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

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.

Inclusion Criteria:

• Healthy individuals ages 18-35 years of age

• Physical conditioning allowing intermittent, moderate exercise for four hours. Ability to complete the exposure exercise regimen without reaching 80% of predicted maximal heart rate. Predicted maximal heart rate will be calculated using the equation (described by Tanaka et al.: [2001] J. Am. Coll. Cardiol.): [208bpm-((0.7) x (age in years))]

• Normal baseline 12-lead EKG .

• Normal lung function

  1. Forced vital capacity (FVC) ≥ 80% of that predicted for gender, ethnicity, age and height (according to NHANESIII guidelines).
  2. Forced expiratory volume in one second (FEV1) ≥ 80%of that predicted for gender,ethnicity, age and height
  3. FEV1) /FVC ratio≥ 80% of predicted values.

• Oxygen saturation ≥ 96% on room air.

Exclusion Criteria:

• Individuals with a history of acute or chronic cardiovascular disease, chronic respiratory disease, diabetes, rheumatologic diseases, or immunodeficiency state.
• Individuals with a CVD risk score greater than 10% using the ACC/AHA ASCVD risk calculator.
• Individuals with clinically diagnosed asthma.
• Individuals who are allergic to chemical vapors or gases.
• Females who are pregnant, attempting to become pregnant, or breastfeeding.
• Individuals that are unable or unwilling to stop for at least two weeks prior to the study taking medications, vitamins or supplements that the investigators believe may impact the results of the study. Those not specifically mentioned here may be reviewed by the investigators prior to an individual's inclusion in the study.
• Individuals who smoke/vape more than 2 times per month and have smoked/vaped within 4 weeks prior to all study visits.
• Individuals living with a smoker who smokes inside the house.
• Individuals with a body mass index (BMI) >35 or <18. Body mass index is calculated by dividing the weight in kilograms by the square of the height in meters.
• Individuals with occupational exposures to high levels of vapors, dust, gases, or fumes on an on-going basis.
• Individuals with uncontrolled hypertension (≥150 systolic or ≥90 diastolic).
• Individuals that do not understand or speak English.
• Individuals that are unable to perform the exercise required for the study.
• Individuals that are taking beta blocker medications.
• Individuals with a history of skin allergies to adhesives used in securing EKG electrodes.
• Individuals with unspecified diseases, conditions, or medications that might influence the responses to the exposures, as judged by the medical staff.
• Individuals that are unwilling or unable to stop taking over-the-counter pain medications such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), or other non-steroidal anti-inflammatory ("NSAID") medications for 48 hours prior to the exposures and post-exposure visits.
• Individuals that are taking systemic steroids or beta-blocker medications.
• Individuals with a hemoglobin A1c (HbA1c) level > 6.4%.

Temporary Exclusion Criteria:

• Individuals suffering from acute respiratory illness within four weeks prior to any of the study exposure series.
• Individuals that have been exposed to smoke and fumes within 24 hours of any study visit.
• Individuals that have engaged in strenuous exercise within 24 hours of any study visit.
• Individuals that have been exposed to ozone-based home air purifiers within 24 hours of any study visit.
• Individuals unable to avoid drinking alcohol for 24 hours prior to all study visits.
• Individual unable to avoid caffeine for 12 hours prior to all study visits and during each study visit.
• Individuals that have been exposed to unvented household combustion sources (gas stoves, lit fireplaces, oil/kerosene heaters) within 48 hours of any study visit.
• Individuals that have been exposed to or have consumed any agent or have undertaken any activity within 24 hours of any study visit that the investigators believe may compromise the results of the study.

IPD will not be shared.