Characterization of Tissue-Specific Immune Responses to Bronchoscopic Instillation of Mycobacterial Antigens Into the Human Lung

This is an interventional basic science trial for Healthy focused on measuring Tuberculin Purified Protein Derivative, PPD, antigen-specific immune cells in airways Read More

• INCLUSION CRITERIA:

Adults 18-64 years old will be recruited for the two groups (non-LTBI controls vs confirmed LTBI). The lower limit of this age range is based on the need for invasive bronchoscopic procedures and exposure to radiation, both of which carry more risk at younger ages. In addition, most adults present with post-primary or reactivation TB that most often occurs radiographically in the upper lobes of the lungs, often with cavitation. Conversely, children and rare adults with primary TB have non-cavitary disease in the lower lobes. The higher limit of this age range is based on the known property of immune senescence, i.e., the waning of the strength of immune responses with advancing age.

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Ability of subject to understand and the willingness to sign a written informed consent document.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 - 64 years of age
• No significant active medical problems. This would include but not limited to any cardiac disorder (e.g. arrhythmia, valvular disease), pulmonary disease (e.g. asthma requiring chronic medications, chronic bronchitis, emphysema, obstructive sleep apnea), kidney disease (e.g. nephritis, nephrosis), rheumatologic disorder (e.g. inflammatory arthritis), endocrine disorder (e.g. diabetes, thyroid disease), liver disease (e.g. hepatitis), gastrointestinal disorder (e.g. inflammatory bowel disease) or infectious disease (e.g. active tuberculosis).
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and agreement to use such a method during study participation

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnancy as assessed by urinary or plasma HCG or breastfeeding

• History of clinically significant respiratory dysfunction 3 months prior to participating

  • Evidence of new pulmonary infection
  • History of any chronic lung infections or chronic lung disease
  • History of pulmonary hypertension
  • Need for supplemental oxygen administration at rest
• Current use or inability to suspend use of any anticoagulant therapy including platelet inhibitors (e.g. aspirin, NSAIDs, within 7 days, clopidogrel or systemic anticoagulants (warfarin, enoxaparin, or DOAC) within 14 days of study bronchoscopy or inability to suspend aspirin 7 days prior to study bronchoscopy
• Any symptoms consistent with infection including fever, chills, night sweats, or unexplained weight loss
• A history of a necrotic reaction to a tuberculin skin test, including during screening
• A history of human immunodeficiency virus (HIV) infection
• A history of coughing up blood in the last 3 months
• Cigarette smoking, vaping or recreational drug use within the past 6 months (self-reported)
• If there is any discrepancy in tuberculin skin test and Interferon Gamma Release Assay test results (i.e. PPD+ but IGRA- or PPD- but IGRA+)
• Refusal or inability to undergo bronchoscopy, or a history of poor tolerance of a bronchoscopy
• If undergoing PET-CT imaging during this study places a participant over his/her annual radiation dose limit. Radiation exposure within the previous 12 months of >= 2.3 rem
• BMI > 40
• Diabetes
• Known life-threatening allergic reaction to Tuberculin, Lidocaine, Midazolam, Fentanyl or medications of similar classes
• Presence of any immunosuppressive diseases, including cancers with the exception of non-melanomatous skin cancer.
• Use of any systemic immunosuppressive medications, including corticosteroids (e.g., prednisone) or biological agents in the last 6 months prior to enrollment
• Any medical, psychiatric, social condition, occupational reason or other responsibility, in the judgement of the investigator, that is a contraindication to protocol participation or impairs a participant s ability to give informed consent
• Positive for COVID-19. (with-in 6 months prior to enrollment self-reported and or via PCR)