Research Changed Directions

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.

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.

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

Recruitment will be from the referral base of the responsible investigator and other physicians, and review of admissions and hospital database. Patients, who may qualify for this study, will be identified by chart review, physician referral, and recruited by study investigators. The source of potential subjects will be the population of potential subjects with TB (smokers or non smokers), and with both TB and COPD, as defined before. Accrual will be random with no bias as to gender or racial/ethnic group.

All results of the proposed studies will be published in international peer-reviewed scientific journals, presented at meetings in Qatar, the regional and international conferences, and disseminated through the local Qatari media, seminars and lectures for high school and college students. The original data will be available to interested investigators using the conventional standards of biomedical science.