Susceptible Subgroups Research Articles

Air Pollution and Acute Myocardial Infarction Hospital Admission in Alberta, Canada: A Three-Step Procedure Case-Crossover Study.

Adverse associations between air pollution and myocardial infarction (MI) are widely reported in medical literature. However, inconsistency and sensitivity of the findings are still big concerns. An exploratory investigation was undertaken to examine associations between air pollutants and risk of acute MI (AMI) hospitalization in Alberta, Canada. A time stratified case-crossover design was used to assess the transient effect of five air pollutants (carbon monoxide (CO), nitrogen dioxide (NO2), nitric oxide (NO), ozone (O3) and particulate matter with an aerodynamic diameter ≤2.5 (PM2.5)) on the risk of AMI hospitalization over the period 1999–2009. Subgroups were predefined to see if any susceptible group of individuals existed. A three-step procedure, including univariate analysis, multivariate analysis, and bootstrap model averaging, was used. The multivariate analysis was used in an effort to address adjustment uncertainty; whereas the bootstrap technique was used as a way to account for regression model uncertainty. There were 25,894 AMI hospital admissions during the 11-year period. Estimating health effects that are properly adjusted for all possible confounding factors and accounting for model uncertainty are important for making interpretations of air pollution–health effect associations. The most robust findings included: (1) only 1-day lag NO2 concentrations (6-, 12- or 24-hour average), but not those of CO, NO, O3 or PM2.5, were associated with an elevated risk of AMI hospitalization; (2) evidence was suggested for an effect of elevated risk of hospitalization for NSTEMI (Non-ST Segment Elevation Myocardial Infarction), but not for STEMI (ST segment elevation myocardial infarction); and (3) susceptible subgroups included elders (age ≥65) and elders with hypertension. As this was only an exploratory study there is a need to replicate these findings with other methodologies and datasets.

Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial.

ObjectivesDeficiencies of vitamin B12 and folate are associated with delayed development and neurological manifestations. The objective of this study was to measure the effect of daily supplementation of vitamin B12 and/or folic acid on development in young North Indian children.MethodsIn a randomized, double blind trial, children aged six to 30 months, received supplement with placebo or vitamin B12 and/or folic acid for six months. Children were allocated in a 1:1:1:1 ratio in a factorial design and in blocks of 16. We measured development in 422 children by the Ages and Stages Questionnaire 3rd ed. at the end of the intervention.ResultsCompared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively. The effect was highest in susceptible subgroups consisting of stunted children, those with high plasma homocysteine (> 10 μmol/L) or in those who were younger than 24 at end study. With the exception of a significant improvement on gross motor scores by vitamin B12 alone, supplementation of either vitamin alone had no effect on any of the outcomes.ConclusionOur findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children.Trial RegistrationClinicalTrials.gov NCT00717730

Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail.

Of the approximately 34 identified Biomphalaria species,Biomphalaria alexandrina represents the intermediate host of Schistosoma mansoni in Egypt. Using parasitological and SOD1 enzyme assay, this study aimed to elucidate the impact of the age of B. alexandrina snails on their genetic variability and internal defence against S. mansoni infection. Susceptible and resistant snails were reared individually for self-reproduction; four subgroups of their progeny were used in experiment. The young susceptible subgroup showed the highest infection rate, the shortest pre-patent period, the highest total cercarial production, the highest mortality rate and the lowest SOD1 activity. Among the young and adult susceptible subgroups, 8% and 26% were found to be resistant, indicating the inheritance of resistance alleles from parents. The adult resistant subgroup, however, contained only resistant snails and showed the highest enzyme activity. The complex interaction between snail age, genetic background and internal defence resulted in great variability in compatibility patterns, with the highest significant difference between young susceptible and adult resistant snails. The results demonstrate that resistance alleles function to a greater degree in adults, with higher SOD1 activity and provide potential implications for Biomphalaria control. The identification of the most susceptible snail age enables determination of the best timing for applying molluscicides. Moreover, adult resistant snails could be beneficial in biological snail control.

The effect of heat waves on mortality in susceptible groups: a cohort study of a mediterranean and a northern European City.

