Purpose: The primary purpose of this study is to measure pulmonary function, symptoms, and pulmonary inflammatory responses in healthy young adults during and immediately after exposure to a low concentration of ozone (0.070 ppm) or clean air for 6.6 hours while undergoing moderate intermittent exercise. This concentration is the current EPA NAAQS standard for ozone.

Potential health effects of ozone have been extensively studied over decades at various levels of exposure concentration and for varying time periods in young healthy adult subjects. Effects of ozone have been well documented particularly for decrements of lung function and an influx of neutrophils and other markers of pulmonary inflammation. The majority of those studies were done at ozone concentrations between 0.12 and 0.40 ppm, considerably higher than the current EPA NAAQS ozone standard of 0.070 ppm, and at exposure durations of two hours, even though the current standard is an 8-hour standard. However, a small number of studies have assessed changes in lung function following exposure to low levels of ozone for several hours. These latter studies have shown that exposure to ozone for 6.6 hours at concentrations between 0.06 and 0.08 ppm causes mild reversible decrements in lung function (1.7-10%) as measured by forced vital capacity (FVC) and forced expired volume at 1 s (FEV1) immediately after exposure in healthy young adults. In addition, in one study an increase in ozone-induced neutrophils was seen in induced sputum following exposure to 0.06 ppm ozone (8) and in bronchoalveolar lavage fluid) following exposure to 0.08 ppm ozone (9). The EPA is considering whether the current ozone NAAQS standard at 0.070 is protective and has asked EPA researchers to conduct a study similar to those done at 0.06 and 0.08 ppm.

Inclusion Criteria:

1. Healthy men and women between 18 and 35 years of age.

2. Physical conditions allowing sustained moderate exercise for 6.6 hours.

3. Normal lung function (NHANES III):

   1. FVC > 80 % of that predicted for gender, ethnicity, age and height.
   2. FEV1 > 80 % of that predicted for gender, ethnicity, age and height.
   3. FEV1/FVC ratio > 80 % of predicted values

4. Oxygen saturation > 94 %.

5. Total symptom Score no greater than 20 (out of a possible 60-see accompanying score sheet) with a value no greater than 3 for any one score. No more than one score may be equal to 3.

Exclusion Criteria:

1. Individuals with a diagnosis of COVID-19 and/or hospitalized for COVID-19.
2. Individuals who are not "up to date," [meaning a person has received all recommended COVID-19 vaccines, including any booster dose(s) when eligible with their COVID vaccines as defined by the CDC.]
3. A history of acute and chronic cardiovascular disease, chronic respiratory disease, diabetes,rheumatologic diseases, immunodeficiency state.
4. An acute respiratory illness within 4 weeks.
5. Subjects who are asthmatic or have a history of asthma.
6. Allergic to chemical vapors or gases.
7. Any allergic symptoms during the time of participation in the study
8. Female subjects who are currently pregnant, attempting to become pregnant or breastfeeding
9. Subjects currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the ozone challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). Medications not specifically mentioned here may be reviewed by the investigators prior to a subject's inclusion in the study.
10. Current and past smokers within 2 years, or subjects with a smoking history of at least a pack of cigarettes a day for more than 10 years over your lifetime. This includes vaping, hookah,and e-cigarettes.
11. Uncontrolled hypertension (> 140 systolic, > 90 diastolic). Blood pressure readings equal to or greater that 140 Systolic and equal to or greater that 90 diastolic.
12. Subjects who do not understand or speak English
13. Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with ozone inhalation challenge or exercise, will be a basis for exclusion.

Temporary exclusion criteria:

1. Individuals who have had an acute respiratory illness within 4 weeks.

2. Individuals who have active allergies.

3. Individuals that have engaged in strenuous exercise within 24 hours of any study visit.

4. Individuals unable to avoid drinking alcohol for 24 hours prior to all study visits.

5. Individuals who have been exposed to smoke and fumes for 24 hours before all visits.

6. Individuals that have used an ozone-based home air purifier for 24 hours before all visits.

7. Individuals that have eaten or drank anything for 2 hours prior to the sputum training/screening day visit.

8. Individuals should avoid caffeine for 12 hours prior to all study visits.

9. Individuals should refrain from all over the counter anti-inflammatory agents including those for allergies, and anti-inflammatory drugs or antioxidants for a period of one week prior to the train and to the exposure.

10. 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.

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TRC Environmental Corporation, who is on-site contractor responsible for the exposure operation will randomize the subjects into either air or ozone arms, neither subjects nor staff involved in conduct of experiments will be informed of exposure conditions.