Clinical trial NCT02021747: Biologic Basis Of Increased Susceptibility Of Smokers To Pulmonary Infection With Mycobacterium Tuberculosis
Official title: Biologic Basis Of Increased Susceptibility Of Smokers To Pulmonary Infection With Mycobacterium Tuberculosis
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Tuberculosis
Chronic Obstructive Pulmonary Disease
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Hamad Medical Corporation
name: Weill Cornell Medical College in Qatar
First posted: 2013-12-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Alveolar Macrophage
timeFrame: 1 week
Secondary outcomes:
Other outcomes:
Locations:
city: Doha
country: Qatar
facility: Hamad Medical Corporation
Study officials:
affiliation: Weill Medical College of Cornell University
name: Ronald Crystal, MD
role: PRINCIPAL_INVESTIGATOR
References: