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Biomedical subjects

David C Christiani

Publications and source records attributed to David C Christiani.

At least 73 records · Page 4Linked to original sources

Dietary intake of Cruciferous vegetables, Glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population.

OBJECTIVE: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk. METHODS: Hospital-based case-control study of 716 Caucasian lung cancer cases and 939 spouse and friend controls conducted in Boston, Massachussetts between 1992 and 2000. Dietary intake was collected through a food frequency questionnaire and blood was obtained for genotyping. Logistic regression models were adjusted for age, gender, total calories and smoking variables. RESULTS: Higher intakes of cruciferous vegetables reduced lung cancer risk among GSTM1 present individuals (odds ratio (OR)highest versus lowest tertile = 0.61, 95% confidence interval (CI) = 0.39-0.95) but not among GSTM1 null individuals (OR(highest versus lowest tertile) = 1.15, 95% CI = 0.78-1.68). We observed statistically significant interactions between GSTM1 and cruciferous vegetable intake overall (likelihood ratio test (LRT): p = 0.05) and among current smokers (LRT: p = 0.01). No significant interactions were observed for GSTT1 or the combined GSTM1/T1 genotype. CONCLUSIONS: In our study, higher cruciferous vegetable intake reduced lung cancer risk only among individuals with the GSTM1 present genotype. Our findings differed from prior studies that specifically assessed isothiocyanates found in cruciferous vegetables or evaluated Asian study populations with higher levels of cruciferous vegetable consumption.

Aged↗

Epidemiology, biologic behavior, and natural history of mesothelioma.

Malignant pleural mesothelioma has a well described natural history but poorly defined pathogenesis. It is strongly associated with asbestos exposure. A predominantly locally invasive disease, the success of more aggressive life-prolonging therapies has increased the potential for the development of distant metastases in survivors. Recently described new risk factors may increase the incidence of this disease in future generations, underscoring the need for a more in-depth understanding of its pathobiology. This article reviews the current body of knowledge about the occurrence, distribution, presentation, and natural history of malignant pleural mesothelioma.

Asbestos↗

Comparison of fine particle measurements from a direct-reading instrument and a gravimetric sampling method.

Particulate air pollution, specifically the fine particle fraction (PM2.5), has been associated with increased cardiopulmonary morbidity and mortality in general population studies. Occupational exposure to fine particulate matter can exceed ambient levels by a large factor. Due to increased interest in the health effects of particulate matter, many particle sampling methods have been developed In this study, two such measurement methods were used simultaneously and compared. PM2.5 was sampled using a filter-based gravimetric sampling method and a direct-reading instrument, the TSI Inc. model 8520 DUSTTRAK aerosol monitor. Both sampling methods were used to determine the PM2.5 exposure in a group of boilermakers exposed to welding fumes and residual fuel oil ash. The geometric mean PM2.5 concentration was 0.30 mg/m3 (GSD 3.25) and 0.31 mg/m3 (GSD 2.90)from the DUSTTRAK and gravimetric method, respectively. The Spearman rank correlation coefficient for the gravimetric and DUSTTRAK PM2.5 concentrations was 0.68. Linear regression models indicated that log, DUSTTRAK PM2.5 concentrations significantly predicted loge gravimetric PM2.5 concentrations (p < 0.01). The association between log(e) DUSTTRAK and log, gravimetric PM2.5 concentrations was found to be modified by surrogate measures for seasonal variation and type of aerosol. PM2.5 measurements from the DUSTTRAK are well correlated and highly predictive of measurements from the gravimetric sampling method for the aerosols in these work environments. However, results from this study suggest that aerosol particle characteristics may affect the relationship between the gravimetric and DUSTTRAK PM2.5 measurements. Recalibration of the DUSTTRAK for the specific aerosol, as recommended by the manufacturer, may be necessary to produce valid measures of airborne particulate matter.

Aerosols↗

Using exposure prediction rules for exposure assessment: an example on whole-body vibration in taxi drivers.

