Alveolar macrophage-epithelial cell interaction following exposure to atmospheric particles induces the release of mediators involved in monocyte mobilization and recruitment

Background

Studies from our laboratory have shown that human alveolar macrophages (AM) and bronchial epithelial cells (HBEC) exposed to ambient particles (PM₁₀) in vitro increase their production of inflammatory mediators and that supernatants from PM₁₀-exposed cells shorten the transit time of monocytes through the bone marrow and promote their release into the circulation.

Methods

The present study concerns co-culture of AM and HBEC exposed to PM₁₀ (EHC-93) and the production of mediators involved in monocyte kinetics measured at both the mRNA and protein levels. The experiments were also designed to determine the role of the adhesive interaction between these cells via the intercellular adhesion molecule (ICAM)-1 in the production of these mediators.

Results

AM/HBEC co-cultures exposed to 100 μg/ml of PM₁₀ for 2 or 24 h increased their levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, macrophage inflammatory protein (MIP)-1β, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6 and ICAM-1 mRNA, compared to exposed AM or HBEC mono-cultures, or control non-exposed co-cultures. The levels of GM-CSF, M-CSF, MIP-1β and IL-6 increased in co-cultured supernatants collected after 24 h exposure compared to control cells (p < 0.05). There was synergy between AM and HBEC in the production of GM-CSF, MIP-1β and IL-6. But neither pretreatment of HBEC with blocking antibodies against ICAM-1 nor cross-linking of ICAM-1 on HBEC blocked the PM₁₀-induced increase in co-culture mRNA expression.

Conclusion

We conclude that an ICAM-1 independent interaction between AM and HBEC, lung cells that process inhaled particles, increases the production and release of mediators that enhance bone marrow turnover of monocytes and their recruitment into tissues. We speculate that this interaction amplifies PM₁₀-induced lung inflammation and contributes to both the pulmonary and systemic morbidity associated with exposure to air pollution.     

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.     

Estimation of Short-Term Effects of Air Pollution on Stroke Hospital Admissions in Wuhan,China

Background and Objective

High concentrations of air pollutants have been linked to increased incidence of stroke in North America and Europe but not yet assessed in mainland China. The aim of this study is to evaluate the association between stroke hospitalization and short-term elevation of air pollutants in Wuhan, China.

Methods

Daily mean NO₂, SO₂ and PM₁₀ levels, temperature and humidity were obtained from 2006 through 2008. Data on stroke hospitalizations (ICD 10: I60–I69) at four hospitals in Wuhan were obtained for the same period. A time-stratified case-crossover design was performed by season (April-September and October-March) to assess effects of pollutants on stroke hospital admissions.

Results

Pollution levels were higher in October-March with averages of 136.1 µg/m³ for PM₁₀, 63.6 µg/m³ for NO₂ and 71.0 µg/m³ for SO₂ than in April-September when averages were 102.0 µg/m³, 41.7 µg/m³ and 41.7 µg/m³, respectively (p<.001). During the cold season, every 10 µg/m³ increase in NO₂ was associated with a 2.9% (95%C.I. 1.2%–4.6%) increase in stroke admissions on the same day. Every 10 ug/m³ increase in PM₁₀ daily concentration was significantly associated with an approximate 1% (95% C.I. 0.1%–1.4%) increase in stroke hospitalization. A two-pollutant model indicated that NO₂ was associated with stroke admissions when controlling for PM₁₀. During the warm season, no significant associations were noted for any of the pollutants.

Conclusions

Exposure to NO₂ is significantly associated with stroke hospitalizations during the cold season in Wuhan, China when pollution levels are 50% greater than in the warm season. Larger and multi-center studies in Chinese cities are warranted to validate our findings.     

Environmental Particulate Matter Induces Murine Intestinal Inflammatory Responses and Alters the Gut Microbiome

Background

Particulate matter (PM) is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions.

Methods

Wild-type 129/SvEv mice were gavaged with Ottawa urban PM₁₀ (EHC-93) for 7–14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM₁₀ for measurement of proliferation. Long-term effects of exposure (35 days) on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10^−/−) mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum.

