Pro- and anti-inflammatory cytokines in threatened miscarriages

OBJECTIVE: The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatenedmiscarriage (TM) and subsequent outcome. STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF , interferon gamma (IFN ), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS: Monocyte expression of TNF and circulating levels of TNF , IFN , IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF /IL-10, IFN /IL-10, and TNF /IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome. CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage.peer-reviewe

The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome

TNFα receptors, TNF-R1 and TNF-R2, mediate the biological activities of the multifunctional cytokine, tumor necrosis factor alpha, TNFα. These receptors have a central role in human pregnancy. Although each receptor induces distinct intracellular signals, they also have co-operative and overlapping effects. The membrane bound TNF-R1 carries out most of the pro-inflammatory activities of TNFα, especially those that are rapid, while TNF-R2 is involved in the late long-term effects of this cytokine. The soluble forms of these receptors can bind to TNFα, neutralizing its effects. In normal human pregnancy, TNFα receptors are present in the maternal circulation, placenta, amniotic fluid, and coelomic cavity. Changes in TNFα and its receptors are associated with adverse pregnancy outcomes, including miscarriage, preterm labor and preeclampsia. Advances in anti-TNFα therapy may have potential use in the management of complicated pregnancies.peer-reviewe

A comparison of short-term and long-term air pollution exposure associations with mortality in two cohorts in Scotland

Air pollution–mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales. We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure–mortality associations in cohort participants and with short-term exposure–mortality associations in the general population from which the cohorts were selected. We assessed short-to-medium–term exposure–mortality associations in the Renfrew–Paisley and Collaborative cohorts (using nested case–control data sets), and compared them with long-term exposure–mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium–term exposure–mortality associations in the general population (using time-series analyses). For the Renfrew–Paisley cohort (15,331 participants), BS exposure–mortality associations were observed in nested case–control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m3 increases in 3-day lag BS, respectively}. Exposure–mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: –0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m3 increases in 31-day BS in case–control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m3 increase in geometic mean BS for 1970–1979, in survival analysis]. After adjusting for individual-level exposure and potential confounders, short-term exposure–mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure–mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures

Total and water-soluble trace metal content of urban background PM10, PM2.5 and black smoke in Edinburgh, UK

Toxicological studies have implicated trace metals in airborne particles as possible contributors to respiratory and/or cardiovascular inflammation. As part of an epidemiological study, co-located 24 h samples of PM10, PM2.5 and black smoke (BS) were collected for 1 year at an urban background site in Edinburgh, and each sample sequentially extracted with ultra-pure water, then concentrated HNO3/HCl, and analysed for Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd and Pb. This yields a comprehensive data set for UK urban airborne trace metal. The median (n>349) daily water-soluble metal concentration in PM2.5 ranged from 0.05 ng m−3 for Ti to 5.1 ng m−3 for Pb; and in PM10 from 0.18 ng m−3 for Ti to 11.7 ng m−3 for Fe. Median daily total (i.e. water+acid-extractable) metal concentration in PM2.5 ranged from 0.3 ng m−3 for As to 27.6 ng m−3 for Fe; and in PM10 from 0.37 ng m−3 for As to 183 ng m−3 for Fe. The PM2.5:PM10 ratio varied considerably with metal, from 70% for V, As, Cd and Pb. The 11 trace metals constituted proportionally more of the PM10-2.5 fraction than of the PM2.5 fraction (0.9%). The proportion of water-soluble metal in each size-fraction varied considerably, from 50% water-soluble V, Zn, As and Cd in PM2.5. Although Fe generally dominated the trace metal, water-soluble metal also contained significant Zn, Pb and Cu, and for all size and solubility fractions >90% of trace metal was comprised of Fe, Zn, Pb and Cu. Statistical analyses suggested three main sources: traffic; static combustion; and crustal. The association of metals with traffic (Cu, Fe, Mn, Pb, Zn) was consistent with traffic-induced non-exhaust "resuspension" rather than direct exhaust emission. Meteorology contributed to the wide variation in daily trace metal concentration. The proportion of trace metal in particles varied significantly with the air mass source and was highest on days for trajectories traversing over land. For Mn, Fe, Cu, Zn, As and Pb there was greater correlation of metal concentration with BS mass than with either PM10 or PM2.5 mass, suggesting that BS reflectance monitoring could be a cost-effective surrogate measure of particle metal concentration in urban background air

