Jing-Shiang Hwang

Cardiovascular effects of nickel in ambient air.

Background Fine particulate matter (FPM) in ambient air causes premature mortality due to cardiac disease in susceptible populations. Objective Our objective in this study was to determine the most influential FPM components. Methods A mouse model of atherosclerosis (ApoE−/−) was exposed to either filtered air or concentrated FPM (CAPs) in Tuxedo, New York (85 μg/m3 average, 6 hr/day, 5 days/week, for 6 months), and the FPM elemental composition was determined for each day. We also examined associations between PM components and mortality for two population studies: National Mortality and Morbidity Air Pollution Study (NMMAPS) and Hong Kong. Results For the CAPs-exposed mice, the average of nickel was 43 ng/m3, but on 14 days, there were Ni peaks at ~ 175 ng/m3 and unusually low FPM and vanadium. For those days, back-trajectory analyses identified a remote Ni point source. Electrocardiographic measurements on CAPs-exposed and sham-exposed mice showed Ni to be significantly associated with acute changes in heart rate and its variability. In NMMAPS, daily mortality rates in the 60 cities with recent speciation data were significantly associated with average Ni and V, but not with other measured species. Also, the Hong Kong sulfur intervention produced sharp drops in sulfur dioxide, Ni, and V, but not other components, corresponding to the intervention-related reduction in cardiovascular and pulmonary mortality. Conclusions Known biological mechanisms cannot account for the significant associations between Ni with the acute cardiac function changes in the mice or with cardiovascular mortality in people at low ambient air concentrations; therefore, further research is needed.

Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan

BACKGROUND Taiwan established a nationwide surveillance system for human immunodeficiency virus (HIV) infection in 1989 and adopted a policy to provide all HIV-infected citizens with free access to highly active antiretroviral therapy (HAART) beginning in April 1997. This provided an opportunity to determine the effect of the widespread use of HAART on the evolution of the HIV epidemic. METHODS We analyzed national HIV surveillance data. The HIV transmission rate was estimated by use of an exponential model of HIV epidemic evolution, with statistical projection over the interval between infection and detection to fit the surveillance data. RESULTS By the end of 2002, the cumulative number of HIV-infected citizens in Taiwan had reached 4390 (0.019% of the total population). After free access to HAART was established, the estimated HIV transmission rate decreased by 53% (0.391 vs. 0.184 new cases/prevalent case-year [95% confidence interval, 31%-65%]). There was no statistically significant change in the incidence of syphilis, in the general population or among HIV-positive patients, during the same period. CONCLUSION Providing free HAART to all HIV-infected citizens was associated with a 53% decrease in the HIV transmission rate and contributed to the control of the HIV epidemic in Taiwan.

Air Pollution Exposure Potentiates Hypertension Through Reactive Oxygen Species-Mediated Activation of Rho/ROCK

Objective—Fine particulate matter <2.5 &mgr;m (PM2.5) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM2.5 in the angiotensin II (AII) infusion model. Methods and Results—Sprague-Dawley rats were exposed to PM2.5 or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII were implanted and the responses studied over a week. Mean concentration of PM2.5 inside the chamber was 79.1±7.4 &mgr;g/m3. After AII infusion, mean arterial pressure was significantly higher in PM2.5-AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was potentiated with exaggerated relaxation to the Rho-kinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM2.5-AII group. Superoxide (O2·−) production in aorta was increased in the PM2.5-AII compared to the FA group, inhibitable by apocynin and L-NAME with coordinate upregulation of NAD(P)H oxidase subunits p22phox and p47phox and depletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM2.5 was associated with an increase in ROCK activity, phosphorylation of myosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific antioxidant N-Acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevented MLC and MYPT-1 phosphorylation by UFP suggesting a O2·−-mediated mechanism for PM2.5 and UFP effects. Conclusions—Short-term air pollution exaggerates hypertension through O2·−-mediated upregulation of the Rho/ROCK pathway.

Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. IV. Characterization of acute and chronic effects of ambient air fine particulate matter exposures on heart-rate variability.

