D C Christiani

Massachusetts General Hospital, Boston, Massachusetts, United States

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Publications (317)1590.4 Total impact

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    ABSTRACT: The aim of this study was to estimate the effect of exposure to secondhand tobacco smoke on the incidence of lung adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/ MIA). Data from seven case-control studies participating in the International Lung Cancer Consortium (ILCCO) were pooled, resulting in 625 cases of AIS/MIA and 7, 403 controls, of whom 170 cases and 3, 035 controls were never smokers. Unconditional logistic regression was used to estimate adjusted ORs (ORadj) and 95% confidence intervals (CI), controlling for age, sex, race, smoking status (ever/never), and pack-years of smoking. Study center was included in the models as a randomeffects intercept term. Ever versus never exposure to secondhand tobacco smoke was positively associated with AIS/MIA incidence in all subjects (ORadj = 1.48; 95%CI, 1.14-1.93) and in never smokers (ORadj = 1.45; 95% CI, 1.00-2.12). There was, however, appreciable heterogeneity of ORadj across studies (P = 0.01), and the pooled estimates were largely influenced by one large study (40% of all cases and 30% of all controls). These findings provide weak evidence for an effect of secondhand tobacco smoke exposure on AIS/MIA incidence. Further studies are needed to assess the impact of secondhand tobacco smoke exposure using the newly recommended classification of subtypes of lung adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 24(12); 1902-6.
    No preview · Article · Oct 2015 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Background: Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk. Methods: Fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural Bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. We assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. Inductively coupled plasma mass spectrometry was used to measure inorganic arsenic concentration in drinking water. Candidate single-nucleotide polymorphisms were identified through review of the literature. Results: Drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively. Conclusion: Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways. Birth Defects Research (Part A) 103:754-762, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Sep 2015 · Birth Defects Research Part A Clinical and Molecular Teratology
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    ABSTRACT: Background Tobacco workers are exposed to several respiratory occupational sensitizers.MethodsA representative cross-sectional study was carried out on 2469 tobacco family farming growers. Gender-stratified multivariate analyses evaluated the association between wheezing and socio-demographic, behavioral, and occupational variables.ResultsWheezing prevalence was 11.0% with no difference between genders. Among men, age, smoking, strenuous work, pesticide use, contact with vegetable dust and dried tobacco dust, lifting sticks with tobacco leaves to the curing barns, and green tobacco sickness (GTS) were risk factors for wheezing. Among women, family history of asthma, tying hands of tobacco, strenuous work, contact with chemical disinfectants, and GTS were positively associated with wheezing. Harvesting lower tobacco leaves was a protective factor for the outcome in both genders.Conclusions Pesticides, dusts exposure, and GTS were risk factors for wheezing. The synergic effect of these factors needs to be better evaluated to improve prevention. Am. J. Ind. Med. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Sep 2015 · American Journal of Industrial Medicine
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    ABSTRACT: Stunting affects 26.7% of children worldwide, and little is known about its effects on the outcomes of childhood pneumonia. We evaluated the effect of stunting on the outcomes of pneumonia among children enrolled in two large clinical trials. We analyzed data from two WHO and USAID-sponsored inpatient treatment trials, the Severe Pneumonia Evaluation Antimicrobial Research study (n=958) and the Amoxicillin Penicillin Pneumonia International Study (n=1702), which enrolled children aged 2-59 months across 16 sites in LMICs. We assessed the effect of stunting (height-for-age Z score < -2) on treatment outcome and time to resolution of hypoxemic pneumonia. Among 2542 (96%) children with valid data for height, 28% were stunted and 12.8% failed treatment by 5 days. The failure rate among stunted patients was 16.0% vs. 11.5% among non-stunted patients (unadjusted RR = 1.24 [95% CI 1.08, 1.41]; adjusted RR = 1.28 [95% CI 1.10, 1.48]). An inverse relationship was observed between height and failure rates, even among non-stunted children. Among 845 patients with hypoxemic pneumonia, stunting was associated with a lower probability of normalization of respiratory rate (HR = 0.63 [95% CI 0.52, 0.75]) and oxygen saturation (HR = 0.74 [95% CI 0.61, 0.89]). Stunting increases the risk of treatment failure and is associated with a longer course of recovery in children with pneumonia. Strategies to decrease stunting may decrease the burden of adverse outcomes in childhood pneumonia in low-resource settings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · Tropical Medicine & International Health
  • Adam Gaffney · David C Christiani
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    ABSTRACT: Environmental and occupational pulmonary diseases impose a substantial burden of morbidity and mortality on the global population. However, it has been long observed that only some of those who are exposed to pulmonary toxicants go on to develop disease; increasingly, it is being recognized that genetic differences may underlie some of this person-to-person variability. Studies performed throughout the globe are demonstrating important gene-environment interactions for diseases as diverse as chronic beryllium disease, coal workers' pneumoconiosis, silicosis, asbestosis, byssinosis, occupational asthma, and pollution-associated asthma. These findings have, in many instances, elucidated the pathogenesis of these highly complex diseases. At the same time, however, translation of this research into clinical practice has, for good reasons, proceeded slowly. No genetic test has yet emerged with sufficiently robust operating characteristics to be clearly useful or practicable in an occupational or environmental setting. In addition, occupational genetic testing raises serious ethical and policy concerns. Therefore, the primary objective must remain ensuring that the workplace and the environment are safe for all. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    No preview · Article · Jun 2015 · Seminars in Respiratory and Critical Care Medicine
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    ABSTRACT: Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients. We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants. Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations. Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration.
