Environmental and Genetic Factors on Lung Function
Conditions
Keywords
genetic: CXCR3 polymorphism rs2280964
Brief summary
The purpose of this research study to understand how environmental and genetic factors may be involved in lung function. 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 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.
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
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Prior enrollment in the NIEHS Environmental Polymorphism Registry located in the greater Raleigh-Durham area * Wild type or homozygous (female)/hemizygous (male - since sex-linked) expression of the CXCR3 polymorphism rs2280964
Exclusion criteria
* Current smokers of tobacco products including e-cigarettes or those with previous smoking history within the prior 5 years * BMI less than 37 kg/m2 * 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 (O3) Induced Epithelial Permeability, as Measured by the Level of Clara Cell Secretory Protein | Baseline, 21 days | This measure is defined by the comparing each individuals baseline (following filtered air challenge) to the ozone response. The investigators will perform two tests on this response as a means of confirmation. The individual will have blood drawn to obtain serum and a bronchoscopy to obtain bronchoalveolar lavage. The serum will be used to determine the level of clara cell secretory protein. This is measured by enzyme-linked immunosorbent assay (ELISA). The value is reported as ng/mL. |
| Change in Ozone (O3) Induced Epithelial Permeability, as Measured by Albumin Level (ug/mL) | Baseline, 21 days | This measure is defined by the comparing each individuals baseline (following filtered air challenge) to the ozone response. The investigators will perform two tests on this response as a means of confirmation. The individual will have blood drawn to obtain serum and a bronchoscopy to obtain bronchoalveolar lavage. The bronchoalveolar lavage will be similarly used to define the albumin level. Albumin is also measured by ELISA. The value is reported at ug/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ozone O3 Induced Alterations in Gene Expression of Airway Epithelial Cells, and Bronchoalveolar Lavage Cells | Baseline, 21 days | Measured by real-time PCR |
| Change in Ozone (O3) Induced Bronchoalveolar Lavage CXCL11 Levels | Baseline, 21 days | CXCL11, or C-X-C motif chemokine 11, is a protein that acts as a chemoattractant and plays a role in regulating cell migration. Measured by multiplex ELISA. |
| Change in Ozone (O3) Induced Bronchoalveolar Lavage CXCL10 Levels | Baseline, 21 days | CXCL10 is a cytokine that has multiple roles, such as modulating innate and adaptive immune response, regulating cell growth and angiostatic effects. Measured by multiplex ELISA. |
| Change in Ozone (O3) Induced Bronchoalveolar Lavage IFN-γ Levels | Baseline, 21 days | Interferon-gamma (IFN-γ) is a cytokine that plays an important role in inducing and modulating an array of immune responses. Measured by multiplex ELISA. |
| Change in Ozone (O3) Induced Bronchoalveolar Lavage CXCL9 Levels | Baseline, 21 days | CXCL9, or C-X-C motif chemokine ligand 9, is a small cytokine that plays a role in inflammation, tumor growth, and other processes. Measured by multiplex ELISA. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRobert Tighe, MD
Duke University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.91 years STANDARD_DEVIATION 4.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 5 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
None listed