Results

Short-term treatment of wild-type mice with PM₁₀ altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10^−/− mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10^−/− mice had increased disease as evidenced by enhanced histological damage.

Conclusions

Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine.     

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.     

Influence of weather and atmospheric pollution on physical activity in patients with COPD

Rationale

Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.

Methods

Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM₁₀ and ozone (O₃) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.

Results

Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O₃ levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM₁₀ reduced activity (p = 0.018) but not during the weekend.

Conclusions

Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users.     

Inflammation and Airway Microbiota during Cystic Fibrosis Pulmonary Exacerbations

Background

Pulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.

Objective

To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.

Methods

Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0–3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.

Results

Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = −0.67, p<0.001), decreased FEV_1% predicted (r = 0.49, p = 0.03) and increased CRP (r = −0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.

Conclusions

Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.     

Acute Effects of Particulate Matter and Black Carbon from Seasonal Fires on Peak Expiratory Flow of Schoolchildren in the Brazilian Amazon

Background

Panel studies have shown adverse effects of air pollution from biomass burning on children''s health. This study estimated the effect of current levels of outdoor air pollution in the Amazonian dry season on peak expiratory flow (PEF).

Methods

A panel study with 234 schoolchildren from 6 to 15 years old living in the municipality of Tangará da Serra, Brazil was conducted. PEF was measured daily in the dry season in 2008. Mixed-effects models and unified modelling repeated for every child were applied. Time trends, temperature, humidity, and subject characteristics were regarded. Inhalable particulate matter (PM₁₀), fine particulate matter (PM_2.5), and black carbon (BC) effects were evaluated based on 24-hour exposure lagged by 1 to 5 days and the averages of 2 or 3 days. Polynomial distributed lag models (PDLM) were also applied.

Results

The analyses revealed reductions in PEF for PM₁₀ and PM_2.5 increases of 10 µg/m³ and 1 µg/m³ for BC. For PM₁₀, the reductions varied from 0.15 (confidence interval (CI)95%: −0.29; −0.01) to 0.25 l/min (CI95%: −0.40; −0.10). For PM_2.5, they ranged from 0.46 (CI95%: −0.86 to −0.06) to 0.54 l/min (CI95%:−0.95; −0.14). As for BC, the reduction was approximately 1.40 l/min. In relation to PDLM, adverse effects were noticed in models based on the exposure on the current day through the previous 3 days (PDLM 0–3) and on the current day through the previous 5 days (PDLM 0–5), specially for PM₁₀. For all children, for PDLM 0–5 the global effect was important for PM₁₀, with PEF reduction of 0.31 l/min (CI95%: −0.56; −0.05). Also, reductions in lags 3 and 4 were observed. These associations were stronger for children between 6 and 8 years old.

Conclusion

Reductions in PEF were associated with air pollution, mainly for lagged exposures of 3 to 5 days and for younger children.     

Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

Background

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.

Methods

We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.

Results

Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).

Conclusions

Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users.     

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.     

Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study

Introduction

The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV₁, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.

Methods

Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.

Results

Sputum neutrophil % increased with GOLD stage. There was a weak association between % sputum neutrophils and FEV₁ % predicted (univariate r² = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression). Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre. There were no associations between neutrophils and exacerbation rates or emphysema. Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak. The mean change over 1 year in neutrophil % was an increase of 3.5%.

Conclusions

Sputum neutrophil measurements in COPD are associated weakly with FEV₁ % predicted and health status. Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation.     

Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative

Introduction

Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD.

Methods

Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUV_max), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with β-coefficients (β) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors.

Results

Vascular inflammation (measured as SUV_max) was greater (P < 0.001) in patients with sacroiliitis (mean ± SD = 7.33 ± 2.09) defined by CT compared to those without sacroiliitis (6.39 ± 1.49, P = 0.038). There were associations between PsA and aortic inflammation (β = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (β = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (χ² = 124.6, P < 0.001).

Conclusions

Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings.

Electronic supplementary material

The online version of this article (doi:10.1186/ar4676) contains supplementary material, which is available to authorized users.     

