Lung Injury, Acute, Symptoms and Signs, Neutrophilia Acute
Conditions
Keywords
lungs, ozone concentration, exercise, inflammation, symptoms
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICAL0.070 ppm ozone concentration
The concentration of ozone a subject will randomly receive on a visit for 6.6 hours in a controlled atmospheric chamber while performing moderate intermittent exercise.
BIOLOGICALClean air (0.0 ppm ozone)
Same subject will randomly receive clean air on another visit separated by at least one week for 6.6 hours in the same controlled atmospheric chamber while performing moderate intermittent exercise.
Sponsors
University of North Carolina
Martin W. Case
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
This is a randomized, double-blind, cross-over study with two arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FVC | measured (pre) before starting 6.6 hours of exercise | forced vital capacity |
| Change in FVC | change measured (post) immediately after 6.6 hours of exercise | change in forced vital capacity |
| FEV1 | measured (pre) before starting 6.6 hours of exercise | forced expiratory volume in 1 second |
| Change in FEV1 | change measured (post) immediately after 6.6 hours of exercise | change in forced expiratory volume in 1 second |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % neutrophils collected by induced sputum | baseline: training/qualification day | Subjects will breathe a hypertonic saline solution from an ultrasonic nebulizer through a mouthpiece at saline concentrations of 3%, 4%, and 5%. After each inhalation period subjects be asked to cough up the expectorate in a sterile cup for analysis of neutrophil cells influx |
| change in % neutrophils collected by induced sputum | 18 hours post exposure | Subjects will breathe a hypertonic saline solution from an ultrasonic nebulizer through a mouthpiece at saline concentrations of 3%, 4%, and 5%. After each inhalation period subjects be asked to cough up the expectorate in a sterile cup for analysis/quantitation of neutrophil cells influx |
Countries
United States
Contacts
Primary ContactMartin W Case, B.S.
Backup ContactAndrea Davis, R.N.
Outcome results
None listed