title: Exposure to medium and high ambient levels of ozone causes adverse systemic inflammatory and cardiac autonomic effects.
abstract: Epidemiological evidence suggests that exposure to ozone increases cardiovascular morbidity. However, the specific biological mechanisms mediating ozone-associated cardiovascular effects are unknown. To determine whether short-term exposure to ambient levels of ozone causes changes in biomarkers of cardiovascular disease including heart rate variability (HRV), systemic inflammation, and coagulability, 26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h with intermittent exercise. HRV was measured and blood samples were obtained immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after exposure. Regression modeling was used to examine dose-response trends between the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent adverse changes in the frequency domains of HRV across exposures consistent with increased sympathetic tone [increase of (parameter estimate ± SE) 0.4 ± 0.2 and 0.3 ± 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose-dependent increase in serum C-reactive protein (CRP) across exposures at 24 h [increase of 0.61 ± 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)]. Changes in HRV and CRP did not correlate with ozone-induced local lung inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and CRP were associated with each other after adjustment for age and ozone level. Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic effects that may contribute to the cardiovascular mortality associated with short-term exposure.
authors: Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California; Pulmonary Research Group, San Francisco Veterans Affairs Medical Center, San Francisco, California; mehrdad.arjomandi@ucsf.edu.
authors: Mehrdad
authors: M
authors: Arjomandi
authors: Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California;
authors: Hofer
authors: H
authors: Wong
authors: Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California;
authors: Aneesh
authors: A
authors: Donde
authors: Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California; Pulmonary Research Group, San Francisco Veterans Affairs Medical Center, San Francisco, California;
authors: Jessica
authors: J
authors: Frelinger
authors: Pulmonary Research Group, San Francisco Veterans Affairs Medical Center, San Francisco, California;
authors: Sarah
authors: S
authors: Dalton
authors: Pulmonary Research Group, San Francisco Veterans Affairs Medical Center, San Francisco, California;
authors: Wendy
authors: W
authors: Ching
authors: Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California;
authors: Karron
authors: K
authors: Power
authors: Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California; School of Public Health, University of California Berkeley, Berkeley, California.
authors: John R
authors: JR
authors: Balmes
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D019570:Inhalation Exposure / Q000009:adverse effects; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010126:Ozone / Q000009:adverse effects*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D013997:Time Factors; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D010126:Ozone; D002097:C-Reactive Protein; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: airway inflammation; heart rate variability; inhalational exposure; ozone; systemic inflammation