Imaging Sex Differences in Smoking-Induced Pulmonary Inflammation

The purpose of this research is to measure the extent of lung inflammation between different groups of participants using a radioactive tracer called \[18F\]NOS. A radioactive tracer is a type of imaging drug that is labeled with a radioactive tag and injected into the body.

This study will see how the tracer is taken up in the lungs using an imaging scan called Positron Emission Tomography / Computed Tomography (PET/CT). \[18F\]NOS is an experimental radioactive molecule used in PET imaging to measure inflammation in various organs in the body. Investigators are interested in studying whether there are differences in lung inflammation between E-cigarette users (vapers) cigarette smokers and non-smokers. \[18F\]NOS has not yet been approved by the Food and Drug Administration (FDA) for use except in a research study. The use of \[18F\]NOS in this study is allowed under an Investigational New Drug Application approved by the FDA.

Investigators are also going to be studying how the information from the PET/CT scan compares to other markers of inflammation in the blood. During the PET scan, Investigators will image Brain and Lungs in order to see if there is a difference between inflammation seen in the brain and the lungs and if these differences change depending on whether a subject is a smoker, e-cigarette user or non-smoker.

Consented participant in this study will undergo one (1) experimental \[18F\]NOS PET/CT scan. During the scan, PET/CT images will be taken of participant chest/torso in order to capture their lungs and a short image will be taken of their brain. Blood samples will be taken at various time points to test for markers of inflammation and to measure the concentration of the tracer in participants blood during the scan and participants will undergo some specific psychological questionnaires and tasks.

Eligibility Criteria:
Inclusion Criteria:

1. Participants will be 18-45 years of age
2. Subject must meet one of the following criteria:

   NIC vapers: current e-cigarette use of nicotine at least 5 days per week for the past year, no current combustible cigarette use, cannabis vaping, or cannabis smoking during the 30 days prior to study enrollment

   CAN vapers: current e-cigarette use of cannabis at least 5 days per week for the past year, no current combustible cigarette use, cannabis smoking, or nicotine vaping during the 30 days prior to study enrollment

   Cigarette smokers: current cigarette smoking of at least 5 cigarettes per day, 4 days per week for the past year with no e-cigarette use (cannabis or nicotine) during the 30 days prior to study enrollment

   Dual combustible and e-cigarette users: current e-cigarette use of cannabis and/or nicotine at least 5 days per week for the past year with cigarette or cannabis smoking during the 30 day prior to study enrollment

   Non-Smokers: reported non-smoking history or \< 100 lifetime cigarettes, \< 100 e-cigarette use episodes, and \< 100 lifetime cannabis use episodes
3. Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria:

1. Females who are pregnant or breast feeding at the time of screening will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on scan day.
2. Current untreated and unstable diagnosis of substance use disorder, except nicotine use disorder or cannabis use disorder
3. Positive urine drug screen for opiates, methamphetamine or cocaine at screening
4. Reported regular use of nicotine or cannabis products (except edibles) other than ENDS, cigarettes, or cannabis bowls, pipes, or blunts (e.g., smokeless tobacco, nicotine replacement therapy, wax, shatter, tinctures)
5. Current unstable and/or untreated major depression or psychotic disorder per medical record review or self-reported
6. Use of inhaled or oral corticosteroids or anti-inflammatory medications per medical record review or self-report
7. History of lung trauma
8. Active (or within the previous 4 weeks of screening) lung infection or lung disease that impact uptake of \[18F\]NOS (e.g. tuberculosis, cystic fibrosis)
9. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
10. Any current or past medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study