Abstract Long-term exposure to fine particulate air pollution (PM2.5) has been associated with increased risk of death from cardiopulmonary diseases. Cardiac function parameters have also been affected by ambient particulate matter (PM) exposure, including heart-rate variability (HRV), a measure of autonomic function that has been recognized as a well-defined, quantitative indicator of autonomic dysfunction. However, the role of HRV in ambient PM-induced cardiovascular effects is not fully understood. In an accompanying article, we report significant decreasing patterns of heart rate (HR), body temperature, and physical activity for mice lacking apoliproprotein (ApoE−/−) over 5 mo of exposure to concentrated ambient PM (CAPs), with smaller and nonsignificant changes for C57 mice. In this article, we report the effects of subchronic CAPs exposure on HRV parameters that are sensitive to cardiac sympathetic and parasympathetic nerve activity. The standard deviation of normal to normal beat intervals (SDNN) and the square root of the mean squared differences of successive RR intervals (RMSSD) in the late afternoon and overnight for the ApoE−/− mice showed a gradual increase for the first 6 wk, a decline for about 12 more wk, and a slight turn upward at the end of the study period. For C57 mice, there were no chronic effect changes of SDNN or RMSSD in the late afternoon, and a slight increase after 6 wk for the overnight period. The response patterns of ApoE−/− mice indicated a perturbation of the homeostatic function in the cardiovascular system (initial enhancement and later depression of the HRV parameters). Our results complement the findings in human panel and controlled CAPs exposure studies in demonstrating that increased levels of particle pollution are able to perturb cardiac autonomic function, which may lead to adverse cardiovascular outcomes.

Effects of Concentrated Ambient Particles on Heart Rate, Blood Pressure, and Cardiac Contractility in Spontaneously Hypertensive Rats

Epidemiological studies have shown that particulate matter (PM) air pollution is associated with cardiovascular mortality and morbidity, especially for particles with aerodynamic diameters under 2.5 μm (PM2.5). Recent studies have revealed an association between PM pollution and autonomic functions including heart rate (HR), blood pressure (BP), and heart-rate variability. However, the association and linking mechanisms have not been clearly demonstrated in animal studies. Utilizing a novel approach that employs a mixed-effects model to overcome the problems of variations in diseased animals and circadian cycles, we have previously demonstrated an association between concentrated PM2.5 and changes of HR and BP in pulmonary hypertensive rats. The objective of this study is to test the plausibility of this methodology and to demonstrate the particle effects under different pathophysiology. The feasibility of cardiac contractility (measured as QA interval, QAI) as an indicator for PM toxicology was also explored. Four spontaneously hypertensive (SH) rats were repeatedly exposed to concentrated PM2.5 during spring and summer. The mass concentration of particles during the 5 h of exposure was 202.0 ± 68.8 (mean ± SE) and 141.0 ± 54.9 μg/m3 for spring and summer experiments, respectively. During spring exposures, the maximum increase of HR and mean BP noted at the end of exposure were 51.6 bpm (p < .001) and 8.7 mm Hg (p = .002), respectively. The maximum decrease of QAI noted at the same time was 1.6 ms (p = .001). Though a similar pattern was demonstrated during summer exposures, the responses were less prominent. We conclude that concentrated PM2.5 may increase HR and mean BP and decrease QAI in SH rats. Our results also show that QAI may be used as an indicator in PM toxicology.

Increased risks of chronic kidney disease associated with prescribed Chinese herbal products suspected to contain aristolochic acid

Aim:  Nephropathy associated with aristolochic acid (AA) has been documented by human and animal studies. Ancient Chinese herbology claimed to reduce toxicity in their mixtures. It was the objective of this study to determine the risk of chronic kidney disease (CKD) associated with AA‐related Chinese herbal products (CHP) or mixtures of herbs in a national cohort.

