Environmental Research Group
Lung Biology »
In VitroPM screening program
Strong epidemiological evidence supports an association between the mass of small particles in the air and
increased rates of cardiac and pulmonary illness and death. However the strength of these associations
differs significantly between cities and countries suggesting that the concentration of particles
in the air alone is not the only driving force for these effects.
In light of this, a considerable research effort is underway to identify those characteristics
of airborne particles responsible for their effects, and related to this, the biological mechanisms
underlying their toxicity. To address these issues we have developed screening procedures,
which assesses the capacity of these particles to oxidise a range of protective molecules
present within the thin layer of liquid which lines the respiratory tract.
This is illustrated in the right hand figure as the dense band labelled Sf, overlaying the lung surface.
This measurement of oxidative capacity effectively integrates a number of particle characteristics
including size, surface area and composition yielding a single measure of biological
activity that can be used as a denominator for the mass of particles in the air.
There is a variation in the activity of PM collected from various sites within Europe.
It has been proposed that the capacity of inhaled particles to cause biological oxidations results
in lung injury and the development of inflammation and may underpin many of the health effects
reported in exposed populations. After establishing particle activity it is possible through the
use of specific metal inhibitors, or the removal of organic species, to establish where the bulk
of this activity resides. Thus this screening procedure also permits the identification of the
toxic components of environmental particulates.
Human Challenge program
Working with colleagues in Umeå in Northern Sweden we undertake human challenge studies to investigate
the impact of controlled exposures to diesel and gasoline exhaust, as well as single gas exposures
with ozone and nitrogen dioxide on the lung. These studies are performed in both healthy volunteers
and subjects with pre-existing respiratory disease. At set periods after exposure to environmentally
relevant concentrations of these agents airway responses are examined by inserting a catheter
(a bronchoscope) into the lung and washing the surface of the airways with saline, a procedure known as lavage.
The cells recovered using this method can then be measured to determine the extent of inflammation as well
as the concentration of proteins related to lung injury. In addition the concentration of antioxidants
are determined to establish the extent of particle-induced oxidative stress. Small tissue samples
are also be obtained using this method allowing a range of inflammatory and injury markers to be
examined in the tissue.
In addition we have also performed airway instillation experiments where particles collected from
the environment are instilled directly to the airway to determine their pro-inflammatory and oxidative capacity.
This work allows us to compare the activity of the particles established in our screening procedure
with the airway effects observed in subjects breathing these same particles. It also permits us to
examine the mechanisms by which inhaled particles and gases impact upon the lung.
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