BACKGROUND: It is often difficult and expensive to make direct measurements of an individual's occupational or environmental exposures in large epidemiologic studies. METHODS: In this study, we used information collected in validation studies to develop a prediction rule for assessing exposure in a study with no direct measurement. We established a prediction rule through mixed-effect modeling of direct measurement data and information on observable exposure predictors and their interactions. Specifically, we used 383 measures of whole-body vibration from 247 professional taxi drivers and attempted to quantify vibration exposures for individuals in a large study on low back pain. RESULTS: Using the "jackknife method," we found that our prediction rule had an acceptably low relative prediction error of 11% (95% confidence interval-10-12%). Implementing the prediction rule would result in measurement errors independent of low back pain and of all identified and observable predictors of whole-body vibration. We applied the predicted levels to compute each person's daily exposure, and found a strong association between the predicted daily whole-body vibration exposure and prevalence of low back pain. This supported the construct validity of the exposure prediction rule. CONCLUSIONS: The predictive and construct validity of our prediction rule suggests that this general statistical approach can be useful in other occupational settings to improve the quality of exposure assessment.

Adult↗

Is chronic airway obstruction from cotton dust exposure reversible?

BACKGROUND: Exposure to cotton dust is known to cause chronic airway obstruction, but there is little information on whether the obstructive impairment is reversible after the exposure stops. METHODS: Longitudinal changes in lung function were evaluated among 429 cotton textile workers and 449 silk workers in Shanghai, China, beginning in 1981. Both active and retired workers were tested every 4 to 6 years for 15 years. RESULTS: Overall, cotton workers had greater annual declines in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Compared with active workers, retired cotton workers had lower annual loss of FEV1, although the retired workers had a greater loss during their active employment than the currently active workers. No such trends were detected in silk workers. Annual declines in FEV1 in retired cotton workers were smaller with increasing time since retirement. Multivariate analysis showed that retirement was a substantial contributing factor for improved FEV1 and FVC in the cotton workers, especially among those who did not smoke. Correspondingly, remission of airflow obstruction, defined as a ratio of FEV1 and FVC of less than 70%, was more common in retirees than in the active workers, and more common in nonsmokers than in smokers. CONCLUSION: Chronic airway obstruction related to long-term exposure to cotton dust may be partially reversible after the exposure ceases, although lung function does not return to the level found in unexposed workers.

Adult↗

Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk.

To assess whether differences in genetic susceptibility to oxidative stress modify asbestos-related lung cancer risk (caused by lung inflammation, free radical production), we examined possible interactions between manganese superoxide dismutase (MnSOD) genotypes and asbestos in a hospital-based case-control study of 811 white lung cancer cases and 957 friend/spouse controls. Cumulative lifetime asbestos exposure score (AES) was calculated from self-reported duration and intensity of occupational and nonoccupational exposures. A total of 13.5% of cases and 10% of controls had "high" AES (determined by a priori cut point). The homozygous variant MnSOD genotype was associated with increased lung cancer risk among individuals with zero or "low" AES (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.52-3.01) and no association (OR = 1.00; 95% CI = 0.36-2.73) among the "high" AES group. We observed no statistically significant interaction between MnSOD genotype and asbestos exposure for lung cancer risk.

Adolescent↗

A case-control study of parental occupation, leukemia, and brain tumors in an industrial city in Taiwan.