Interpretation of variations in fine, coarse and black smoke particulate matter concentrations in a northern European city

The PM2.5, PMcoarse and black smoke (BS) particle metrics broadly reflect different source contributions to PM10. The aim of this study was to generate data for PM2.5 at an urban background site in the UK, and to use the daily collocated measurement of PM2.5, PM10 (and hence PMcoarse) and BS to yield insight into source influences on particulate matter for input to developing PM air quality policy. Mean daily PM10, PM2.5 and BS for a year of measurement in Edinburgh were 15.5, 8.5 and 6.6 mu g m(-3). The PM2.5 data were well-within possible future limit values proposed by the European Commission Clean Air For Europe programme. Daily PM2.5 and PM10 were significantly correlated (r(2) = 0.75) with PM2.5 contributing 54%, on average, to PM10. The daily BS:PM10 and BS:PM2.5 ratios were more variable, and significantly lower in summer than in winter, reflecting the greater contribution of non-black photochemical secondary particles to PM10 in summer. Analysis with respect to wind showed a dominant influence of dispersion on BS and PM2.5 but both dispersion and a wind-driven suspension influence on PMcoarse. The latter was higher than in central England (Averaging about one-third of the PMcoarse), and greater for on-shore wind direction, suggesting a sea-salt source for this component in addition to other particle resuspension contributions. Overall, the data showed that excursions in PM10 were driven more by variations in PM2.5 than by PMcoarse or BS. Both PM2.5 and its proportion to PM10 were significantly elevated for aid-masses passing over continental Europe and the British Isles, whereas BS varied less with air-mass origin, supporting the conclusion that concentrations of particulate matter, particularly of finer PM, are strongly influenced by regional scale synoptic meteorology (presumed to be predominantly secondary PM), whereas BS is dominated more by local sources. Comparison of BS with a nearby rural site suggested that approximately three-quarters, on average, of the urban BS was local in origin

Application of passive diffusion tubes to short-term indoor and personal exposure measurement of nitrogen dioxide

Palmes-type passive diffusion tubes were shown to be as accurate in the measurement of indoor NO2 during short-term (2- and 3-d) exposures as during 1-week exposures. The statistical limit of detection for cumulative NO2 in 2- and 3-d exposure was 150 (nL L−1h). The mean coefficient of variation for duplicate 2- and 3-d exposures was < 13%. A pilot study measuring personal, indoor (living room) and outdoor (just outside the home) NO2 over 3 d for 8 volunteers demonstrated the feasibility and reliability of using passive diffusion tubes for short-term personal exposure measurements, and confirmed the necessity of obtaining actual exposure profiles for a specific subpopulation

Associations between short/medium-term variations in black smoke air pollution and mortality in the Glasgow conurbation, UK

To examine associations between short/medium-term variations in black smoke air pollution and mortality in the population of Glasgow and the adjacent towns of Renfrew and Paisley over a 25-year period at different time lags (0–30 days). Generalised linear (Poisson) models were used to investigate the relationship between lagged black smoke concentrations and daily mortality, with allowance for confounding by cold temperature, between 1974 and 1998. When a range of lag periods were investigated significant associations were noted between temperature-adjusted black smoke exposure and all-cause mortality at lag periods of 13–18 and 19–24 days, and respiratory mortality at lag periods of 1–6, 7–12, and 13–18 days. Significant associations between cardiovascular mortality and temperature-adjusted black smoke were not observed. After adjusting for the effects of temperature a 10 μg m−3 increase in black smoke concentration on a given day was associated with a 0.9% [95% Confidence Interval (CI): 0.3–1.5%] increase in all cause mortality and a 3.1% [95% CI:1.4–4.9%] increase in respiratory mortality over the ensuing 30-day period. In contrast for a 10 μg m−3 increase in black smoke concentration over 0–3 day lag period, the temperature adjusted exposure mortality associations were substantially lower (0.2% [95% CI: −0.0–0.4%] and 0.3% [95% CI: −0.2–0.8%] increases for all-cause and respiratory mortality respectively). This study has provided evidence of association between black smoke exposure and mortality at longer lag periods than have been investigated in the majority of time series analyses