    Full-text · Article · Apr 2015 · Critical care (London, England)
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    ABSTRACT: Single nucleotide polymorphisms (SNPs) occur within chromatin-modulating factors; however, little is known about how these variants within the coding sequence impact cancer progression or treatment. Therefore, there is a need to establish their biochemical and/or molecular contribution, their use in sub-classifying patients and their impact on therapeutic response. In this report, we demonstrate that coding SNP-A482 within the lysine tri-demethylase KDM4A/JMJD2A has different allelic frequencies across ethnic populations, associates with differential outcome in non-small cell lung cancer (NSCLC) patients and promotes KDM4A protein turnover. Using an unbiased drug screen against 87 preclinical and clinical compounds, we demonstrate that homozygous SNP-482 cells have increased mTOR inhibitor sensitivity. mTOR inhibitors significantly reduce SNP-A482 protein levels, which parallels the increased drug sensitivity observed with KDM4A depletion. Our data emphasize the importance of using variant status as candidate biomarkers and highlight the importance of studying SNPs in chromatin modifiers to achieve better targeted therapy. Copyright © 2014, American Association for Cancer Research.
    Full-text · Article · Jan 2015 · Cancer Discovery
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    ABSTRACT: Because humans are invariably exposed to complex chemical mixtures, estimating the health effects of multi-pollutant exposures is of critical concern in environmental epidemiology, and to regulatory agencies such as the U.S. Environmental Protection Agency. However, most health effects studies focus on single agents or consider simple two-way interaction models, in part because we lack the statistical methodology to more realistically capture the complexity of mixed exposures. We introduce Bayesian kernel machine regression (BKMR) as a new approach to study mixtures, in which the health outcome is regressed on a flexible function of the mixture (e.g. air pollution or toxic waste) components that is specified using a kernel function. In high-dimensional settings, a novel hierarchical variable selection approach is incorporated to identify important mixture components and account for the correlated structure of the mixture. Simulation studies demonstrate the success of BKMR in estimating the exposure-response function and in identifying the individual components of the mixture responsible for health effects. We demonstrate the features of the method through epidemiology and toxicology applications. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Full-text · Article · Dec 2014 · Biostatistics
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    Qingkun Song · David C Christiani · XiaorongWang · Jun Ren
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    ABSTRACT: This study aimed to investigate the quantitative effects of outdoor air pollution, represented by 10 µg/m3 increment of PM10, on chronic obstructive pulmonary disease in China, United States and European Union through systematic review and meta-analysis. Publications in English and Chinese from PubMed and EMBASE were selected. The Cochrane Review Handbook of Generic Inverse Variance was used to synthesize the pooled effects on incidence, prevalence, mortality and hospital admission. Outdoor air pollution contributed to higher incidence and prevalence of COPD. Short-term exposure was associated with COPD mortality increased by 6%, 1% and 1% in the European Union, the United States and China, respectively (p < 0.05). Chronic PM exposure produced a 10% increase in mortality. In a short-term exposure to 10 µg/m3 PM10 increment COPD mortality was elevated by 1% in China (p < 0.05) and hospital admission enrollment was increased by 1% in China, 2% in United States and 1% in European Union (p < 0.05). Outdoor air pollution contributes to the increasing burdens of COPD.10 µg/m3 increase of PM10 produced significant condition of COPD death and exacerbation in China, United States and European Union. Controlling air pollution will have substantial benefit to COPD morbidity and mortality.
