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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Tuberculosis, Chronic Obstructive Pulmonary Disease

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals with TB<br>Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following: Symptoms consistent with TB Chest X-rays and or chest CT consistent with TB Positive PPD test Positive sputum test | |
| Smokers<br>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: Symptoms consistent with TB Chest X-rays and or chest CT consistent with TB Positive PPD test Positive sputum test | |
| Non-smokers<br>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: Symptoms consistent with TB Chest X-rays and or chest CT consistent with TB Positive PPD test Positive sputum test | |
| Individuals with COPD<br>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: Symptoms consistent with TB Chest X-rays and or chest CT consistent with TB Positive PPD test Positive sputum test | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alveolar Macrophage | Changes in alveolar macrophage | 1 week |