Cardiopulmonary Responses to Exposure to Ozone and Diesel Exhaust
Condition: Respiratory Depression; Blood Pressure
MeSH terms: Respiratory Insufficiency
Study type: Interventional

Summary: 
      The US EPA Clean Air Multiyear research program is moving toward a multi-pollutant approach
      to the assessment of air pollution in response to recommendations by the NRC 2004 and the
      BOSC in 2005. Such an approach better reflects the complexity of real-world air pollution
      problems and parallels evolving scientific and regulatory considerations. Ozone (O3) and
      diesel exhaust (DE) generally are major and important components of ambient air pollution.
      This proposed study will address the agency's goals by investigating the cardiopulmonary
      health effects in healthy human subjects co-exposed to O3 and DE. The findings derived from
      these exposures will provide NCEA findings for risk assessments of O3 and DE, as well as the
      Office of Air and Radiation (includes OTAQ and OAQPS) with information relevant to possible
      modulation of PM-induced health effects and responses by a gaseous co-pollutant for potential
      standard setting. Additionally the findings will address the fundamental driving principle of
      the Clean Air Research strategy related to reduction of health due to air pollutant
      exposures.
    

Detailed description: 
      Numerous epidemiological studies have demonstrated an association between acute and chronic
      exposure to air pollution and various adverse cardiopulmonary effects including mortality,
      respiratory tract infections, exacerbation of asthma symptoms, chronic bronchitis, ischemic
      heart disease, and stroke [1] and other health effects. Understanding the components
      responsible for these effects is difficult because ambient air pollution is a complex mixture
      of gases and particulate matter (PM). In this complex mixture of ambient air pollution, ozone
      (O3) and diesel exhaust (DE) are generally major and important components. Controlled
      exposure of volunteers to either pollutant have resulted in biological effects such as lung
      physiological changes. However it is not known if co-exposure to both pollutants, similar to
      polluted ambient air, can induce additive or synergistic effects. Additionally it is also
      uncertain if exposure to DE, or DE with O3, can alter a subsequent exposure to O3 similar to
      multiple day exposures that the general population receives. This study proposes to examine
      whether co-exposures to O3 and DE can induce additive or synergistic effects, and whether a
      previous DE exposure alters a response upon subsequent exposure to O3. The potential effects
      of O3 on cardiac electrophysiology are also not clear.

      Approximately 15 healthy non-smoking volunteers between the ages of 18 and 55 will be exposed
      in a controlled manner to O3 (approximately mean concentration of 0.3 ppm over the 2 hr
      exposure period), or diesel exhaust (DE; ~300 µg/m3), or a combined O3 and DE exposure while
      undergoing moderate intermittent exercise at the EPA Human Studies Facility. A clean air
      exposure will serve as a control. Primary endpoints for evaluating health effects and
      surrogate responses are changes in lung function and heart rate variability. In addition,
      other cardiopulmonary and vascular biological endpoints will be measured, as well as markers
      of exposure and genetic markers of susceptibility.
    

Intervention name(s): ozone
Intervention type(s): Other
Intervention description(s): Exposure to 300 ppb ozone with intermittent exercise about 20 hr after exposure to each arm (ie, either air, ozone, diesel exhaust, or ozone combined with diesel exhaust)
Other intervention name(s): cas # 10028-15-6; trioxygen
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Diagnostic
Keywords: ozone; diesel; lung function; cardiac electrophysiology; mediators of inflammation and clotting