Air Pollution Flashcards
what ways can you assess the impact of air pollution on health?
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
what problems are there with assessing the impact of air pollution on health?
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
at low levels of Ozone, there is correlation with what?
Hospital admissions for respiratory problems – respect to concentrations
Allergic symptoms e.g. eye irritation
Lung function indices (negative)
at low levels of sulphur dioxide, there is correlation with what?
Mortality
Hospital admissions for respiratory problems
Respiratory symptoms
Lung function indices (negative)
at low levels of particles, there is correlation with what?
Mortality Hospital admissions for respiratory prpblems Respiratory symptoms use of asthma medication lung function indices (negative)
what is the source of sulphur dioxide pollution?
fossil fuel combustion
what is the source of particle pollution?
Main source now motor vehicle emissions rather than uncontrolled coal burning = decrease in larger particles and increase in smaller particles
what is the association between ozone and asthma in healthy people?
10-20% show increase in O3 sensitivity and enhanced responsiveness in a chemical test for asthma – so its not just asthmatics
in healthy people that experience enhanced responsiveness to ozone, why is it the case?
they may be subclinical asthmatics, non-asthmatics with enhanced bronchial reactivity, or be coincidental
what is the association between asthmatics and ozone?
increase in sensitivity to O3, which is greatest in spring (low O3 concentrations, but high levels of other allergens)
what is the correlation between ozone and asthma severity?
no correlation
what is the difference between healthy people and asthmatics exposure to ozone?
exposure of asthmatics to O3 immediate increase in white blood cells and epithelial cells in BLF - but not in healthy people
what forms when nitrogen dioxide and O3 combine?
nitrogen pentoxide
what happens when LOW concentrations of nitrogen dioxide and O3 are given to rats?
synergistic effects on oedema and cellular inflammatory responses in lungs
what happens when CHRONIC EXPOSURE of nitrogen dioxide and O3 are given to rats?
deaths and severe and irreversible pulmonary fibrosis
what are eicosanoids and what do they do?
Prostaglandins and leukotrienes - Promote inflammation, chemotaxis and vascular responses
what is chemotaxis?
migration of wbc etc. to the area
what are cytokines and what do they do?
Interleukins, tumour necrosis factors, platelet derived growth factor - Involved in white blood cell activation and fibroblast proliferation
what inflammatory mediators are produced by the lungs?
eicosanoids
cytokines
ROS
Fibronectin, platelet activating factor, lysosomal enzymes
what are Fibronectin, platelet activating factor, lysosomal enzymes involved in?
Involved in cell adhesion, platelet activation & removal of foreign material
how does phase 1 ozone damage the epithelium?
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
how does phase 2 ozone damage the epithelium?
- Neutrophil infiltration mediated by signalling molecules released from epithelial cells
- Production of further eicosanoids
& cytokines - Release of proteinases by neutrophils -> tissue damage & destruction of proteinase inhibitors
how does phase 3 ozone damage the epithelium?
- Infiltration by eosinophils (asthma)
or monocytes (bronchitis) - Release of growth factors
- Initiation of repair AND Production of antioxidant enzymes
in studies for ozone and immune function, what are the observed effects?
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
what are the Systemic effects of ozone in rodents?
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
how are particles removed from the conducting airways?
Removed by mucociliary escalator
how are particles removed from the alveolar regions?
Phagocytosed by alveolar macrophages & transported towards mucociliary escalator
what happens on a graph during low exposure to particles?
Rate of deposition in alveolar region = rate of clearance by macrophages
rate of clearance by macrophages
Rapid clearance on cessation of exposure
what happens on a graph during high exposure to particles?
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
what is the Mechanism of Fibrosis Induced by Particle Overload?
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
what do Silicates do in terms of ROS?
Silicates increase production of hydroxyl radicals & singlet oxygen -> lipid peroxidation
what does lipid peroxidation lead to?
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
what happens in Enhanced eicosanoid production?
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
what happens in Enhanced cytokine production?
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
