Nan-Hung Hsieh

Assessing the potential exposure risk and control for airborne titanium dioxide and carbon black nanoparticles in the workplace

PurposeThis study assessed the potential exposure risks for workers in the workplace exposed to airborne titanium dioxide nanoparticles (TiO2-NPs) and carbon black nanoparticles (CB-NPs). The risk management control strategies were also developed for the NP engineering workplace.MethodsThe method used in this study was based on the integrated multiple-path particle dosimetry model to estimate the cumulative dose of nanoparticles (NPs) in the human lung. The study then analyzed toxicological effects such as pulmonary cytotoxicity and inflammation and evaluated the health risk associated with exposure to NPs in the workplace. Risk control measures such as the use of ventilating systems and N95 respirator protection are also discussed.Results and discussionThis study found that: (1) the cumulative dose of CB-NPs was greater than that of TiO2-NPs in human lungs; (2) there is a potential health risk to workers exposed to TiO2-NPs and CB-NPs in the absence of control measures in the workplace, with higher health risks associated with CB-NPs than TiO2-NPs; and (3) the use of a ventilating system and an N95 respirator offers greater protection in the workplace and significantly reduces the health risks associated with NP exposure.ConclusionThe present risk management control strategy suggests that the most effective way to reduce airborne NPs is to incorporate the use of a ventilating system combined with N95 respirator protection. This will enable the concentrations of TiO2-NPs and CB-NPs to be reduced to acceptable exposure levels.

Assessing trends and predictors of tuberculosis in Taiwan

BackgroundVariety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines.MethodsThe generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales.ResultsWe found that (i) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person-1 yr-1, (ii) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (iii) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (iv) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations.ConclusionsThe proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.

Assessing the potential risks to zebrafish posed by environmentally relevant copper and silver nanoparticles.

The manufacture of large quantities of engineered nanomaterials (NMs) may lead to unintended contamination of aquatic ecosystems. Biologically based monitoring techniques need to be developed to detect these emerging NMs. The purpose of this study was to develop a risk-based probability model to predict the potential hazards of nanoecotoxicity toward aquatic organisms posed by waterborne copper and silver nanoparticles (Cu/Ag NPs). Published experimental evidence based on Cu/Ag NP-zebrafish (Danio rerio) systems was adopted as the study data. A Hill model was used to reconstruct a concentration-mortality response profile. A cumulative Weibull predictive model was employed to estimate exposure thresholds. The derived probabilistic model can predict the potential risk of environmentally relevant Cu/Ag NPs for major Taiwanese rivers with predicted environmental concentrations of 0.06 (95% confidence interval (CI): 0.01-0.92) mgL(-1) for Cu NPs and 0.04 (0.01-0.11) mgL(-1) for Ag NPs. The results indicated that estimated thresholds were 0.10-0.48mgL(-1) (95% CI) for Cu NPs and 2.69-2.73mgL(-1) for Ag NPs. The probabilities of a risk quotient (RQ) of >1 ranged 17%-81% for zebrafish exposed to Cu NPs. This study found that Ag NP exposure scenarios posed no significant risks to zebrafish (RQ≪0.1).

Assessing the arsenic-contaminated rice (Oryza sativa) associated children skin lesions

The purpose of this study was to assess the potential risk of children skin lesions from arsenic-contaminated rice (Oryza sativa) consumption in West Bengal (India). Published age- and gender-specific skin lesions data in West Bengal were reanalyzed and incorporated into a Weibull dose-response model to predict children skin lesion prevalence. Monomethylarsonous acid (MMA(III)) levels in urine was used as a biomarker that could be predicted from a human physiologically based pharmacokinetic (PBPK) model. This study integrated arsenic contents in irrigation water, bioaccumulation factors of paddy soil, cooking methods, and arsenic bioavailability of cooked rice in gastrointestinal tract into a probabilistic risk model. Results indicated that children aged between 13 and 18 years might pose a relative higher potential risk of skin lesions to arsenic-contaminated cooked rice (odds ratios (ORs)=1.18 (95% CI 1.12-2.15)) than those of 1-6 years children (ORs=0.98 (0.85-1.40)). This study revealed the need to consider the relationships between cooking method and arsenic in cooked rice when assessing the risk associated with children skin lesions from rice consumption. This study suggested that arsenic-associated skin lesions risk from arsenic-contaminated rice consumption would be reduced significantly by adopting traditional rice cooking method (wash until clean; rice:water=1:6; discard excess water) as followed in West Bengal (India) and using water containing lower arsenic (e.g., <10 microg L(-1)) for cooking.

