Macrophage Regulation of Ozone-Induced Lung Inflammation

The purpose of this research study to understand how prior respiratory infections affect the susceptibility to lung inflammation following environmental exposures.

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.

Eligibility Criteria:
Inclusion Criteria:

* Individuals between 18-55 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity)
* Individuals with knowledge of prior SARS-CoV-2 infection history allowing them to be segregated into one of three cohorts

  * Cohort 1 - No history of SARS-CoV-2 infection (defined as no symptoms consisted with SARS-CoV-2 nor history of a positive SARS-CoV-2 test)
  * Cohort 2 - Documented mild SARS-CoV-2 infection (a positive test, either PCR- or antigen-based) but with mild to no symptoms and no evidence of a lower respiratory tract infection (including no hospitalization, and no oxygen use)
  * Cohort 3 - History of SARS-CoV-2 infection and symptoms/imaging consistent with a lower respiratory tract infection who have recovered, are \>6 months out from their infection, and have normal lung function (spirometry with FVC, FEV1 and FEV1/FVC)

    * There will be no maximal period from SARS-CoV-2 infection for inclusion in the study, the minimal period will be \>6 months out from infection

Exclusion Criteria:

* Individuals with prior SARS-CoV-2 pneumonia who have ongoing respiratory symptoms, are still using supplemental oxygen, or have abnormal lung function
* Individuals with prior SARS-CoV-2 infection that cannot provide documentation of a positive test
* 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 \< 4 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.