Lacrimal Cytokines Assessment in Subjects Exposed to Different Levels of Ambient Air Pollution in a Large Metropolitan Area

Background

Air pollution is one of the most environmental health concerns in the world and has serious impact on human health, particularly in the mucous membranes of the respiratory tract and eyes. However, ocular hazardous effects to air pollutants are scarcely found in the literature.

Design

Panel study to evaluate the effect of different levels of ambient air pollution on lacrimal film cytokine levels of outdoor workers from a large metropolitan area.

Methods

Thirty healthy male workers, among them nineteen professionals who work on streets (taxi drivers and traffic controllers, high pollutants exposure, Group 1) and eleven workers of a Forest Institute (Group 2, lower pollutants exposure compared to group 1) were evaluated twice, 15 days apart. Exposure to ambient PM_2.5 (particulate matter equal or smaller than 2.5 μm) was 24 hour individually collected and the collection of tears was performed to measure interleukins (IL) 2, 4, 5 and 10 and interferon gamma (IFN-γ) levels. Data from both groups were compared using Student’s t test or Mann- Whitney test for cytokines. Individual PM_2.5 levels were categorized in tertiles (lower, middle and upper) and compared using one-way ANOVA. Relationship between PM_2.5 and cytokine levels was evaluated using generalized estimating equations (GEE).

Results

PM_2.5 levels in the three categories differed significantly (lower: ≤22 μg/m³; middle: 23–37.5 μg/m³; upper: >37.5 μg/m³; p<0.001). The subjects from the two groups were distributed unevenly in the lower category (Group 1 = 8%; Group 2 = 92%), the middle category (Group 1 = 89%; Group 2 = 11%) and the upper category (Group 1 = 100%). A significant relationship was found between IL-5 and IL-10 and PM_2.5 levels of the group 1, with an average decrease of 1.65 pg/mL of IL-5 level and of 0.78 pg/mL of IL-10 level in tear samples for each increment of 50 μg/m3 of PM_2.5 (p = 0.01 and p = 0.003, respectively).

Conclusion

High levels of PM_2.5 exposure is associated with decrease of IL-5 and IL-10 levels suggesting a possible modulatory action of ambient air pollution on ocular surface immune response.     

Characterizing the Indoor-Outdoor Relationship of Fine Particulate Matter in Non-Heating Season for Urban Residences in Beijing

Objective

Ambient fine particulate matter (PM_2.5) pollution is currently a major public health concern in Chinese urban areas. However, PM_2.5 exposure primarily occurs indoors. Given such, we conducted this study to characterize the indoor-outdoor relationship of PM_2.5 mass concentrations for urban residences in Beijing.

Methods

In this study, 24-h real-time indoor and ambient PM_2.5 mass concentrations were concurrently collected for 41 urban residences in the non-heating season. The diurnal variation of pollutant concentrations was characterized. Pearson correlation analysis was used to examine the correlation between indoor and ambient PM_2.5 mass concentrations. Regression analysis with ordinary least square was employed to characterize the influences of a variety of factors on PM_2.5 mass concentration.

Results

Hourly ambient PM_2.5 mass concentrations were 3–280 μg/m³ with a median of 58 μg/m³, and hourly indoor counterpart were 4–193 μg/m³ with a median of 34 μg/m³. The median indoor/ambient ratio of PM_2.5 mass concentration was 0.62. The diurnal variation of residential indoor and ambient PM_2.5 mass concentrations tracked with each other well. Strong correlation was found between indoor and ambient PM_2.5 mass concentrations on the community basis (coefficients: r≥0.90, p<0.0001), and the ambient data explained ≥84% variance of the indoor data. Regression analysis suggested that the variables, such as traffic conditions, indoor smoking activities, indoor cleaning activities, indoor plants and number of occupants, had significant influences on the indoor PM_2.5 mass concentrations.

