols, acetates, aromatic
  hydrocarbons)
• Lung effects
• enter body through lungs
• damage to other organs more so than lungs
• pulmonary edema tracheobronchitis.

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Airborne hazards Radiation

• Radiation
• Non-ionising radiation (electromagnetic
  waves-infrared, ultraviolet, microwave, laser,
  radar, radio frequency)
• Ionizing radiation (alpha, beta, gamma rays,
  neutron particles x-rays)
• Sources
• Mining radioactive ores
• Industry
• Medicine, power plants, equipment used in
  industry (high energy electrical equip., lasers,
  microwaves, radar)
• Lung effects
• Electromagnetic waves can cause thermal burns.
  Ionising radiation can cause cancer.

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Airborne hazards Biological hazards

• Bacteria, viruses, fungi
• Sources
• Health care child care facilities, poorly
  maintained ventilation systems, biological
  research labs, animal care processing
  facilities
• Lung effects
• Depends on type of hazard. Can be minor allergies
  lung infections to cancer. Vaccinations for
  some.

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Smoking

• Smoking contributes to lung disease
• Impairs lungs natural defense mechanisms
  irritates airways inhibits work of ciliary
  cells
• Oxidants are one toxic component of cigarette
  smoke. They can damage the DNA of lung cells much
  like the sun damages skin cells.

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Smoking

• Smoking is leading cause of serious lung disease
  certain types of cancer
• Synergistic effect with other pulmonary
  carcinogens (asbestos, chromium/uranium
  compounds, arsenic)
• Increases lung cancer risk
• Smokers develop lung disease cancer more
  readily diseases progress more rapidly

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Air pollution

• Air pollution may be defined as the presence in
  the air (outdoor atmosphere) of one or more
  contaminants or combinations thereof in such
  quantities and of such durations as may be or
  tend to be injurious to human, animal or plant
  life, or property, or which unreasonably
  interferes with the comfortable enjoyment of life
  or property or conduct of business.

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Who is at risk?

• Everyone faces increased risk of harm from
  exposure to these hazardous air pollutants.
• Particularly
• Children and teenagers
• Older adults
• Pregnant women
• People with asthma and other lung diseases
• People with cardiovascular diseases
• Diabetics
• People with low incomes
• People who work or exercise outdoors and
• Others with existing health problems

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Industrial Toxicants that Produce Disease of the
Respiratory Tract
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Fine particles, or haze, restrict our ability to
see long distances
Unadjusted Hourly conc. of fine particles 4
?g/m3
Hartford Oct. 8, 2002 4 p.m. EDT
Unadjusted Hourly conc. of fine particles 24
?g/m3
Hartford Oct. 2, 2002 4 p.m. EDT
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Bad Air Quality

• Ozone
• Particulate Matter
• Nitrogen Dioxide
• Sulfur Dioxide
• Hazardous Air Pollutants (Toxins)
• Carbon Monoxide

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The ozone storyGood Ozone Protect us from UV
light
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Bad Ozone

• Ground-level or "bad" ozone is not emitted
  directly into the air, but is created by chemical
  reactions between oxides of nitrogen (NOx) and
  volatile organic compounds (VOC) in the presence
  of sunlight. Emissions from industrial facilities
  and electric utilities, motor vehicle exhaust,
  gasoline vapours, and chemical solvents are some
  of the major sources of NOx and VOC.

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Ozone pollution basics
Lung attack Ozone http//www.airinfonow.org/html
/lungattack/lungplay.htm
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Particulate Matter matters

• Particulate matter (PM) is a complex mixture of
  organic and inorganic substances.

• PM pollution consists of materials (including
  dust, smoke, and soot), that are directly emitted
  into the air or result from the transformation of
  gaseous pollutants.

Image from http//www.epa.gov/eogapti1/
module3/distribu/distribu.htm
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Where Does PM Originate?

• Particles come from natural sources (e.g.,
  volcanic eruptions) and human activities such as
  burning fossil fuels, incinerating wastes, and
  smelting metals.
• Sources may emit PM directly into the environment
  or emit precursors such as sulfur dioxide (SO2),
  nitrogen dioxide (NO2), and volatile organic
  compounds (VOCs), which are transformed through
  atmospheric chemistry to form PM.

VOCs NO2 SO2
PM
Ammonia (NH3)
Ammonia (NH3)
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Sources of PM and PM Precursors
Stationary Sources (power plants,
factories) NO2, SO2, PM
Mobile Sources (vehicles) VOCs, NO2, PM
Natural Sources (forest fires, volcanoes) PM
Area Sources (drycleaners, gas stations) VOCs
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The Role of Inversions

• An inversion is an extremely stable layer of the
  atmosphere that forms over areas.
• Temperature inversions trap pollutants close to
  the ground. These inversions involve layers of
  hot air sitting above cooler air near ground
  level. When particles accumulate in the air
  layer, they are unable to rise into the
  atmosphere where winds will disperse them.

