Search

Background Results of studies evaluating the relationship between asthma occurrence and early life antibiotic use have been conflicting. The aim of this study was to investigate the relationship between occurrence of asthma in children and systemic antibiotic use in the first year of life based on an incidence density study with careful consideration of the temporal aspects of the determinant-outcome relationship. Methods We conducted an incidence density study nested in a data collection project with information on 1128 mother–child pairs. Systemic antibiotic use in the first year of life was defined as excessive (≥ 4 courses) vs. non-excessive ( Results Forty-seven first asthma events and 147 population moments were included. Excessive systemic antibiotic use in the first year of life showed more than twice the incidence density of asthma compared to non-excessive use (adjusted IDR [95% CI]: 2.18 [0.98, 4.87], p = 0.06). The association was more pronounced in children who have had lower respiratory tract infections (LRTIs) in the first year of life compared to children who had no LRTIs in the first year of life (adjusted IDR [95% CI]: 5.17 [1.19, 22.52] versus 1.49 [0.54, 4.14]). Conclusions Excessive use of systemic antibiotics in the first year of life may play a role in the genesis of asthma in children. This effect is modified by the occurrence of LRTIs in the first year of life, with a stronger association observed in children experiencing LRTIs in the first year of life.

BackgroundAnxiety is frequently encountered in general practice, but figures regarding prevalence and incidence in this healthcare setting remain scarce.AimTo provide insight about the trends in prevalence and incidence of anxiety in Belgian general practice, as well as the comorbidities and treatment of anxiety in this context.Design and settingRetrospective cohort study using the INTEGO morbidity registration network, with clinical data from over 600 000 patients in Flanders, Belgium.MethodTrends in age-standardised prevalence and incidence of anxiety from 2000 to 2021 as well as prescriptions in patients with prevalent anxiety were analysed with joinpoint regression. Comorbidity profiles were analysed using the Cochran–Armitage test and the Jonckheere–Terpstra test.ResultsDuring the 22-year study period, 8451 unique patients with anxiety were identified. The prevalence of anxiety diagnoses rose significantly during this period, from 1.1% in 2000 to 4.8% in 2021. The overall incidence rate rose from 1.1/1000 patient–years (PY) in 2000 to 9.9/1000 PY in 2021. The average chronic disease count per patient increased significantly during the study period, from 1.5 to 2.3 chronic conditions. The most frequent comorbidities in patients with anxiety in 2017–2021 were malignancy (20.1%), hypertension (18.2%), and irritable bowel syndrome (13.5%). The proportion of patients treated with psychoactive medication rose from 25.7% to almost 40% over the study period.ConclusionA significantly increasing prevalence and incidence of physician-registered anxiety was found in the study. Patients with anxiety tend to become more complex, with more comorbidities. Treatment for anxiety in Belgian primary care is very dependent on medication.

ispartof: EUROPEAN RESPIRATORY JOURNAL vol:60 issue:1 ispartof: location:England status: published

Background Depression is a common mental disorder in family practice with an impact on global health. The aim of this study is to provide insight in the trends of epidemiological measures as well as pharmacological treatments and comorbidities of depression. Methods A study using data from INTEGO, a family practice registration network in Flanders, Belgium. Trends in age-standardized prevalence and incidence of depression from 2000 to 2019 as well as antidepressant prescriptions in prevalent depression cases were analyzed with join point regression. Comorbidity profiles were explored using the Cochran-Armitage test and the Jonckheere-Terpstra test. Results We identified 538 299 patients older than 15 years during the study period. We found an increasing trend in the age-standardized prevalence of depression from 6.73 % in 2000 to 9.20 % in 2019. For the incidence of depression, a decreasing trend was observed from 2000 to 2015 with an incidence of 9.42/1000 in 2000 and 6.89/1000 in 2015, followed by an increasing trend from 2015 to 2019 (incidence of 13.64/1000 in 2019). The average number of chronic diseases per patient with depression increased significantly during the study period (from 1.2 to 1.8), and the proportion of patients relative to the whole study population that received at least one antidepressant prescription per year increased between 2000 and 2019 from 26.44% to 40.16%. Conclusions The prevalence of depression increases while the incidence sharply rises, but only in recent years. Patients with depression tend to have more comorbidities, making a multi-faceted approach to these patients more important.

Background: Exposure to green spaces is associated with improved mental health and may reduce risk of suicide. Here, we investigate the association between long-term exposure to residential surrounding greenness and sui-cide mortality. Methods: We used data from the 2001 Belgian census linked to mortality register data (2001-2011). We included all registered individuals aged 18 years or older at baseline (2001) residing in the five largest urban areas in Belgium (n = 3,549,514). Suicide mortality was defined using the tenth revision of the World Health Organi-sation International Classification of Diseases (ICD-10) codes X60-X84, Y10-Y34, and Y870. Surrounding greenness was measured using the Normalized Difference Vegetation Index (NDVI) within a 300 m and 1,000 m buffer around the residential address at baseline. To assess the association between residential surrounding greenness and suicide mortality, we applied Cox proportional hazards models with age as the underlying time scale. Models were adjusted for age, sex, living arrangement, migrant background, educational attainment, neighbourhood socio-economic position. We additionally explored potential mediation by residential outdoor nitrogen dioxide (NO2) concentrations. Finally, we assessed potential effect modification by various socio-demographic characteristics of the population (sex, age, educational attainment, migrant background, and neighbourhood socio-economic position). Associations are expressed as hazard ratios and their 95% confidence intervals (CI) for an interquartile range (IQR) increase in residential surrounding greenness. Results: We observed a 7% (95%CI 0.89-0.97) and 6% (95%CI 0.90-0.98) risk reduction of suicide mortality for an IQR increase in residential surrounding greenness for buffers of 300 m and 1,000 m, respectively. Further-more, this association was independent of exposure to NO2. After stratification, the inverse association was only apparent among women, and residents of Belgian origin, and that it was stronger among residents aged 36 or older, those with high level of education, and residents of most deprived neighbourhoods. Conclusion: Our results suggest that urban green spaces may protect against suicide mortality, but this beneficial effect may not be equally distributed across all strata of the population.

Background:Childhood cognitive development depends on neuroimmune interactions. Immunomodulation by early-life microbial exposure may influence neuropsychological function. In this study, we investigate the association between residential indoor microbiota and cognition and behavior among preschoolers. Results:Indoor-settled dust bacterial and fungal characteristics were assessed using 16S and ITS amplicon sequencing (microbial diversity) and qPCR measurements (microbial loads). Child behavior was assessed using four scales: peer relationship, emotional, conduct, and hyperactivity was assessed by the Strengths and Difficulties Questionnaire (SDQ). Cognitive function was assessed using four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB) software. The first two tasks were designed to assess attention and psychomotor speed (Motor Screening (MOT) and Big/Little Circle (BLC)) and the last two to evaluate the child's visual recognition/working memory (Spatial Span (SSP) and Delayed Matching to Sample (DMS)). Among the 172 included children (age 4-6 years), we observed a 51% (95%CI;75%;9%) lower odds of children scoring not normal for hyperactivity and a decrease of 3.20% (95%CI, -6.01%; -0.30%) in BLC response time, for every IQR increase in fungal Shannon diversity. Contrarily, microbial loads were directly associated with SDQ scales and response time. For example, a 2-fold increase in Gram-positive bacterial load was associated with 70% (95%CI 18%; 156%) higher odds of scoring not normal for hyperactivity and an increase of 5.17% (95%CI 0.87%; 9.65%) in DMS response time. Conclusions:Our findings show that early-life exposure to diverse indoor fungal communities is associated with better behavioral and cognitive outcomes, whereas higher indoor microbial load was associated with worse outcomes. ENVIRONAGE birth cohort was supported by the EU research council (ERC-2012-StG310898), Research Foundation Flanders (FWO) (G073315N/ G048420N), and Methusalem. Indoor dust measurements were funded by FWO (grant number 151809N). Lidia Casas is a recipient of a post-doctoral fellowship a of the Research Foundation Flanders (FWO), grant number 12I1517N. The work at the Finnish Institute for Health and Welfare was supported by the Academy of Finland grant 296817. The authors acknowledge funding from the Special Research Fund (BOF) from Hasselt University granted to LR (BOF20DOC15).