Colour of sputum is a marker for bacterial colonisation in chronic obstructive pulmonary disease

Background

Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations. We assessed risk factors for bacterial colonisation in COPD.

Methods

Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis. Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥10² colony-forming units (CFU)/mL on quantitative bacterial culture. Colonised patients were divided into high (>10⁵ CFU/mL) or low (<10⁵ CFU/mL) bacterial load.

Results

A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV₁] [% predicted] 46.4%) were evaluated. Bacterial colonisation was demonstrated in 58 (48.7%) patients. Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour. Thirty-six patients (62% of those colonised) had a high bacterial load. More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture. In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001). Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum.

Conclusions

Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs. Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised.     

Abbott RealTime HBV Assay Is More Sensitive in Detection of Low Viral Load and Little Impacted by Drug Resistant Mutation in Chronic Hepatitis B Patients under Nucleot(s)ide Analogues Therapy

Background

Selection of drug-resistant strains may lead to failure of HBV antiviral therapy. There is little information whether there is detection difference in drug resistant mutations between different viral load assays of HBV.

Objectives

This study is aimed to investigate whether there is drug-resistant strains related detection difference between Abbott RealTime HBV (RealTime) and CobasAmpliPrep/CobasTaqMan HBV assays 2.0 (TaqMan).

Study Design

One hundred and thirty-four CHB patients who received HBV anti-viral therapy were enrolled. HBV virological markers were tested 3 months apart regularly. Serum HBV DNA levels were determined using the TaqMan and RealTime. YMDD (rt180M and rt204V) mutation was checked in patients who experienced virologic breakthrough (VBT).

Results

The correlation of HBV DNA observed between the RealTime and TaqMan was good for all 571 samples (R² = 0.797; P<0.001). However, the correlation in the 434 samples with HBV DNA level <3 log₁₀ IU/ml was not as good as in all samples (R² = 0.457). Overall, 21.5% of samples had a detection difference of ≥1 log₁₀ IU/ml with 91.9% of these having HBV DNA level <3 log₁₀ IU/ml. Twenty-four patients experiencedVBT. Three of these patients had acquired the YMDD mutation and exhibited discordant viral load results between the two methods tested. In each case, persistent HBV DNA was detected by RealTime and undetectable with TaqMan. Of the patients who experienced a VBT and had acquired YMDD mutation, 4.7% had undetectable HBV DNA by TaqMan while all were detectable with RealTime.

Conclusions

RealTime assay is more sensitive and is little impacted by the development of drug resistant mutation.     

How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan

Background

Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy.

Methods

We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables.

Results

An increase in ozone (O₃) levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO₂), CO, nitrate dioxide (NO₂), and particulate matter (PM₁₀ and PM_2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association.

Conclusions

Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.     

Acute Effects of Particulate Air Pollution on the Incidence of Coronary Heart Disease in Shanghai,China

Introduction

Evidence based on ecological studies in China suggests that short-term exposure to particulate matter (PM) is associated with cardiovascular mortality. However, there is less evidence of PM-related morbidity for coronary heart disease (CHD) in China. This study aims to investigate the relationship between acute PM exposure and CHD incidence in people aged above 40 in Shanghai.

Methods

Daily CHD events during 2005–2012 were identified from outpatient and emergency department visits. Daily average concentrations for particulate matter with aerodynamic diameter less than 10 microns (PM₁₀) were collected over the 8-year period. Particulate matter with aerodynamic diameter less than 2.5 microns (PM_2.5) were measured from 2009 to 2012. Analyses were performed using quasi-poisson regression models adjusting for confounders, including long-term trend, seasonality, day of the week, public holiday and meteorological factors. The effects were also examined by gender and age group (41–65 years, and >65 years).

Results

There were 619928 CHD outpatient and emergency department visits. The average concentrations of PM₁₀ and PM_2.5 were 81.7μg/m³ and 38.6μg/m³, respectively. Elevated exposure to PM₁₀ and PM_2.5 was related with increased risk of CHD outpatients and emergency department visits in a short time course. A 10 μg/m³ increase in the 2-day PM₁₀ and PM_2.5 was associated with increase of 0.23% (95% CI: 0.12%, 0.34%) and 0.74% (95% CI: 0.44%, 1.04%) in CHD morbidity, respectively. The associations appeared to be more evident in the male and the elderly.

