Wei-Te Wu

Six-month follow-up study of health markers of nanomaterials among workers handling engineered nanomaterials

Abstract The aim of this study was to identify the health hazards and possible exposure surveillance markers of workers exposed to nanoparticles during manufacturing and application in comparison to a group of unexposed workers. For this longitudinal study, we recruited 158 nanomaterial-handling workers and 104 non-exposed workers from 14 manufacturing plants in Taiwan (baseline). Among them, 124 nanomaterial-handling workers and 77 unexposed workers were monitored 6 months later. We investigated pulmonary and cardiovascular disease markers, inflammation and oxidative stress markers, antioxidant enzymes and genotoxicity markers. Antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and cardiovascular markers (vascular cell adhesion molecule, paraoxonase) were significantly associated with nanomaterial-handling during the 6-month follow-up period. In addition, the small airway damage marker (Clara cell protein 16) and lung function test parameters were also significantly associated with handling nanomaterials. The study markers and lung function tests are possible markers that could be useful for surveillance of nanomaterial-handling workers.

Effect of Nanoparticles Exposure on Fractional Exhaled Nitric Oxide (FENO) in Workers Exposed to Nanomaterials

Fractional exhaled nitric oxide (FENO) measurement is a useful diagnostic test of airway inflammation. However, there have been few studies of FENO in workers exposed to nanomaterials. The purpose of this study was to examine the effect of nanoparticle (NP) exposure on FENO and to assess whether the FENO is increased in workers exposed to nanomaterials (NM). In this study, both exposed workers and non-exposed controls were recruited from NM handling plants in Taiwan. A total of 437 subjects (exposed group = 241, non-exposed group = 196) completed the FENO and spirometric measurements from 2009–2011. The authors used a control-banding (CB) matrix to categorize the risk level of each participant. In a multivariate linear regression analysis, this study found a significant association between risk level 2 of NP exposure and FENO. Furthermore, asthma, allergic rhinitis, peak expiratory flow rate (PEFR), and NF-κB were also significantly associated with FENO. When the multivariate logistic regression model was adjusted for confounders, nano-TiO2 in all of the NM exposed categories had a significantly increased risk in FENO > 35 ppb. This study found associations between the risk level of NP exposure and FENO (particularly noteworthy for Nano-TiO2). Monitoring FENO in the lung could open up a window into the role nitric oxide (NO) may play in pathogenesis.

The Association between Obstructive Sleep Apnea and Metabolic Markers and Lipid Profiles

Purpose The purpose of this study was to investigate the association between apnea-hypopnea index (AHI) and metabolic markers and whether the elevated risk of Metabolic Syndrome (MetS) is related to Obstructive Sleep Apnea (OSA). Methods This cross-sectional study recruited 246 male bus drivers from one transportation company in Taiwan. Each participant was evaluated by a polysomnography (PSG) test and by blood lipids examination. Severity of OSA was categorized according to the apnea-hypopnea index (AHI). Results The results showed that a 73.3% prevalence of MetS in OSA (AHI > 15) and a 80.0% prevalence of MetS in severe OSA (AHI > 30) were found. After adjusting for confounding variables, an increased level of Body-Mass Index (BMI) and two non-MetS cardiovascular risk factors, total cholesterol/HDL-C ratio and TG/HDL-C ratio was significantly associated with AHI in subjects with severe OSA. MetS was about three times to be present in subjects with severe OSA, even adjusted for BMI. Conclusions The findings showed a high prevalence of MetS in OSA among professional drivers, especially in the severe group category. BMI was the major contributing factor to OSA. However, the present study did not find a sensitive clinical marker of a detrimental metabolic profile in OSA patients.

Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwan between 1979 and 2007.

BACKGROUND AND OBJECTIVE In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. METHODS The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. RESULTS A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. CONCLUSION After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures.