Introduction: Pesticides, including herbicides, are widely used for agricultural and sanitary reasons and concerns have been raised about their various health effects. Little research has been done into the extent to which agricultural land use in the residential surroundings contributes to (internal) exposure of pesticides. Objectives: We investigated the associations between the proportion of agricultural land use around the residence and the exposure to pesticides in adolescents in Flanders (Belgium).Material and methods: We included 424 adolescents participating in the fourth Flemish Environment and Health Study (FLEHS IV) between 2016 and 2020. The residential address of all participants was geocoded and the proportion of agricultural land use around the residence was estimated in several buffers (300 m, 500 m, 1000 m and 2000 m). The concentrations of the following biomarkers of pesticides were measured in urine and adjusted for the specific gravity: glyphosate and its metabolite, aminomethyl-phosphonic acid (AMPA); 3-phenoxybenzoic acid (3-PBA); 3,5,6-trichloro-2-pyridinol (TCPy) and 2,4-dichlophenoxy-acetic acid (2,4-D). We categorized the pesticide biomarkers in three categories according to the exposure levels and used ordinal logistic regression models adjusted for sex, season and household education to estimate the odds ratio for an increase in an interquartile range (IQR) of proportion of agricultural land use. We also used binary logistic regression models in which the category of highest exposure was compared to the category of lowest exposure. In addition, we explored potential effect modification by sex and season.Results: We found a significant association between the proportion of agricultural land use in a buffer of 2000 m around the residence and the levels of urinary AMPA divided into three categories (OR = 1.35 for an IQR in-crease in the proportion of agricultural land use around residence; 95% CI: 1.00-1.83). This association was less pronounced and not statistically significant for the other studied pesticides (OR ranging between 0.95 and 1.16). Stratified analysis showed the strongest association of the proportion of agricultural land use within 2000 m buffers for AMPA among boys (OR = 1.89; 95% CI: 1.19-3.04). Results using smaller buffers were comparable, but did not reach statistical significance. This paper is based on research conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS, 2016–2020), funded by the Government of Flanders, Department of Environment & Spatial Development and the European H2020 Human Biomonitoring program HBM4EU. We kindly want to thank Flemming Nielsen for his contribution to this study.

Background Living in greener areas is associated with slower cognitive decline and reduced dementia risk among older adults, but the evidence with neurodegenerative disease mortality is scarce. We studied the association between residential surrounding greenness and neurodegenerative disease mortality in older adults. Methods We used data from the 2001 Belgian census linked to mortality register data during 2001–2014. We included individuals aged 60 years or older and residing in the five largest Belgian urban areas at baseline (2001). Exposure to residential surrounding greenness was assessed using the 2006 Normalized Difference Vegetation Index (NDVI) within 500-m from residence. We considered all neurodegenerative diseases and four specific outcomes: Alzheimer’s disease, vascular dementia, unspecified dementia, and Parkinson’s disease. We fitted Cox proportional hazard models to obtain hazard ratios (HR) and 95% confidence intervals (CI) of the associations between one interquartile range (IQR) increment in surrounding greenness and neurodegenerative disease mortality outcomes, adjusted for census-based covariates. Furthermore, we evaluated the potential role of 2010 air pollution (PM2.5 and NO2) concentrations, and we explored effect modification by sociodemographic characteristics. Results From 1,134,502 individuals included at baseline, 6.1% died from neurodegenerative diseases during follow-up. After full adjustment, one IQR (0.22) increment of surrounding greenness was associated with a 4–5% reduction in premature mortality from all neurodegenerative diseases, Alzheimer’s disease, vascular and unspecified dementia [e.g., for Alzheimer’s disease mortality: HR 0.95 (95%CI: 0.93, 0.98)]. No association was found with Parkinson’s disease mortality. Main associations remained for all neurodegenerative disease mortality when accounting for air pollution, but not for the majority of specific mortality outcomes. Associations were strongest in the lower educated and residents from most deprived neighbourhoods. Conclusions Living near greener spaces may reduce the risk of neurodegenerative disease mortality among older adults, potentially independent from air pollution. Socioeconomically disadvantaged groups may experience the greatest beneficial effect.

IntroductionObesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults.MethodsWe used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visitt. The relative risk (RR) of obesity att+1associated with asthma attwas estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity.ResultsWe included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II—III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association.ConclusionThis is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Domestic cleaners have an increased risk of asthma-like and other respiratory symptoms and conditions. Uncertainty exists about which products are most hazardous. We aimed to investigate, among professional domestic cleaners, the associations of ocular/respiratory outcomes with using specific types of products at work and with the ability to choose their own products. Among domestic cleaners employed by “service vouchers” companies in Belgium, we administered an online questionnaire on ocular/respiratory symptoms (frequency and time relation to workdays), frequency of use of 40 types of products, and ability to choose one’s own products. Work-relatedness was defined as symptoms improving/disappearing on days off-work. We studied associations between frequency of product-use with work-related outcomes (eye irritation, rhinitis symptoms, sore throat, laryngeal symptoms, asthma symptoms, cough) and with chronic bronchitis, using multivariable logistic and elastic net regression. Adjusted odds ratios (OR) with 95%-confidence intervals were obtained per time a product was used per week. Among 1,586 domestic cleaners (99% women), the number of times sprays were used (median 13/week) was significantly associated with all outcomes (ORs between 1.012 and 1.024 per time sprays were used per week). Bleach/disinfectant-containing liquid products were associated with all outcomes, except for laryngeal symptoms (ORs 1.086 to 1.150); ammonia with work-related upper airway symptoms and chronic bronchitis. Cleaners able to choose their own products had fewer work-related eye symptoms (OR 0.728;0.556–0.954), rhinitis (OR 0.735;0.571–0.946) and cough (OR 0.671;0.520–0.865). Using elastic net regression, work-related rhinitis was most strongly associated with mould removal spray (OR 1.108;1.006–1.248), carpet/seat/curtain spray (OR 1.099;1.001–1.304) and ammonia (OR 1.081;1.002–1.372); work-related asthma with carpet/seat/curtain spray (OR 1.103;1.017–1.322), mould removal spray (OR 1.029;0.995–1.199) and drain cleaner (OR 1.023;0.979–1.302). In a large group of domestic cleaners, we documented that cleaning products have a range of adverse respiratory effects. Empowering cleaners to choose their products may reduce the burden of symptoms. Domestic cleaners have an increased risk of asthma-like and other respiratory symptoms and conditions. Uncertainty exists about which products are most hazardous. We aimed to investigate, among professional domestic cleaners, the associations of ocular/respiratory outcomes with using specific types of products at work and with the ability to choose their own products. Among domestic cleaners employed by “service vouchers” companies in Belgium, we administered an online questionnaire on ocular/respiratory symptoms (frequency and time relation to workdays), frequency of use of 40 types of products, and ability to choose one’s own products. Work-relatedness was defined as symptoms improving/disappearing on days off-work. We studied associations between frequency of product-use with work-related outcomes (eye irritation, rhinitis symptoms, sore throat, laryngeal symptoms, asthma symptoms, cough) and with chronic bronchitis, using multivariable logistic and elastic net regression. Adjusted odds ratios (OR) with 95%-confidence intervals were obtained per time a product was used per week. Among 1,586 domestic cleaners (99% women), the number of times sprays were used (median 13/week) was significantly associated with all outcomes (ORs between 1.012 and 1.024 per time sprays were used per week). Bleach/disinfectant-containing liquid products were associated with all outcomes, except for laryngeal symptoms (ORs 1.086 to 1.150); ammonia with work-related upper airway symptoms and chronic bronchitis. Cleaners able to choose their own products had fewer work-related eye symptoms (OR 0.728;0.556–0.954), rhinitis (OR 0.735;0.571–0.946) and cough (OR 0.671;0.520–0.865). Using elastic net regression, work-related rhinitis was most strongly associated with mould removal spray (OR 1.108;1.006–1.248), carpet/seat/curtain spray (OR 1.099;1.001–1.304) and ammonia (OR 1.081;1.002–1.372); work-related asthma with carpet/seat/curtain spray (OR 1.103;1.017–1.322), mould removal spray (OR 1.029;0.995–1.199) and drain cleaner (OR 1.023;0.979–1.302). In a large group of domestic cleaners, we documented that cleaning products have a range of adverse respiratory effects. Empowering cleaners to choose their products may reduce the burden of symptoms. ispartof: Environment International vol:162 ispartof: location:Netherlands status: published

