Biologic Basis Of Increased Susceptibility Of Smokers To Pulmonary Infection With Mycobacterium Tuberculosis

Weill Cornell Medicine (WCM)

Status: Withdrawn

Conditions: Tuberculosis; Chronic Obstructive Pulmonary Disease

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT02021747

NPRP 5-400-3-107 (Other Identifier)

14-00055 [JIRB]

11262/11 (Other Identifier)

Details and patient eligibility

About

Identify a biologic (molecular) basis for the increased susceptibility of cigarette smokers to pulmonary TB (Mtb) by testing the hypothesis that smoking reprograms AM polarization towards a distinct phenotype associated with impaired host defense function against Mtb and that normalization of that phenotype via therapeutic modulation of the Alveolar Macrophage (AM) polarization or smoking cessation can restore the anti-Mtb host defense function of AM.

Full description

Samples from Non-Smokers with TB, Smokers with TB and Smokers with COPD and TB will be collected in Qatar under JIRB 14-00055. All subjects will be undergoing a clinical bronchoscopy as part of their disease evaluation and will be asked to give additional samples for research. All "in vivo" processing of specimens from subjects with TB will be performed in Qatar. Mycobacterium tuberculosis infection (Mtb) continues to have a detrimental impact of public health worldwide. Based on the epidemiological evidence linking smoking, COPD and Mtb, and our preliminary data we hypothesize that smoking reprograms Alveolar Macrophages (AM) polarization towards a distinct phenotype associated with impaired host defense function against Myobacterium tuberculosis (Mtb) and that normalization of that phenotype via therapeutic modulation of the Alveolar Macrophages (AM) polarization or smoking cessation can restore the anti-Mtb host defense function of AM.

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Smokers and Non-smokers with TB

Inclusion Criteria:

• Must provide informed consent
• Current smokers and non-smokers
• Undergoing clinical bronchoscopy as required by their doctor for evaluation of their disease
• Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following:
• Symptoms consistent with TB
• Chest xray and or chest CT with TB
• Positive PPD test
• Positive sputum test

Exclusion Criteria:

• Females who are pregnant or nursing
• History of allergies to xylocaine, lidocaine, versed, valium, atropine, isoproterenol, terbutaline, aminophylline, or any local anesthetic

Smokers with TB and COPD

Inclusion Criteria:

• Must provide informed consent
• Current smokers with COPD
• Undergoing clinical bronchoscopy as required by their doctor for evaluation of their disease
• Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed bu at least one of the following:
• Symptoms consistent with TB
• Chest xray and or chest CT consistent with TB
• Positive PPD test
• Positive sputum test

Exclusion Criteria:

• Non-smokers
• Females who are pregnant or nursing
• History of allergies to xylocaine, lidocaine, versed, valium, atropine, isoproterenol, terbutaline, aminophylline, or any local anesthetic

Trial design

0 participants in 4 patient groups

Individuals with TB

Description:

Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following: 1. Symptoms consistent with TB 2. Chest X-rays and or chest CT consistent with TB 3. Positive PPD test 4. Positive sputum test

Smokers

Description:

Active smoker as evidenced by self report and urine nicotine \>30 ng/mL and urine cotinine \>50 ng/mL Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following: 1. Symptoms consistent with TB 2. Chest X-rays and or chest CT consistent with TB 3. Positive PPD test 4. Positive sputum test

Non-smokers

Description:

Never smokers is defined as someone who has smoked \< 100 cigarettes per lifetime and whose urine nicotine \<2 ng/mL and urine cotinine \<5 ng/mL, at entry into the study Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following: 1. Symptoms consistent with TB 2. Chest X-rays and or chest CT consistent with TB 3. Positive PPD test 4. Positive sputum test

Individuals with COPD

Description:

All study subjects should meet the "Lung Disease" protocol criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following: 1. Symptoms consistent with TB 2. Chest X-rays and or chest CT consistent with TB 3. Positive PPD test 4. Positive sputum test