Synergistic effects of exposure to concentrated ambient fine pollution particles and nitrogen dioxide in humans

Inhal Toxicol. 2012 Oct;24(12):790-7. doi: 10.3109/08958378.2012.718809.


Context: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.

Objectives: Determine if simultaneous exposure to PM and NO₂ results in synergistic interactions.

Materials and methods: Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO₂, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM(2.5)CAPs, 89.5 ± 10.7 µg/m³), or NO₂+PM(2.5)CAPs for 2 h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18 h after exposure. Bronchoalveolar lavage (BAL) was performed 18 h after exposure.

Results: NO₂ exposure alone increased cholesterol and HDL 18 h after exposure, decreased high frequency component of HRV one and 18 h after exposure, decreased QT variability index 1 h after exposure, and increased LDH in BAL fluid. The only significant change with PM(2.5)CAPs was an increase in HDL 1 h after exposure, likely due to the low concentrations of PM(2.5)CAPs in the exposure chamber. Exposure to both NO₂ and PM(2.5)CAPs increased BAL α1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO₂ or PM(2.5)CAPs alone, suggesting possible interactions between the two pollutants.

Discussion and conclusions: NO₂ exposure may produce and enhance acute cardiovascular effects of PM(2.5)CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.

Publication types

  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Air Pollutants / toxicity*
  • Arrhythmias, Cardiac / chemically induced
  • Atmosphere Exposure Chambers
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cardiovascular Agents / toxicity*
  • Cardiovascular System / drug effects*
  • Cardiovascular System / metabolism
  • Cholesterol / blood
  • Drug Synergism
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hypercholesterolemia / chemically induced
  • Lactate Dehydrogenases / metabolism
  • Male
  • Nitrogen Dioxide / toxicity*
  • North Carolina
  • Particulate Matter / toxicity*
  • Young Adult
  • alpha 1-Antitrypsin / metabolism


  • Air Pollutants
  • Cardiovascular Agents
  • Particulate Matter
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin
  • Cholesterol
  • Lactate Dehydrogenases
  • Nitrogen Dioxide