g-Chuan Chan

Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis

BACKGROUND The potential for a global epidemic of asbestos-related diseases is a growing concern. Our aim was to assess the ecological association between national death rates from diseases associated with asbestos and historical consumption of asbestos. METHODS We calculated, for all countries with data, yearly age-adjusted mortality rates by sex (deaths per million population per year) for each disease associated with asbestos (pleural, peritoneal, and all mesothelioma, and asbestosis) in 2000-04 and mean per head asbestos consumption (kg per person per year) in 1960-69. We regressed death rates for the specified diseases against historical asbestos consumption, weighted by the size of sex-specific national populations. FINDINGS Historical asbestos consumption was a significant predictor of death for all mesothelioma in both sexes (adjusted R2=0.74, p<0.0001, 2.4-fold [95% CI 2.0-2.9] mortality increase was predicted per unit consumption increase for men; 0.58, p<0.0001, and 1.6-fold [1.4-1.9] mortality increase was predicted for women); for pleural mesothelioma in men (0.29, p=0.0015, 1.8-fold [1.3-2.5]); for peritoneal mesothelioma in both sexes (0.54, p<0.0001, 2.2-fold [1.6-2.9] for men, 0.35, p=0.0008, and 1.4-fold for women [1.2-1.6]); and for asbestosis in men (0.79, p<0.0001, 2.7-fold [2.2-3.4]). Linear regression lines consistently had intercepts near zero. INTERPRETATION Within the constraints of an ecological study, clear and plausible associations were shown between deaths from the studied diseases and historical asbestos consumption, especially for all mesothelioma in both sexes and asbestosis in men. Our data strongly support the recommendation that all countries should move towards eliminating use of asbestos.

Effects of Asian dust event particles on inflammation markers in peripheral blood and bronchoalveolar lavage in pulmonary hypertensive rats

The health impact of dust events from China has become a concern within China and in its neighboring countries. Previous epidemiological studies have demonstrated an association between particulate matter exposure and cardiopulmonary mortality. Here, we use pulmonary hypertensive rat models to examine inflammation markers in the lung and in peripheral blood after exposure to Asian dust storm particles. Using a nose-only inhalation system, eight pulmonary hypertensive rats were exposed to concentrated ambient particles (CAPs) from an actual Asian dust storm that took place between March 18 and 19, 2002; four control rats were also exposed to room air. Four rats exposed to CAPs of 315.6 g/m3 for 6 h were classified as the low-exposure group, and another four rats exposed to CAPs of 684.5 g/m3 for 4.5 h were classified as the high-exposure group. The animals were sacrificed 36 h after exposure. Inflammation markers in the peripheral blood and in the bronchoalveolar lavage (BAL) were analyzed, and IL-6 in BAL was also determined using ELISA. White blood cell counts in peripheral blood increased with increased CAP exposure levels (P<0.001, test for trend). In BAL analysis, total cell numbers and the proportion of neutrophil also increased with increased CAP levels (P<0.001, test for trend for both markers). Positive dose-response relationships between CAP exposure and total protein (P<0.05) and between CAPs and LDH activity (P<0.05) were also observed. Moreover, IL-6 protein in BAL increasing with CAP levels (P<0.05, test for trend) was demonstrated. Our results revealed that exposure to particulate matters during an Asian dust storm could increase lung inflammation and injury in pulmonary hypertensive rats. Further studies are needed to determine the components of dust storm particles that may contribute to the particle toxicity.

Community-based multiple screening model†‡§¶

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

Personal exposure to submicrometer particles and heart rate variability in human subjects

We conducted a study on two panels of human subjects—9 young adults and 10 elderly patients with lung function impairments—to evaluate whether submicrometer particulate air pollution was associated with heart rate variability (HRV). We measured these subjects’ electrocardiography and personal exposure to number concentrations of submicrometer particles with a size range of 0.02–1 μm (NC0.02–1) continuously during daytime periods. We used linear mixed-effects models to estimate the relationship between NC0.02–1 and log10-transformed HRV, including standard deviation of all normal-to-normal intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF, 0.04–0.15 Hz), and high frequency (HF, 0.15–0.40 Hz), adjusted for age, sex, body mass index, tobacco exposure, and temperature. For the young panel, a 10,000-particle/cm3 increase in NC0.02–1 with 1–4 hr moving average exposure was associated with 0.68–1.35% decreases in SDNN, 1.85–2.58% decreases in r-MSSD, 1.32–1.61% decreases in LF, and 1.57–2.60% decreases in HF. For the elderly panel, a 10,000-particle/cm3 increase in NC0.02–1 with 1–3 hr moving average exposure was associated with 1.72–3.00% decreases in SDNN, 2.72–4.65% decreases in r-MSSD, 3.34–5.04% decreases in LF, and 3.61–5.61% decreases in HF. In conclusion, exposure to NC0.02–1 was associated with decreases in both time-domain and frequency-domain HRV indices in human subjects.

