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

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.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Obstructive Pulmonary Disease; Tuberculosis

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• Qatar
  • Doha, Qatar
    • Hamad Medical Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Individuals with TB; 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; 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; 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; 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?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Hamad Medical Corporation; Weill Cornell Medical College in Qatar
• Investigators: Principal Investigator: Ronald Crystal, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: November 22, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (Estimate): December 27, 2013

Study Record Updates

• Last Update Posted (Actual): May 24, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Tuberculosis
• Other Study ID Numbers: 14-00055 [JIRB]; NPRP 5-400-3-107 (Other Identifier: Qatar National Research Fund); 11262/11 (Other Identifier: HMC IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.