Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis

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.

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.