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Inflammatory Responses to Exposures of Concentrated Ambient Particles in Susceptible Volunteers
This page updated May 11, 2010
Chair’s Air Pollution Seminar |
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Friday, May 28,
2010
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Inflammatory Responses to
Exposures
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Marc Riedl, M.D., M.S.David
Geffen School of Medicine
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Respirable
particulate matter (PM) is associated with harmful cardiopulmonary
effects in humans. To test the hypothesis that individuals with certain
susceptibility factors have heightened inflammatory and airway
responses to PM exposure, a single-blind randomized dose crossover
human study of controlled exposure to filtered air (FA), and
concentrated ambient particles (CAPS) was conducted.
Susceptibility factors of interest included pre-existing asthma and
glutathione-s-transferase mu 1 (GSTM1) null genotype, as absence of
GSTM1 expression has previously been shown to confer susceptibility to
the inflammatory effects of particulates including diesel exhaust
particles and environmental tobacco smoke. We enrolled 10 mild-
moderate asthmatic GSTM1 null subjects, 10 mild- moderate asthmatic
GSTM1 present subjects and 10 healthy GSTM1 present subjects to
determine the short-term effects of CAPS exposure in individuals likely
to be at risk for adverse effects. Outcome measures included
symptom scores, physiologic measures (vital signs, spirometry, exhaled
nitric oxide, heart rate variability) as well as serum, sputum, and
nasal lavage samples for inflammatory biomarkers. Particle
mass concentrations averaged 187µg/m3 for CAPS and 35 µg/m3 for FA
during the 2-hour exposures. During both CAPS and FA exposures,
GSTM1-null asthmatics reported increased symptom scores while decreased
systolic blood pressure was observed in all groups. Mean exhaled nitric
oxide concentration (FeNO) was increased immediately after CAPS
exposure compared to FA for all subjects. Sputum total cell counts
trended higher after CAPS than after FA exposures and nasal lavage IgG4
was increased after CAPS and decreased after FA exposure for the entire
population. Heart rate variability (HRV) data demonstrated
increased heart rate and decreased HRV post-exposure across all groups
regardless of exposure conditions (CAPS or FA). CAPS exposure
and susceptibility group showed minimal effects on HRV changes.
Overall, a few endpoints supported the hypothesis of increased airway
inflammation with CAPS exposure. However, the results did not
demonstrate an effect of asthma or GSTM1 status on the inflammatory
response to CAPS.
Marc Riedl, M.D., M.S., is Assistant Professor of
Medicine and section head of Clinical Immunology and Allergy,
Department of Medicine at the David Geffen School of Medicine,
University of California, Los Angeles (UCLA). Dr. Riedl
received his medical degree from the University of Chicago Pritzker
School of Medicine and completed his Internal Medicine training at
Washington University/Barnes-Jewish Hospital, St Louis. He completed a
fellowship in Allergy/Immunology at UCLA, where he also pursued
advanced work in Clinical Pharmacology and received a Master’s degree
in Clinical Research. Dr. Riedl is a diplomate of the
American Board of Internal Medicine, the American Board of Allergy and
Immunology, and the American Board of Clinical Pharmacology.
At UCLA, he directs the Clinical Immunology and Allergy Consultation
Service, and leads an active clinical research program funded by
federal, state, and industry sponsors. His professional interests
include the development of novel therapeutics for the treatment of
allergic and immunodeficient conditions. Dr.
Riedl is integrally involved in phase I to III development of
investigational drugs, with particular interest in the treatment of
hereditary angioedema and common variable immunodeficiency. Dr. Riedl's
clinical research also includes investigation of compounds to reduce
the inflammatory effects of air pollution. logies.
For information
on this Series please contact: For
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