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      Association between Smoking and Latent Tuberculosis in the U.S. Population: An Analysis of the National Health and Nutrition Examination Survey

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          Abstract

          Background

          Evidence of an association between cigarette smoking and latent tuberculosis infection (LTBI) is based on studies in special populations and/or from high prevalence settings. We sought to evaluate the association between LTBI and smoking in a low prevalence TB setting using population-based data from the National Health and Nutrition Examination Survey (NHANES).

          Methods

          In 1999–2000, NHANES assessed LTBI (defined as a tuberculin skin test measurement ≥10 mm) in participants, and those ≥20 years of age were queried regarding their tobacco use and serum cotinine was measured. We evaluated the association of LTBI with self-reported smoking history and smoking intensity in multivariable logistic regression models that adjusted for known confounders (gender, age, birthplace, race/ethnicity, poverty, education, history of BCG vaccination, and history of household exposure to tuberculosis disease).

          Results

          Estimated LTBI prevalence was 5.3% among those ≥20 years of age. The LTBI prevalence among never smokers, current smokers, and former smokers was 4.1%, 6.6%, and 6.2%, respectively. In a multivariable model, current smoking was associated with LTBI (OR 1.8; 95% CI, 1.1–2.9). The association between smoking and LTBI was strongest for Mexican-American and black individuals. In multivariate analysis stratified by race/ethnicity, cigarette packs per day among Mexican-American smokers and cotinine levels among black smokers, were significantly associated with LTBI.

          Conclusions

          In the large, representative, population-based NHANES sample, smoking was independently associated with significantly increased risks of LTBI. In certain populations, a greater risk of LTBI corresponded with increased smoking exposure.

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          Most cited references27

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          Risk of tuberculosis from exposure to tobacco smoke: a systematic review and meta-analysis.

          There is no consensus whether tobacco smoking increases risk of tuberculosis (TB) infection, disease, or mortality. Whether this is so has substantial implications for tobacco and TB control policies. To quantify the relationship between active tobacco smoking and TB infection, pulmonary disease, and mortality using meta-analytic methods. Eight databases (PubMed, Current Contents, BIOSIS, EMBASE, Web of Science, Centers for Disease Control and Prevention Tobacco Information and Prevention Source [TIPS], Smoking and Health Database [Institute for Science and Health], and National Library of Medicine Gateway) and the Cochrane Tobacco Addiction Group Trials Register were searched for relevant articles published between 1953 and 2005. Included were epidemiologic studies that provided a relative risk (RR) estimate for the association between TB (infection, pulmonary disease, or mortality) and active tobacco smoking stratified by (or adjusted for) at least age and sex and a corresponding 95% confidence interval (CI) (or data for calculation). Excluded were reports of extrapulmonary TB, studies conducted in populations prone to high levels of smoking or high rates of TB, and case-control studies in which controls were not representative of the population that generated the cases, as well as case series, case reports, abstracts, editorials, and literature reviews. Twenty-four studies were included in the meta-analysis. Extracted data included study design, population and diagnostic details, smoking type, and TB outcomes. A random-effects model was used to pool data across studies. Separate analyses were performed for TB infection (6 studies), TB disease (13 studies), and TB mortality (5 studies). For TB infection, the summary RR estimate was 1.73 (95% CI, 1.46-2.04); for TB disease, estimates ranged from 2.33 (95% CI, 1.97-2.75) to 2.66 (95% CI, 2.15-3.28). This suggests an RR of 1.4 to 1.6 for development of disease in an infected population. The TB mortality RRs were mostly below the TB disease RRs, suggesting no additional mortality risk from smoking in those with active TB. The meta-analysis produced evidence that smoking is a risk factor for TB infection and TB disease. However, it is not clear that smoking causes additional mortality risk in persons who already have active TB. Tuberculosis control policies should in the future incorporate tobacco control as a preventive intervention.
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            Optimal serum cotinine levels for distinguishing cigarette smokers and nonsmokers within different racial/ethnic groups in the United States between 1999 and 2004.