A time-series study of the health effects of water-soluble and total-extractable metal content of airborne particulate matter

To assess whether adverse acute cardiopulmonary health outcomes are associated with concentration of trace metals in airborne particulate matter. Daily PM10 and PM2.5 were collected for1 year in Edinburgh, UK, and the water-soluble and total extractable content of 11 trace metals determined in each sample. Time series were analysed using generalised additive Poisson regression models, including adjustment for minimum temperature and loess smoothing of trends.Methods were explored of extending the time series of metal concentration in daily PM10 for the previous 7 years using multiple regression of the variation in metal content for the 1 year of measurements and the associated variation in air mass source region and other concurrently measured potential predictor variables. The 1 year of direct measurements showed no evidence of significant associations of particle-bound metal concentration with health outcomes beyond that expected by chance. Analysis of the extended time series showed significant positive associations with cardiovascular admissions both for total PM10 and for a number of the metals (eg, Cu, Fe, Ni, V, Zn) but the metal effects were no longer significant after adjusting for PM10. Within the limitations of the study power,the epidemiological results have not provided evidence for associations between particle-bound metal concentrations and adverse health outcomes that are substantially greater than for total PM. The generally strong correlations between metal and total PM suggest that quantifying independent effects of PM metal exposure on health will be difficult, even using more powerful time series of direct measurements

Intercomparison of five PM10 monitoring devices and the implications for exposure measurement in epidemiological research

Five different instruments for the determination of the mass concentration of PM10 in air were compared side-by-side for up to 33 days in an undisturbed indoor environment: a tripod mounted BGI Inc. PQ100 gravimetric sampler with a US EPA certified Graseby Andersen PM10 inlet; an Airmetrics Minivol static gravimetric sampler; a Casella cyclone gravimetric personal sampler; an Institute of Occupational Medicine gravimetric PM10 personal sampler; and two TSI Inc. Dustrak real-time optical scattering personal samplers. For 24 h sampling of ambient PM10 concentrations around 10 microg m(-3), the estimated measurement uncertainty for the two gravimetric personal samplers was larger (approximately +/- 20%) compared with estimated measurement uncertainty for the PQ100/Graseby Andersen sampler (< +/- 5%). Measurement uncertainty for the Dustraks was lower (approximately +/- 15% on average) but calibration of the optical response against a reference PM10 method is essential since the Dustraks systematically over-read PM10 determined gravimetrically by a factor approximately 2.2. However, once calibrated, the Dustrak devices demonstrated excellent functionality in terms of ease of portability and real-time data acquisition. Estimated measurement uncertainty for PM10 concentrations determined with the Minivol were +/- 5%. The Minivol data correlated well with PQ100/Graseby Andersen data (r= 0.97, n = 18) but were, on average, 23% greater. The reason for the systematic discrepancy could not be traced. Intercomparison experiments such as these are essential for assessing measurement error and revealing systematic bias. Application of two Dustraks demonstrated the spatial and temporal variability of exposure to PM10 in different walking and transport microenvironments in the city of Edinburgh, UK. For example, very large exposures to PM10 were identified for the lower deck of a double-decker tour bus compared with the open upper deck of the same vehicle. The variability observed emphasises the need to determine truly personal exposure profiles of PM10 for quantifying exposure response relationships for epidemiological studies