Fluctuation analysis-based risk assessment for respiratory virus activity and air pollution associated asthma incidence

Abstract Asthma is a growing epidemic worldwide. Exacerbations of asthma have been associated with bacterial and viral respiratory tract infections and air pollution. We correlated the asthma admission rates with fluctuations in respiratory virus activity and traffic-related air pollution, namely particulate matter with an aerodynamic diameter ≤10μm (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3). A probabilistic risk assessment framework was developed based on a detrended fluctuation analysis to predict future respiratory virus and air pollutant associated asthma incidence. Results indicated a strong association between asthma admission rate and influenza (r =0.80, p <0.05) and SO2 level (r =0.73, p <0.05) in Taiwan in the period 2001–2008. No significant correlation was found for asthma admission and PM10, O3, NO2, and CO. The proposed fluctuation analysis provides a simple correlation exponent describing the complex interactions of respiratory viruses and air pollutants with asthma. This study revealed that there was a 95% probability of having exceeded 2987 asthma admissions per 100,000 population. It was unlikely (30% probability) that the asthma admission rate exceeded 3492 per 100,000 population. The probability of asthma admission risk can be limited to below 50% by keeping the correlation exponent of influenza to below 0.9. We concluded that fluctuation analysis based risk assessment provides a novel predictor of asthma incidence.

Quantitative links between arsenic exposure and influenza A (H1N1) infection-associated lung function exacerbations risk.

The objective of this study was to link arsenic exposure and influenza A (H1N1) infection‐induced respiratory effects to assess the impact of arsenic‐contaminated drinking water on exacerbation risk of A (H1N1)‐associated lung function. The homogeneous Poisson process was used to approximate the related processes between arsenic exposure and influenza‐associated lung function exacerbation risk. We found that (i) estimated arsenic‐induced forced expiratory volume in 1 second (FEV1) reducing rates ranged from 0.116 to 0.179 mL/μg for age 15–85 years, (ii) estimated arsenic‐induced A (H1N1) viral load increasing rate was 0.5 mL/μg, (iii) estimated A (H1N1) virus‐induced FEV1 reducing rate was 0.10 mL/logTCID50, and (iv) the relationship between arsenic exposure and A (H1N1)‐associated respiratory symptoms scores (RSS) can be described by a Hill model. Here we showed that maximum RSS at day 2 postinfection for Taiwan, West Bengal (India), and the United States were estimated to be in the severe range of 0.83, 0.89, and 0.81, respectively, indicating that chronic arsenic exposure and A (H1N1) infection together are most likely to pose potential exacerbations risk of lung function, although a 50% probability of lung function exacerbations risk induced by arsenic and influenza infection was within the mild and moderate ranges of RSS at day 1 and 2 postinfection. We concluded that avoidance of drinking arsenic‐containing water could significantly reduce influenza respiratory illness and that need will become increasingly urgent as the novel H1N1 pandemic influenza virus infects people worldwide.