Cancer incidence of Taiwanese shipbreaking workers who have been potentially exposed to asbestos

BACKGROUND Shipbreaking remains one of the most dangerous jobs worldwide. Shipbreaking workers are exposed to many hazardous chemicals, especially asbestos. Unfortunately, long-term follow-up studies of cancer incidence patterns in shipbreaking workers are lacking. This study examines whether there is an increased risk of cancer among male shipbreaking workers over a 24-year follow-up period. METHODS 4155 male shipbreaking workers information was retrospectively collected from Kaohsiungs Shipbreaking Workers Union database from 1985. The study cohort was linked to the Taiwan Cancer Registry from 1985 to 2008 for new cancer cases. The expected number of cancers for shipbreaking workers was calculated by using the age (5-year intervals) and calendar time-specific annual rates of cancer incidence with reference to the general population of Taiwan from 1985 to 2008. Standardized incidence ratios (SIRs) were calculated as relative risk estimates. The hazard ratio (HR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores for asbestos. RESULTS After consideration of a 5-year latency period, an elevated incidence of overall cancer (N=368; SIR=1.13 (1.01-1.25)), oral cavity cancer (N=83; SIR=1.99 (1.58-2.46)), and trachea, bronchus, and lung cancers (N=53; SIR=1.36 (1.02-1.78)) was found among male shipbreaking employees. Moreover, mesothelioma cases were found in those who had the occupation of flame cutter. The high asbestos exposure group was associated with an increased SIR of developing overall cancer and oral cancer, whether we considered a 5-year or 10-year latency period. CONCLUSION Asbestos-related diseases, including lung cancer and mesothelioma, were seen in excess in these shipbreaking workers and some cases appeared to have a dose-dependent relationship. Preventative measures among male shipbreaking workers should be researched further.

Health impacts associated with the implementation of a national petrol-lead phase-out program (PLPOP): Evidence from Taiwan between 1981 and 2007

BACKGROUND AND OBJECTIVE In 1981, a petrol-lead phase-out program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was set out to examine whether the reduction of environmental lead emissions would result in the decrease in mortality rates of various diseases based on national data between 1981 and 2007. METHOD The national mortality data were obtained from the Office of Statistics of the Taiwan Department of Health (Taiwan DOH). Standardized mortality ratios (SMRs) were calculated based on 2000 WHO world standard population. Gasoline consumptions were obtained from the Bureau of Energy. RESULTS The mean blood lead levels (BLLs) had decreased dramatically from approximately 20.14μg/dl in the leaded petrol phase to 3μg/dl or lower in the unleaded petrol phase. From 1981 to 2007, the mortality (per 100,000 people) was decreased from 146.2 to 43.8 for cerebrovascular disease, from 85.3 to 44.4 for heart disease, from 35.4 to 6.6 for hypertensive disease, from 21.3 to 17.3 for nephrosis, and from 810.2 to 491.6 for all causes. By taking the confounders (including economic growth rate, per capita income, tobacco consumption, and medical resources) into account, the decreases in SMRs for all causes, cerebrovascular disease, and nephrosis were found to be highly correlated with the decrease in petrol lead emissions (p-values=0.001, <0.001, 0.020, respectively). CONCLUSION Our results clearly show that the implementation of the PLPOP was associated with a decline in mortality rates in several diseases that have been associated with lead exposure, even after adjustment for a number of relevant confounders.

Cancer Attributable to Asbestos Exposure in Shipbreaking Workers: A Matched-Cohort Study

Purpose Long-term follow-up studies of asbestos-related cancer in shipbreaking workers are lacking. This study examines the relationship between cancer incidence and asbestos exposure among former Taiwan shipbreaking workers. Methods A total of 4,427 shipbreaking workers and 22,135 population-based matched controls were successfully followed in this study. The study cohort was linked to the Taiwan Cancer Registry for new cancer cases. The adjusted hazard ratio (aHR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores (TEP) for asbestos. Results Follow-up generated 109,932 person-years, with 940 deaths and 436 cancer cases, among 4,427 shipbreaking workers from 1985 to 2008. The high asbestos exposure group also had a statistically significant increase in the risk of overall cancer (aHR= 1.71; 95% CI: 1.42-2.05), esophagus cancer (aHR= 2.31; 95% CI: 1.00-5.41), liver and intrahepatic bile duct cancer (aHR= 1.60; 95% CI: 1.08-2.36), and trachea, bronchus, and lung cancer (aHR= 3.08; 95% CI: 1.80-5.25). Mesothelioma cases were found in the high asbestos exposure group. Moreover, overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer were seen in a dose-dependent relationship with asbestos exposure. Conclusions This study presented the elevated trend of asbestos exposure with cancer incidence for overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer among shipbreaking workers. Those workers previously exposed to asbestos should receive persistent monitoring in order to early detect adverse health outcomes.