BackgroundClimate change is projected to increase the number and intensity of extreme weather events, for example heat waves. Heat waves have adverse health effects, especially for the elderly, since chronic diseases are more frequent in that group than in the population overall. The aim of the study was to investigate mortality during heat waves in an adult population aged 50 years or over, as well as in susceptible subgroups of that population in Rome and Stockholm during the summer periods from 2000 to 2008.MethodsWe collected daily number of deaths occurring between 15th May and 15th September each year for the population above 50 as well as the susceptible subgroups. Heat wave days were defined as two or more days exceeding the city specific 95th percentile of maximum apparent temperature (MAT). The relationship between heat waves and all-cause non-accidental mortality was investigated through time series modelling, adjusting for time trends.ResultsThe percent increase in daily mortality during heat waves as compared to normal summer days was, in the 50+ population, 22% (95% Confidence Interval (CI): 18-26%) in Rome and 8% (95% CI: 3-12%) in Stockholm. Subgroup specific increase in mortality in Rome ranged from 7% (95% CI:–17-39%) among survivors of myocardial infarction to 25% in the COPD (95% CI:9-43%) and diabetes (95% CI:14-37%) subgroups. In Stockholm the range was from 10% (95% CI: 2-19%) for congestive heart failure to 33% (95% CI: 10-61%) for the psychiatric subgroup.ConclusionsMortality during heat waves increased in both Rome and Stockholm for the 50+ population as well as in the considered subgroups. It should be evaluated if protective measures should be directed towards susceptible groups, rather than the population as a whole.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-015-0012-0) contains supplementary material, which is available to authorized users.

Colonization by Legionella spp. of water networks in residential buildings of the Province of Pisa, Italy.

Despite the increase of community acquired cases of legionellosis in Italy over the last years, the Italian guidelines do not give indications for prevention and control of Legionella in the hot water networks (or centralized conditioning systems) of residential buildings. We performed a survey on eight medium sized apartment buildings in the Pisa district to assess the prevalence of Legionella spp. in the water network and the respondance to drinking water requisites at the point of use, according to the Italian norms. For each building two hot water and three cold water samples (located at water entrance from the aqueduct network into the building pipework, at the exit from pressure autoclave, and at a remote tap) were collected. Legionella was detected in 20% of residential buildings, mostly in those with a central hot water production system. The study highlights a condition of potential risk for susceptible population subgroups and supports the need for measures of risk assessment and control.

Media impact switching surface during an infectious disease outbreak.

There are many challenges to quantifying and evaluating the media impact on the control of emerging infectious diseases. We modeled such media impacts using a piecewise smooth function depending on both the case number and its rate of change. The proposed model was then converted into a switching system, with the switching surface determined by a functional relationship between susceptible populations and different subgroups of infectives. By parameterizing the proposed model with the 2009 A/H1N1 influenza outbreak data in the Shaanxi province of China, we observed that media impact switched off almost as the epidemic peaked. Our analysis implies that media coverage significantly delayed the epidemic's peak and decreased the severity of the outbreak. Moreover, media impacts are not always effective in lowering the disease transmission during the entire outbreak, but switch on and off in a highly nonlinear fashion with the greatest effect during the early stage of the outbreak. The finding draws the attention to the important role of informing the public about ‘the rate of change of case numbers' rather than ‘the absolute number of cases' to alter behavioral changes, through a self-adaptive media impact switching on and off, for better control of disease transmission.

Central and peripheral changes underlying susceptibility and resistance to social defeat stress – A proteomic profiling study

The social defeat mouse model is used as a preclinical model for major depressive disorder (MDD). This model is of interest, as mice subjected to chronic social defeat can be separated into stress susceptible (SS) and resilient (SR) subgroups that differ in defined behavioural and physiological characteristics. Here, we have carried out proteomic analyses of serum and brain samples from SS (n=12), SR (n=12) and unstressed control (n=12) mice, using two analytical platforms to gain insight into the underlying molecular pathways that distinguish these subgroups. Multiplex immunoassay profiling was performed using sera collected after 10 days of chronic social defeat. This analysis identified peripheral alterations in proteins mostly associated with inflammation in SS mice, whereas growth factors and hormones were changed predominantly in the SR subgroup. Label free liquid chromatography mass spectrometry (LC–MSE) profiling of frontal cortex revealed a significant increase in myelin-associated proteins [2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CN37), mylein basic protein (MBP), and myelin proteolipid protein (MYPR)] in the SR group, suggesting that resilience to social stress might be mediated through activation of oligodendrogenesis. Taken together, these results provide the first proteomic evidence of differential effects on oligodendrocyte function between susceptible and resilient subgroups in the social defeat model and suggest that neuronal conductivity or central nervous system maintenance in the frontal cortex are involved in the adaptive response to stress. These changes appear to be reflected by serum alterations in inflammation and growth-related proteins, which could be used as biomarkers for predicting or monitoring stress response.