We conducted a case-control study in an industrial city in Taiwan to determine whether parents of newly diagnosed patients who were younger than 30 years old with leukemia or brain tumors or the patients themselves were more likely to have been employed in certain occupations or industries. Job histories were collected for parents (and for subjects if they worked) on 103 newly diagnosed cases of leukemia, 74 newly diagnosed cases of brain tumors, and 417 controls matched for age and sex. All jobs since the age of 16 that the subjects held for more than 6 months, a total of approximately 4,000 jobs, were coded for occupation and industry according the standard four-digit system used in Taiwan. Matched-pair analyses were performed comparing cases and controls among all jobs held by subjects and both parents using four-digit occupation and industry codes. Separate analyses also were performed for parental jobs held during the preconception, perinatal, and postnatal periods. Odds ratios (ORs) were adjusted for subject smoking, parental smoking, and exposure to medical radiation. Certain industry and occupation four-digit codes were significantly associated with increased odds ratios of childhood tumors. Including work during any or all periods, leukemias were more common in children of fathers who had worked (1) as wood treaters (adjusted OR 16.03, 95% confidence interval CI = 1.77-145.5), and (2) as building finishers and related trades workers (adjusted OR 4.08, 95% CI = 1.12-14.8), whereas brain tumors were more common in children of mothers who had worked (1) in electronic parts and components manufacturing (adjusted OR 13.78, 95% CI = 1.47-129.0) and 2) as textile and garment workers (adjusted OR 7.25, 95% CI = 1.42-37.0), as well as in subjects who had worked with certain electronic parts and components (adjusted OR 28.67, 95% CI = 2.88-285.6). Leukemias were more common in children of fathers who had worked in the preconception period (1) as wood treaters (adjusted OR 12.17, 95% CI = 1.36-109.2), (2) as building finishers and related trades workers (adjusted OR 4.08, 95% CI = 1.12-14.8), (3) as electronic equipment assemblers (adjusted OR 4.56, 95% CI = I 1.05-19.9), and (4) as certain other assemblers (adjusted OR 10.24, 95% CI = 1.02-102.6). In addition, leukemias were more common in children of fathers who had worked in the perinatal period (1) as wood treaters (adjusted OR 13.08, 95% CI = 1.36-125.5) and (2) as building finishers and related trades workers (adjusted OR 4.51, 95% CI = 1.04-19.6). Brain tumors were more common in children of mothers who had worked in the preconception period (1) in electronic parts and components manufacturing (adjusted OR 11.81, 95% CI = 1.20-116.3), and (2) as textile and garment workers (adjusted OR 7.25, 95% CI = 1.18-31.0).

Adolescent↗

TLR4 Asp299Gly and Thr399Ile polymorphisms are very rare in the Chinese population.

Endotoxin is an important component of bio-aerosols that contribute to airway inflammation and airflow obstruction. Toll-like receptor 4 (TLR4) mediates the host response to bacterial lipopolysaccharide (LPS), and the Asp299Gly and Thr399Ile polymorphisms have been associated with the development of respiratory diseases. We hypothesized that TLR4 polymorphisms may be associated with a decline of lung function in cotton workers who were exposed continuously to endotoxin. We investigated these two polymorphisms in our 20-year longitudinal cohort of Han Chinese cotton and silk textile workers. The two polymorphisms were genotyped using TaqMan and PCR-restriction fragment length polymorphism methods. No homozygous or heterozygous variant genotypes of the Asp299Gly and Thr339Ile polymorphisms were detected in 491 samples of this population. Our results suggest that the TLR4 Asp299Gly and Thr339Ile polymorphisms are very rare in the Chinese population.

Adult↗

On the use of biomarkers for environmental health research.

This article discusses the growing interest in the use of biomarker data in environmental health research and considers some of the challenging statistical issues that arise. We specify a modeling framework that links environmental exposure, biomarkers and outcome, and discuss in conceptual terms how such a formulation could be used to inform dose response modeling for the purpose of quantitative risk assessment. We then analyse some biomarker data from a case-control study designed to elucidate the mechanisms of smoking induced lung cancer. Because of sample size limitations, we use a likelihood-based analysis which subsumes both cohort and case-control designs as special cases. Our analysis allows us to 1) investigate the extent to which the markers explain the pathway from exposure to outcome; 2) quantify the degree to which biomarker data can improve on predicting outcome over and above exposure; and 3) estimate the association among multiple markers.

Biomarkers↗

Antimony: an unlikely confounder in the relationship between well water arsenic and health outcomes in Bangladesh.

