Healthy
Conditions
Brief summary
The purpose of this research study to understand how environmental and genetic factors may be involved in lung function. Healthy Study participants will undergo a 1-day screening that includes a blood draw and breathing testing, return for a two-day series of testing to include blood draw, and brief breathing test before and after an inhaled challenge with either filtered air (FA) or ozone (O3). Participants return the next day for a brief breathing test, a blood draw and a procedure called bronchoscopy performed under conscious sedation to evaluate the lung after the challenge. Participants then return 18 - 20 days later to repeat the two-day series of testing to be challenged with the exposure not received on the first series, (FA or O3). Each visit will take about 3 - 3.5 hours. Follow-up phone calls from the study team will occur at 24 hours after each 2-day test series. Total study duration is about one to one-and a half months.
Detailed description
In brief, at V1 subjects will be assessed for baseline spirometry and venous blood analysis prior to exposure. The venous blood will be used to obtain PMNs for apoptosis assays, and serum for CFH and sCD163 levels. Additionally, this will be used to measure cytokines and growth factors. At each visit, if the subject is female, there will be a urine pregnancy test performed. Following this initial assessment, subjects will be challenged with FA or O3 and then spirometry will be performed, and venous blood will be obtained immediately following the exposure (V2). The subjects will then return 20 hours ±4h later for follow up studies (V3). There will be spirometry, a venous blood draw and urine pregnancy testing (if female) followed by bronchoscopy. At bronchoscopy, vital signs will be determined, including O2 sat. Patient then undergo an 18-20 day washout period before they are brought back in for V4 for the alternate challenge. This will follow the same protocol as outline above in the initial exposure and use the same series of analysis as the first set of visits. Therefore, we will fully characterize the biological response to ozone and filtered air in these same subjects.
Interventions
DRUGOzone
Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3).
OTHERFiltered Air
Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air.
Sponsors
Robert Tighe, MD
National Institutes of Health (NIH)
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
• Individuals between 18-35 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity)
Exclusion criteria
* Current smokers of tobacco products including e-cigarettes or those with previous smoking history within the prior 5 years * Pregnant women and women who are presently lactating. * Subjects that have received antibiotic administration or an upper respiratory infection within the previous 4 weeks * College and graduate students or employees who are under direct supervision by any of the investigators in this protocol * Alcohol or illicit substance abuse * Chronic cardio/pulmonary respiratory disorders or other medical conditions as determined by the investigator * Increased airway hyperresponsiveness at baseline as measured by a positive methacholine challenge response (methacholine PC20 FEV1 \< 8 mg/ml) * Subjects will be requested to refrain from antihistamines, nonsteroidal anti-inflammatory agents, antioxidants (e.g. beta-carotene, selenium, and lutein) and supplemental vitamins (e.g. C and E), for 1 week prior to, and during testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ozone Induced Efferocytosis of Lung Macrophages (Ability to Clear Dead or Dying Cells) | Baseline, 21 days | Efferocytosis is defined by determining the number of apoptotic PMNs phagocytized by alveolar macrophages (BAL cytospins) versus the total number of macrophages ('efferocytic index'). The efferocytic index is a measure of how efficiently macrophages engulf and clear apoptotic (dying) cells. It can be determined by counting the number of macrophages that have a phagocytosed apoptotic body and dividing it by the total number of macrophages counted. A higher value is considered better. |
| Change in Ozone Induced Phagocytosis of Lung Macrophages (Ability to Clear Debris or Bacteria) | Baseline, 21 days | Bronchoalveolar macrophages are incubated with pHrodo™ dye-labeled particles. Macrophage phagocytosis will be defined by determining the number of macrophages that contain fluorescent particles versus the total macrophages. Cell free hemoglobin and soluble CD163 - both are measured by commercial ELISA kit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ozone Induced Increase in Cell Free Hemoglobin in Bronchoalveolar Lavage Fluid | Baseline, 21 days | Measured by spectroscopy. |
| Change in Ozone Induced Increase in Soluble CD163 in Bronchoalveolar Lavage Fluid | Baseline, 21 days | Measured by enzyme-linked immunosorbent assay (ELISA) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRobert Tighe, MD
Duke University
Participant flow
Recruitment details
Subjects were recruited from Duke University campus and surrounding Durham, NC, community using advertisement in newspapers, mailings, and the campus student newspaper. Subjects were screened to determine eligibility per protocol inclusion and exclusion criteria.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 23.75 years STANDARD_DEVIATION 3.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 1 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
None listed