    Preview · Article · Nov 2014 · International journal of environmental research and public health
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    ABSTRACT: It is well-known that metabolism of benzene is required for the induction of toxicity and consequent health problems. Therefore, genetic variation in benzene (BZ) metabolism genes can influence health outcomes. However, large population studies are needed to provide more evidence for such relationship. We have conducted a large population investigation (385 BZ-exposed shoe workers and 197 matched healthy controls) on the association between inheritance of certain BZ metabolizing genes and the expression of micronuclei (MN). The latter was based on the cytokinesis-blocked MN assay. We analyzed the polymorphisms of GSTM1, GSTT1, GSTP1 (rs1695), CYP2E1 (rs3813867), CYP2E1 (rs2031920), CYP2E1 (rs6413432), mEH exon 3 (rs1051740), mEH exon 4 (rs2234922). Univariate Poisson regression analysis demonstrated that the BZ-exposed workers had significantly increased MN frequency compared with the controls (FR = 1.84, 95% CI: 1.56-2.18; P < 0.001), and showed a cumulative exposure dose--response relationship. The CYP2E1 rs3813867 mutant allele (CC+ GC) (FR 1.15, 95% CI 1.02–1.29; P = 0. 020) and rs2031920 variant allele (CT + TT) (FR = 1.23, 95% CI: 1.09–1.37, P<0.01) was associated with higher MN frequency significantly compared with the wild genotype separately. Furthermore, the MN frequency in rs2031920 variant allele (CT + TT) (FR = 1.17, 95% CI: 1.04–1.31, P<0.01) was also higher than the wild genotype when the age, gender and cumulative exposure dose was adjusted in Poisson regression. In addition, the CYP2E1 (However, GSTM1null, GSTT1null, GSTP1 rs1695, rs6413432, rs1051740 and rs2234922 polymorphisms showed no association with MN frequency. Our results indicate that two promoter polymorphisms in the CYP2E1 gene, especially the rs2031920 variant allele, were involved with the BZ-induction of MN and may contribute to risk of cancer among exposed workers.
    No preview · Article · Sep 2014 · International journal of hygiene and environmental health
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    Yuewei Liu · Yi Rong · Kyle Steenland · David C Christiani · Xiji Huang · Tangchun Wu · Weihong Chen
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    ABSTRACT: Background: The association between crystalline silica exposure and risk of heart disease mortality remains less clear. Methods: We investigated a cohort of 42,572 Chinese workers who were potentially exposed to crystalline silica and followed from 1960 to 2003. Cumulative silica exposure was estimated by linking a job-exposure matrix to each person's work history. Low-level silica exposure was defined as never having held a job with an exposure higher than 0.1 mg/m. We estimated hazard ratios (HRs) in exposure-response analyses using Cox proportional hazards model. Results: We identified 2846 deaths from heart disease during an average of 35 years follow-up. Positive exposure-response trends were observed for cumulative silica exposure associated with mortality from total heart disease (HRs for increasing quartiles of cumulative silica exposure compared with the unexposed group = 0.89, 1.09, 1.32, 2.10; P for linear trend < 0.001) and pulmonary heart disease (0.92, 1.39, 2.47, 5.46; P for linear trend < 0.001). These positive trends remained among workers with both high- and low-level silica exposure. There was also a positive trend for ischemic heart disease among workers with low-level exposure, with quartile HRs of 1.04, 1.13, 1.52, and 1.60 (P for linear trend < 0.001). Conclusion: Low-level crystalline silica exposure was associated with increased mortality from heart disease, including pulmonary heart disease and ischemic heart disease, whereas high-level exposure mainly increased mortality from pulmonary heart disease. Current permissible exposure limits for crystalline silica in many countries may be insufficient to protect people from deaths due to heart disease.
    Full-text · Article · Jul 2014 · Epidemiology (Cambridge, Mass.)
