Person: Christiani, David
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Christiani
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Christiani, David
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Publication Validation of a Dish-Based Semiquantitative Food Questionnaire in Rural Bangladesh(MDPI, 2017) Lin, Pi-I. D.; Bromage, Sabri; Mostofa, Md. Golam; Allen, Joseph; Oken, Emily; Kile, Molly Louise; Christiani, DavidA locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We assessed the validity of a 42-item dish-based semi-quantitative food frequency questionnaire (FFQ) using two 3-day food diaries (FDs). We selected a random subset of 47 families (190 participants) from a longitudinal arsenic biomonitoring study in Bangladesh to administer the FFQ. Two 3-day FDs were completed by the female head of the households and we used an adult male equivalent method to estimate the FD for the other participants. Food and nutrient intakes measured by FFQ and FD were compared using Pearson’s and Spearman’s correlation, paired t-test, percent difference, cross-classification, weighted Kappa, and Bland–Altman analysis. Results showed good validity for total energy intake (paired t-test, p < 0.05; percent difference <10%), with no presence of proportional bias (Bland–Altman correlation, p > 0.05). After energy-adjustment and de-attenuation for within-person variation, macronutrient intakes had excellent correlations ranging from 0.55 to 0.70. Validity for micronutrients was mixed. High intraclass correlation coefficients (ICCs) were found for most nutrients between the two seasons, except vitamin A. This dish-based FFQ provided adequate validity to assess and rank long-term dietary intake in rural Bangladesh for most food groups and nutrients, and should be useful for studying dietary-disease relationships.Publication Effect of Body Mass Index on Left Ventricular Mass in Career Male Firefighters(2017) Korre, Maria; Porto, Luiz Guilherme G.; Farioli, Andrea; Yang, Justin; Christiani, David; Christophi, Costas; Lombardi, David; Kovacs, Richard J.; Mastouri, Ronald; Abbasi, Siddique; Steigner, Michael; Moffatt, Steven; Smith, Denise; Kales, StefanosLeft ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD) events; increased LV mass is common among US firefighters and plays a major role in firefighter sudden cardiac death. We aim to identify significant predictors of LV mass among firefighters. Cross-sectional study of 400 career male firefighters selected by an enriched randomization strategy. Weighted analyses were performed based on the total number of risk factors per subject with inverse probability weighting. LV mass was assessed by echocardiography (ECHO) and cardiac magnetic resonance, and normalized (indexed) for height. CVD risk parameters included vital signs at rest, body mass index (BMI)–defined obesity, obstructive sleep apnea risk, low cardiorespiratory fitness, and physical activity. Linear regression models were performed. In multivariate analyses, BMI was the only consistent significant independent predictor of LV mass indexes (all, p <0.001). A 1-unit decrease in BMI was associated with 1-unit (g/m1.7) reduction of LV mass/height1.7 after adjustment for age, obstructive sleep apnea risk, and cardiorespiratory fitness. In conclusion, after height-indexing ECHO-measured and cardiac magnetic resonance–measured LV mass, BMI was found to be a major driver of LV mass among firefighters. Our findings taken together with previous research suggest that reducing obesity will improve CVD risk profiles and decrease on-duty CVD and sudden cardiac death events in the fire service. Our results may also support targeted noninvasive screening for LV hypertrophy with ECHO among obese firefighters.Publication Application of linear mixed-effects model with LASSO to identify metal components associated with cardiac autonomic responses among welders: a repeated measures study(BMJ Publishing Group, 2017) Zhang, Jinming; Cavallari, Jennifer M; Fang, Shona C; Weisskopf, Marc; Lin, Xihong; Mittleman, Murray; Christiani, DavidBackground: Environmental and occupational exposure to metals is ubiquitous worldwide, and understanding the hazardous metal components in this complex mixture is essential for environmental and occupational regulations. Objective: To identify hazardous components from metal mixtures that are associated with alterations in cardiac autonomic responses. Methods: Urinary concentrations of 16 types of metals were examined and ‘acceleration capacity’ (AC) and ‘deceleration capacity’ (DC), indicators of cardiac autonomic effects, were quantified from ECG recordings among 54 welders. We fitted linear mixed-effects models with least absolute shrinkage and selection operator (LASSO) to identify metal components that are associated with AC and DC. The Bayesian Information Criterion was used as the criterion for model selection procedures. Results: Mercury and chromium were selected for DC analysis, whereas mercury, chromium and manganese were selected for AC analysis through the LASSO approach. When we fitted the linear mixed-effects models with ‘selected’ metal components only, the effect of mercury remained significant. Every 1 µg/L increase in urinary mercury was associated with −0.58 ms (−1.03, –0.13) changes in DC and 0.67 ms (0.25, 