Recent in vitro studies have suggested a potential role for antimony as a confounder in human health studies related to arsenic in drinking water. We measured tube-well water concentrations of antimony and arsenic in the Pabna region of Bangladesh, where arsenic concentrations are known to be elevated and the concentrations of antimony have not yet been thoroughly documented. Two hundred forty-five tube-well water samples were collected from various regions in Pabna, Bangladesh, as part of an ongoing case-control study. Water samples were analyzed for arsenic and antimony concentrations by inductively coupled plasma-mass spectrometry using U.S. Environmental Protection Agency method 200.8. The arsenic concentrations in the tube-well water samples ranged from < 1 microg/L to 747 microg/L. All 245 water samples had antimony concentrations < 1 microg/L. Based on consideration of the concentrations used the in vitro studies compared with field-observed concentrations, our results do not support the hypothesis that antimony would be a significant confounder in observed relationships between arsenic exposure through drinking water and potential health outcomes in Pabna, Bangladesh.

Antimony↗

Urinary 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates.

Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter <or= 2.5 micro m (PM2.5) and oxidative DNA damage and repair, as indicated by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, in a group of boilermakers exposed to ROFA and metal fumes. Twenty workers (50% smokers) were monitored for 5 days during an overhaul of oil-fired boilers. The median occupational PM2.5 8-hr time-weighted average was 0.44 mg/m3 (25th-75th percentile, 0.29-0.76). The mean +/- SE creatinine-adjusted 8-OHdG levels were 13.26 +/- 1.04 micro g/g in urine samples collected pre-workshift and 15.22 +/- 0.99 micro g/g in the post-workshift samples. The urinary 8-OHdG levels were significantly greater in the post-workshift samples than in the pre-workshift samples (p = 0.02), after adjusting for urinary cotinine levels, chronic bronchitis status, and age. Linear mixed models indicated a significant exposure-response association between PM2.5 exposure and urinary 8-OHdG levels (p = 0.03). Each 1-mg/m3 incremental increase in PM2.5 exposure was associated with an increase of 1.67 micro g/g (95% confidence interval, 0.21-3.14) in 8-OHdG levels. PM2.5 vanadium, manganese, nickel, and lead exposures also were positively associated with 8-OHdG levels (p <or= 0.05). This study suggests that a relatively young and healthy cohort of boilermakers may experience an increased risk of developing oxidative DNA injury after exposure to high levels of metal-containing particulate matter.

8-Hydroxy-2'-Deoxyguanosine↗

Polymorphism in the surfactant protein-B gene, gender, and the risk of direct pulmonary injury and ARDS.

STUDY OBJECTIVE: Major risk factors for ARDS have been identified. However, only a minority of patients with such risks develops ARDS. It is likely that, given the same type and degree of insult, there are heritable determinants of susceptibility to ARDS. To investigate the possibility of variable genetic susceptibility to ARDS, we examined the association between ARDS and a polymorphism in intron 4 of the surfactant protein-B (SP-B) gene. DESIGN: Nested case-control study conducted from September 1999 to March 2001. SETTING: Four adult medical and surgical ICUs at a tertiary academic center. PATIENTS: One hundred eighty-nine patients meeting study criteria for a defined risk factor for ARDS were enrolled and prospectively followed. MEASUREMENTS AND RESULTS: Seventy-two patients (38%) developed ARDS. After stratification by gender and adjustment for potential confounders, there was a significantly increased odds for women with the variant SP-B gene to develop ARDS compared to women homozygous for the wild-type allele (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.1 to 18.8; p = 0.03). Women with the variant SP-B polymorphism also had significantly increased odds of having a direct pulmonary injury such as aspiration or pneumonia as a risk factor for ARDS as opposed to an indirect pulmonary risk for ARDS (OR, 4.6; 95% CI, 1.1 to 19.9; p = 0.04). No such association with ARDS or direct pulmonary injury was found for men. CONCLUSION: The variant polymorphism of the SP-B gene is associated with ARDS and with direct pulmonary injury in women, but not in men. Further study is needed to confirm the association between the variant SP-B gene, and gender, ARDS, and direct pulmonary injury.

Adolescent↗

Knee pain and driving duration: a secondary analysis of the Taxi Drivers' Health Study.