Association between the XRCC6 polymorphisms and cancer risks: a systematic review and meta-analysis.

A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms and cancer risks, and the results remained inconsistent and inconclusive.To assess the effect of XRCC6 polymorphisms on cancer susceptibility, we conducted a meta-analysis, up to May 23rd 2014, 6267 cases with different types of tumor and 7536 controls from 20 published case–control studies. Summary odds ratios and corresponding 95% confidence intervals for XRCC6 polymorphism and cancer risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses, logistic meta-regression analyses and Galbraith plot. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed.The rs2267437 polymorphism was associated with a significant increase in risks of overall cancers, breast cancer, renal cell carcinoma and hepatocellular carcinoma, and it could increase the cancer risk in Asian population; the rs5751129 polymorphism could increase the cancer risk in overall cancers; the rs132770 polymorphism was associated with the increased renal cell carcinoma risk; furthermore, the rs132793 polymorphism could decrease breast cancer risk and increase risks in “other cancers”.Overall, the results provided evidences that the single nucleotide polymorphisms in XRCC6 promoter region might play different roles in various cancers, indicating different cancers have different tumorigenesis mechanisms. Our studies may perhaps supplement for the disease monitoring of cancers in the future, and additional studies to determine the exact molecular mechanism might provide us with interventions to protect the susceptible subgroups.

Modification of the Effect of Ambient Air Pollution on Pediatric Asthma Emergency Visits: Susceptible Subpopulations

Epidemiologic and experimental research supports the conclusion that certain outdoor air pollutants cause exacerbations of asthmatic symptoms among children with asthma.1,2 Similarly, there is a growing body of literature describing how in utero and early life experiences affect physiological development and influence sensitivity to environmental factors throughout life.3 Unfortunately, most large population-based studies of associations between short-term changes in ambient air pollutant concentrations and asthma exacerbations have lacked data on early-life risk factors, whereas the cohort studies that include such information are often too small to support investigation of effect-measure modification among potentially susceptible subgroups. In the U.S. state of Georgia, data on live birth records have been linked with pediatric emergency department visits by staff at the Office of Health Indicators for Planning at the Georgia Department of Public Health. Additionally, in metropolitan Atlanta there are several long-running air quality measurement campaigns that include, among other more commonly measured pollutants, daily measurements from four monitoring stations of speciated particulate matter less than 2.5 microns in diameter (PM2.5). We used these two data resources to estimate the rate ratio (RR) relating short-term changes in air pollutant concentrations to emergency department (ED) visits for asthma or wheeze and to investigate whether there was evidence for effect-measure modification of the RR by various risk factors available from the linked dataset. Although we examined effect-measure modification for eight different factors, we had particular a priori interest in investigating whether susceptibility might have varied by gestational age, as accumulating evidence suggests that children born preterm have long-term decrements in lung function.4,5

Prenatal exposure to PCB-153, p,p′-DDE and birth outcomes in 9000 mother–child pairs: Exposure–response relationship and effect modifiers

Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p′-DDE) can impair fetal growth; however, the exposure–response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure–response relationship between PCB-153 and p-p′-DDE and birth outcomes; to evaluate whether any no exposure–effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother–child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure–response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194g (95% CI −314, −74) per 1μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure–response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association.

Perspectives in Household Air Pollution Research: Who Will Benefit from Interventions?

Household air pollution from solid fuel combustion in inefficient and poorly vented cookstoves is estimated to be responsible for 3.9 million premature deaths per year and 4.8 % of the global burden of disease, making it the third leading risk factor for morbidity and mortality worldwide. Despite increasing recognition surrounding this global environmental health problem, much remains to be elucidated regarding exposure response relationships, particularly among potentially susceptible population subgroups. Given that many of the communities most affected by household air pollution exposures also experience elevated exposures to poverty, psychosocial stressors, other environmental pollutants, and comorbid conditions, research needs to correctly specify risks due to these potentially interacting risk factors. Although suggestive evidence exists for differential improvements in health following reductions in ambient air pollution concentrations among specific subgroups, the question remains as to who will benefit and to what extent from efforts to reduce exposures to emissions from household solid fuel combustion. The ability to know what to expect from cookstove interventions and to accurately describe the presence of distinct subgroup responses is crucial to reduce uncertainty and to encourage policy makers to enact change.

