Search

Early-life indoor bacterial exposure is associated with the risk of asthma, but the roles of specific bacterial genera are poorly understood. We sought to determine whether individual bacterial genera in indoor microbiota predict the development of asthma. Dust samples from living rooms were collected at 2 months of age. The dust microbiota was characterized by using Illumina MiSeq sequencing amplicons of the bacterial 16S ribosomal RNA gene. Children (n = 373) were followed up for ever asthma until the age of 10.5 years. Richness was inversely associated with asthma after adjustments (P =.03). The phylogenetic microbiota composition in asthmatics patients' homes was characteristically different from that in nonasthmatic subjects' homes (P =.02, weighted UniFrac, adjusted association, permutational multivariate analysis of variance, PERMANOVA-S). The first 2 axis scores of principal coordinate analysis of the weighted UniFrac distance matrix were inversely associated with asthma. Of 658 genera detected in the dust samples, the relative abundances of 41 genera correlated (r > |0.4|) with one of these axes. Lactococcus genus was a risk factor for asthma (adjusted odds ratio, 1.36 [95% CI, 1.13-1.63] per interquartile range change). The abundance of 12 bacterial genera (mostly from the Actinomycetales order) was associated with lower asthma risk (P <.10), although not independently of each other. The sum relative abundance of these 12 intercorrelated genera was significantly protective and explained the majority of the association of richness with less asthma. Our data confirm that phylogenetic differences in the microbiota of infants' homes are associated with subsequent asthma risk and suggest that communities of selected bacteria are more strongly linked to asthma protection than individual bacterial taxa or mere richness. [ABSTRACT FROM AUTHOR]

The contamination levels and patterns of perfluoroalkyl acids (PFAAs) and their precursors in indoor air of children's bedrooms in Finland, Northern Europe, were investigated. Our study is among the most comprehensive indoor air monitoring studies (n = 57) and to our knowledge the first one to analyse air in children's bedrooms for PFASs (17 PFAAs and 9 precursors, including two acrylates, 6:2 FTAC and 6:2 FTMAC). The most frequently detected compound was 8:2 fluorotelomer alcohol (8:2 FTOH) with the highest median concentration (3570 pg/m 3 ). FTOH concentrations were generally similar to previous studies, indicating that in 2014/2015 the impact of the industrial transition had been minor on FTOH levels in indoor air. However, in contrast to earlier studies (with one exception), median concentrations of 6:2 FTOH were higher than 10:2 FTOH. The C8 PFAAs are still the most abundant acids, even though they have now been phased out by major manufacturers. The mean concentrations of FOSE/As, especially MeFOSE (89.9 pg/m 3 ), were at least an order of magnitude lower compared to previous studies. Collectively the comparison of FTOHs, PFAAs and FOSE/FOSAs with previous studies indicates that indoor air levels of PFASs display a time lag to changes in production of several years. This is the first indoor air study investigating 6:2 FTMAC, which was frequently detected (58%) and displayed some of the highest maximum concentrations (13 000 pg/m 3 ). There were several statistically significant correlations between particular house and room characteristics and PFAS concentrations, most interestingly higher EtFOSE air concentrations in rooms with plastic floors compared to wood or laminate. [ABSTRACT FROM AUTHOR]

Background: Recently, the bacterial diversity of the intestinal flora and the diversity of various environmental factors during infancy have been linked to the development of allergies in childhood. Food is an important environmental exposure, but the role of food diversity in the development of asthma and allergies in childhood is poorly defined. Objective: We studied the associations between food diversity during the first year of life and the development of asthma and allergies by age 5 years. Methods: In a Finnish birth cohort we analyzed data on 3142 consecutively born children. We studied food diversity at 3, 4, 6, and 12 months of age. Asthma, wheeze, atopic eczema, and allergic rhinitis were measured by using the International Study of Asthma and Allergies in Childhood questionnaire at age 5 years. Results: By 3 and 4 months of age, food diversity was not associated with any of the allergic end points. By 6 months of age, less food diversity was associated with increased risk of allergic rhinitis but not with the other end points. By 12 months of age, less food diversity was associated with increased risk of any asthma, atopic asthma, wheeze, and allergic rhinitis. Conclusion: Less food diversity during the first year of life might increase the risk of asthma and allergies in childhood. The mechanisms for this association are unclear, but increased dietary antigen exposure might contribute to this link. [Copyright &y& Elsevier]

