Environmental and Genetic Factors on Lung Function Clinical Trial
Official title:
CXCL10/CXCR3 Regulation of Ozone-Induced Epithelial Permeability
| Verified date | February 2024 |
| Source | Duke University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 14 |
| Est. completion date | January 24, 2024 |
| Est. primary completion date | November 29, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 45 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Duke Asthma, Allergy, and Airway Center | Durham | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Robert Tighe, MD |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in Ozone (O3) induced epithelial permeability, as measured by the level of clara cell secretory protein (ng/mL) | 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. Each value will be compared to the individuals filtered air control and reported as a fold change from baseline. These are independent values but are both accepted in the literature as measures of epithelial permeability. | Baseline, 21 days | |
| Primary | Change in Ozone (O3) induced epithelial permeability, as measured by albumin level (ug/mL) | 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. Each value will be compared to the individuals filtered air control and reported as a fold change from baseline. These are independent values but are both accepted in the literature as measures of epithelial permeability. | Baseline, 21 days | |
| Secondary | Change in Ozone O3 induced alterations in gene expression of airway epithelial cells, and bronchoalveolar lavage cells | Measured by real-time PCR | Baseline, 21 days | |
| Secondary | Change in Ozone O3 induced alterations in bronchoalveolar lavage cytokines and growth factors | Measured by multiplex ELISA | Baseline, 21 days |