Total exposure to airborne particulate matter in cities: The effect of biomass combustion

The study deals with the seasonal variability of PM exposure and the effect that biomass combustion has upon it in the urban environment. The study is based on measurements, chemical analyses and modeling results performed in Thessaloniki (Greece). The measurements campaign included the assessment of outdoor and indoor air quality and the evaluation of biomass use for domestic heating. The outdoor measurements highlighted a significant increase of PM10 (from 30.1 to 73.1μg/m3) and PM2.5 (from 19.4 to 62.7μg/m3) concentrations during the transition from the warm to the cold period of the year 2012 compared to 2011. The increase in ambient air PM during the winter was attributed to the use of biomass burning for space heating. The latter was verified by the presence of levoglucosan in the PM (concentrations up to 8μg/m3), especially for samples taken from the urban background site. Outdoor PM concentrations were also modeled using an artificial neural network model taking into account major meteorological parameters; the latter explained more than 90% of PM10 and PM2.5day-to-day variability. Indoor concentrations followed a similar pattern, while in the case of fireplace use, average daily concentrations rise to 10μg/m3 and 14μg/m3 for PM2.5 and PM10 respectively. Indoor air concentrations were affected the most by the ambient air particle infiltration. Indoor air quality went down after 3h of open fire biomass combustion for space heating. Personal exposure was significantly determined by overall indoor air quality. Yet, dynamic exposure analysis revealed that peaks of intake do not correspond to peaks of ambient air PM concentrations altering thus total exposure patterns. Thus, cost-effective public health protection has to aim at reducing the exposure profile of susceptible population sub-groups combining awareness raising, emission reduction measures and financial incentives to influence the choice of space heating systems.

Listeria monocytogenes dose response revisited--incorporating adjustments for variability in strain virulence and host susceptibility.

Evaluations of Listeria monocytogenes dose-response relationships are crucially important for risk assessment and risk management, but are complicated by considerable variability across population subgroups and L. monocytogenes strains. Despite difficulties associated with the collection of adequate data from outbreak investigations or sporadic cases, the limitations of currently available animal models, and the inability to conduct human volunteer studies, some of the available data now allow refinements of the well-established exponential L. monocytogenes dose response to more adequately represent extremely susceptible population subgroups and highly virulent L. monocytogenes strains. Here, a model incorporating adjustments for variability in L. monocytogenes strain virulence and host susceptibility was derived for 11 population subgroups with similar underlying comorbidities using data from multiple sources, including human surveillance and food survey data. In light of the unique inherent properties of L. monocytogenes dose response, a lognormal-Poisson dose-response model was chosen, and proved able to reconcile dose-response relationships developed based on surveillance data with outbreak data. This model was compared to a classical beta-Poisson dose-response model, which was insufficiently flexible for modeling the specific case of L. monocytogenes dose-response relationships, especially in outbreak situations. Overall, the modeling results suggest that most listeriosis cases are linked to the ingestion of food contaminated with medium to high concentrations of L. monocytogenes. While additional data are needed to refine the derived model and to better characterize and quantify the variability in L. monocytogenes strain virulence and individual host susceptibility, the framework derived here represents a promising approach to more adequately characterize the risk of listeriosis in highly susceptible population subgroups.

Weighted road density and allergic disease in children at high risk of developing asthma.

BackgroundEvidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma.MethodsWe examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis.ResultsWeighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06–1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01–1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03–1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children.ConclusionAssociations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma.

Chronic PM2.5 exposure and inflammation: Determining sensitive subgroups in mid-life women

BackgroundSeveral cohort studies report associations between chronic exposure to ambient fine particles (PM2.5) and cardiovascular mortality. Uncertainty exists about biological mechanisms responsible for this observation, but systemic inflammation has been postulated. In addition, the subgroups susceptible to inflammation have not been fully elucidated. MethodsWe investigated whether certain subgroups are susceptible to the effects of long-term exposure to PM2.5 on C-reactive protein (CRP), a marker of inflammation directly linked to subsequent cardiovascular disease. We used data from the SWAN cohort of 1923 mid-life women with up to five annual repeated measures of CRP. Linear mixed and GEE models accounting for repeated measurements within an individual were used to estimate the effects of prior-year PM2.5 exposure on CRP. We examined CRP as a continuous and as binary outcome for CRP greater than 3mg/l, a level of clinical significance. ResultsWe found strong associations between PM2.5 and CRP among several subgroups. For example a 10µg/m3 increase in annual PM2.5 more than doubled the risk of CRP greater than 3mg/l in older diabetics, smokers and the unmarried. Larger effects were also observed among those with low income, high blood pressure, or who were using hormone therapy, with indications of a protective effects for those using statins or consuming moderate amounts of alcohol. ConclusionsIn this study, we observed significant associations between long-term exposure to PM2.5 and CRP in several susceptible subgroups. This suggests a plausible pathway by which exposure to particulate matter may be associated with increased risk of cardiovascular disease.