Conclusions

PM_2.5 of ambient origin made dominant contribution to residential indoor PM_2.5 exposure in the non-heating season under the high ambient fine particle pollution condition. Nonetheless, the large inter-residence variability of infiltration factor of ambient PM_2.5 raised the concern of exposure misclassification when using ambient PM_2.5 mass concentrations as exposure surrogates. PM_2.5 of indoor origin still had minor influence on indoor PM_2.5 mass concentrations, particularly at 11:00–13:00 and 22:00–0:00. The predictive models suggested that particles from traffic emission, secondary aerosols, particles from indoor smoking, resuspended particles due to indoor cleaning and particles related to indoor plants contributed to indoor PM_2.5 mass concentrations in this study. Real-time ventilation measurements and improvement of questionnaire design to involve more variables subject to built environment were recommended to enhance the performance of the predictive models.     

PM2.5 Spatiotemporal Variations and the Relationship with Meteorological Factors during 2013-2014 in Beijing,China

Objective

Limited information is available regarding spatiotemporal variations of particles with median aerodynamic diameter < 2.5 μm (PM_2.5) at high resolutions, and their relationships with meteorological factors in Beijing, China. This study aimed to detect spatiotemporal change patterns of PM_2.5 from August 2013 to July 2014 in Beijing, and to assess the relationship between PM_2.5 and meteorological factors.

Methods

Daily and hourly PM_2.5 data from the Beijing Environmental Protection Bureau (BJEPB) were analyzed separately. Ordinary kriging (OK) interpolation, time-series graphs, Spearman correlation coefficient and coefficient of divergence (COD) were used to describe the spatiotemporal variations of PM_2.5. The Kruskal-Wallis H test, Bonferroni correction, and Mann-Whitney U test were used to assess differences in PM_2.5 levels associated with spatial and temporal factors including season, region, daytime and day of week. Relationships between daily PM_2.5 and meteorological variables were analyzed using the generalized additive mixed model (GAMM).

Results

Annual mean and median of PM_2.5 concentrations were 88.07 μg/m³ and 71.00 μg/m³, respectively, from August 2013 to July 2014. PM_2.5 concentration was significantly higher in winter (P < 0.0083) and in the southern part of the city (P < 0.0167). Day to day variation of PM_2.5 showed a long-term trend of fluctuations, with 2–6 peaks each month. PM_2.5 concentration was significantly higher in the night than day (P < 0.0167). Meteorological factors were associated with daily PM_2.5 concentration using the GAMM model (R ² = 0.59, AIC = 7373.84).

Conclusion

PM_2.5 pollution in Beijing shows strong spatiotemporal variations. Meteorological factors influence the PM_2.5 concentration with certain patterns. Generally, prior day wind speed, sunlight hours and precipitation are negatively correlated with PM_2.5, whereas relative humidity and air pressure three days earlier are positively correlated with PM_2.5.     

Air Pollution and Stillbirth Risk: Exposure to Airborne Particulate Matter during Pregnancy Is Associated with Fetal Death

Objective

To test the hypothesis that exposure to fine particulate air pollution (PM_2.5) is associated with stillbirth.

Study Design

Geo-spatial population-based cohort study using Ohio birth records (2006-2010) and local measures of PM_2.5, recorded by the EPA (2005-2010) via 57 monitoring stations across Ohio. Geographic coordinates of the mother’s residence for each birth were linked to the nearest PM_2.5 monitoring station and monthly exposure averages calculated. The association between stillbirth and increased PM_2.5 levels was estimated, with adjustment for maternal age, race, education level, quantity of prenatal care, smoking, and season of conception.

Results

There were 349,188 live births and 1,848 stillbirths of non-anomalous singletons (20-42 weeks) with residence ≤10 km of a monitor station in Ohio during the study period. The mean PM_2.5 level in Ohio was 13.3 μg/m³ [±1.8 SD, IQR(Q1: 12.1, Q3: 14.4, IQR: 2.3)], higher than the current EPA standard of 12 μg/m³. High average PM_2.5 exposure through pregnancy was not associated with a significant increase in stillbirth risk, _adjOR 1.21(95% CI 0.96,1.53), nor was it increased with high exposure in the 1^st or 2^nd trimester. However, exposure to high levels of PM_2.5 in the third trimester of pregnancy was associated with 42% increased stillbirth risk, _adjOR 1.42(1.06,1.91).

Conclusions

Exposure to high levels of fine particulate air pollution in the third trimester of pregnancy is associated with increased stillbirth risk. Although the risk increase associated with high PM_2.5 levels is modest, the potential impact on overall stillbirth rates could be robust as all pregnant women are potentially at risk.     