Little is known about the potential role of indoor plants in shaping the indoor microbiota. Within the ENVIRONAGE birth cohort, we collected settled dust and performed 16S and ITS amplicon sequencing and qPCR measurements to characterize the indoor microbiota, including bacterial and fungal loads and Chao1 richness, Shannon, and Simpson diversity indices. For 155 households, we obtained information on the number of indoor plants. We performed linear regression models adjusted for several a priori chosen covariables. Overall, an increase in indoor plants and density was associated with increased microbial diversity, but not load. For example, we found an increase of 64 (95%CI:3;125) and 26 (95%CI:4;48) units of bacterial and fungal taxa richness, respectively, in households with more than three plants compared to no plants. Our results support the hypothesis that indoor plants can enrich indoor microbial diversity, while impacts on microbial loads are not obvious. ispartof: INDOOR AIR vol:32 issue:3 ispartof: location:England status: published

BACKGROUND: Residential green space has been associated with mental health benefits, but how such associations vary with green space types is insufficiently known. OBJECTIVE: We aimed to investigate associations between types and quantities of green space and sales of mood disorder medication in Belgium. METHODS: We used aggregated sales data of psycholeptics and psychoanaleptics prescribed to adults from 2006 to 2014. Generalized mixed effects models were used to investigate associations between relative covers of woodland, low-green, grassland, and garden, and average annual medication sales. Models were adjusted for socio-economic background variables, urban-rural differences, and administrative region, and included random effects of latitude and longitude. RESULTS: Urban census tracts were associated with 9-10% higher medication sales. In nationwide models, a 10% increase in relative cover of woodland, garden, and grass was associated with a 1-2% decrease in medication sales. The same association was found for low green but only for men. In stratified models, a 10% increase in relative cover of any green space type in urban census tracts was associated with a decrease of medication sales by 1-3%. In rural census tracts, no protective associations between green space and mood disorder medication sales were observed, with the exception of relative woodland cover for women (-1%), and low green was associated with higher medication sales (+6-7%). CONCLUSIONS: Taken together, these results suggest that living in green environments may be beneficial for adult mental health. Woodland exposure seemed the most beneficial, but the amount of green space was more important than the type. Results underline the importance of conserving green space in our living environment, for the conservation of biodiversity and for human health. ispartof: Environmental Reserach vol:211 ispartof: location:Netherlands status: published

BackgroundOver the past decade, the Global Lung Function Initiative (GLI) Network has published all-age reference equations on spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) and lung volumes.MethodsWe evaluated the appropriateness of these equations in an adult Caucasian population. Retrospective lung function data on subjects who performed tests prior to a diagnostic sleep investigation were analysed. From the medical records, lung healthy, lifetime nonsmoking, nonobese subjects were selected, resulting in a population of 1311 subjects (68% male; age range 18–88 years).ResultsMultiple linear regression analysis revealed that lung function z-scores did not differ between subjects with and without sleep apnoea but did depend on height and age. The average forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score was 0 but exhibited an inverse association with height in both sexes (p1 and FVC in both sexes were larger than predicted (mean±sd z-score +0.30±0.96 or 104±13% pred; pDLCO were adequately predicted. However, DLCO z-scores were inversely associated with height in males and age in females (pConclusionGLI reference equations provide an adequate fit in Belgian adults. However, the GLI-proposed LLN is too low for our Antwerp population, resulting in underdiagnosis of disease. Furthermore, airway obstruction and diffusion disorders might be misclassified due to height and age associations.

Green space could influence adult cognition and childhood neurodevelopment , and is hypothesized to be partly driven by epigenetic modifications. However, it remains unknown whether some of these associations are already evident during foetal development. Similar biological signals shape the developmental processes in the foetal brain and placenta.Therefore, we hypothesize that green space can modify epigenetic processes of cognition-related pathways in placental tissue, such as DNA-methylation of the serotonin receptor HTR2A. HTR2A-methylation was determined within 327 placentas from the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort using bisulphite-PCR-pyrosequencing. Total green space exposure was calculated using high-resolution land cover data derived from the Green Map of Flanders in seven buffers (50 m-3 km) and stratified into low (a priori chosen covariables. For an IQR increment in total green space within a 1,000 m, 2,000 m and 3,000 m buffer the methylation of HTR2A increased with 1.47% (95%CI:0.17;2.78), 1.52% (95%CI:0.21;2.83) and 1.42% (95%CI:0.15;2.69), respectively. Additionally,, we found 3.00% (95%CI:1.09;4.91) and 1.98% (95%CI:0.28;3.68) higher HTR2A-methylation when comparing residences with and without the presence of nature in a 50 m and 100 m buffer, respectively. The methylation status of HTR2A in placental tissue is positively associated with maternal green space exposure. Future research is needed to understand better how these epigenetic changes are related to functional modifications in the placenta and the consequent implications for foetal development.

Background: Temperature may trigger the risk of suicide, however, the extent and shape of the associations show geographical variation. Here, we investigate the short-term effects of temperature on suicide deaths occurring in Brussels between January 1st, 2002 and December 31st, 2011. Methods: We conducted a bidirectional time-stratified case-crossover study with cases being suicide deaths occurring among Brussels residents aged 5 years or older. Cases were matched by day of the week with control days from the same month and year. The exposure was the daily average temperature measured at the Uccle station (Brussels) and obtained from the Belgian Royal Meteorological Institute. We combined conditional logistic regression with distributed lag non-linear models (DLNM) to obtain one week (lag 0-6) cumulative risk ratios (RR) and their 95% confidence intervals (CI) for the effects of moderate and extreme cold (5th and 1st percentiles of temperature, respectively) and moderate and extreme heat (95th and 99th percentiles of temperature, respectively), relative to the median temperature. Results: In total, 1891 suicide deaths were included. The median temperature was 11.6 degrees C, moderate and extreme cold temperatures were 0 and -3.1 degrees C, respectively, and moderate and extreme high temperatures were 20.9 and 24.4 degrees C, respectively. The cumulative risk of suicide mortality was almost twice higher among lags 0 to 6 for both moderate and extreme heat, relative to the period median temperature (e.g. moderate heat RR = 1.80 CI:1.27-2.54). No statistically significant associations were observed for cold temperatures. Conclusions: In Brussels, a western European city with temperate climate, high temperatures may trigger suicide deaths up to one week later. In the context of climate change, adaptation strategies must take into consideration the effects of temperature on mental health.