Integrating health profile with survival for quality of life assessment

In cohort studies or clinical trials, measurements of quality of life (QoL) were averaged across available individuals for each group at given points in time to produce single measures for comparisons. However, estimates of these single measures may be severely biased if substantial mortality occurs over time. The objective of this study is to develop a method that integrates QoL measurement and survival for long-term evaluation of health services. We defined a mean QoL score function over time for an index population as the average QoL score of all individuals both alive and dead at each time point in the population. While a living subjects QoL can be assessed by asking ones subjective preference, the score of a decedent can be assigned a fixed value depending on the specific facet on health profile. The mean QoL score function over time is reduced to a single measure of expected cumulative QoL score, which is the area under the curve of mean QoL score function over a given time interval and can be estimated by taking a random sample from a cross-sectional survey. For the QoL score function to be extrapolated to life-long, it requires the assumption that the disease causes premature death or a long-term moderate impairment of QoL. We provided methods and computer programs for estimating mean QoL score functions and the reduced single measures for use in comparisons. A cohort of 779 breast cancer patients from Chiangmai, Thailand were followed for 12 years to demonstrate the proposed methods. The data included the 12-year complete survival records and QoL scores on 233 patients collected from a cross-sectional survey using WHOQOL questionnaire and standard gamble method. The expected cumulative QoL scores using utility and psychometric scales were compared among patients in four groups of clinical stages in this cohort for time from onset up to 12 years and life-long. We conclude that such an integration of QoL measurement with survival can be useful for the evaluation of health service and clinical decision.

Estimation of Life Expectancy and the Expected Years of Life Lost in Patients with Major Cancers : Extrapolation of Survival Curves under High-Censored Rates

OBJECTIVES There exists a lack of extrapolation methods for long-term survival analysis when censored rates are high (25-50%). This study aimed at estimating life expectancy (LE) after the diagnosis of cancer and the expected years of life lost (EYLL) using a newly developed semiparametric method. METHODS Patients (n = 425,294) diagnosed with 17 different types of major cancer were enrolled. All of the patients were registered with the Taiwan Cancer Registry between 1990 and 2001; their survivals were followed through the end of 2004. The survival function for an age- and sex-matched reference population was generated using the Monte Carlo method from the life table of the general population. Lifetime survival of the cancer patients (up to 50 years) were obtained using linear extrapolation of a logit-transformed curve of the survival ratio between the cancer and reference populations. The estimates were compared with the results from the extrapolation of fitted Weibull models. RESULTS The 15-year survival, LE, and EYLL for 17 different types of cancer were determined, of which the LE of breast, cervical, ovarian, and skin cancers exceeded 15 years; nasopharyneal, leukemia, bladder, kidney, and colorectal cancers exceeded 10 years. Validity tests indicated that the relative biases of the extrapolated estimates were usually <5% under high censoring rates. CONCLUSIONS The newly developed method is feasible and relatively accurate to project LE and EYLL, which could also be merged with data pertaining to quality of life, for a more detailed outcome assessment in the future.

Cancer risks in a population with prolonged low dose-rate γ-radiation exposure in radiocontaminated buildings, 1983 – 2002

Purpose: To assess cancer risks in a population that received prolonged low dose-rate γ-irradiation for about 10 years as a result of occupying buildings containing 60Co-contaminated steel in Taiwan. Materials and methods: The cancer risks were compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for age and gender. The association of cancer risks with excess cumulative exposure was further evaluated for their relative risks by the Poisson multiple regression analysis. Result: A total of 7271 people were registered as the exposed population, with 101,560 person-years at risk. The average excess cumulative exposure was approximately 47.8 mSv (range < 1 – 2,363 mSv). A total of 141 exposed subjects with various cancers were observed, while 95 developed leukemia or solid cancers after more than 2 or 10 years initial residence in contaminated buildings respectively. The SIR were significantly higher for all leukemia except chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 – 7.4) in men, and marginally significant for thyroid cancers (n = 6, SIR = 2.6, 95% CI 1.0 – 5.7) in women. On the other hand, all cancers combined, all solid cancers combined were shown to exhibit significant exposure-dependent increased risks in individuals with the initial exposure before the age of 30, but not beyond this age. Conclusions: The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.

Respiratory symptoms of primary school children living in a petrochemical polluted area in Taiwan.

In 1994–1995 a cross‐sectional epidemiological study investigating the respiratory health of school children in two Taiwan areas was conducted; one area was located in a region with petrochemical manufacturing complexes (Linyuan), and the other was situated in a reference area with no local industrial emissions (Taihsi). All primary school children residing in the two areas were involved in the study. Four hundred seventy children were studied in the area with high exposure to industrial emissions, and 611 children lived in the reference area. Respiratory health was assessed by evaluation of the childrens respiratory symptoms and illnesses, using a parent‐completed questionnaire.