OBJECTIVES: We explored a postulated association between daily driving time and knee pain. METHODS: We used data from the Taxi Drivers' Health Study to estimate 1-year prevalence of knee pain as assessed by the Nordic musculoskeletal questionnaire. RESULTS: Among 1242 drivers, the prevalence of knee pain, stratified by duration of daily driving (< or = 6, > 6 through 8, > 8 through 10, and > 10 hours), was 11%, 17%, 19%, and 22%, respectively. Compared with driving 6 or fewer hours per day, the odds ratio of knee pain prevalence for driving more than 6 hours per day was 2.52 (95% confidence interval = 1.36, 4.65) after we adjusted for socioeconomic, work-related, and personal factors in the multiple logistic regression. CONCLUSIONS: The dose-related association between driving duration and knee pain raises concerns about work-related knee joint disorders among professional drivers.

Absenteeism↗

Smoking status and occupational exposure affects oxidative DNA injury in boilermakers exposed to metal fume and residual oil fly ash.

Epidemiologic studies demonstrate increased cancer incidence among workers exposed to polycyclic aromatic hydrocarbons (PAH) and metals, probably through cumulative oxidative DNA damage in response to carcinogens. Boilermakers are exposed to particulates of residual oil fly ash (ROFA) and metal fume that contain carcinogenic PAH and metals. We conducted a repeated-measures cohort study in boilermakers during the overhaul of an oil-fired boiler to determine a possible association between the level of 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an oxidative injury biomarker) and biomarkers of PAH (1-hydroxypyrene; 1-OHP) and metal exposure. Preshift and postshift urine samples were analyzed for 8-OH-dG, cotinine, 1-OHP, and metals. Generalized estimating equations were used to model the multivariate relationship of 8-OH-dG to the explanatory variables of interest. Biomarker levels were determined for 181 urine samples from 20 male subjects (mean age 45 years, 50% smokers). Metal and 1-OHP levels increased cross-week and were affected by smoking status. Levels of 8-OH-dG were higher in nonsmokers at the start of the workweek yet declined after occupational exposure to similar levels as in smokers. Multivariate analysis indicated that metal x cotinine interaction terms for nickel, vanadium, chromium, and copper were significantly associated with the 8-OH-dG level, but there were differential effects depending on the metal. This study suggests that oxidative DNA damage in boilermakers is influenced by the interaction between occupational exposures and smoking status. In addition, boilermakers may have reduced ability to repair damaged DNA after ROFA and metal fume exposure. This finding has clinical relevance because these exposures may increase the cancer susceptibility of boilermakers.

8-Hydroxy-2'-Deoxyguanosine↗

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5 (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy controls. RESULTS: The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls. CONCLUSIONS: mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.

Aged↗

Firefighters and on-duty deaths from coronary heart disease: a case control study.

BACKGROUND: Coronary heart disease (CHD) is responsible for 45% of on-duty deaths among United States firefighters. We sought to identify occupational and personal risk factors associated with on-duty CHD death. METHODS: We performed a case-control study, selecting 52 male firefighters whose CHD deaths were investigated by the National Institute for Occupational Safety and Health. We selected two control populations: 51 male firefighters who died of on-duty trauma; and 310 male firefighters examined in 1996/1997, whose vital status and continued professional activity were re-documented in 1998. RESULTS: The circadian pattern of CHD deaths was associated with emergency response calls: 77% of CHD deaths and 61% of emergency dispatches occurred between noon and midnight. Compared to non-emergency duties, fire suppression (OR = 64.1, 95% CI 7.4-556); training (OR = 7.6, 95% CI 1.8-31.3) and alarm response (OR = 5.6, 95% CI 1.1-28.8) carried significantly higher relative risks of CHD death. Compared to the active firefighters, the CHD victims had a significantly higher prevalence of cardiovascular risk factors in multivariate regression models: age >or= 45 years (OR 6.5, 95% CI 2.6-15.9), current smoking (OR 7.0, 95% CI 2.8-17.4), hypertension (OR 4.7, 95% CI 2.0-11.1), and a prior diagnosis of arterial-occlusive disease (OR 15.6, 95% CI 3.5-68.6). CONCLUSIONS: Our findings strongly support that most on-duty CHD fatalities are work-precipitated and occur in firefighters with underlying CHD. Improved fitness promotion, medical screening and medical management could prevent many of these premature deaths.

Case-Control Studies↗