Purpose:

The purpose of this protocol is to understand how social factors such as psychosocial stress may modify how people respond to air pollution. Ultimately this will help us understand health disparities from poor air quality.

Participants:

Up to 40 healthy adults,18-33 years old with different perception of stress will participate and complete this study.

Procedures (methods):

Subjects will be exposed to clean air and to ozone ( 300ppb) for 2 hours in a controlled environment chamber. Cardiac, vascular, pulmonary and cognitive function will be evaluated pre, immediately post and 18 hr post exposure.

The primary endpoint will be Heart Rate Variability . Secondary endpoints will include pulmonary function, analysis of blood clotting/coagulation factors, biomarkers of stress, cognitive function, radial artery pulse wave measurements and analysis of soluble factors present in plasma.

Over the past decades, air quality in the U.S. has improved significantly. Even so, millions of people in the U.S. still live in counties that do not meet air quality standards for one or more pollutants. Ozone is a major component of photochemical smog and is one of the most thoroughly studied gaseous pollutants. Controlled human exposure studies have been critical in demonstrating that it can cause airway inflammation 1-3, including increases in neutrophil infiltration into the lung and the production of pro-inflammatory mediators 4,5[, and ultimately decrements in lung function [reviewed in 6]. More recent studies have shown that ozone can also increase vascular inflammation, as well as alter autonomic nervous system control of heart rate and cardiac repolarization 7. Numerous epidemiological studies have also demonstrated an association between acute and chronic exposure to ambient levels of ozone and various health effects most notably asthma 6. These studies have also highlighted a need to incorporate social and nonchemical factors into risk assessments 8. Similarly, social factors such as psychological stress are now regarded as important contributors to asthma outcomes 9,10. This protocol is aimed at investigating how stress impacts health responses to air pollutants. Since psychosocial stress-related susceptibility has been proposed to explain social disparities, this will help us understand which populations and individuals are at increased risk from air pollution.

This protocol is designed to determine whether nonchemical stressors exacerbate ozone effects. In particular we will focus on elevated psychosocial stress as it has been shown to contribute to several adverse health outcomes, most notably, to cardiovascular disease. The physiological mechanism by which psychosocial stress leads to health effects is due, at least in part, to elevated circulating glucocorticoids, or stress hormones, which are regulated by the hypothalamic-pituitary-adrenal (HPA). In the last 30 years the concept of allostasis has evolved. Allostasis is the process whereby an organism adapts to the demands of the environment. An allostatic load model applies this concept to chronic stress11. In this model the perception of threat over long time intervals (perceived stress) can cause over-activation of the HPA-axis resulting in changes in physiological systems as chemical imbalances in autonomic nervous system, central nervous system, neuroendocrine, and immune system activity. Factors such as genetics, behavior, life events and diet can impact this model. To our knowledge no clinical study has investigated the link between air pollution effects on cardiovascular disease and psychosocial stress. However, several studies have now shown an association between stress and respiratory outcomes to air pollution. Claugherty and colleagues (2007) found an association between traffic-related air pollution and asthma solely among children exposed to violence 12. Shankardass and colleagues demonstrated that children from stressful households are more susceptible to the effects of traffic-related pollution on the development of asthma 13. In that study, stress was evaluated using the Perceived Stress Scale (PSS) developed by Dr. Sheldon Cohen of Carnegie Mellon University. This is the most widely used psychological instrument for measuring the perception of stress and has been validated in multiple studies. We will use this scale to evaluate the degree to which subjects appraise situations in their life as stressful. Heart rate variability (HRV) is considered to be a reliable biomarker of stress. Chronic stress has been shown to be associated with decreases in HRV 14. Since acute ozone exposure can also cause changes in HRV, we have chosen HRV as our primary endpoint. We hypothesize that the imbalance between the sympathetic and the parasympathetic nervous system caused by chronic stress will result in altered responses to ozone exposure that will be reflected by HRV.](streamdown:incomplete-link)

Inclusion Criteria:

• Healthy men and women between 18 and 33 years of age.

  1. 4-point Perceived Stress Symptom score <2 or >6

  2. Physical conditioning allowing intermittent, moderate exercise for two hours.

  3. 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))]

  4. Normal baseline 12-lead resting EKG, or if the automated reading is not normal the EKG must be approved by a study cardiologist.

  5. Normal lung function Forced vital capacity (FVC) ≥ 80% of that predicted for gender, ethnicity, age and height (according to NHANESIII guidelines).

     Forced expiratory volume in one second (FEV1) ≥ 80%of that predicted for gender, ethnicity, age and height.

     FEV1/FVC ratio ≥ 80% of predicted values.

  6. 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.

  2. Individuals with a Framingham risk score (Hard Coronary Heart Disease; HCHD; 10-year risk) ≥10.

  3. Individuals with asthma or a history of asthma. 4. Individuals who are allergic to chemical vapors or gases. 5. Females who are pregnant, attempting to become pregnant, or breastfeeding. 6. Individuals that are unwilling or unable to stop taking vitamin C or E, or medications that may impact the results of ozone challenge such at least two weeks prior to the study and for the duration of the study. Medications not specifically mentioned here may be reviewed by the investigators prior to an individual's inclusion in the study.

  7. Individuals who have smoked tobacco during the last five years or those with a history of >5 pack years.

  8. Individuals living with a smoker who smokes inside the house. 9. 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.

  10. Individuals with occupational exposures to high levels of vapors, dust, gases, or fumes on an on-going basis.

  11. Individuals with uncontrolled hypertension (≥150 systolic or ≥90 diastolic).

  12. Individuals that do not understand or speak English. 13. Individuals that are unable to perform the exercise required for the study. 14. Individuals that are taking beta blocker medications. 15. Individuals with a history of skin allergies to adhesives used in securing EKG electrodes.

  16. Individuals with unspecified diseases, conditions, or medications that might influence the responses to the exposures, as judged by the medical staff.

  17. 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.

  18. Individuals that are taking systemic steroids or beta-blocker medications. 19. Individuals with a hemoglobin A1c (HbA1c) level > 6.4%.

Temporary Exclusion Criteria

1. Individuals with active seasonal allergies during the time of participation in the study.
2. Individuals suffering from acute respiratory illness within four weeks prior to any of the study exposure series.
3. Individuals that have been exposed to smoke and fumes within 24 hours of any study visit.
4. Individuals that have consumed alcohol within 24 hours of any study visit.
5. Individuals that have engaged in strenuous exercise within 24 hours of any study visit.
6. Individuals that have been exposed to ozone-based home air purifiers within 24 hours of any study visit.
7. Individuals that have been exposed to unvented household combustion sources (gas stoves, lit fireplaces, oil/kerosene heaters) within 48 hours of any study visit.