1.10) changes in AC. Conclusion: Our study suggests that exposure to several metals is associated with impaired cardiac autonomic functions. Our findings should be replicated in future studies with larger sample sizes.Publication Lung cancer mortality of residents living near petrochemical industrial complexes: a meta-analysis(BioMed Central, 2017) Lin, Cheng-Kuan; Hung, Huei-Yang; Christiani, David; Forastiere, Francesco; Lin, Ro-TingBackground: Lung cancer, as the leading cause of cancer mortality worldwide, has been linked to environmental factors, such as air pollution. Residential exposure to petrochemicals is considered a possible cause of lung cancer for the nearby population, but results are inconsistent across previous studies. Therefore, we performed a meta-analysis to estimate the pooled risk and to identify possible factors leading to the heterogeneity among studies. Methods: The standard process of selecting studies followed the Cochrane meta-analysis guideline of identification, screening, eligibility, and inclusion. We assessed the quality of selected studies using the Newcastle-Ottawa scale. Reported point estimates and 95% confidence intervals were extracted or calculated to estimate the pooled risk. Air quality standards were summarized and treated as a surrogate of exposure to air pollution in the studied countries. Funnel plots, Begg’s test and Egger’s test were conducted to diagnose publication bias. Meta-regressions were performed to identify explanatory variables of heterogeneity across studies. Results: A total of 2,017,365 people living nearby petrochemical industrial complexes (PICs) from 13 independent studied population were included in the analysis. The pooled risk of lung cancer mortality for residents living nearby PICs was 1.03-fold higher than people living in non-PIC areas (95% CI = 0.98–1.09), with a low heterogeneity among studies (I 2 = 25.3%). Such effect was stronger by a factor of 12.6% for the year of follow-up started 1 year earlier (p-value = 0.034). Conclusions: Our meta-analysis gathering current evidence suggests only a slightly higher risk of lung cancer mortality among residents living nearby PICs, albeit such association didn’t receive statistically significance. Reasons for higher risks of early residential exposure to PICs might be attributable to the lack of or less stringent air pollution regulations. Electronic supplementary material The online version of this article (10.1186/s12940-017-0309-2) contains supplementary material, which is available to authorized users.Publication Application of the key characteristics of carcinogens in cancer hazard identification(Oxford University Press, 2018) Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David; Beland, Frederick A; Smith, Martyn TAbstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification.Publication Tie2 protects the vasculature against thrombus formation in systemic inflammation(American Society for Clinical Investigation, 2018-03-05) Higgins, Sarah; De Ceunynck, Karen; Kellum, John; Chen, Xiuying; Gu, Xuesong; Chaudhry, Sharjeel; Schulman, Sol; Libermann, Towia; Lu, Shulin; Shapiro, Nathan; Christiani, David; Flaumenhaft, Robert; Parikh, &Disordered coagulation contributes to death in sepsis and lacks effective treatments. Existing markers of disseminated intravascular coagulation (DIC) reflect its sequelae rather than its causes, delaying diagnosis and treatment. Here we show that disruption of the endothelial Tie2 axis is a sentinel event in septic DIC. Proteomics in septic DIC patients revealed a network involving inflammation and coagulation with the Tie2 antagonist, Angiopoietin-2 (Angpt-2), occupying a central node. Angpt-2 was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality in two large independent cohorts (combined N = 1077). In endotoxemic mice, reduced Tie2 signaling preceded signs of overt DIC. During this early phase, intravital imaging of microvascular injury revealed excessive fibrin accumulation, a pattern remarkably mimicked by Tie2 deficiency even without inflammation. Conversely, Tie2 activation normalized pro-thrombotic responses by inhibiting endothelial tissue factor and phosphatidylserine exposure. Critically, Tie2 activation had no adverse effects on bleeding. These results mechanistically implicate Tie2 signaling as a central regulator of microvascular thrombus formation in septic DIC and indicate that circulating markers of the Tie2 axis could facilitate earlier diagnosis. Finally, interventions targeting Tie2 may normalize coagulation in inflammatory states while averting the bleeding risks of current DIC therapies.Publication A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases(Springer Science and Business Media LLC, 2018-05-21) Zhu, Zhaozhong; Lee, Phil; Chaffin, Mark; Chung, Wonil; Loh, Po-Ru; Lu, Quan; Christiani, David; Liang, LimingClinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg = 0.75, P = 6.84 × 10−62). Cross-trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci. Computational analysis showed that shared genetic loci are enriched in immune/inflammatory systems and tissues with epithelium cells. Our work identifies common genetic architectures shared between asthma and allergy and will help to advance understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases.Publication