Association between Air Pollutants and Asthma Emergency Room Visits and Hospital Admissions in Time Series Studies: A Systematic Review and Meta-Analysis

Background

Air pollution constitutes a significant stimulus of asthma exacerbations; however, the impacts of exposure to major air pollutants on asthma-related hospital admissions and emergency room visits (ERVs) have not been fully determined.

Objective

We sought to quantify the associations between short-term exposure to air pollutants [ozone (O₃), carbon monoxide (CO), nitrogen dioxide (NO₂), sulfur dioxide (SO₂), and particulate matter ≤10μm (PM₁₀) and PM_2.5] and the asthma-related emergency room visits (ERV) and hospitalizations.

Methods

Systematic computerized searches without language limitation were performed. Pooled relative risks (RRs) and 95% confidence intervals (95%CIs) were estimated using the random-effect models. Sensitivity analyses and subgroup analyses were also performed.

Results

After screening of 246 studies, 87 were included in our analyses. Air pollutants were associated with significantly increased risks of asthma ERVs and hospitalizations [O₃: RR(95%CI), 1.009 (1.006, 1.011); I² = 87.8%, population-attributable fraction (PAF) (95%CI): 0.8 (0.6, 1.1); CO: RR(95%CI), 1.045 (1.029, 1.061); I² = 85.7%, PAF (95%CI): 4.3 (2.8, 5.7); NO₂: RR(95%CI), 1.018 (1.014, 1.022); I² = 87.6%, PAF (95%CI): 1.8 (1.4, 2.2); SO₂: RR(95%CI), 1.011 (1.007, 1.015); I² = 77.1%, PAF (95%CI): 1.1 (0.7, 1.5); PM₁₀: RR(95%CI), 1.010 (1.008, 1.013); I² = 69.1%, PAF (95%CI): 1.1 (0.8, 1.3); PM_2.5: RR(95%CI), 1.023 (1.015, 1.031); I² = 82.8%, PAF (95%CI): 2.3 (1.5, 3.1)]. Sensitivity analyses yielded compatible findings as compared with the overall analyses without publication bias. Stronger associations were found in hospitalized males, children and elderly patients in warm seasons with lag of 2 days or greater.

Conclusion

Short-term exposures to air pollutants account for increased risks of asthma-related ERVs and hospitalizations that constitute a considerable healthcare utilization and socioeconomic burden.     

Long-Term Once-Daily Tiotropium Respimat? Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised,Placebo-Controlled Study

Background

This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β₂-agonist (LABA).

Methods

285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209). Primary objective: to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV₁) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.

Results

At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV₁ and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.

Conclusions

The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.

Trial Registration

ClinicalTrials.gov NCT01340209     

Organisational Factors Induce Prolonged Emergency Department Length of Stay in Elderly Patients – A Retrospective Cohort Study

Study objective

To assess the association of patient and organisational factors with emergency department length of stay (ED-LOS) in elderly ED patients (226565 years old) and in younger patients (<65 years old).

Methods

A retrospective cohort study of internal medicine patients visiting the emergency department between September 1^st 2010 and August 31^st 2011 was performed. All emergency department visits by internal medicine patients 226565 years old and a random sample of internal medicine patients <65 years old were included. Organisational factors were defined as non-medical factors. ED-LOS is defined as the time between ED arrival and ED discharge or admission. Prolonged ED-LOS is defined as ≥75^th percentile of ED-LOS in the study population, which was 208 minutes.

Results

Data on 1782 emergency department visits by elderly patients and 597 emergency department visits by younger patients were analysed. Prolonged ED-LOS in elderly patients was associated with three organisational factors: >1 consultation during the emergency department visit (odds ratio (OR) 3.2, 95% confidence interval (CI) 2.3–4.3), a higher number of diagnostic tests (OR 1.2, 95% CI 1.16–1.33) and evaluation by a medical student or non-trainee resident compared with a medical specialist (OR 4.2, 95% CI 2.0–8.8 and OR 2.3, 95% CI 1.4–3.9). In younger patients, prolonged ED-LOS was associated with >1 consultation (OR 2.6, 95% CI 1.4–4.6). Factors associated with shorter ED-LOS were arrival during nights or weekends as well as a high urgency level in elderly patients and self-referral in younger patients.