Background: Emerging evidence questions current recommendations on the timing of infant feeding for the prevention of childhood allergies. The evidence for asthma is inconclusive. Objective: We sought to investigate the associations between the duration of breast-feeding and timing of introduction of complementary foods and the development of asthma and allergies by the age of 5 years. Methods: Data were analyzed for 3781 consecutively born children. The dietary exposures were categorized into thirds and analyzed as time-dependent variables. Asthma, allergic rhinitis, and atopic eczema end points were assessed by using the International Study of Asthma and Allergies in Childhood questionnaire, whereas IgE antibodies were analyzed from serum samples at the age of 5 years. Cox proportional hazard and logistic regressions were used for the analyses. Results: The median duration of exclusive and total breast-feeding was 1.4 months (interquartile range, 0.2-3.5 months) and 7.0 months (interquartile range, 4.0-11.0 months), respectively. Total breast-feeding of 9.5 months or less was associated with an increased risk of nonatopic asthma. Introduction of wheat, rye, oats, or barley at 5 to 5.5 months was inversely associated with asthma and allergic rhinitis, whereas introduction of other cereals at less than 4.5 months increased the risk of atopic eczema. Introduction of egg at 11 months or less was inversely associated with asthma, allergic rhinitis, and atopic sensitization, whereas introduction of fish at 9 months or less was inversely associated with allergic rhinitis and atopic sensitization. Conclusion: Early introduction of wheat, rye, oats, and barley cereals; fish; and egg (respective to the timing of introduction of each food) seems to decrease the risk of asthma, allergic rhinitis, and atopic sensitization in childhood. Longer duration of total breast-feeding, rather than its exclusivity, was protective against the development of nonatopic but not atopic asthma, suggesting a potential differing effect of breast-feeding on different asthma phenotypes. [Copyright &y& Elsevier]

Background: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. Objective: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Method: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Results: Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P grass = 1.6 × 10−9; P AR = 8.0 × 10−3). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P grass = 9.4 × 10−9; P AR = 3.8 × 10−8). The third genome-wide significant variant was rs17513503 (Pgrass = 1.2 × 10−8; PAR = 7.4 × 10−7) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. Conclusions: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. [ABSTRACT FROM AUTHOR]

Background: Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life. Objective: We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring. Methods: Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990–1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests. Results: Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56–13.0]; OR, 2.53 [95% CI, 1.19–5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44–22.03]; OR, 3.37 [95% CI, 1.46–7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring. Conclusion: The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children [Copyright &y& Elsevier]

Background: It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants. Objective: To investigate the relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences. Methods: As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-γ, IL-10, and TNF-α. Results: Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen''s egg, cow''s milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-γ production, but not with IL-5 and IL-10. Conclusion: Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-γ production. [Copyright &y& Elsevier]

Background: Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age. Objective: We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort. Methods: Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers. Results: Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow''s milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood. Conclusions: Maternal exposure during pregnancy influences atopic sensitization patterns in cord blood. The (microbial) context of allergen contact possibly modifies the risk of atopic sensitization. [Copyright &y& Elsevier]

Abstract: Background and Objective: When estimating incidence risk ratios in follow-up studies, subjects testing positive for the disease at baseline are excluded. Although the effect of disease misclassification on estimated incidence risk ratios has otherwise been extensively explored, the effect of disease misclassification at baseline has not previously been analyzed. Study Design and Setting: The design was theoretical calculations assuming dichotomous disease and a follow-up study with a baseline and a follow-up examination, analyzed using cumulative incidence. Calculations consider nondifferential misclassification of disease mainly at baseline, but no misclassification of exposure. Results: Nondifferential misclassification of disease at baseline can lead to bias either away or toward null in estimated cumulative incidence risk ratios. This bias is mainly a function of sensitivity at baseline, because imperfect sensitivity leads to failure to exclude all diseased subjects from the follow-up. Imperfect specificity at baseline has less effect. Bias is increased with high true prevalence of disease and low true incidence. Bias is also increased with large differences in true risk ratios at baseline and at follow-up, because observed incidence risk ratios in the presence of misclassification reflect both the true association at baseline and at follow-up. Conclusion: Nondifferential disease misclassification at baseline examination of a follow-up study can lead to over- or underestimation of the cumulative incidence risk ratios. The bias can be substantial for disease with low incidence and high prevalence, such as asthma or myocardial infarction. The results underscore the need to select a highly sensitive test for disease at baseline to exclude all diseased subjects from the follow-up. [Copyright &y& Elsevier]

Background: Exposure to environmental microbes in early life might lead to type 1-skewed T cell responses and therefore reduce the risk of allergic diseases. Objective: To investigate whether the cytokine responses at birth and at age 3 months are associated with environmental factors, especially exposure to microbes. Living in a farm, level of house dust endotoxin, cleanliness of the home, and presence of cats and dogs in the household were studied as possible determinants of cytokine production. Methods: Twelve farmers'' and 17 nonfarmers'' children were studied. Production of IL-4, IL-6, TNF-α, and IFN-γ in cord blood and in peripheral blood at 3 months was measured after 8-hour and 24-hour stimulation with phorbol ester plus concanavalin A. Results: IFN-γ responses at age 3 months were associated with farming (median, 53 vs 17 pg/mL; P = .019) and cats and dogs (49 vs 14 pg/mL; P = .014) (8 hours). Change in IFN-γ–producing capacity from birth to 3 months was larger in children with higher than median endotoxin concentration in bed dust (P = .038) and in children with a cat or dog (P = .005) (8 hours). Increased IL-6 responses at birth were associated with cat or dog exposure (P = .004; 8 hours) and endotoxin level in settled dust (P = .039; 24 hours). Conclusion: The development of IFN-γ–producing capacity during the first 3 months of life is associated with farming, endotoxin in house dust, and cat and dog exposure. These environmental characteristics may indicate some microbial exposure capable of driving developing immune system toward TH1 responses. [Copyright &y& Elsevier]

Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α–induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection. We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective" farms or LPS. NF-κB signaling–related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P <.05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling–associated gene expression toward an anti-inflammatory state (P <.001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma. Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment. [ABSTRACT FROM AUTHOR]

Background Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. Objective We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Methods Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. Results The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. Conclusions LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function. [ABSTRACT FROM AUTHOR]

Background Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown. Objectives We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect. Methods The Protection Against Allergy—Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the “usually” consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples. Results The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI, 0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of ω-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI, 0.11-0.81). Conclusion Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of ω-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators. [ABSTRACT FROM AUTHOR]

Background Breast-feeding is protective against respiratory infections in early life. Given the co-evolutionary adaptations of humans and cattle, bovine milk might exert similar anti-infective effects in human infants. Objective To study effects of consumption of raw and processed cow's milk on common infections in infants. Methods The PASTURE birth cohort followed 983 infants from rural areas in Austria, Finland, France, Germany, and Switzerland, for the first year of life, covering 37,306 person-weeks. Consumption of different types of cow's milk and occurrence of rhinitis, respiratory tract infections, otitis, and fever were assessed by weekly health diaries. C-reactive protein levels were assessed using blood samples taken at 12 months. Results When contrasted with ultra-heat treated milk, raw milk consumption was inversely associated with occurrence of rhinitis (adjusted odds ratio from longitudinal models [95% CI]: 0.71 [0.54-0.94]), respiratory tract infections (0.77 [0.59-0.99]), otitis (0.14 [0.05-0.42]), and fever (0.69 [0.47-1.01]). Boiled farm milk showed similar but weaker associations. Industrially processed pasteurized milk was inversely associated with fever. Raw farm milk consumption was inversely associated with C-reactive protein levels at 12 months (geometric means ratio [95% CI]: 0.66 [0.45-0.98]). Conclusions Early life consumption of raw cow's milk reduced the risk of manifest respiratory infections and fever by about 30%. If the health hazards of raw milk could be overcome, the public health impact of minimally processed but pathogen-free milk might be enormous, given the high prevalence of respiratory infections in the first year of life and the associated direct and indirect costs. [ABSTRACT FROM AUTHOR]

Background: The role of dietary factors in the development of allergies is a topic of debate, especially the potential associations between infant feeding practices and allergic diseases. Previously, we reported that increased food diversity introduced during the first year of life reduced the risk of atopic dermatitis. Objective: In this study we investigated the association between the introduction of food during the first year of life and the development of asthma, allergic rhinitis, food allergy, or atopic sensitization, taking precautions to address reverse causality. We further analyzed the association between food diversity and gene expression of T-cell markers and of Cε germline transcript, reflecting antibody isotype switching to IgE, measured at 6 years of age. Methods: Eight hundred fifty-six children who participated in a birth cohort study, Protection Against Allergy Study in Rural Environments/EFRAIM, were included. Feeding practices were reported by parents in monthly diaries during the first year of life. Data on environmental factors and allergic diseases were collected from questionnaires administered from birth up to 6 years of age. Results: An increased diversity of complementary food introduced in the first year of life was inversely associated with asthma with a dose-response effect (adjusted odds ratio with each additional food item introduced, 0.74 [95% CI, 0.61-0.89]). A similar effect was observed for food allergy and food sensitization. Furthermore, increased food diversity was significantly associated with an increased expression of forkhead box protein 3 and a decreased expression of Cε germline transcript. Conclusion: An increased diversity of food within the first year of life might have a protective effect on asthma, food allergy, and food sensitization and is associated with increased expression of a marker for regulatory T cells. [Copyright &y& Elsevier]