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden. Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477). Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991–1993, 1999–2002 and 2010–2013. Disease status was classified in 2010–2013, when the subjects were aged 40–68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated. Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life. The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood., The coexistence of asthma and COPD is generally diagnosed in older persons. Nonetheless, prevention of this condition should start in childhood. As a priority, maternal and personal smoking avoidance should be encouraged. https://bit.ly/3uQCmIX

Climate change leads to more days with extremely hot temperatures. Previous analyses of heat waves have documented a short-term rise in mortality. The results on the relationship between high temperatures and hospitalisations, especially in vulnerable patients admitted to nursing homes, are inconsistent. The objective of this research was to examine the discrepancy between heat-related mortality and morbidity in nursing homes. A time-stratified case-crossover study about the impact of heat waves on mortality and hospitalisations between 1 January 2013 and 31 December 2017 was conducted in 10 nursing homes over 5 years in Flanders, Belgium. In this study, the events were deaths and hospitalisations. We selected our control days during the same month as the events and matched them by day of the week. Heat waves were the exposure. Conditional logistic regression models were applied. The associations were reported as odds ratios at lag 0, 1, 2, and 3 and their 95% confidence intervals. In the investigated time period, 3048 hospitalisations took place and 1888 residents died. The conditional logistic regression showed that odds ratios of mortality and hospitalisations during heat waves were 1.61 (95% confidence interval 1.10-2.37) and 0.96 (95% confidence interval 0.67-1.36), respectively, at lag 0. Therefore, the increase in mortality during heat waves was statistically significant, but no significant changes in hospitalisations were obtained. Our result suggests that heat waves have an adverse effect on mortality in Flemish nursing homes but have no significant effect on the number of hospitalisations. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:18 issue:20 ispartof: location:Switzerland status: published

This study examines the associations between residential urban green spaces (UGS) and self-perceived health and natural cause mortality, applying an intersectional approach across gender, education and migrant background. We used data from the 2001 Belgian census linked to register data on emigration and mortality for the period 2001–2014, including 571,558 individuals aged 16–80 residing in Brussels (80% response rate). Residential UGS were assessed with the Normalized Difference Vegetation Index (NDVI) within a 300 m buffer from the residential address and perceived neighbourhood greenness. Multilevel logistic and Cox proportional hazards regression models were conducted to estimate associations between UGS and poor self-perceived health at baseline and natural cause mortality during follow-up. Residential UGS were inversely associated with both outcomes, but there were differences between groups. The strongest beneficial associations among women were found in the lower educated, regardless of their migrant background. For men the strongest association was found in those with tertiary education and Belgian origin. No significant beneficial associations were found in men originating from low and middle-income countries. Applying an intersectionality approach is crucial to understand health inequalities related to UGS exposure. Further research in different geographical contexts is needed to contrast our findings.

As part of a broader multidisciplinary research project dealing with the association between health and green/blue environments, this paper aims at exploring the spatial variation of medication reimbursements within Belgium. These data were potentially and a priori considered as a proxy for health. This paper is purely exploratory: statistical maps, correlations, PCAs and cluster analyses corroborate the results. Five groups of medications prescribed for health disorders associated with the environment have been selected. We show that – at the level of the municipalities – the spatial distributions of the five medication groups are positively correlated to each other (medication consumption co-vary positively in space, whatever their type), but are independent of the environmental and socio-economic conditions measured. Against our expectation, they prove to be negatively correlated to air pollution and green spaces. Strikingly, the spatial distribution of medication prescriptions follows the linguistic border between Flanders and Wallonia. This implies that the observed differences are mainly due to administrative/political regional differences in terms of health policies, medical schools, pharmaceutical commercial activities, etc. that are hard to quantify (no data, diversity of actors) but should be taken into account in any further explanatory model. Medication reimbursements data correspond to a new type of data, and despite their potential attractiveness for health analyses, extreme care has to be taken when interpreting their spatial variation and their link to health. Cet article s’inscrit dans un projet de recherche multidisciplinaire visant à étudier la relation entre santé et environnement (espaces verts/bleus), et explore tout particulièrement la variation spatiale des remboursements de médicaments prescrits en Belgique. Ces données ont initialement été considérées dans ce projet comme des estimateurs potentiels de la santé. L’analyse se veut essentiellement exploratoire : des cartes statistiques, des coefficients de corrélation, des ACP et des analyses de classification corroborent les résultats.Cinq groupes de médicaments prescrits pour des problèmes de santé associés à l’environnement ont été retenus. Nous montrons que les distributions spatiales des cinq groups de médicaments sont positivement corrélées entre elles (quelle que soit la maladie, les consommations de médicaments co-varient positivement dans l’espace), mais elles sont indépendantes des conditions environnementales et socio-économiques mesurées à l’échelle des communes. Elles sont même négativement corrélées à la pollution de l’air et aux espaces verts. De façon inattendue, la distribution spatiale suit la frontière linguistique entre la Flandre et la Wallonie. Ceci signifie que les différences observées dépendent de conditions administratives/politiques régionales et donc de politiques de santé, d’écoles de médecine, d’activités commerciales des firmes pharmaceutiques, etc., autant d’éléments extrêmement difficiles à quantifier (pas de données, diversité des acteurs) mais qui devraient être pris en compte dans tout modèle explicatif. Nous en déduisons que si les données de remboursement des prescriptions de médicaments constituent une nouvelle source potentiellement utile, une grande prudence reste de mise quant à l’interprétation de leur variation spatiale et leur lien avec la santé. Este artículo se enmarca en un proyecto de investigación multidisciplinaria enfocada a estudiar la relación entre la salud y el medio ambiente (espacios verdes / azul) y, en particular, explora la variación espacial de los reembolsos en medicamentos recetados en Bélgica. Tales datos se consideraron en un principio como posibles estimadores de la salud y cuyo procesamiento, resultados y análisis se desarrollan a partir de un enfoque esencialmente exploratorio: mapas estadísticos, coeficientes de correlación, ACP y análisis de clasificación. Se seleccionaron cinco grupos de medicamentos recetados por patologías de la salud vinculadas al medio ambiente. Se expresa que a escala comunal las distribuciones espaciales de esto grupos están correlacionadas positivamente entre sí (independiente de la enfermedad, el consumo de estos covaría positivamente en el espacio), pero son independientes de las condiciones ambientales y socioeconómicas, incluso se correlacionan negativamente con la contaminación del aire y áreas verdes. Inesperadamente, la distribución espacial sigue la frontera lingüística entre las regiones Flamenca y Valonia, significando que las diferencias observadas dependen de las condiciones administrativas / políticas regionales y, por tanto, de las políticas de salud, facultades de medicina, estrategias comerciales de las empresas farmacéuticas, etc., Todos elementos extremadamente difíciles de cuantificar (sin datos, diversidad de actores) pero que deberían ser considerados en cualquier modelo explicativo. Deducimos que, si bien los reembolsos de prescripciones de medicamentos son una nueva fuente de datos potencialmente útil, se debe tener elevada precaución al interpretar su variación espacial y vínculo con la salud.

Hayat Bentouhami, Lidia Casas, Joost Weyler University of Antwerp, Social Epidemiology and Health Policy, Wilrijk, 2610, BelgiumCorrespondence: Hayat BentouhamiUniversity of Antwerp, Social Epidemiology and Health Policy, Doornstraat 331, Wilrijk, 2610, BelgiumTel +32 475 33 92 03Email hayat_bentouhami@hotmail.comAbstract: “Theoretical design” comprises the development of an occurrence relation and the specification of the study domain. In explanatory research, the occurrence relation causally relates one determinant to the occurrence (of an event or a state) taking into account other relevant characteristics (confounders and modifiers). Conflicting results in explanatory research might be (partially) explained by differences in the “theoretical design” or by a mismatch between the “theoretical design” and the “design of data collection”. In this critical review, the reporting of “theoretical design” is assessed in articles on the association between early life antibiotic use and the occurrence of asthma. Articles investigating a relationship between early life antibiotic use and the occurrence of asthma were searched in PubMed and systematically selected for critical review. The full text was read and important elements of study design were extracted (the research question/hypothesis, seven key elements of “theoretical design” (measure of occurrence, case (event or state) definition, conceptualization (and operationalization) of the exposure, temporal relation between outcome and exposure, confounders and effect modifiers taken into account and the domain of the study), the method of data collection and the method of data processing). A comparison was made between articles published before and after the publication of the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) statement (2007). Sixty-three articles were included for review. Thirteen articles reported the seven key elements of “theoretical design” that were questioned. No marked differences in reporting were observed pre- and post-STROBE. All articles reported some key elements of “theoretical design”; however, the reporting is not structured and not linked to the concept of “theoretical design”. Conceptualizing, delineating and explicit reporting of “theoretical design” is quintessential for the quality and transparency of explanatory research.Keywords: theoretical study design, occurrence function, etiological research, antibiotic use, asthma