Conclusion

Organisational factors, such as a higher number of consultations and tests in the emergency department and a lower seniority of the physician, were the main aspects associated with prolonged ED-LOS in elderly patients. Optimisation of the organisation and coordination of emergency care is important to accommodate the needs of the continuously growing number of elderly patients in a better way.     

Positive Association between APOA5 rs662799 Polymorphism and Coronary Heart Disease: A Case-Control Study and Meta-Analysis

Objective

Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism.

Methods

We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software.

Results

Significant differences were observed between CHD cases and controls at the level of both genotype (χ² = 8.964, df = 2, P = 0.011) and allele (χ² = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089–1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ² = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088–1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001).

Conclusion

Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.     

Ambient Temperature and Cerebrovascular Hemodynamics in the Elderly

Background and Purpose

Some prior studies have linked ambient temperature with risk of cerebrovascular events. If causal, the pathophysiologic mechanisms underlying this putative association remain unknown. Temperature-related changes in cerebral vascular function may play a role, but this hypothesis has not been previously evaluated.

Methods

We evaluated the association between ambient temperature and cerebral vascular function among 432 participants ≥65 years old from the MOBILIZE Boston Study with data on cerebrovascular blood flow, cerebrovascular resistance, and cerebrovascular reactivity in the middle cerebral artery. We used linear regression models to assess the association of mean ambient temperature in the previous 1 to 28 days with cerebrovascular hemodynamics adjusting for potential confounding factors.

Results

A 10°C increase in the 21-day moving average of ambient temperature was associated with a 10.1% (95% confidence interval [CI], 2.2%, 17.3%) lower blood flow velocity, a 9.0% (95% CI, 0.7%, 18.0%) higher cerebrovascular resistance, and a 15.3% (95%CI, 2.7%, 26.4%) lower cerebral vasoreactivity. Further adjustment for ozone and fine particulate matter (PM_2.5) did not materially alter the results. However, we found statistically significant interactions between ambient temperature and PM_2.5 such that the association between temperature and blood flow velocity was attenuated at higher levels of PM_2.5.

Conclusions

In this elderly population, we found that ambient temperature was negatively associated with cerebral blood flow velocity and cerebrovascular vasoreactivity and positively associated with cerebrovascular resistance. Changes in vascular function may partly underlie the observed associations between ambient temperature and risk of cerebrovascular events.     

Laboratory Evaluation of the Shinyei PPD42NS Low-Cost Particulate Matter Sensor

Objective

Finely resolved PM2.5 exposure measurements at the level of individual participants or over a targeted geographic area can be challenging due to the cost, size and weight of the monitoring equipment. We propose re-purposing the low-cost, portable and lightweight Shinyei PPD42NS particle counter as a particle counting device. Previous field deployment of this sensor suggests that it captures trends in ambient PM2.5 concentrations, but important characteristics of the sensor response have yet to be determined. Laboratory testing was undertaken in order to characterize performance.

Methods

The Shinyei sensors, in-line with a TSI Aerosol Particle Sizer (APS) model 3321, tracked particle decay within an aerosol exposure chamber. Test atmospheres were composed of monodisperse polystyrene spheres with diameters of 0.75, 1, 2 3 and 6 um as well as a polydisperse atmosphere of ASHRAE test dust #1.

Results

Two-minute block averages of the sensor response provide a measurement with low random error, within sensor, for particles in the 0.75–6μm range with a limit of detection of 1 μg/m3. The response slope of the sensors is idiomatic, and each sensor requires a unique response curve. A linear model captures the sensor response for concentrations below 50 μg/m3 and for concentrations above 50 μg/m³ a non-linear function captures the response and saturates at 800 μg/m³. The Limit of Detection (LOD) is 1 μg/m³. The response time is on the order of minutes, making it appropriate for tracking short-term changes in concentration.