Background: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+CD25+, FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases. [Copyright &y& Elsevier]

Background: There is conflicting evidence on whether allergen-specific memory is primed prenatally, whether this priming affects persistent immunologic effects, and whether it is modulated by the first environmental exposures in infancy. Objective: We sought to explore the course of atopic sensitization between birth and 12 months of age. Methods: Specific IgE levels for 6 food and 13 common inhalant allergens were assessed in cord blood and 1-year blood samples in the Protection against Allergy–Study in Rural Environments (PASTURE) birth cohort including 793 children from rural regions of 5 European countries. Detailed information on children’s health, nutrition, and farm-related exposures was gathered by using a pregnancy questionnaire, 2 questionnaires at 2 and 12 months of age, and a diary covering the time in between. Results: Sensitization was more common at 12 months of age than at birth for almost all specificities. On an individual level, persistent sensitization to the same allergens was rare (1%), whereas transient (only at birth, 11%) and incident (only at 12 months, 34%) sensitization was seen in substantial proportions of children. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, with the strongest associations for food allergens (odds ratio [OR], 10.6; 95% CI, 6.0-18.6) and the weakest associations for seasonal allergens (OR, 1.64; 95% CI, 0.94-2.86). Associations of maternal sensitization with incident sensitization were also seen. Incident sensitization was related to distinct prenatal and postnatal environmental exposures of mother and child, such as consumption of cereals for incident sensitization to seasonal allergens (OR, 0.66; 95% CI, 0.50-0.88). Conclusion: IgE sensitization patterns change between birth and 12 months and are related to maternal and environmental influences. [Copyright &y& Elsevier]

Soft-tissue sarcoma is one of the few specific tumors thought to be caused by polychlorinated dibenzo- p -dioxins and dibenzofurans (PCDD/Fs) and specifically TCDD. Evidence is, however, based on questionnaire-based case-control studies, and on very few cancer cases in cohort studies at high occupational exposures to chlorophenols or chlorophenoxy acid herbicides with dioxin impurities. Recall bias has been suspected to influence the reporting of exposure, but this possibility has never been adequately put to test. In the present study 87 cancer patients and 308 controls answered a questionnaire asking their exposure to wood preservatives, fungicides and herbicides, and insecticides, and their PCDD/F concentrations were also measured. After matching for age and area 67–69 sarcoma patients and 153–156 controls were available for the study depending on the chemical group, 1–3 controls for each sarcoma patient. Sarcoma patients reported exposure to these chemicals significantly more often than controls did, odds ratios were 6.7 for wood preservatives (p = 0.02), 16 for fungicides and herbicides (p = 0.01), and 4.9 for insecticides (p = 0.06). There was no association, when the analysis was based on measured PCDD/F concentrations (odds ratios close to 1). Although it is not possible to exclude the role of the main chemical as the cause with certainty, the results indicate that recall bias is very likely in previous studies. Thus the causality between contaminant PCDD/Fs and soft tissue sarcoma cannot be considered proven. [ABSTRACT FROM AUTHOR]

Background: There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures. Objective: We sought to determine environmental and nutritional exposures associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child''s life. Methods: For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n = 938) and year 1 (n = 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis. Results: Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers (P for multifactorial multivariate ANOVA = .041), significantly so for TLR7 (adjusted geometric means ratio [aGMR], 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found. Conclusion: Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life. [Copyright &y& Elsevier]