Background Microbial exposures in early childhood direct the development of the immune system and their diversity may influence the risk of allergy development. We aimed to determine whether the indoor microbial diversity at early-life is associated with the development of allergic rhinitis and inhalant atopy. Methods The study population included children within two birth cohorts: Finnish rural-suburban LUKAS (N = 312), and German urban LISA from Munich and Leipzig study centers (N = 248). The indoor microbiota diversity (Chao1 richness and Shannon entropy) was characterized from floor dust samples collected at the child age of 2–3 months by Illumina MiSeq sequencing of bacterial and fungal DNA amplicons. Allergic rhinitis and inhalant atopy were determined at the age of 10 years and analyzed using logistic regression models. Results High bacterial richness (aOR 0.19, 95%CI 0.09–0.42 for middle and aOR 0.12, 95%CI 0.05–0.29 for highest vs. lowest tertile) and Shannon entropy were associated with lower risk of allergic rhinitis in LISA, and similar trend was seen in LUKAS. We observed some significant associations between bacterial and fungal diversity measured and the risk of inhalant atopy, but the associations were inconsistent between the two cohorts. High bacterial diversity tended to be associated with increased risk of inhalant atopy in rural areas, but lower risk in more urban areas. Fungal diversity tended to be associated with increased risk of inhalant atopy only in LISA. Conclusions Our study suggests that a higher bacterial diversity may reduce the risk of allergic rhinitis later in childhood. The environment-dependent heterogeneity in the associations with inhalant atopy – visible here as inconsistent results between two differing cohorts - suggests that specific constituents of the diversity may be relevant.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and a rare complication of pulmonary embolism (PE) [1]. It is characterised by increased pulmonary vascular resistance (PVR), due to unresolved fibro-thrombotic material obstructing large pulmonary arteries, and secondary microvasculopathy. Various factors are suspected to be involved in the pathogenesis and progression of CTEPH, including inflammatory thrombosis, dysregulated fibrinolysis and deficient angiogenesis [2]. The gold standard therapy is a surgical approach, namely pulmonary endarterectomy (PEA), consisting of removal of obstructing fibro-thrombotic material. Although long-term exposure to air pollution might influence several factors potentially contributing to the pathogenesis of CTEPH, including pulmonary and systemic inflammation, pro-thrombotic changes, oxidative stress, endothelial dysfunction and vasoconstriction [3, 4], no study has so far investigated the relationship between air pollution and CTEPH. Interestingly, epidemiologic and translational data supports the plausibility of a link between air pollution exposure, right ventricle failure and pulmonary hypertension (PH) [5–7]. Moreover, exposure to traffic-related air pollution was recently demonstrated being associated with disease severity and impaired survival in pulmonary arterial hypertension (PAH), characterised by progressive occlusion of precapillary arteries [8]. Eventually, a potential role of air pollution as a risk factor for developing venous thromboembolism has been suggested [9]. We consequently hypothesised that exposure to common air pollutants including particles with an aerodynamic diameter less than 2.5 or 10 µm (PM2.5, PM10), nitrogen dioxide (NO2), black carbon (BC) and traffic-related air pollution could influence the progression of CTEPH and interfere with disease outcomes. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Swinnen has nothing to disclose. Conflict of interest: Dr. Bijnens has nothing to disclose. Conflict of interest: Dr. Casas reports grants from Research Foundation Flanders (FWO), outside the submitted work. Conflict of interest: Dr. Nawrot has nothing to disclose. Conflict of interest: Dr. Delcroix reports grants and personal fees from Actelion/J&J, personal fees from Bayer, personal fees from MSD, personal fees from Reata, personal fees from Bellerophon, personal fees from Acceleron, outside the submitted work. Conflict of interest: Dr. Quarck has nothing to disclose. Conflict of interest: Dr. Belge reports personal fees from Actelion/Janssen, personal fees from MSD/Bayer, outside the submitted work.

In previous studies, the strength of the association between childhood asthma and environmental tobacco smoke (ETS) differed depending on the way ETS was assessed and the type of study conducted. We investigated the relationship between asthma occurrence in children and recent exposure to ETS based on an incidence-density study driven by the explicit formulation of a theoretical design. Additionally, we assessed whether the relationship is modified by perinatal ETS exposure and parental inhalation atopy. The event was conceptualized as ‘first doctor’s diagnosis of asthma’. Population time was probed by sampling population moments. Exposure to ETS was conceptualized as recent exposure (1 year prior to diagnosis or at sampling) and perinatal exposure (in utero and/or during the first year of life). Thirty-nine events and 117 population moments were included. There was no indication for effect modification by perinatal exposure to ETS or parental inhalation atopy. After adjustment for confounding, an association was observed between occurrence of a first asthma diagnosis and recent ETS exposure: incidence-density ratio 4.94 (95% confidence interval 1.21, 20.13). Asthma occurrence in children is associated with recent exposure to ETS, and this association seems not to be modified by perinatal ETS exposure or parental inhalation atopy.

Background: The influence of outdoor green space on microbial communities indoors has scarcely been investigated. Here, we study the associations between nearby residential green space and residential indoor microbiota. Methods: We collected settled dust from 176 living rooms of participants of the ENVIRONAGE birth cohort. We performed 16S and ITS amplicon sequencing, and quantitative PCR measurements of total bacterial and fungal loads to calculate bacterial and fungal diversity measures (Chao1 richness, Shannon and Simpson diversity indices) and relative abundance of individual taxa. Green spaces were estimated within 50m and 100m buffers around the residential address. We defined total residential green space using high-resolution land-cover data, further stratified in low-growing (height3m). We used land-use data to calculate the residential nature. We ran linear regression models, adjusting for confounders and other potential determinants. Results are expressed as units change for an interquartile range (IQR) increase in residential green space and their 95% confidence intervals (CI). Results: After adjustment, we observed statistically significant associations between the indoor microbial diversity indices and nearby residential green space. For bacteria, the Shannon index was directly associated with residential nature (e.g. 0.08 units increase (CI:0.02,0.13) per IQR increase in nature within a 50m buffer). Fungal diversity was directly associated with high-growing residential green and inversely with low-growing green. For example, an IQR increase in high-growing green within a 50m buffer was associated with increases in 0.14 (CI:0.01,0.27) and 0.02 (CI:0.008,0.04) units in the Shannon and Simpson indices, respectively. Conclusions: Nearby green space determines the diversity of indoor environment microbiota, and the type of green differently impacts bacterial and fungal diversity. Further research is needed to investigate in more detail possible microbial taxa compositions underlying the observed changes in indoor microbiota diversity and to explore their contribution to beneficial health effects associated with green space exposure.

Background and objectives: Previous studies have suggested that air pollution is associated with depression and anxiety symptoms. Here, we investigate the association between personal exposure to NO2 and perceived stress and mood in a panel of healthy elderly persons. Methods: In a one-year panel study, we included 20 healthy volunteers (10 male-female couples aged 58-76 years) with air pollution and health parameters measured every two months (120 observations). We measured personal exposure to NO2 in the previous 5 days, perceived stress using the Perceived Stress Scale (PSS) and positive and negative affect with the Positive and Negative Affect Schedule (PANAS). We used linear and Poisson mixed models to evaluate the associations between the health outcomes and NO2 adjusted for age, sex, temperature in the previous 5 days, sunlight in the previous day and physical activity (daily average number of steps on the previous week). Also, the interaction terms between NO2 and physical activity were tested. We report % changes for PSS scores and unit changes (beta) for positive and negative affect, and their 95% confidence intervals (CI), for changes in 10 mu g/m(3) of NO2. Results: After adjustment, an increase by 10 mu g/m(3) in NO2 concentrations was associated with a decrease of 1.3 points in the positive affect (95% CI -2.49 to - 0.17) and an increase of 0.11 points in the negative affect (95% CI 0.02 to 0.20). The association with positive affect was stronger when physical activity was below median value of 9,362 steps per day (beta = -2.68; CI: 4.87 to - 0.49); p-value for interaction was 0.08. No statistically significant associations were observed with perceived stress. Conclusion: Short-term exposure to air pollution may produce non-pathological alterations in mood in healthy elderly population.