Global DNA methylation and oxidative stress biomarkers in workers exposed to metal oxide nanoparticles

This is the first study to assess global methylation, oxidative DNA damage, and lipid peroxidation in workers with occupational exposure to metal oxide nanomaterials (NMs). Urinary and white blood cell (WBC) 8-hydroxydeoxyguanosine (8-OHdG), and exhaled breath condensate (EBC) 8-isoprostane were measured as oxidative stress biomarkers. WBC global methylation was measured as an epigenetic alteration. Exposure to TiO2, SiO2, and indium tin oxide (ITO) resulted in significantly higher oxidative biomarkers such as urinary 8-OHdG and EBC 8-isoprostane. However, significantly higher WBC 8-OHdG and lower global methylation were only observed in ITO handling workers. Significant positive correlations were noted between WBC and urinary 8-OHdG (Spearman correlation r=0.256, p=0.003). Furthermore, a significant negative correlation was found between WBC 8-OHdG and global methylation (r=-0.272, p=0.002). These results suggest that exposure to metal oxide NMs may lead to global methylation, DNA oxidative damage, and lipid peroxidation.

Mortality among shipbreaking workers in Taiwan—A retrospective cohort study from 1985 to 2008†‡

BACKGROUND Shipbreaking workers are typically exposed to a wide range of hazardous chemicals. However, long-term follow-up studies of their mortality patterns are lacking. This study examined mortality among shipbreaking workers over a 24-year follow-up period. METHODS A total of 4,962 shipbreaking workers were recruited from the database of the Kaohsiung Shipbreaking Workers Union. The data were then linked to the Taiwan National Death Registry from 1985 to 2008. The mortality ratios-standardized for age and calendar years-(SMRs) for various causes of deaths were calculated with reference to the general population of Taiwan. RESULTS Among men workers, a statistically significant increased SMR was observed for all causes (SMR = 1.28), all cancers (SMR = 1.26; particularly noteworthy for lesions of oral and nasopharyngeal: SMR 2.03, liver: SMR 4.63, and lung: SMR 1.36), cirrhosis of the liver (SMR = 1.32), and accidents (SMR = 1.91). A statistically significant increase in mortality was observed for respiratory system cancer (SMR = 1.87) and lung cancer (SMR = 1.91) among workers with a longer duration of employment (≥7 years). The result also showed that among shipbreaking workers who were still alive, two people had mesothelioma and 10 people have asbestosis. CONCLUSIONS Those employed in shipbreaking industries experienced an increase in mortality from all causes. The increased SMR for lung cancer was probably related to asbestos, metals, and welding fume exposure.

Changing blood lead levels and DNA damage (comet assay) among immigrant women in Taiwan

BACKGROUND International marriage has had a rapid growth in recent years in Taiwan. However, little is known about the blood lead levels and DNA damage levels among immigrant women from resource-limited countries. OBJECTIVE This study (a) explored differences between immigrant women and native women in demographic characteristics, blood lead levels, and DNA damage levels, and (b) identified risk factors that are associated with blood lead concentrations and DNA damage levels after immigration. METHODS We used a structured questionnaire to collect data on socio-demographic status from (a) 71 immigrant women who had resettled in 2006 in Taichung, Taiwan and (b) 83 native women who live in the same area. Each study participant provided blood samples for lead and metal measurements, complete blood count examination, and the comet assay to measure degree of DNA damage. RESULTS Immigrant women had higher mean blood lead concentration (2.23+/-1.63 vs. 1.63+/-1.00 microg/dl; p=0.04) and lower mean blood zinc level (6.22+/-2.22 vs. 6.89+/-2.44 mg/l; p=0.07) than native women. Resettlement time was a determinant to decrease blood lead and DNA damage levels among immigrants in Taiwan. Multiple linear regression analysis confirmed a statistically significant association between blood lead level and DNA damage, while zinc had a protective effect. CONCLUSIONS Public health agencies should focus on primary prevention and providing screening programs for this vulnerable population. An immigrant womens cohort should been established to follow-up and improve for elevated lead exposure families.