Air Pollution

Question 1

what ways can you assess the impact of air pollution on health?

Answer 1

Mortality
Hospital admissions/GP visits for respiratory problems
Incidence/duration/severity of respiratory problems
Changes in lung fucti9on indices, e.g. forced expiratory volume
Pulmonary oedema
Inflammatory mediators/inflammatory cells in bronchoalveolar lavage fluid (BLF)
Decrease in antioxidants in BLF
Markers of ROS damage in exhaled breath, e.g. aldehydes
Evidence of genetic damage

Question 2

what problems are there with assessing the impact of air pollution on health?

Answer 2

Mixtures of pollutants –ozone, particulates, nitrous oxide?
Composition varies with time and space
Chosen end point may influence results
Results may not indicate severity of problem - i.e. Would they have died anyway? 24hr difference? Or would they have lived 3-5 years more had the pollution levels not been so high? Different types of concern

Some groups high risk i.e. children, elderly and those with respiratory disease
May other variables influence outcome, e.g. weather, infections, antioxidant consumption

Question 3

at low levels of Ozone, there is correlation with what?

Answer 3

Hospital admissions for respiratory problems – respect to concentrations
Allergic symptoms e.g. eye irritation
Lung function indices (negative)

Question 4

at low levels of sulphur dioxide, there is correlation with what?

Answer 4

Mortality
Hospital admissions for respiratory problems
Respiratory symptoms
Lung function indices (negative)

Question 5

at low levels of particles, there is correlation with what?

Answer 5

Mortality
Hospital admissions for  respiratory prpblems
Respiratory symptoms
use of asthma medication
lung function indices (negative)

Question 6

what is the source of sulphur dioxide pollution?

Answer 6

fossil fuel combustion

Question 7

what is the source of particle pollution?

Answer 7

Main source now motor vehicle emissions rather than uncontrolled coal burning = decrease in larger particles and increase in smaller particles

Question 8

what is the association between ozone and asthma in healthy people?

Answer 8

10-20% show increase in O3 sensitivity and enhanced responsiveness in a chemical test for asthma – so its not just asthmatics

Question 9

in healthy people that experience enhanced responsiveness to ozone, why is it the case?

Answer 9

they may be subclinical asthmatics, non-asthmatics with enhanced bronchial reactivity, or be coincidental

Question 10

what is the association between asthmatics and ozone?

Answer 10

increase in sensitivity to O3, which is greatest in spring (low O3 concentrations, but high levels of other allergens)

Question 11

what is the correlation between ozone and asthma severity?

Answer 11

no correlation

Question 12

what is the difference between healthy people and asthmatics exposure to ozone?

Answer 12

exposure of asthmatics to O3 immediate increase in white blood cells and epithelial cells in BLF - but not in healthy people

Question 13

what forms when nitrogen dioxide and O3 combine?

Answer 13

nitrogen pentoxide

Question 14

what happens when LOW concentrations of nitrogen dioxide and O3 are given to rats?

Answer 14

synergistic effects on oedema and cellular inflammatory responses in lungs

Question 15

what happens when CHRONIC EXPOSURE of nitrogen dioxide and O3 are given to rats?

Answer 15

deaths and severe and irreversible pulmonary fibrosis

Question 16

what are eicosanoids and what do they do?

Answer 16

Prostaglandins and leukotrienes - Promote inflammation, chemotaxis and vascular responses

Question 17

what is chemotaxis?

Answer 17

migration of wbc etc. to the area

Question 18

what are cytokines and what do they do?

Answer 18

Interleukins, tumour necrosis factors, platelet derived growth factor - Involved in white blood cell activation and fibroblast proliferation

Question 19

what inflammatory mediators are produced by the lungs?

Answer 19

eicosanoids
cytokines
ROS
Fibronectin, platelet activating factor, lysosomal enzymes

Question 20

what are Fibronectin, platelet activating factor, lysosomal enzymes involved in?

Answer 20

Involved in cell adhesion, platelet activation & removal of foreign material

Question 21

how does phase 1 ozone damage the epithelium?