Whole blood microRNA markers are associated with acute respiratory distress syndrome(Springer International Publishing, 2017) Zhu, Zhaozhong; Liang, Liming; Zhang, Ruyang; Wei, Yongyue; Su, Li; Tejera, Paula; Guo, Yichen; Wang, Zhaoxi; Lu, Quan; Baccarelli, Andrea; Zhu, Xi; Bajwa, Ednan; Taylor Thompson, B.; Shi, Guo-Ping; Christiani, DavidBackground: MicroRNAs (miRNAs) can play important roles in inflammation and infection, which are common manifestations of acute respiratory distress syndrome (ARDS). We assessed if whole blood miRNAs were potential diagnostic biomarkers for human ARDS. Methods: This nested case-control study (N = 530) examined a cohort of ARDS patients and critically ill at-risk controls. Whole blood miRNA profiles and logistic regression analyses identified miRNAs correlated with ARDS. Stratification analysis also assessed selected miRNA markers for their role in sepsis and pneumonia associated with ARDS. Receiver operating characteristic (ROC) analysis evaluated miRNA diagnostic performance, along with Lung Injury Prediction Score (LIPS). Results: Statistical analyses were performed on 294 miRNAs, selected from 754 miRNAs after quality control screening. Logistic regression identified 22 miRNAs from a 156-patient discovery cohort as potential risk or protective markers of ARDS. Three miRNAs—miR-181a, miR-92a, and miR-424—from the discovery cohort remained significantly associated with ARDS in a 373-patient independent validation cohort (FDR q < 0.05) and meta-analysis (p < 0.001). ROC analyses demonstrated a LIPS baseline area-under-the-curve (AUC) value of ARDS of 0.708 (95% CI 0.651–0.766). Addition of miR-181a, miR-92a, and miR-424 to LIPS increased baseline AUC to 0.723 (95% CI 0.667–0.778), with a relative integrated discrimination improvement of 2.40 (p = 0.005) and a category-free net reclassification index of 27.21% (p = 0.01). Conclusions: miR-181a and miR-92a are risk biomarkers for ARDS, whereas miR-424 is a protective biomarker. Addition of these miRNAs to LIPS can improve the risk estimate for ARDS. Electronic supplementary material The online version of this article (10.1186/s40635-017-0155-0) contains supplementary material, which is available to authorized users.Publication Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma(Elsevier, 2018) Wang, Zhaoxi; Wei, Yongyue; Zhang, Ruyang; Su, Li; Gogarten, Stephanie M.; Liu, Geoffrey; Brennan, Paul; Field, John K.; McKay, James D.; Lissowska, Jolanta; Swiatkowska, Beata; Janout, Vladimir; Bolca, Ciprian; Kontic, Milica; Scelo, Ghislaine; Zaridze, David; Laurie, Cathy C.; Doheny, Kimberly F.; Pugh, Elizabeth K.; Marosy, Beth A.; Hetrick, Kurt N.; Xiao, Xiangjun; Pikielny, Claudio; Hung, Rayjean J.; Amos, Christopher I.; Lin, Xihong; Christiani, DavidRecent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome. A large, complex, and robust gene network containing well-known lung cancer-related genes, including EGFR and TERT, was identified from combined gene lists for lung adenocarcinoma. Members of the hypoxia-inducible factor (HIF) gene family were at the center of this network. Subsequent sequencing of network hub genes within a subset of samples from the Transdisciplinary Research in Cancer of the Lung-International Lung Cancer Consortium (TRICL-ILCCO) consortium revealed a SNP (rs12614710) in EPAS1 associated with NSCLC that reached genome-wide significance (OR = 1.50; 95% CI: 1.31–1.72; p = 7.75 × 10−9). Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (p = .03). Additional functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression.Publication A multi‐omic study reveals BTG2 as a reliable prognostic marker for early‐stage non‐small cell lung cancer(John Wiley and Sons Inc., 2018) Shen, Sipeng; Zhang, Ruyang; Guo, Yichen; Loehrer, Elizabeth; Wei, Yongyue; Zhu, Ying; Yuan, Qianyu; Moran, Sebastian; Fleischer, Thomas; Bjaanæs, Maria M.; Karlsson, Anna; Planck, Maria; Staaf, Johan; Helland, Åslaug; Esteller, Manel; Su, Li; Chen, Feng; Christiani, DavidB‐cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be downregulated in several types of cancer. In this study, we investigated a potential role for BTG2 in early‐stage non‐small cell lung cancer (NSCLC) survival. We analysed BTG2 methylation data from 1230 early‐stage NSCLC patients from five international cohorts, as well as gene expression data from 3038 lung cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167, cg23371584) that detected BTG2 hypermethylation in tumour tissues were associated with lower overall survival. The prognostic model based on methylation could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51–2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 expression was positively correlated with survival in each cohort (HR range, 0.28–0.68), which we confirmed with meta‐analysis (HR = 0.61, 95% CI 0.54–0.68). The three CpG probes were all negatively correlated with BTG2 expression. Importantly, an integrative model of BTG2 methylation, expression and clinical information showed better predictive ability in the training set and validation set. In conclusion, the methylation and integrated prognostic signatures based on BTG2 are stable and reliable biomarkers for early‐stage NSCLC. They may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future.