            Cotinine, a metabolite of nicotine, is widely used to distinguish smokers from nonsmokers in epidemiologic studies and smoking-cessation clinical trials. As the magnitude of secondhand smoke exposure declines because of proportionally fewer smokers and more clean-indoor-air regulations, the optimal cotinine cutpoint with which to distinguish smokers from nonsmokers is expected to change. The authors analyzed data on 3,078 smokers and 13,078 nonsmokers from the National Health and Nutrition Examination Survey for 1999-2004. Optimal serum cotinine concentrations for discriminating smokers from nonsmokers were determined using receiver operator characteristic curve analysis. Optimal cotinine cutpoints were 3.08 ng/mL (sensitivity = 96.3%, specificity = 97.4%) and 2.99 ng/mL (sensitivity = 86.5%, specificity = 93.1%) for adults and adolescents, respectively. Among adults, optimal cutpoints differed by race/ethnicity: They were 5.92 ng/mL, 4.85 ng/mL, and 0.84 ng/mL for non-Hispanic blacks, non-Hispanic whites, and Mexican Americans, respectively. Among adolescents, cutpoints were 2.77 ng/mL, 2.95 ng/mL, and 1.18 ng/mL for non-Hispanic blacks, non-Hispanic whites, and Mexican Americans, respectively. Use of the currently accepted cutpoint of 14 ng/mL overestimates the number of nonsmokers in comparison with the proposed new overall cutpoint of 3 ng/mL or the race/ethnicity-specific cutpoints of 1-6 ng/mL.
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              Innate immunity to Mycobacterium tuberculosis.

              The different manifestations of infection with Mycobacterium tuberculosis reflect the balance between the bacillus and host defense mechanisms. Traditionally, protective immunity to tuberculosis has been ascribed to T-cell-mediated immunity, with CD4(+) T cells playing a crucial role. Recent immunological and genetic studies support the long-standing notion that innate immunity is also relevant in tuberculosis. In this review, emphasis is on these natural, innate host defense mechanisms, referring to experimental data (e.g., studies in gene knockout mice) and epidemiological, immunological, and genetic studies in human tuberculosis. The first step in the innate host defense is cellular uptake of M. tuberculosis, which involves different cellular receptors and humoral factors. Toll-like receptors seem to play a crucial role in immune recognition of M. tuberculosis, which is the next step. The subsequent inflammatory response is regulated by production of pro- and anti-inflammatory cytokines and chemokines. Different natural effector mechanisms for killing of M. tuberculosis have now been identified. Finally, the innate host response is necessary for induction of adaptive immunity to M. tuberculosis. These basic mechanisms augment our understanding of disease pathogenesis and clinical course and will be of help in designing adjunctive treatment strategies.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                8 November 2012
                : 7
                : 11
                : e49050
                Affiliations
                [1 ]Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States of America
                [2 ]Department of Global Health, University of Washington, Seattle, Washington, United States of America
                [3 ]Public Health - Seattle & King County, TB Control Program, Seattle, Washington, United States of America
                [4 ]Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
                San Francisco General Hospital, University of California San Francisco, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: DJH MC KC MN. Performed the experiments: DJH. Analyzed the data: DJH MC JRO KC MN. Wrote the paper: DJH MC JRO EO MA KC MN.

                Article
                PONE-D-12-19861
                10.1371/journal.pone.0049050
                3493513
                23145066
                24789104-c614-4a80-b5ce-89cf1af578d9
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 July 2012
                : 3 October 2012
                Page count
                Pages: 6
                Funding
                This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health [K23 AI 85036-01 to DJH]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Epidemiology
                Clinical Epidemiology
                Infectious Disease Epidemiology
                Survey Methods
                Infectious Diseases
                Bacterial Diseases
                Mycobacterium
                Tuberculosis
                Tropical Diseases (Non-Neglected)
                Tuberculosis
                Public Health
                Pulmonology
                Smoking Related Disorders

                Uncategorized
                Uncategorized

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