Background: Wheezing among children below the age of six (pre-schoolers) is common and often triggered by environmental factors. Moreover, evidence on which to base recommendations for its management is limited, resulting in high numbers of prescriptions and costs. This study aims to describe the spatial differences in asthma medication sales for children aged 0 to 5 years in Belgium, and to evaluate the correlations with socio-economic and environmental factors.. Methods: This ecological study includes information on prescribed and sold asthma medication (R03 ATC code) for all the pre-schoolers registered in Belgium, aggregated at the municipality and smaller administrative levels, in 2014. A case was defined as a pre-schooler having purchased prescribed R03 medication at least once in 2014. We mapped the number of cases, the prevalence of medication purchase (n cases/n registered pre-schoolers) and the costs per case (€) at different administrative levels. We used symbol maps for the number of cases and choropleth maps for prevalence and costs per case using Jenks discretization at the municipal level, and standard deviation at finer scales. Finally, we calculated Pearson correlations of medication prevalence and costs per case with socio-economic (population density and area median income), and environmental (PM10, pig density and green spaces) factors. Results: The number of medication purchases was large in cities. The prevalence of purchase was higher in the French- than in the Flemish-speaking region, showing a sharp linguistic border. The cost per case was concentrated in one specific region in the north-west of Belgium. We found inverse correlations of prevalence of purchase with area median income and PM10 concentrations, and positive moderate correlations with green spaces and pig density. The costs per case were weakly but positively correlated with PM10 concentrations and green spaces, and moderately with pig density. Conclusions: In Belgium, the geographical distribution of purchases of prescribed asthma medication for pre-schoolers is only weakly correlated with some environmental factors. The existence of clear differences in prevalence of purchase between Flemish and French-speaking regions suggests that the observed geographical distribution is strongly driven by regional differences in medical practice. This work was funded by the Belgian Science Policy Office (BELSPO), grant number: BR/143/A3/GRESP-HEALTH. Lidia Casas is recipient of a post-doctoral fellowship of the Research Foundation Flanders (FWO), grant number 12I1517N. The authors acknowledge the Intermutualistisch Agentschap - Agence Inter-Mutualiste (IMA-AIM) for providing the health data.

Background: Living in green environments has been associated with various health benefits, but the evidence for positive effects on respiratory health in children is ambiguous. Objective: To investigate if residential exposure to different types of green space is associated with childhood asthma prevalence in Belgium. Methods: Asthma prevalence was estimated from sales data of reimbursed medication for obstructive airway disease (OAD) prescribed to children between 2010 and 2014, aggregated at census tract level (n = 1872) by sex and age group (6–12 and 13–18 years). Generalized log-linear mixed effects models with repeated measures were used to estimate effects of relative covers of forest, grassland and garden in the census tract of the residence on OAD medication sales. Models were adjusted for air pollution (PM10), housing quality and administrative region. Results: Consistent associations between OAD medication sales and relative covers of grassland and garden were observed (unadjusted parameter estimates per IQR increase of relative cover, range across four strata: grassland, β = 0.15–0.17; garden, β = 0.13–0.17). The associations remained significant after adjusting for housing quality and chronic air pollution (adjusted parameter estimates per IQR increase of relative cover, range across four strata: grassland, β = 0.10–0.14; garden, β = 0.07–0.09). There was no association between OAD medication sales and forest cover. Conclusions: Based on aggregated data, we found that living in close proximity to areas with high grass cover (grasslands, but also residential gardens) may negatively impact child respiratory health. Potential allergic and non-allergic mechanisms that underlie this association include elevated exposure to grass pollen and fungi and reduced exposure to environmental biodiversity. Reducing the dominance of grass in public and private green space might be beneficial to reduce the childhood asthma burden and may simultaneously improve the ecological value of urban green space. All health data were anonymized by aggregation to census tract level and were used under license of IMA-AIM. The protocol for this study did not require ethics approval. ispartof: Environmental Research vol:189 ispartof: location:Netherlands status: published

Background Short-term exposure to ambient air pollution triggers acute cardiovascular events. Here, we evaluate the association of exposure to ambient air pollution with two intermediate cardiovascular endpoints: blood pressure and carotid stiffness. Methods In a one-year panel study, we included 20 healthy volunteers (10 male-female couples aged 59–75 years) with air pollution and health parameters measured every two months at their region of residence (Leuven, Belgium) and twice during two ten-day periods in two locations, one with higher (Milan, Italy) and one with lower (Vindeln, Sweden) air pollution levels (220 observations). We measured blood pressure, carotid arterial stiffness, personal exposure to NO2, and ambient concentrations of PM10, PM2.5, and NO2. We used linear mixed models to evaluate the associations between the health outcomes and the air pollutants. Results Compared with Leuven, exposure to pollutants was higher in Milan and lower in Vindeln, with the highest contrast for NO2 (median 20.7 μg/m3 (IQR:7.4) vs 65.1 μg/m3 (9.0) and 4.5 mg/m3 (0.8), respectively). We did not observe significant associations between either systolic or diastolic blood pressure and variations in air pollution. However, we found significant associations between arterial stiffness and 5 day average exposure to the studied pollutants. The strongest associations were observed for PM10 with carotid distensibility (DC) and compliance (CC) coefficients, and the young elastic modulus (YEM): 4.3% (95%CI:7.0;1.5) increase in DC, 4.7% (95%CI:7.1;2.3) increase in CC and 4.2% (95%CI:1.1;7.3) decrease in YEM for each 10 μg/m3 decreases in PM10. Conclusions Our study suggests that short-term exposure to air pollution results in reductions in carotid elasticity among elderly population. Electronic supplementary material The online version of this article (10.1186/s12940-018-0425-7) contains supplementary material, which is available to authorized users.

Background and Purpose— Epidemiological studies suggest an association between stroke incidence and stroke mortality and long-term exposure to particulate matter (PM) air pollution. However, the magnitude of the association is still unclear. Methods— We searched the Pubmed citation database for epidemiological studies and reviews on stroke and PM exposure. Then, we carried out a meta-analysis to quantify the pooled association between stroke incidence and mortality and long-term exposure to PM. Meta-analyses were performed for stroke events and stroke mortality and for PM 10 and PM 2.5 separately and jointly. Results— We identified 20 studies, including a total of >10 million people, on long-term PM exposure and stroke event or stroke mortality. For exposure to PM 10 (including estimated exposure to PM 10 from studies using PM 2.5 ), the pooled hazard ratio for each 10-μg/m 3 increment in PM 10 was 1.061 (95% confidence interval, 1.018–1.105) and 1.080 (0.992–1.177) for overall stroke events and stroke mortality, respectively. A stratified analysis by continent revealed that the association between stroke and long-term PM 10 exposure was positive in North America (1.062 [1.015–1.110]) and Europe (1.057 [0.973–1.148]), but studies in Asia (1.010 [0.885–1.153]) showed a high degree of heterogeneity. Considering exposure to PM 2.5 (Europe and North America combined), the hazard ratios for a 5-μg/m 3 increment were 1.064 (1.021–1.109) and 1.125 (1.007–1.256) for stroke events and mortality, respectively. Conclusions— The scientific evidence of the past decade identifies long-term exposure to PM, and PM 2.5 in particular, as a risk factor for stroke. However, we found some currently unexplained geographical variability in this association.