Source http//www.epa.gov/apti/ course422/
ce1.html
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PM10 PM2.5

• Particles found in ambient air range in size from
  a few nanometres (nm) to several hundred
  micrometres (µm) in diameter.
• PM10 refers to the mass concentration (expressed
  in µg m3) of particulate matter that is
  generally less than 10 millionths of a metre (10
  µm) in diameter.
• PM2.5 refers to the mass concentration of
  particles less than 2.5 µm in diameter.

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Particulate Matter Size Matters

• Particles larger than 10 µm are trapped in the
  nose and throat and never reach the lungs.
• Particles 10 µm in diameter or less are of most
  concern for their effects on human health.

• Particles between 5 and 10 µm are removed by
  physical processes in the throat.
• Particles smaller than 5 µm reach the bronchial
  tubes.
• Particles 2.5 µm in diameter or smaller are
  breathed into the deepest portions of the lungs.

Image PM2.5. By D. Hershey. From New York State
Department of Environmental Conservation.
http//www.dec.state.ny.us/website/dar/baqs/micro/
two.html
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PM2.5

• Lung attack PM2.5 http//www.airinfonow.org/html
  /lungattack/lungplay.htm

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Great smog - London
London, 1952
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What Adverse Health Effects Have Been Linked to
PM?

• Premature death
• Lung cancer
• Development of chronic lung disease
• Heart attacks
• heart and lung disease
• Decreased lung function
• Pre-term birth
• Low birth weight

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Global satellite-derived map of PM2.5 averaged
over 2001-2006
Sourcehttp//www.nasa.gov/topics/earth/features/h
ealth-sapping.html
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Increasing Evidence of Cardiovascular Effects
Until the mid 1990s, most research focused on the
association of PM exposure with respiratory
disease. Since then, there has been growing
evidence of cardiovascular health effects from
PM.
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Integrating Toxicology, Epidemiology and Clinical
Studies

• Toxicological, clinical and epidemiological
  studies have increased understanding of the
  mechanism of action by which PM leads to
  mortality and lung and heart disease.

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Toxicology, Epidemiology and Clinical Studies

• At right are stained photomicrographs of
  abdominal arteries from mice exposed to filtered
  air and air polluted with fine particulate
  matter, with the increased arterial blockage in
  the PM-exposed mice providing scientific support
  for the link between PM and atherosclerosis found
  in a study of human subjects (Kunzli et al.,
  2005).

Sun et al. JAMA, 2005
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How Does PM Cause Health Effects?

• Several theories have been advanced as to the
  mechanism of action. It is likely that more than
  one mechanism is involved in causing PM-related
  health effects. Theories include the following

1. PM leads to lung irritation which leads to
   increase permeability in lung tissue
2. PM increases susceptibility to viral and
   bacterial pathogens leading to pneumonia in
   vulnerable persons who are unable to clear these
   infections
3. PM aggravates the severity of chronic lung
   diseases causing rapid loss of airway function

• PM causes inflammation of lung tissue, resulting
  in the release of chemicals that impact heart
  function
• PM causes changes in blood chemistry that results
  in clots that can cause heart attacks.

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Air Quality Index

• The purpose of the AQI is to help you understand
  what local air quality means to your health.

Freddy
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How to use the AQI
Step 1 Determine whether you (or your family) are likely to be at risk from air pollution.
Step 2 If you may be at risk, and are planning strenuous activity outdoors, check the air pollution forecast.
Step 3 Use the health messages corresponding to the highest forecast level of pollution as a guide.
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Air Quality Index (UK)
Sourcehttp//www.comeap.org.uk/images/stories/Doc
uments/Reports/comeap20review20of20the20uk20a
ir20quality20index.pdf
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Health Advice to Accompany the Air Quality Index
Enjoy your usual outdoor activities.
At-risk individuals should consider reducing
strenuous physical activity, particularly
outdoors. General population could enjoy usual
outdoor activities.
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Health Advice to Accompany the Air Quality Index
At-risk individuals should reduce strenuous
physical exertion, particularly outdoors, and
particularly if they experience symptoms. People
with asthma may find they need to use their
reliever inhaler more often. Older people should
also reduce physical exertion. Anyone
experiencing discomfort such as sore eyes, cough
or sore throat should consider reducing activity,
particularly outdoors.
Adults and children with lung problems, adults
with heart problems, and older people, should
avoid strenuous physical activity. People with
asthma may find they need to use their reliever
inhaler more often. Reduce physical exertion,
particularly outdoors, especially if you
experience symptoms such as cough or sore throat.
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