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    ABSTRACT: Exposure to environmental polycyclic aromatic hydrocarbons (PAHs) has been associated with increased risk of cancer, but evidence for gender differences in this association is limited. The aim of this study was to examine the gender differences in PAHs caused early genotoxic effects such as oxidative stress and chromosome damage, which are potential carcinogenic etiology of PAHs. A total of 478 nonsmoking workers (272 men and 206 women) from a coke oven plant were recruited. We determined 16 environmental PAHs in their workplaces, and measured concentrations of 12 urinary PAH metabolites (OH-PAHs), plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), and micronucleus frequencies in lymphocytes in all subjects. It showed that, women working at the office, adjacent to the coke oven, and on the bottom or side of the coke oven displayed significantly higher levels of urinary 8-OHdG and 8-iso-PGF2α, and lymphocytic micronucleus frequencies compared with men working at above areas, respectively (all P < 0.05). These gender differences remain significant after adjusted for potential confounders and urinary ΣOH-PAHs or plasma BPDE-Alb adducts. A significant interaction existed between gender and BPDE-Alb adducts on increasing micronucleus frequencies (Pinteraction < 0.001). We further stratified all workers by the tertiles of urinary ΣOH-PAHs or plasma BPDE-Alb adducts, and the above gender differences were more evident in the median- and high-exposure groups (all P < 0.05). In conclusion, women were more susceptible than men to oxidative stress and chromosome damage induced by PAHs, which may add potential evidence underlying gender differences in PAH exposure-related lung cacinogenesis. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Jul 2014 · Environmental and Molecular Mutagenesis
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    ABSTRACT: This study aimed to characterise the cardiovascular inflammatory response to secondhand smoke (SHS) exposure among non-smoking construction workers.
    No preview · Article · Jun 2014 · Occupational and Environmental Medicine
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    ABSTRACT: Whether cessation of exposure to endotoxin containing organic dusts leads to transient vs. sustained improvement of lung function is unknown.
    No preview · Article · Jun 2014 · Occupational and Environmental Medicine
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    ABSTRACT: Workplace and contextual factors that may affect risk for worker injury are not well described. This study used results from an employee job satisfaction survey to construct aggregate indicators of the work environment and estimate the relative contribution of those factors to injury rates in a manufacturing cohort. Principal components analysis was used to construct four plant-level factors from responses to a 32 question survey of the entire workforce, administered in 2006. Multilevel Poisson regression was used to evaluate the relationship between injury rate, individual-level and plant-level risk factors, unionisation and plant type. Plant-level 'work stress' (incident rate ratio (IRR)=0.50, 95% CI 0.28 to 0.90) was significant in the multilevel model, indicating the rate of injury for an average individual in that plant was halved (conditional on plant) when job stress decreased by a tertile. 'Overall satisfaction', 'work environment' and 'perception of supervisor' showed the same trend but were not significant. Unionisation was protective (IRR=0.40, 95% CI 0.17 to 0.95) as was any plant type compared with smelter. We demonstrated utility of data from a human resources survey to construct indicators of the work environment. Our research suggests that aspects of the work environment, particularly work stress and unionisation, may have a significant effect on risk for occupational injury, emphasising the need for further multilevel studies. Our work would suggest monitoring of employee perceptions of job stress and the possible inclusion of stress management as a component of risk reduction programmes.
    Full-text · Article · Apr 2014 · Occupational and environmental medicine
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    ABSTRACT: To investigate the effects of the urinary metabolite profiles of background exposure to the atmospheric pollutants polycyclic aromatic hydrocarbon (PAH) and Framingham risk score (FRS), which assesses an individual's cardiovascular disease risk, on heart rate variability (HRV). The study conducted from April to May 2011 in Wuhan, China, included 1978 adult residents with completed questionnaires, physical examinations, blood and urine samples, and 5-min HRV indices (including SD of all normal to normal intervals (SDNN), root mean square successive difference (rMSSD), low frequency (LF), high frequency (HF) and their ratio (LF/HF), and total power) obtained from 3-channel Holter monitor. 12 urinary PAH metabolites were measured by gas chromatography-mass spectrometry. FRS was calculated by age, sex, lipid profiles, blood pressure, diabetes and smoking status. Linear regression models were constructed after adjusting for potential confounders. Elevated total concentration of hydroxynaphthalene (ΣOHNa) was significantly associated, in a dose-responsive manner, with decreased SDNN and LF/HF (ptrend=0.014 and 0.007, respectively); elevated total concentration of hydroxyfluorene (ΣOHFlu) was significantly associated with reduced SDNN, LF and LF/HF (ptrend=0.027, 0.003, and <0.0001, respectively); and elevated total concentration of all PAH metabolites (ΣOH-PAHs) was associated with decreased LF and LF/HF (ptrend=0.005 and <0.0001, respectively). Moreover, increasing quartiles of FRS were significantly associated with decreased HRV indices, except LF/HF (all ptrend<0.0001). Interestingly, individuals in low-risk subgroups had greater decreases in SDNN, LF and LF/HF in relation to ΣOH-PAHs, ΣOHNa and ΣOHFlu than those in high-risk subgroups (all p<0.05). Environmental PAH exposure may differentially affect HRV based on individual coronary risk profiles.