Answer 21

Ozone & airway epithelial cell plasma membrane
attacks lipids and proteins

LIPIDS:
Active products attack on other cell components AND Eicosanoid production = cytokine production

PROTEINS:
Failure to destroy inflammatory & neuropeptides due to enzyme damage = cytokine production

Question 22

how does phase 2 ozone damage the epithelium?

Answer 22

1. Neutrophil infiltration mediated by signalling molecules released from epithelial cells
2. Production of further eicosanoids
   & cytokines
3. Release of proteinases by neutrophils -> tissue damage & destruction of proteinase inhibitors

Question 23

how does phase 3 ozone damage the epithelium?

Answer 23

1. Infiltration by eosinophils (asthma)
   or monocytes (bronchitis)
2. Release of growth factors
3. Initiation of repair AND Production of antioxidant enzymes

Question 24

in studies for ozone and immune function, what are the observed effects?

Answer 24

1) Lymphoid organ weight and cellularity
2) Functional capacity of lymphocytes in the absence of antigenic stimulation e.g. T cell proliferation induced by Con A
3) Response of lymphocytes to antigen
4) Ability of alveolar macrophages to perform phagocytosis
5) Host response to infectious agents

Question 25

what are the Systemic effects of ozone in rodents?

Answer 25

1) Increase in vassal and cytokine stimulated production of nitric oxide by liver 2) Increase in hepatic protein synthesis 3) May be mediated by cytokines e.g. interleukin-1 and tumour necrosis factor–α 4) Acute decrease in phagocytic capacity of peritoneal macrophages 5) May be mediated via prostaglandins

Question 26

how are particles removed from the conducting airways?

Answer 26

Removed by mucociliary escalator

Question 27

how are particles removed from the alveolar regions?

Answer 27

Phagocytosed by alveolar macrophages & transported towards mucociliary escalator

Question 28

what happens on a graph during low exposure to particles?

Answer 28

Rate of deposition in alveolar region = rate of clearance by macrophages rate of clearance by macrophages Rapid clearance on cessation of exposure

Question 29

what happens on a graph during high exposure to particles?

Answer 29

Rate of deposition > rate of clearance Slow clearance on cessation of exposure Deposition can be irreversible, e.g. due to uptake of particles by epithelial cells & accumulation of particles in interstitium

Question 30

what is the Mechanism of Fibrosis Induced by Particle Overload?

Answer 30

particle over load means uptake by epithelial cells and alveolar macrophages and neutrophils uptake by endothelial cells causes damage to epithelium uptake by alveolar macrophages and neutrophils causes release of enzymes and ROS which also causes damage to epithelium uptake by alveolar macrophages and neutrophils also causes direct fibroblast proliferation the damage to the epithelium causes direct fibroblast proliferation the damage to the epithelium also increases access to the interstitium which leads to uptake by interstitial macrophages which releases growth factors which lead to fibroblast proliferation

Question 31

what do Silicates do in terms of ROS?

Answer 31

Silicates increase production of hydroxyl radicals & singlet oxygen -> lipid peroxidation

Question 32

what does lipid peroxidation lead to?

Answer 32

Promotion of lipid peroxidation correlated with ability of silicates to cause red cell haemolysis & release of enzymes from alveolar macrophages, but not with ability to promote production of hydroxyl radicals

Question 33

what happens in Enhanced eicosanoid production?

Answer 33

1) Silicates increase eicosanoid production by alveolar macrophages 2) May be mediated via interaction of silicates with plasma membrane, via internalised material or indirectly via ROS 3) Inflammation caused by silicates reduced if eicosanoid production inhibited, e.g. by steroids

Question 34

what happens in Enhanced cytokine production?

Answer 34

1) Human alveolar macrophages from individuals exposed to silicates produce increased levels of cytokines 2) Human alveolar macrophages incubated with amorphous or crystalline silica -> increase in cytokine production 3) May be mediated via interaction of silicates with plasma membrane, via internalised material or indirectly via ROS