Conclusion

Short-term exposure to high levels of PM₁₀ and PM_2.5 was associated with increased risk of CHD outpatient and emergency department visits. Season, gender and age were effect modifiers of their association.     

Association of Plasma IL-6 and Hsp70 with HRV at Different Levels of PAHs Metabolites

Background

Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with reduced heart rate variability (HRV), a strong predictor of cardiovascular diseases, but the mechanism is not well understood.

Objectives

We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.

Methods

HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas chromatography-mass spectrometry.

Results

We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all P _trend<0.05); and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP) and low frequency (LF) (P _trend = 0.014 and 0.006, respectively). In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all P _trend<0.05), but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN), TP and LF in the low-PAHs metabolites groups (all P _trend<0.05). We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.

Conclusions

In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.     

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.     

MMP7 Shedding of Syndecan-1 Facilitates Re-Epithelialization by Affecting α2β1 Integrin Activation

Background

Lung injury promotes the expression of matrix metalloproteinase-7 (MMP7, matrilysin), which is required for neutrophil recruitment and re-epithelialization. MMP7 governs the lung inflammatory response through the shedding of syndecan-1. Because inflammation and repair are related events, we evaluated the role of syndecan-1 shedding in lung re-epithelialization.

Methodology/Principal Finding

Epithelial injury induced syndecan-1 shedding from wild-type epithelium but not from Mmp7^−/− mice in vitro and in vivo. Moreover, cell migration and wound closure was enhanced by MMP7 shedding of syndecan-1. Additionally, we found that syndecan-1 augmented cell adhesion to collagen by controlling the affinity state of the α₂β₁ integrin.

Conclusion/Significance

MMP7 shedding of syndecan-1 facilitates wound closure by causing the α₂β₁ integrin to assume a less active conformation thereby removing restrictions to migration. MMP7 acts in the lungs to regulate inflammation and repair, and our data now show that both these functions are controlled through the shedding of syndecan-1.     

Tourniquet-Applied Upper Limb Orthopaedic Surgery Results in Increased Inflammation and Changes to Leukocyte,Coagulation and Endothelial Markers

Purpose

During this pilot clinical study, patients scheduled for elective tourniquet-applied upper limb orthopaedic surgery were recruited to investigate the effects of surgery on various biological markers (n = 10 patients).

Methods

Three venous blood samples were collected from the arm at the ante-cubital fossa, at baseline (pre-operatively), 5 and 15 minutes after reperfusion (post-operatively). Neutrophil and monocyte leukocyte sub-populations were isolated by density gradient centrifugation techniques. Leukocyte activation was investigated by measuring the cell surface expression of CD62L (L-selectin), CD11b (Mac-1) and the intracellular production of hydrogen peroxide (H2O2), via flow cytometry. C-reactive protein (CRP) was measured using a clinical chemistry analyser. Plasma concentrations of protein C and von Willebrand factor (vWF) were measured using enzyme-linked fluorescent assays (ELFA).

Results

Following tourniquet-applied upper limb orthopaedic surgery, there was a decrease in neutrophil CD62L expression (p = 0.001), an increase in CD11b expression and in the intracellular production of H2O2 by neutrophils and monocytes (p<0.05). An increase in CRP concentration (p<0.001), a decrease in protein C concentration (p = 0.004), with a trend towards elevated vWF levels (p = 0.232) were also observed during this time.

Conclusions

Conventionally, patients undergoing orthopaedic surgery have been monitored in the peri-operative period by means of CRP, which is a non-specific marker of inflammation. This test cannot differentiate between inflammation due to current or pre-existing disease processes and the development of ischaemia-reperfusion injury surgery. The findings from this study suggest that markers such as CD11b, protein C and H₂O₂ may provide alternative ways of assessing leukocyte and coagulation activation peri-operatively. It is proposed that by allowing orthopaedic surgeons access to laboratory markers such as CD11b, protein C and H₂O₂, an accurate assessment of the extent of inflammation due to surgery per se could be made.