Conclusions

When paired with prior evaluation, these sensors are appropriate for use as ambient particle counters for low and medium concentrations of respirable particles (< 100 ug/m³). Multiple sensors deployed over a spatial grid would provide valuable spatio-temporal variability in PM2.5 and could be used to validate exposure models. When paired with GPS tracking, these devices have the potential to provide time and space resolved exposure measurements for a large number of participants, thus increasing the power of a study.     

Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice

Background

Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking.

Objective

Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS).

Methods

Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl₂ (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder.

Results

SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca²⁺ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration.

Conclusions

Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in the pathogenesis of the enuresis and infections observed the SCD patients.     

Short-Term Effects of Particulate Matter on Stroke Attack: Meta-Regression and Meta-Analyses

Background and Purpose

Currently there are more and more studies on the association between short-term effects of exposure to particulate matter (PM) and the morbidity of stroke attack, but few have focused on stroke subtypes. The objective of this study is to assess the relationship between PM and stroke subtypes attack, which is uncertain now.

Methods

Meta-analyses, meta-regression and subgroup analyses were conducted to investigate the association between short-term effects of exposure to PM and the morbidity of different stroke subtypes from a number of epidemiologic studies (from 1997 to 2012).

Results

Nineteen articles were identified. Odds ratio (OR) of stroke attack associated with particular matter (“thoracic particles” [PM₁₀]<10 µm in aerodynamic diameter, “fine particles” [PM_2.5]<2.5 µm in aerodynamic diameter) increment of 10 µg/m³ was as effect size. PM₁₀ exposure was related to an increase in risk of stroke attack (OR per 10 µg/m³ = 1.004, 95%CI: 1.001∼1.008) and PM_2.5 exposure was not significantly associated with stroke attack (OR per 10 µg/m³ = 0.999, 95%CI: 0.994∼1.003). But when focused on stroke subtypes, PM_2.5 (OR per 10 µg/m³ = 1.025; 95%CI, 1.001∼1.049) and PM₁₀ (OR per 10 µg/m³ = 1.013; 95%CI, 1.001∼1.025) exposure were statistically significantly associated with an increased risk of ischemic stroke attack, while PM_2.5 (all the studies showed no significant association) and PM₁₀ (OR per 10 µg/m³ = 1.007; 95%CI, 0.992∼1.022) exposure were not associated with an increased risk of hemorrhagic stroke attack. Meta-regression found study design and area were two effective covariates.

Conclusion

PM_2.5 and PM₁₀ had different effects on different stroke subtypes. In the future, it''s worthwhile to study the effects of PM to ischemic stroke and hemorrhagic stroke, respectively.     

Leishmanicidal Effect of Synthetic trans-Resveratrol Analogs

Background

Stilbene-based compounds show antitumoral, antioxidant, antihistaminic, anti-inflammatory and antimicrobial activities. Here, we evaluated the effect of the trans-resveratrol analogs, pterostilbene, piceatannol, polydatin and oxyresveratrol, against Leishmania amazonensis.

Methodology/Principal Findings

Our results demonstrated a low murine macrophage cytotoxicity of all four analogs. Moreover, pterostilbene, piceatannol, polydatin and oxyresveratrol showed an anti-L. amazonensis activity with IC₅₀ values of 18 μM, 65 μM, 95 μM and 65 μM for promastigotes, respectively. For intracellular amastigotes, the IC₅₀ values of the analogs were 33.2 μM, 45 μM, 29 μM and 30.5 μM, respectively. Among the analogs assayed only piceatannol altered the cell cycle of the parasite, increasing 5-fold the cells in the Sub-G0 phase and decreasing 1.7-fold the cells in the G0-G1 phase. Piceatannol also changed the parasite mitochondrial membrane potential (ΔΨm) and increased the number of annexin-V positive promastigotes, which suggests incidental death.

Conclusion/Significance

Among the analogs tested, piceatannol, which is a metabolite of resveratrol, was the more promising candidate for future studies regarding treatment of leishmaniasis.     

Comparison of the Effects of Air Pollution on Outpatient and Inpatient Visits for Asthma: A Population-Based Study in Taiwan

Background

A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan.

Methods

Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants.

