Responses to Exposure to Low Levels of Concentrated Ambient Particles in Healthy Young Adults
Condition: Exposure to Pollution
Study type: Interventional

Summary: 
      Purpose: To determine whether exposure to levels of fine particles that are close to the
      current standard will cause cardiovascular changes in healthy individuals.
    

Detailed description: 
      Air pollution is associated with several adverse health outcomes. Specifically, ambient fine
      particulate matter ≤2.5 μg/m3 (PM2.5) is associated with increased mortality and increased
      risk for respiratory and cardiovascular disease It has been estimated that worldwide over 3.2
      million premature deaths and over 74 million years of healthy life lost were attributable to
      ambient particulate matter pollution, making it one of the top global health risk factors .
      Further, an estimated 22% of disability-adjusted life-years for heart disease are
      attributable to ambient particulate matter pollution. Similarly, it is estimated that air
      pollution exposure contributed to about 6% (3.7 million) of all deaths in 2012, with 40% of
      those coming from coronary artery disease (CAD). More than 100 time-series and case-crossover
      analyses have demonstrated associations of short term PM2.5 exposure with myocardial
      infarctions (MIs); aggravated asthma and increased risk for hospitalizations and mortality.
      These studies suggest that the acute health effects of air pollution particularly affect
      infants and children, older adults, and those with underlying disease, such as diabetes and
      cardiovascular disease (Pope, 2014). In healthy and younger individuals (<65 year old) these
      same studies observe associations between air pollution and subclinical biomarkers of
      inflammation, coagulation and oxidative stress but not for any clinical outcomes. This has
      led the American Heart Association to state that" Despite theoretical statistical risks
      ascribed to all individuals, this elevated risk from exposure is not equally distributed
      within a population. At present-day levels, PM2.5 likely poses an acute threat principally to
      susceptible people, even if seemingly healthy, such as the elderly and those with
      (unrecognized) existing coronary artery or structural heart disease."

      Controlled human exposure studies are a critical component of the health risk assessment for
      ozone because of their ability to establish exposure-response relationships at low doses and
      have therefore weighed heavily in deliberations when the U.S. EPA has considered the National
      Ambient Air Quality Standard (NAAQS). In contrast, for PM2.5, controlled exposure studies
      have been used primarily to demonstrate biological plausibility. that is the potential for
      particulate matter to exert extra-pulmonary effects. These studies have shown that healthy
      volunteers primarily exhibit mild pulmonary inflammation, decreases in heart rate variability
      and changes in blood factors associated with blood coagulation following exposure to
      concentrated air particles (CAPs), most show no change in lung function and none result in
      cardiac arrhythmia. Nearly all these studies have been conducted at realistic but high levels
      of PM2.5 (typically above 100 µg/m3). Currently the EPA 24-hour fine particle standard is
      35µg/m3, a value based predominantly on epidemiologic studies. While epidemiologic studies
      suggest that similar effects can occur at lower levels, it is difficult for these association
      studies to conclusively demonstrate because of the problems in disassociating the effects of
      PM2.5 from other pollutants and confounders. Only a controlled human exposure study can
      determine directly whether PM2.5 can alter cardiovascular endpoints at lower concentrations.
      Four hours represents a typical exposure duration to particulate matter during the course of
      the day.
    

Intervention name(s): Clean Air; PM2.5
Intervention type(s): Other; Other
Intervention description(s): Each subject will be exposed to clean air for 4 hours. Subjects will exercise on a bike or treadmill. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/min/m2BSA followed by a 15 minute rest period.; Each subject will be exposed up to 35-50 μg/m3 PM2.5 for 4 hours. Subjects will exercise on a bike or treadmill. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/min/m2BSA followed by a 15 minute rest period.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Clean Air
Concentrated PM2.5
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Controlled Human Exposure Study; Cardiovascular