Regional response of dengue fever epidemics to interannual variation and related climate variability

Dengue is a major international public health concern and one of the most important vector-borne diseases. The purpose of this article is to investigate the association among temperature, rainfall, relative humidity, and dengue fever by incorporating the lag effect and examining the dominant interannual model of the modern climate, the El Niño Southern Oscillation (ENSO), in the southern region of Taiwan. We built a linear Poisson regression model by including linear time treads and statistical indicators, verified with disease data in the 2004–2013 period. Here we showed that regional climatic factors in association with the interannual climate variability expressed by the ENSO phenomenon had a significant influence on the dynamics of urban dengue fever in southern Taiwan. The 2–4-month lag of statistical indicators of regional climate factors together with the 4-month lagged Pacific surface temperature (SST) anomaly in the proposed Poisson regression model could capture the regional dengue incidence patterns well. The statistical indicators of mean and coefficient of variation of temperature showed the greatest impact on the dengue incidence rate. We also found that the dengue incidence rate increased significantly with the lag effect of the warmer SST. The ability to forecast regional dengue incidence in southern Taiwan could permit pretreatment of mosquito habitats adjacent to human habitations with highly effective insecticides that would be released at the time of the high-temperature season.

Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in consumer products, therapeutic agents, and drug delivery systems. However, the fate and behavior of ZnO NPs in living organisms are not well described. The purpose of this study was to develop a physiologically based pharmacokinetic model to describe the dynamic interactions of 65ZnO NPs in mice. We estimated key physicochemical parameters of partition coefficients and excretion or elimination rates, based on our previously published data quantifying the biodistributions of 10 nm and 71 nm 65ZnO NPs and zinc nitrate (65Zn(NO3)2) in various mice tissues. The time-dependent partition coefficients and excretion or elimination rates were used to construct our physiologically based pharmacokinetic model. In general, tissue partition coefficients of 65ZnO NPs were greater than those of 65Zn(NO3)2, particularly the lung partition coefficient of 10 nm 65ZnO NPs. Sensitivity analysis revealed that 71 nm 65ZnO NPs and 65Zn(NO3)2 were sensitive to excretion and elimination rates in the liver and gastrointestinal tract. Although the partition coefficient of the brain was relative low, it increased time-dependently for 65ZnO NPs and 65Zn(NO3)2. The simulation of 65Zn(NO3)2 was well fitted with the experimental data. However, replacing partition coefficients of 65ZnO NPs with those of 65Zn(NO3)2 after day 7 greatly improved the fitness of simulation, suggesting that ZnO NPs might decompose to zinc ion after day 7. In this study, we successfully established a potentially predictive dynamic model for slowly decomposed NPs. More caution is suggested for exposure to 65ZnO NPs <10 nm because those small 65ZnO NPs tend to accumulate in the body for a relatively longer time than 71 nm 65ZnO NPs and 65Zn(NO3)2 do.

A Probabilistic Transmission and Population Dynamic Model to Assess Tuberculosis Infection Risk

The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well-established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site-specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53-67%) was larger than that of exogenous reinfection (32-47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age-weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R₀) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R₀ estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25-27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36-66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan-based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality.

Assessing coughing-induced influenza droplet transmission and implications for infection risk control

Indoor transmission of respiratory droplets bearing influenza within humans poses high risks to respiratory function deterioration and death. Therefore, we aimed to develop a framework for quantifying the influenza infection risk based on the relationships between inhaled/exhaled respiratory droplets and airborne transmission dynamics in a ventilated airspace. An experiment was conducted to measure the size distribution of influenza-containing droplets produced by coughing for a better understanding of potential influenza spread. Here we integrated influenza population transmission dynamics, a human respiratory tract model, and a control measure approach to examine the indoor environment-virus-host interactions. A probabilistic risk model was implemented to assess size-specific infection risk for potentially transmissible influenza droplets indoors. Our results found that there was a 50% probability of the basic reproduction number (R0) exceeding 1 for small-size influenza droplets of 0·3-0·4 µm, implicating a potentially high indoor infection risk to humans. However, a combination of public health interventions with enhanced ventilation could substantially contain indoor influenza infection. Moreover, the present dynamic simulation and control measure assessment provide insights into why indoor transmissible influenza droplet-induced infection is occurring not only in upper lung regions but also in the lower respiratory tract, not normally considered at infection risk.