Results

The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend  = 0.013) for carbon monoxide (CO), 1.10 (P-trend  = 0.015) for nitrogen dioxide (NO₂), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM₁₀) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO_2, and 1.13 (P-trend <0.0001) for PM₁₀. For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO_2, and 1.10 (P-trend = 0.001) for PM₁₀. For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend  = 0.003) for NO₂ and 1.10 (P-trend  = 0.006) for PM_10. For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend  = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups.

Conclusions

There were positive associations between CO levels and childhood inpatient visits as well as NO₂, CO and PM₁₀ and outpatient visits.     

Blood Lead Levels in Children Aged 0–6 Years Old in Hunan Province,China from 2009–2013

Objectives

The aim of this study is to describe blood lead levels (BLLs) and the prevalence of elevated blood lead levels (EBLLs) in children aged 0–6 years old and to analyze the BLL trend in children from 2009 to 2013 in China.

Methods

A total of 124,376 children aged 0–6 years old were recruited for this study from January 1^st 2009 to December 31^st 2013. Their blood lead levels were analyzed using atomic absorption spectrometry.

Results

The median BLL was 64.3 μg/L (IQR: 49.6–81.0), and the range was 4.3–799.0 μg/L. Blood lead levels were significantly higher in boys (66.0 μg/L) than in girls (61.9 μg/L) (P<0.001). The overall prevalence of BLLs≥100 μg/L was 10.54% in children aged 0–6 years in Hunan Province. Between 2009 and 2013, the prevalence of EBLLs (≥100 μg/L) decreased from 18.31% to 4.26% in children aged 0–6 years and increased with age. The prevalence of EBLLs has dramatically decreased in two stages (2009–2010 and 2012–2013), with a slight fluctuation in 2010 and 2011.

Conclusions

Both BLLs and the prevalence of EBLLs in children aged 0–6 years old declined substantially from 2009 to 2013 in Hunan Province; however, both remain at unacceptably high levels compared to developed countries. Comprehensive strategies are required to further reduce blood lead levels in children.     

Elevated Steady State WBC and Platelet Counts Are Associated with Frequent Emergency Room Use in Adults with Sickle Cell Anemia

Introduction

Sickle cell anemia has many sequelae that result in emergency department (ED) use, but a minority of patients with sickle cell disease are frequent utilizers and make up the majority of ED visits. If patients who are likely to be frequent ED can be identified in steady state, they can be treated with disease modifying agents in an attempt to reduce ED use frequency. We sought to identify steady state markers for frequent ED use.

Methods

We identified all patients with SS/Sβ0 seen at our facilities in 2012. Health care utilization over the entire year was calculated and ED visit numbers categorized as either 0–1, 2–5, or 6 or more visits a year. Steady state and acutely active laboratory parameters were collected and analyzed using analysis of variance models and odds ratios.

Results

432 adult sickle cell patients were identified, ages 18–87, 54% female, and 38% had been prescribed hydroxyurea. Of the 432 patients,192 had 0–1 visits in the year, 144 had 2–5 visits in the year, and 96 had >6 visits for a total of 2259 visits. Those who had >6 visits accounted for 1750 (77%) of the total visits for the year. When steady state laboratory markers were examined, each additional 50x109/L platelets was associated with 22% greater risk (p < .001); each 1x109/L of WBC was associated with 11% greater risk (p = .003), and each 1g/dL Hb was associated with 23% lower risk (p = .007) of >6 ED visits/year. We did not observe a relationship between baseline HbF, LDH or reticulocyte count with >6 ED visits.

Conclusion

Patients with elevated white blood cell counts, elevated platelet counts, and low hemoglobin levels exhibited higher risk for frequent ED utilization and could be candidates for early and aggressive therapy with disease modifying agents.     

TGF-β1-Mediated Differentiation of Fibroblasts Is Associated with Increased Mitochondrial Content and Cellular Respiration

Objectivs

Cytokine-dependent activation of fibroblasts to myofibroblasts, a key event in fibrosis, is accompanied by phenotypic changes with increased secretory and contractile properties dependent on increased energy utilization, yet changes in the energetic profile of these cells are not fully described. We hypothesize that the TGF-β1-mediated transformation of myofibroblasts is associated with an increase in mitochondrial content and function when compared to naive fibroblasts.