Background: Environmental factors can affect the development of atopic dermatitis, and this was described to be already effective during pregnancy and in early life. An important early postnatal exposure is nutrition, although its association with allergic disease remains unclear. Objective: We sought to determine prospectively whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality. Methods: One thousand forty-one children who participated in the Protection Against Allergy–Study in Rural Environments birth cohort study were included in the current study. Atopic dermatitis was defined by a doctor''s diagnosis reported by the parents of children up to 4 years of age, by questionnaires, and/or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life. Feeding practices were reported by parents in monthly diaries between the 3rd and 12th months of life. Results: The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life (adjusted odds ratio for atopic dermatitis with each additional major food item introduced, 0.76; 95% CI, 0.65-0.88). The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis (adjusted odds ratio, 0.41; 95% CI, 0.23-0.73). Conclusion: As early-life exposure, the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis. [Copyright &y& Elsevier]

Background: Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection. Objectives: To investigate associations between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families. Methods: Supernatants from phorbol 12-myristate 13-acetate/ionomycin–stimulated CB mononuclear cells were assessed for the production of IFN-γ, TNF-α, IL-5, IL-10, and IL-12. Results: Significantly higher levels of IFN-γ and TNF-α in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-γ and TNF-α in umbilical blood. Conclusion: Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth. [Copyright &y& Elsevier]

Background: Markers for microbial groups are commonly measured in house dust samples to assess indoor exposure to microbes in studies on asthma and allergy. However, little is known about the sources of different microbes. A better understanding of the nature and origin of microbes present in the immediate environment of human beings is crucial if one wants to elucidate protective as well as adverse effects on human health. Objective: To determine the extent to which the bacterial composition of mattress and floor dust reflects the presence of the human body in relation to other environmental sources. Methods: House dust and skin surface swab samples of occupants in 4 homes were collected and analyzed for their bacterial content, using a culture-independent methodology. Bacterial sequences analyzed from the different house dusts and skin surface swabs represented random samples of bacteria present in a given sample. Highly similar sequences were grouped to assess biodiversity and to draw conclusions about the sources of bacteria. Results: The bacterial flora in the house dust samples was found to be highly diverse and dominated by gram-positive bacteria. To a considerable extent, the presence of different bacterial groups was attributed to human sources. In the individuals'' mattress dust samples, 69% to 88% of the bacterial sequences analyzed were associated with human origins. The respective percentages for the individual floor dusts ranged from 45% to 55%. Conclusion: Our study indicates that human-derived bacteria account for a large part of the mainly gram-positive bacterial content in house dust. [Copyright &y& Elsevier]

The number of ultrafine particles may be a more health relevant characteristic of ambient particulate matter than the conventionally measured mass. Epidemiological time series studies typically use a central site to characterize human exposure to outdoor air pollution. There is currently very limited information how well measurements at a central site reflect temporal and spatial variation across an urban area for particle number concentrations (PNC). The main objective of the study was to assess the spatial variation of PNC compared to the mass concentration of particles with diameter less than 10 or 2.5μm (PM10 and PM2.5). Continuous measurements of PM10, PM2.5, PNC and soot concentrations were conducted at a central site during October 2002–March 2004 in four cities spread over Europe (Amsterdam, Athens, Birmingham and Helsinki). The same measurements were conducted directly outside 152 homes spread over the metropolitan areas. Each home was monitored during 1 week. We assessed the temporal correlation and the variability of absolute concentrations. For all particle indices, including particle number, temporal correlation of 24-h average concentrations was high. The median correlation for PNC per city ranged between 0.67 and 0.76. For PM2.5 median correlation ranged between 0.79 and 0.98. The median correlation for hourly average PNC was lower (range 0.56–0.66). Absolute concentration levels varied substantially more within cities for PNC and coarse particles than for PM2.5. Measurements at the central site reflected the temporal variation of 24-h average concentrations for all particle indices at the selected homes across the urban area. A central site could not assess absolute concentrations across the urban areas for particle number. [Copyright &y& Elsevier]

The infants of mothers with elevated depressive symptoms (EDS) postpartum appear to be at increased risk of somatic health problems during their first 12 months of life in low- and lower-middle-income countries. However, in higher-income countries, knowledge of this association is scarce. We sought to examine whether maternal reports of infant health problems, adherence to vaccination schedules and analgesic supply to the infant during the first 12 months of life differ between mothers with and without postpartum EDS. Altogether, 969 women who were enrolled in the Kuopio Birth Cohort study (www.kubico.fi) during 2012–2017 were included in this investigation. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale during pregnancy (1st and/or 3rd trimester) and at eight weeks postpartum. Infant health data were collected as a part of a 12-month online follow-up questionnaire for mothers and were based on self-reports of either maternal observations or physician-determined diagnoses. Postpartum EDS were associated with a 2- to 5-fold increased likelihood of abnormal crying and paroxysmal wheezing (based on parental observations), as well as gastroesophageal reflux and food allergy (based on physician-determined diagnoses). Mothers with postpartum EDS also supplied their infants with analgesic medication for longer periods. Adherence to vaccination schedules was similar between the examined groups. In conclusion, infants of mothers with postpartum EDS may be more likely to experience health problems or to be perceived by their mother as having health problems, and thus receive more medications. • Postpartum depressive symptoms associated with somatic infant health conditions. • Associations were independent of depressive symptoms during pregnancy. • Postpartum depressive symptoms associated with infant analgesic consumption. • Postpartum depressive symptoms and vaccination adherence were not associated. [ABSTRACT FROM AUTHOR]