IL-6 activated JAK/STAT3 pathway and sensitivity to Hsp90 inhibitors in multiple myeloma.

Modern anti-cancer treatment involves targeted therapy that aims at inactivating particular oncoproteins or signaling pathways in a cancer-type-specific manner. A number of potent targeted therapies affecting oncogenic kinases or receptor tyrosine kinases have revolutionized anti-cancer treatment. These drugs inactivate signaling pathways that cancer cells depend on and therefore inhibit their proliferation and survival. Molecular chaperones of the Hsp90 family (heat shock protein 90) support the integrity, folding and function of many proteins involved in proliferation, survival, DNA damage and repair. Hsp90 proteins are thus required to maintain activity of a large variety of oncogenic proteins, including members of the JAK/STAT and the PI3K pathways. Accordingly cancer cells rely on Hsp90 proteins and their expression is often elevated in malignant cells. In line with this, inhibitors of Hsp90 (Hsp90-Is) have demonstrated potent antitumor activity in preclinical studies. While Hsp90-Is can be considered as targeted therapy, their broad effects on multiple signaling pathways make it difficult to predict the therapeutic outcome. Multiple myeloma (MM) is one of the tumor types with elevated Hsp90 levels. Hsp90-Is demonstrated promising activity in preclinical studies of MM and in several clinical trials. However, large variability in response questioned the use of Hsp90-Is as single drugs in the treatment of myeloma. A critical factor in targeted therapies, including Hsp90-Is, is identification of susceptible subgroups of patients. Predictive biomarkers in each particular tumor type are important in order to use anti-cancer drugs in a rational way. Interestingly, levels of Hsp90 expression has not proven to be decisive for treatment response and hence stratification of myeloma patients. Others and we have recently found that MM cells with an IL-6-activated JAK/STAT3 pathway are particularly sensitive to Hsp90-Is. In this review we will discuss these findings, both in terms of molecular mechanisms and applications for selection of MM patients amenable to Hsp90-I treatment in an individually targeted treatment strategy.

Do children’s upper respiratory tract infections benefit from probiotics?

BackgroundThe microbiota of the gastrointestinal tract have profound influence at multiple levels, even on the development and maintenance of lung immunity and inflammation. Aim of this review is to evaluate the current knowledge about the specific impact on children’s respiratory tract infections from probiotics, live microbes with the power to modify intestinal microbial populations and exert subsequent benefits for the host.DiscussionThe role of probiotics in gastrointestinal and allergic diseases has been largely assessed, but the number of studies performed so far in the field of respiratory tract infections is small, though some data show that probiotic administration might display clinical advantages. Probiotic strain identity and host genetic differences may account for differential modulation of immune responses by probiotics. Current laboratory and clinical data regarding the possibility of the role of probiotics on preventing the development of respiratory tract infections are contradictory, and are somewhat insufficient to recommend strongly their routine use. Further study of gastrointestinal-respiratory interactions is likely to yield important insights into the pathogenesis of different pulmonary diseases, and improve our knowledge in the prophylactic role of probiotics in children affected by recurrent upper respiratory tract infections.SummaryA better understanding of the effects of different probiotic strains and a deeper insight into their mechanisms of action are needed for the validation of specific strains carrying a potential to modify the frequency and severity of RTIs in infants and children. No data have been collected in pediatric patients with chronic underlying diseases, and yet there are no published data concerning treatment of RTIs with probiotics. The very few studies published so far do not indicate which micro-organism or administration regimen might exert beneficial effects as a prevention tool of RTIs both in healthy children and in those with recurrent RTIs. Further research to establish the role of probiotics in the treatment and prevention of RTIs, including those involving the lower respiratory tract, are required and should also clarify if any susceptible subgroups of respiratory diseases exist, and how these subgroups benefit from supplementation with certain probiotic strains.