Methods

Cultured NIH/3T3 mouse fibroblasts treated with TGF-β1, a profibrotic cytokine, or vehicle were assessed for transformation to myofibroblasts (appearance of α-smooth muscle actin [α-SMA] stress fibers) and associated changes in mitochondrial content and functions using laser confocal microscopy, Seahorse respirometry, multi-well plate reader and biochemical protocols. Expression of mitochondrial-specific proteins was determined using western blotting, and the mitochondrial DNA quantified using Mitochondrial DNA isolation kit.

Results

Treatment with TGF-β1 (5 ng/mL) induced transformation of naive fibroblasts into myofibroblasts with a threefold increase in the expression of α-SMA (6.85 ± 0.27 RU) compared to cells not treated with TGF-β1 (2.52 ± 0.11 RU). TGF-β1 exposure increased the number of mitochondria in the cells, as monitored by membrane potential sensitive dye tetramethylrhodamine, and expression of mitochondria-specific proteins; voltage-dependent anion channels (0.54 ± 0.05 vs. 0.23 ± 0.05 RU) and adenine nucleotide transporter (0.61 ± 0.11 vs. 0.22 ± 0.05 RU), as well as mitochondrial DNA content (530 ± 12 μg DNA/10⁶ cells vs. 307 ± 9 μg DNA/10⁶ cells in control). TGF-β1 treatment was associated with an increase in mitochondrial function with a twofold increase in baseline oxygen consumption rate (2.25 ± 0.03 vs. 1.13 ± 0.1 nmol O₂/min/10⁶ cells) and FCCP-induced mitochondrial respiration (2.87 ± 0.03 vs. 1.46 ± 0.15 nmol O₂/min/10⁶ cells).

Conclusions

TGF-β1 induced differentiation of fibroblasts is accompanied by energetic remodeling of myofibroblasts with an increase in mitochondrial respiration and mitochondrial content.     

Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity—A Taiwanese Population-Based Cohort Study

Objectives

Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia.

Methods

We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0–729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 ± 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling.

Results

Patients with fibromyalgia had a mean age of 44.1 ± 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 10³ person-years) and reference subjects (n = 15,162; 9.26 per 10³ person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61–1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43–1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity).

Conclusions

Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia.     

Fine Particulate Air Pollution and Hospital Emergency Room Visits for Respiratory Disease in Urban Areas in Beijing,China, in 2013

BackgroundHeavy fine particulate matter (PM_2.5) air pollution occurs frequently in China. However, epidemiological research on the association between short-term exposure to PM_2.5 pollution and respiratory disease morbidity is still limited. This study aimed to explore the association between PM_2.5 pollution and hospital emergency room visits (ERV) for total and cause-specific respiratory diseases in urban areas in Beijing.MethodsDaily counts of respiratory ERV from Jan 1 to Dec 31, 2013, were obtained from ten general hospitals located in urban areas in Beijing. Concurrently, data on PM_2.5 were collected from the Beijing Environmental Protection Bureau, including 17 ambient air quality monitoring stations. A generalized-additive model was used to explore the respiratory effects of PM_2.5, after controlling for confounding variables. Subgroup analyses were also conducted by age and gender.ResultsA total of 92,464 respiratory emergency visits were recorded during the study period. The mean daily PM_2.5 concentration was 102.1±73.6 μg/m³. Every 10 μg/m³ increase in PM_2.5 concentration at lag₀ was associated with an increase in ERV, as follows: 0.23% for total respiratory disease (95% confidence interval [CI]: 0.11%-0.34%), 0.19% for upper respiratory tract infection (URTI) (95%CI: 0.04%-0.35%), 0.34% for lower respiratory tract infection (LRTI) (95%CI: 0.14%-0.53%) and 1.46% for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (95%CI: 0.13%-2.79%). The strongest association was identified between AECOPD and PM_2.5 concentration at lag_0-3 (3.15%, 95%CI: 1.39%-4.91%). The estimated effects were robust after adjusting for SO₂, O₃, CO and NO₂. Females and people 60 years of age and older demonstrated a higher risk of respiratory disease after PM_2.5 exposure.ConclusionPM_2.5 was significantly associated with respiratory ERV, particularly for URTI, LRTI and AECOPD in Beijing. The susceptibility to PM_2.5 pollution varied by gender and age.