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Is there a
difference in the uptake of ultrafine particles in healthy subjects,
asthmatics and smokers?
Traffic related air pollution is
held to contribute to pulmonary diseases and reactive airways effects. It
has been proposed that the world-wide increased prevalence of allergy and
asthma might be caused by exposure to air pollution. The uptake and
distribution of ultrafine combustion particles have not been studied in
humans. The consequences of exposure to ultrafine particles in subjects who
have already an increased pulmonary epithelial permeability, are not known.
The objectives of
the study are to modify a clinically used method to produce ultrafine
radiolabelled particles, and to use these particles to determine whether
there is a difference in lung retention between healthy subjects,
asthmatics and smokers. Further, to determine the uptake of ultrafine
particles into the systemic circulation. The hypothesis is that due to
various degrees of respiratory epithelial inflammation, a greater part of
the ultrafine particles can pass the lung barrier of asthmatics and to an
even greater extent among smokers.
The measurement of
lung clearance of inhaled 99mTc-Iabelled carbon particles,
Technegas, will be used to assess the uptake. Technegas is an ultrafine
radioactive aerosol normally used for lung scintigraphy. The particle size
distributions will be measured by use of the particles electrical mobility.
The amount ultrafine particles entering the blood system will be determined
by radioactivity in urine. The working plan includes generation of a
stable aerosol of 99mTc-Iabelled ultrafine particles <100 nm
by dilution of the aerosol produced by a Technegas generator. ln a study
on voluntary humans the uptake of inhaled ultrafine particles will be
measured in healthy subjects, asthmatics and smokers. The leakage, i.e.
the activity not bound to particles in the aerosol, will be estimated in
vitro in order to measure the correct uptake of particles. By ultra
filtration it is possible to separate particles from the fraction of
activity that is not bound to particles.
A continuation is
planned for a third year with the generation of particles labelled with
isotopes other than 99mTc, i.e. 111In with a
half-life of 2,8 days, which will enable us to follow clearance up to
about 30 days in a study on human volunteers. We also intend to generate 99mTc-Iabelled
ultrafine particles of different sizes by alteration of temperature,
aerosol concentration and time factor. A study on healthy volunteers will
reveal if the size of the ultrafine particles have any influence on the
uptake.
Results will be
presented according to the plan for dissemination within SNAP. |
