ONES Grant: CXCL10/CXCR3 Regulation of Ozone-Induced Epithelial Permeability

CXCL10/CXCR3 Regulation of Ozone-Induced Epithelial Permeability

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.

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.