    No preview · Article · Mar 2014 · Occupational and environmental medicine
  • David C Christiani

    No preview · Article · Mar 2014 · Chest
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    ABSTRACT: ABSTRACT Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland firefighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 μm and a fine particle mode with a mass median aerodynamic diameter <0.5 μm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p <0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a file containing additional information on historical studies of wildland fire exposures, a file containing the daily-exposure-severity questionnaire completed by wildland firefighter participants at the end of each day, and a file containing additional details of the investigation of correlations between carbon monoxide concentrations and other measured exposure factors in the current study.].
    Full-text · Article · Feb 2014 · Journal of Occupational and Environmental Hygiene
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    ABSTRACT: In the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients. A tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis. Of the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases' spouses, sisters/brothers and those who were in contact with female Index Cases. The present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world.
    Full-text · Article · Feb 2014 · BMC Infectious Diseases
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    ABSTRACT: Mutations in the IDH1 and IDH2 (IDH1/2) genes occur in ~20% of intrahepatic cholangiocarcinoma (ICC) and lead to accumulation of 2-hydroxyglutarate (2HG) in the tumor tissue. However, it remains unknown whether IDH1/2 mutations can lead to high levels of 2HG circulating in the blood and whether serum 2HG can be used as a biomarker for IDH1/2 mutational status and tumor burden in ICC. We initially measured serum 2HG concentration in blood samples collected from 31 ICC patients in a Screening cohort. Findings were validated across 38 resected ICC patients from a second cohort with tumor volume measures. Circulating levels of 2HG were evaluated relative to IDH1/2 mutational status, tumor burden and a number of clinical variables. Circulating levels of 2HG in the Screening cohort were significantly elevated in patients with IDH1/2-mutant (median 478 ng/ml) versus IDH1/2-wild-type (median 118 ng/ml) tumors (p<0.001). This significance was maintained in the Validation cohort (343 ng/ml vs 55 ng/ml, p<0.0001) and levels of 2HG directly correlated with tumor burden in IDH1/2-mutant cases (p<0.05). Serum 2HG levels >170 ng/ml could predict the presence of an IDH1/2 mutation with a sensitivity of 83% and a specificity of 90%. No differences were noted between the allelic variants IDH1 or IDH2 in regards to the levels of circulating 2HG. This study indicates that circulating 2HG may be a surrogate biomarker of IDH1 or IDH2 mutation status in ICC and that circulating 2HG levels may correlate directly with tumor burden.
    Full-text · Article · Jan 2014 · Clinical Cancer Research

Publication Stats

9k Citations
1,590.40 Total Impact Points


  • 1997-2015
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1995-2015
    • Harvard University
      • Department of Environmental Health
      Cambridge, Massachusetts, United States
  • 2014
    • Huazhong University of Science and Technology
      • School of Public Health
      Wu-han-shih, Hubei, China
  • 1987-2014
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2006
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2003
    • Capital Medical University
      Peping, Beijing, China
  • 1999-2001
    • Shanghai Medical University
      • • Department of Environmental Health
      • • School of Public Health
      Shanghai, Shanghai Shi, China
  • 2000
    • Wisconsin State Laboratory of Hygiene
      Madison, Wisconsin, United States
    • Boston University
      • Department of Pediatrics
      Boston, MA, United States
  • 1994-2000
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 1991
    • Memorial Hospital of Rhode Island
      Pawtucket, Rhode Island, United States