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Concentrated Ambient Ultrafine Particle Exposure Induces Cardiac Changes in Young Healthy Volunteers

¹ Human Studies Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina; ² Brody School of Medicine at East Carolina University, Greenville, North Carolina; ³ TRC Corporation, Chapel Hill, North Carolina; and ⁴ Center for Environmental Medicine, Asthma and Lung Biology, Chapel Hill, North Carolina

Correspondence and requests for reprints should be addressed to James M. Samet, Ph.D., EPA Human Studies Division, 104 Mason Farm Road, Chapel Hill, NC 27599-7315. E-mail: samet.james{at}epa.gov

Rationale: Exposure to ambient ultrafine particles has been associated with cardiopulmonary toxicity and mortality. Adverse effects specifically linked to ultrafine particles include loss of sympathovagal balance and altered hemostasis.

Objectives: To characterize the effects of acute exposure to ambient ultrafine particles in young healthy humans.

Methods: Nineteen healthy nonsmoking male and female subjects between the ages of 18 and 35 were exposed to filtered air or to an atmosphere in which captured ultrafine (<0.16 µm) particles were concentrated by a factor of up to 20-fold over ambient levels with the use of particle concentrators fitted with size-selective outlets (ultrafine concentrated ambient particles [UFCAPs]). Subjects underwent bronchoalveolar lavage 18 hours after each exposure. Cardiovascular endpoints measured included pulmonary function, clinical chemistry, and hematological parameters, as well as heart rate variability and repolarization indices.

Measurements and Main Results: Exposure to UFCAPs was statistically associated with an increase in frequency domain markers of heart rate variability, specifically indicative of elevated vagal input to the heart. Consistent with this finding were increases in the variance associated with the duration of the QT interval. In addition, UFCAP exposure resulted in a significant increase in blood levels of the fibrin degradation product D-dimer as well as a modest elevation in the inflammatory chemokine IL-8 recovered in the lavage fluid.

Conclusions: These findings show mild inflammatory and prothrombic responses and are suggestive of alterations in cardiac repolarization induced by UFCAP inhalation.

Key Words: particulate matter • human • clinical study • heart rate variability • bronchoalveolar lavage

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Exposure to ambient ultrafine particles is associated with adverse health effects. The mechanisms involved are not understood. What This Study Adds to the Field This study shows that exposure to ultrafine particles results in prothrombotic and proinflammatory responses as well as alterations in cardiac repolarization.