Effects of Particle Size Fractions on Reducing Heart Rate Variability in Cardiac and Hypertensive Patients

It is still unknown whether the associations between particulate matter (PM) and heart rate variability (HRV) differ by particle sizes with aerodynamic diameters between 0.3 μm and 1.0 μm (PM0.3–1.0), between 1.0 μm and 2.5 μm (PM1.0–2.5), and between 2.5 μm and 10 μm (PM2.5–10). We measured electrocardiographics and PM exposures in 10 patients with coronary heart disease and 16 patients with either prehypertension or hypertension. The outcome variables were standard deviation of all normal-to-normal (NN) intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF; 0.04–0.15 Hz), high frequency (HF; 0.15–0.40 Hz), and LF:HF ratio for HRV. The pollution variables were mass concentrations of PM0.3–1.0, PM1.0–2.5, and PM2.5–10. We used linear mixed-effects models to examine the association between PM exposures and log10-transformed HRV indices, adjusting for key personal and environmental attributes. We found that PM0.3–1.0 exposures at 1- to 4-hr moving averages were associated with SDNN and r-MSSD in both cardiac and hypertensive patients. For an interquartile increase in PM0.3–1.0, there were 1.49–4.88% decreases in SDNN and 2.73–8.25% decreases in r-MSSD. PM0.3–1.0 exposures were also associated with decreases in LF and HF for hypertensive patients at 1- to 3-hr moving averages except for cardiac patients at moving averages of 2 or 3 hr. By contrast, we found that HRV was not associated with either PM1.0–2.5 or PM2.5–10. HRV reduction in susceptible population was associated with PM0.3–1.0 but was not associated with either PM1.0–2.5 or PM2.5–10.

Community-based multiple screening model: design, implementation, and analysis of 42,387 participants.

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

SARS in Hospital Emergency Room

Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.

Ambient influenza and avian influenza virus during dust storm days and background days.

Background The spread of influenza and highly pathogenic avian influenza (H5N1) presents a significant threat to human health. Avian influenza outbreaks in downwind areas of Asian dust storms (ADS) suggest that viruses might be transported by dust storms. Objectives We developed a technique to measure ambient influenza and avian influenza viruses. We then used this technique to measure concentrations of these viruses on ADS days and background days, and to assess the relationships between ambient influenza and avian influenza viruses, and air pollutants. Methods A high-volume air sampler was used in parallel with a filter cassette to evaluate spiked samples and unspiked samples. Then, air samples were monitored during ADS seasons using a filter cassette coupled with a real-time quantitative polymerase chain reaction (qPCR) assay. Air samples were monitored during ADS season (1 January to 31 May 2006). Results We successfully quantified ambient influenza virus using the filtration/real-time qPCR method during ADS days and background days. To our knowledge, this is the first report describing the concentration of influenza virus in ambient air. In both the spiked and unspiked samples, the concentration of influenza virus sampled using the filter cassette was higher than that using the high-volume sampler. The concentration of ambient influenza A virus was significantly higher during the ADS days than during the background days. Conclusions Our data imply the possibility of long-range transport of influenza virus.

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.

CONTRIBUTION OF ENDOTOXIN IN MACROPHAGE CYTOKINE RESPONSE TO AMBIENT PARTICLES IN VITRO

Ambient particles may cause pulmonary inflammation with ensuing morbidity. Particle-induced production of proinflammatory cytokines in vitro has been used as an indicator of particle toxicity. To identify particle components that were related to particle toxicity, Andersen dichotomous impactors were used to collect ambient fine (PM 2.5 ) and coarse (PM 2.5-10 ) particles in central Taiwan with extraction in endotoxin-free water. Mouse mono-cyte-macrophage cell line RAW 264.7 cells were exposed to particle extracts at 40 g/ml for 16 h, and tumor necrosis factor-alpha (TNF- f ) was measured in the medium by enzyme-linked immunosorbent assay (ELISA). Cell viabilities were all greater than 82%. Coarse particles stimulated higher TNF- f production than fine particles, and this was associated with greater particulate endotoxin content. Polymyxin B inhibited 42% of TNF- f production elicited by coarse particles and 32% of TNF- f production elicited by fine particles. In fine particles, TNF- f production was negatively correlated with Zn content, while no element in coarse particles correlated with TNF- f production. Results suggest that endotoxin and other components may be important factors for TNF- f production by macrophages in vitro.