Airway effects of traffic-related air pollution on outdoor workers

Traffic-related air pollution has been well documented to be associated with increased risks of airway diseases in the general population. Particularly, susceptible subgroups have included children and endurance athletes exercising outdoors. Relatively little has been published on the risks for outdoor workers. The purpose of this review is to identify the relative airway risks of outdoor work in areas with increased vehicular air pollution. We found a small body of recent literature published on this topic. Most of the relevant studies have focused on traffic police, petrol pump workers, and highway workers, especially in the urban areas of high traffic pollution. These studies suggest increases in respiratory symptoms and reduction in spirometric indices in nonsmoking workers in these occupations when compared with control individuals. Research is needed to investigate the relationship with duration of exposures in these workers, and to determine the duration and reversibility of effects in order to develop standards for safe working exposures. A significant impact on airway function and respiratory symptoms has been reported from outdoor work with exposure to traffic pollution. Further research is needed to confirm these associations and to develop standards for safe outdoor work in urban settings.

Sodium Excretion and Risk of Developing Coronary Heart Disease

Despite compelling evidence for sodium's adverse effects on blood pressure, it remains uncertain whether excess sodium intake is a risk factor for coronary heart disease (CHD) in the overall population and in potentially more susceptible subgroups. We prospectively followed 7543 adults aged 28 to 75 years and free of cardiovascular and kidney disease in 1997/1998 of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Sodium excretion was measured in two 24-hour urine collections at baseline. Potential susceptibility factors were blood pressure and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median 24-hour sodium excretion was 137 mmol (Q1-Q3, 106-171 mmol). During a median follow-up of 10.5 (Q1-Q3: 9.9-10.8) years, 452 CHD events occurred. In the entire cohort, there was no association between each 1-g/d (43 mmol/24 h) increment in sodium excretion and CHD risk (adjusted hazard ratio, 1.07; 95% confidence interval, 0.98-1.18; P=0.15). However, the association of sodium excretion with CHD risk tended to be modified by mean arterial pressure (Pinteraction=0.08) and was modified by NT-proBNP (Pinteraction=0.002). When stratified, each 1-g/d increment in sodium excretion was associated with an increased risk for CHD in subjects with hypertension (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; n=2363) and in subjects with NT-proBNP concentrations above the sex-specific median (adjusted hazard ratio, 1.16; 95% confidence interval, 1.03-1.30; n=3771). Overall, there was no association between sodium excretion and risk of CHD. The association between sodium excretion and CHD risk was modified by NT-proBNP. Higher sodium excretion was associated with an increased CHD risk among subjects with increased NT-proBNP concentrations or with hypertension.

Association between maternal COMT gene polymorphisms and fetal neural tube defects risk in a Chinese population

Maternal tea consumption was reported to increase the risk of fetal neural tube defects (NTDs). Catechol-O-methyltransferase (COMT) may be involved in the metabolism of polyphenolic methylation of tea, thus influence the risk of fetal NTDs. A total of 576 fetuses or newborns with NTDs and 594 healthy newborns were included in the case-control study. Information on maternal tea consumption, sociodemographic characteristics, reproductive history, and related behavior was collected through face-to-face interviews. Maternal blood samples were collected to examine polymorphisms in COMT, and the possible interaction of COMT and tea consumption was analyzed. After controlling for potential confounders, homozygotes of rs737865 showed an elevated risk for total NTDs (odds ratio [OR] = 2.04, 95% confidence interval [CI], 1.24-3.35) and for the anencephaly subtype (OR = 1.99, 95% CI, 1.17-3.39). The CC genotype of rs4633 was positively associated with the overall risk of NTDs (OR = 3.66, 95% CI, 1.05-12.83). Heterozygotes for rs4680 were associated with a decreased risk of spina bifida (OR = 0.71, 95% CI, 0.51-0.98). The COMT rs4680 A allele was negatively related with the risk of spina bifida, with adjusted OR = 0.64 (95% CI, 0.45-0.89). An interaction between tea consumption (1 to 2 cups/day) and the rs4680AA/AG genotype was found in the spina bifida subtype (Pinteraction = .08). Several COMT variants were associated with elevated risk of NTDs in a Chinese population. Maternal tea consumption may be associated with an increased risk for fetal NTDs in genetically susceptible subgroups.