Developmental exposure to phthalates may be associated with adverse health outcomes but information on the variability and predictors of urinary phthalate metabolite concentrations during pregnancy is limited. We evaluated in Spanish pregnant women (n=391) the reproducibility of urinary phthalate metabolite concentrations and predictors of exposure. We measured mono-(4-methyl-7-hydroxyoctyl) phthalate (7-OHMMeOP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-carboxyhexyl) phthalate (MCMHP), mono-benzyl phthalate (MBzP), monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) in two spot urine samples collected in the first and third pregnancy trimesters. Questionnaires on predictors and food-frequency questionnaires were administered in the first and/or third pregnancy trimesters. Using creatinine-adjusted phthalate metabolite concentrations (log(10)-trasformed) we calculated intraclass correlation coefficients (ICCs). Linear mixed and regression models assessed the associations between predictors and phthalate metabolites. The ICCs ranged from 0.24 to 0.07 and were higher for MBzP, MEP, MiBP, and lower for MEOHP and MEHHP. Overweight, lower education and social class, and less frequent consumption of organic food were associated with higher levels of some phthalate metabolites. The use of household cleaning products (bleach, ammonia, glass cleaners, oven cleaning sprays and degreasing products) at least once per week during pregnancy was associated with 10-44% higher urinary phthalate metabolites. Bottled-water consumption, consumption of food groups usually stored in plastic containers or cans, use of plastic containers for heating food and cosmetic use were not associated with increased concentrations of phthalate metabolites. This large study with repeated phthalate measurements suggests that, in this Spanish setting, sociodemographic and lifestyle factors and household cleaning product use are better predictors of phthalate exposure levels in pregnant women than average water and food consumption and use of plastic containers and cosmetics. (C) 2014 Elsevier GmbH. All rights reserved.

Microbial exposures in homes of asthmatic adults have been rarely investigated; specificities and implications for respiratory health are not well understood. The objectives of this study were to investigate associations of microbial levels with asthma status, asthma symptoms, bronchial hyperresponsiveness (BHR), and atopy. Mattress dust samples of 199 asthmatics and 198 control subjects from 7 European countries participating in the European Community Respiratory Health Survey II study were analyzed for fungal and bacterial cell wall components and individual taxa. We observed trends for protective associations of higher levels of mostly bacterial markers. Increased levels of muramic acid, a cell wall component predominant in Gram-positive bacteria, tended to be inversely associated with asthma (OR's for different quartiles: II 0.71 [0.39-1.30], III 0.44 [0.23-0.82], and IV 0.60 [0.31-1.18] P for trend .07) and with asthma score (P for trend .06) and with atopy (P for trend .02). These associations were more pronounced in northern Europe. This study among adults across Europe supports a potential protective effect of Gram-positive bacteria in mattress dust and points out that this may be more pronounced in areas where microbial exposure levels are generally lower.

Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation.A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays.15 out of 37 bands detected with DGGE, which had at least a suggestive association (pClostridiumcluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22–0.84) for the fourthversusfirst quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used.In this large international study, the level ofClostridiumcluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies.

In addition to underlying health disorders and socio-economic or community factors, air pollution may trigger suicide mortality. This study evaluates the association between short-term variation in air pollution and 10 years of suicide mortality in Belgium. In a bidirectional time-stratified case-crossover design, 20,533 suicide deaths registered between January 1st 2002 and December 31st 2011 were matched by temperature with control days from the same month and year. We used municipality-level air pollution [particulate matter (PM10) and O-3 concentrations] data and meteorology data. We applied conditional logistic regression models adjusted for duration of sunshine and day of the week to obtain odds ratios (OR) and their 95% CI for an increase of 10 mu g/m(3) in pollutant concentrations over different lag periods (lag 0, 0-1, 0-2, 0-3, 0-4, 0-5, and 0-6 days). Effect modification by season and age was investigated by including interaction terms. We observed significant associations of PM10 and O-3 with suicide during summer (OR ranging from 1.02 to 1.07, p-values = 85 years old (e.g. lag 0-4: OR = 1.17; 95% CI: 1.06-1.29). Recent increases in outdoor air pollutants such as PM10 or O-3 can trigger suicide, particularly during warm periods, even at concentrations below the European thresholds. Furthermore, PM10 may have strong trigger effects among children and elderly population. This work was funded by the Belgian Science Policy Office (BELSPO), Grant Number: BR/143/A3/GRESP-HEALTH. Lidia Casas and Bianca Cox are recipients of post-doctoral fellowships of the Research Foundation Flanders (FWO), Grant Numbers 12I1517N and 12Q0517N, respectively.

Exposure to biocontaminants is associated with behavioural problems and poorer cognitive function. Our study assesses the associations between early life exposure to home dampness, pets and farm animal contact and cognitive function and social competences in 4-year old children, and the associations between these indoor factors and microbial compounds (bacterial endotoxin and fungal extracellular polysaccharides). A Spanish population-based birth-cohort enrolled 482 children, and 424 of them underwent psychometric testing at 4 years of age, including the McCarthy Scales of Child Abilities (MSCA) and the California Preschool Social Competence Scale (CPSCS). Information on pet ownership, farm animal contact and home dampness was periodically reported by the parents through questionnaires. Microbial compounds were measured in living room sofa dust collected at the age of 3 months. Persistent home dampness during early life significantly decreased the general score of MSCA by 4.9 points (95% CI: -8.9; -0.8), and it decreased the CPSCS by 6.5 points (95% Cl: -12.2; -0.9) in the child's bedroom. Cat or dog ownership were not associated with the outcomes, but occasional farm animal contact increased the general cognitive score of MSCA by 5.6 points (95% CI: 1.8; 9.3). Cat and dog ownership were associated with higher levels of endotoxins in home dust. None of the measured microbial compounds were related with the psychometric tests scores. In conclusion, damp housing in early life may have adverse effects on neuropsychological development at 4 years old. More research is needed to explore the possible involvement of mycotoxins in the observed results. (C) 2013 Elsevier GmbH. All rights reserved.

UNLABELLED Early-life exposure to microbial agents may play a protective role in asthma and allergies development. Geographical differences in the prevalence of these diseases exist, but the differences in early-life indoor microbial agent levels and their determinants have been hardly studied. We aimed to describe the early-life levels of endotoxin, extracellular polysaccharides (EPS), and β(1-3)-glucans in living room dust of four geographically spread European birth cohorts (LISA in Germany, PIAMA in the Netherlands, INMA in Spain, and LUKAS2 in Finland) and to assess their determinants. A total of 1572 dust samples from living rooms of participants were analyzed for endotoxin, Penicillium/Aspergillus EPS, and β(1-3)-glucans. Information on potential determinants was obtained through questionnaires. Concentrations of endotoxin, EPS, and β(1-3)-glucans were different across cohorts. Concentrations of endotoxin and EPS were respectively lower and higher in INMA than in other cohorts, while glucans were higher in LUKAS2. Season of sampling, dog ownership, dampness, and the number of people living at home were significantly associated with concentrations of at least one microbial agent, with heterogeneity of effect estimates of the determinants across cohorts. In conclusion, both early-life microbial exposure levels and exposure determinants differ across cohorts derived from diverse European countries. PRACTICAL IMPLICATIONS This study adds evidence of variability in the levels of indoor endotoxin, extracellular polysaccharide, and β(1-3)-glucans across four geographically spread European regions. Furthermore, we observed heterogeneity across regions in the effect of exposure determinants. We hypothesize that the variations observed in our study may play a role in the differences in asthma and allergies prevalences across countries.

