ARB Research Seminar
This page updated June 19, 2013
Inflammatory Responses to Exposures of Concentrated Ambient Particles in Susceptible Volunteers
Marc Riedl, M.D., M.S., David Geffen School of Medicine, University of California, Los Angeles
May 28, 2010
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA
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.