Asthma is a complex entity and one of the most common disorders in the world, affecting much of the workforce [1]. Asthma prevalence in children and adults has shown an increasing trend in the last decades [2], [3], which makes this disorder a major public health concern. Nevertheless, the mechanisms for the high incidence are not yet completely understood. In this regard, epidemiological studies focused on occupational asthma may contribute to unravelling the complexity of the disorder and the agents related to its onset and development. Work-related asthma has been classified as comprising two main entities: sensitiser-induced asthma and irritant-induced asthma (IIA) [4]. The first involves a specific immunological response to a workplace sensitiser. These sensitisers are high-molecular-weight agents acting via the production of specific IgE antibodies or low-molecular-weight chemicals acting via other, hitherto less clarified immunological pathways [5]–[8]. The term IIA refers to asthma caused by exposure to agents that, when inhaled, act as respiratory irritants in the absence of sensitisation [9], [10]. In the 1980s, Brooks et al. [11] described reactive airway dysfunction syndrome. This diagnosis required very strict criteria that restricted the syndrome to the onset of asthma-like symptoms within 24 h after a single, very high exposure to an irritant agent. However, further studies suggested that repeated exposure to lower levels of irritants may also play a role in the onset …

Background: Exposure to indoor allergens during early life may play a role in the development of the immune system and inception of asthma. Objective: To describe the house dust mite (HDM) allergen concentrations in bedroom dust during early life and to evaluate its associations with HDM sensitization, wheezing, and asthma, from birth to school age, in 5 geographically spread European birth cohorts. Methods: We included 4334 children from INMA-Menorca (Spain), BAMSE (Sweden), LISAplus and MAS (Germany), and PIAMA-NHS (the Netherlands). Dust samples were collected from bedrooms during early life and analyzed for Dermatophagoides pteronyssinus (Der p1) and Dermatophagoides farinae (Der f1). HDM concentrations were divided into four categories. Sensitization was determined by specific IgE. Wheezing and asthma information up to 8/10 years was collected through questionnaires. We performed mixed-effects logistic regression models and expressed associations as odds ratios with 95% confidence intervals. Results: House dust mite concentrations varied across cohorts. Mean allergen concentrations were highest in INMA-Menorca (geometric mean (GM) Der p1 = 3.3 μg/g) and LISAplus (GM Der f1 = 2.1 μg/g) and lowest in BAMSE (GM Der p1 = 0.1 μg/g, Der f1 = 0.3 μg/g). Moderate and high HDM concentrations were significantly (P-values < 0.05) associated with 50-90% higher prevalence of HDM sensitization. No significant associations were observed with respiratory outcomes. Conclusion: Our study based on geographically spread regions, a large sample size, and a wide range of allergen concentration shows that HDM allergen concentrations vary across regions and that exposure during early life plays a role in the development of allergic sensitization but not in the development of respiratory outcomes.

To evaluate the effects of household use of cleaning products during pregnancy on infant wheezing and lower respiratory tract infections (LRTI). In four prospective Spanish birth cohorts (n = 2,292), pregnant women reported the use of household cleaning products. When infants were 12-18 months old, current cleaning product use and infant's wheezing and LRTI were reported. Cohort-specific associations between the use of specific products and respiratory outcomes were evaluated using multivariable regression analyses and estimates were combined using random-effects meta-analyses. The period prevalence of LRTI was higher when sprays (combined odds ratio (OR) = 1.29; 95 % confidence interval (CI) 1.04-1.59) or air fresheners (OR = 1.29; CI 1.03-1.63) were used during pregnancy. The odds of wheezing increased with spray (OR = 1.37; CI 1.10-1.69) and solvent (OR = 1.30; CI 1.03-1.62) use. The associations between spray and air freshener use during pregnancy and both outcomes remained apparent when these products were not used after pregnancy. Nevertheless, the estimates were higher when post-natal exposure was included. The use of cleaning sprays, air fresheners and solvents during pregnancy may increase the risk of wheezing and infections in the offspring.

Background: Inflammation is a key factor in the pathogenesis of respiratory diseases. Early life exposure to microbial agents may have an effect on the development of the immune system and on respiratory health later in life. In the present work we aimed to evaluate the associations between early life microbial exposures, and fractional exhaled nitric oxide (FeNO) at school age. Methods: Endotoxin, extracellular polysaccharides (EPS) and beta(1,3)-D-glucan were measured in living room dust collected at 2-3 months of age in homes of participants of three prospective European birth cohorts (LISA, n = 182; PIAMA, n = 244; and INMA, n = 355). Home dampness and pet ownership were periodically reported by the parents through questionnaires. FeNO was measured at age 8 for PIAMA and at age 10/11 for LISA and INMA. Cohort-specific associations between the indoor microbial exposures and FeNO were evaluated using multivariable regression analyses. Estimates were combined using random-effects meta-analyses. Results: FeNO at school age was lower in children exposed to endotoxin at age 2-3 months (beta-0.05, 95% confidence interval (CI) -0.10;-0.01) and in children with reported dog ownership during the first two years of life (GM ratio 0.82, CI 0.70-0.96). FeNO was not significantly associated with early life exposure to EPS, beta(1,3)-D-glucan, indoor dampness and cat ownership. Conclusion: Early life exposure to bacterial endotoxin and early life dog ownership are associated with lower FeNO at school age. Further studies are needed to confirm our results and to unravel the underlying mechanisms and possible clinical relevance of this finding., This work was supported by the European Commission as part of HITEA (Health Effects of Indoor Pollutants: Integrating microbial, toxicological and epidemiological approaches), Grant agreement no. 211488 under the Seventh Framework Programme, Topic ENV.2007.1.2.1.1. Indoor air pollution in Europe: An emerging environmental health issue.r The LISAplus study was funded by the BMBF (Federal Ministry of Education and Research), the Helmholtz Center Munich and the UFZ Leipzig. The PIAMA study is supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; The Netherlands Asthma Fund; The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport. The INMA-Menorca study was funded by Fondo de Investigacion Sanitaria, ISCIII, Ministerio de Sanidad y Servicios Sociales, Spain (Grants 97/0588, 00/0021-2, G03/176, PI061756 and PS0901958), EC Contract QLK4-CT-2000-00263 and Fundacio Roger Torne (Barcelona, Spain).

FRAX is a fracture risk assessment tool to estimate the 10-yr probability of a major osteoporotic fracture or a hip fracture. The aim of the study was to assess the predictive ability of FRAX for major osteoporotic fracture in a cohort of Spanish women. The study was based on a retrospective cohort of women aged 40-90 yr. Patients were followed from their first bone densitometry to the first major osteoporotic fracture event (forearm, proximal humerus, clinical spine, or hip fracture) or for 10 yr whichever comes first. A total of 1231 women were included. Bone mineral density data and self-reported data on risk factors for fracture were obtained. The predictive ability Of FRAX was assessed by analyzing calibration and discrimination, with the calculation of observed-to-expected (O/E) fracture ratios and the receiver operating characteristic (ROC) curve, respectively. A total of 222 women (18.1%) reported at least 1 fracture after the first assessment. The incidence of fracture was 14 (95% confidence interval [CI]: 10-17), 19 (95% CI: 15-23), 28 (95% CI: 21-36), and 67 (95% CI: 8-125) cases per 1000 woman-years in women aged 75 yr, respectively. The O/E ratio was 3.9 (95% CI: 3.4-4.5; p < 0.0001). The area under the ROC curve was 61% (95% CI: 57-65%). FRAX underestimated the risk of major osteoporotic fracture in this cohort of Spanish women, particularly in those with a low risk of fracture according to the clinical factors used in the FRAX tool. Our findings highlight the need for validation studies of FRAX in Spain.

Indoor microbial agents exposure is associated to depressive symptoms in adults and persistent exposure to indoor mould is associated to poorer cognitive function in children. In our study, we aimed to assess the effects of the exposure to indoor factors associated with increased microbial exposure (mould, dampness and pets) on behavioural problems in children aged 10 years, participating in two German birth cohorts. A total of 4860 children were followed until the age of 10 years, and the strengths and difficulties questionnaire (SDQ) was administered to the parents. Indoor factors were assessed through parental reported questionnaires in periodical surveys. Logistic and multinomial regressions adjusting for potential confounders were performed. Prevalences of borderline/abnormal total scores in the SDQ at 10 years of age were higher in children exposed to mould (aOR = 1.23, 95%CI = 1.00-1.56), dampness (aOR = 1.51, 95%CI = 1.10-2.07), and pets (aOR = 1.48, 95%CI = 1.20-1.94). The dimension "emotional symptoms" showed statistically significant risk estimates for mould and pets, meanwhile "conduct problems" and "hyperactivity/inattention" dimensions only did for pets. No significant associations were found for the "peer relationship problems" dimension. We found a significant strong interaction between dampness and pet, the risk of borderline/abnormal scores in the "total difficulties" scale and the "emotional symptoms" dimension for pets' was at least twice the risk in children with reported dampness than in children without. Our findings point to a potential effect of microbial exposure on children's behavioural problems, especially on emotional disorders, probably mediated through neurotoxicity and immune system activation. (C) 2012 Elsevier GmbH. All rights reserved.