Abstract Objective Peripartum depression (PPD) pertaining to depression in pregnancy and postpartum is one of the most common complications around childbirth with enduring adverse effects on mother and child health. Although psychiatric symptoms may improve or worsen over time, relatively little is known about the course of PPD symptoms and possible fluctuations. Methods We applied a person-centered approach to examine PPD symptom patterns across pregnancy and childbirth. 824 women were assessed at three time points: first trimester (T1), third trimester (T2), and again at eight weeks (T3) postpartum. We assessed PPD symptoms, maternal mental health history, and childbirth variables. Results Growth mixture modeling (GMM) analysis revealed four discrete PPD symptom trajectory classes including chronic PPD (1.1%), delayed (10.2%), recovered (7.2%), and resilient (81.5%). Delivery complications were associated with chronic PPD but also with the recovered PPD trajectory class. History of mental health disorders was associated with chronic PPD and the delayed PPD class. Conclusion The findings underscore that significant changes in a woman's depression level can occur across pregnancy and childbirth. While a minority of women experience chronic PDD, for others depression symptoms appear to significantly alleviate over time, suggesting a form of recovery. Our findings support a personalized medicine approach based on the woman's symptom trajectory. Future research is warranted to identify the mechanisms underlying modifications in PPD symptoms severity and those implicated in recovery. [ABSTRACT FROM AUTHOR]

Abstract Studies suggest negative health impacts from early life exposure to per- and polyfluoroalkyl substances (PFASs). However, information on longitudinal exposure to PFASs during childhood is scarce for background-exposed individuals. This study sought to fill this gap by investigating children's longitudinal exposure trends through measurement of PFAS serum concentrations and calculation of body burdens (μg, total in body). Blood of 54 Finnish children was sampled 2005–2015 and analyzed for 20 PFASs at 1, 6 and 10.5 years of age. The body burden was calculated by multiplying the serum concentration by the volume of distribution and the bodyweight for each individual. Associations between serum concentrations or body burdens and parameters, such as sex, breastfeeding duration, body mass index as well as indoor dust and air PFAS concentrations, were evaluated. Serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) decreased significantly (p < 0.001) with age. In contrast to serum concentrations, body burdens stayed unchanged or even increased significantly (p < 0.05), except for PFOA in female children. Breastfeeding duration was positively correlated (p < 0.001) with serum concentrations of PFHxS, PFOS, PFOA and PFNA at 1 year of age. Some associations were found at 10.5 years with sex and indoor PFAS concentrations. Observations of longitudinal decreasing trends of serum concentrations can be misleading for understanding exposure levels from external media during childhood, as the serum concentration is influenced by parallel temporal changes and growth dilution. Body burdens account for growth dilution and thus better reflect differences in early-life to adolescence exposure than serum concentrations. Highlights • Body burden is better marker for early life exposure than serum concentration. • Serum concentrations of PFAAs decreased significantly with children's age. • PFAA body burdens stayed unchanged or increased significantly with children's age. • Breastfeeding duration was positively correlated with children's serum PFAAs. [ABSTRACT FROM AUTHOR]

Abstract We analysed floor dust samples from 65 children's bedrooms in Finland collected in 2014/2015 for 62 different per- and polyfluoroalkyl substances (PFASs) with a simple and highly efficient method. Validation results from the analysis of standard reference material (SRM) 2585 were in good agreement with literature data, while 24 PFASs were quantified for the first time. In the dust samples from children's bedrooms, five perfluoroalkyl carboxylic acids (PFCAs) and perfluorooctane sulfonic acid (PFOS) were detected in more than half of the samples with the highest median concentration of 5.26 ng/g for perfluorooctanoic acid (PFOA). However, the dust samples were dominated by polyfluoroalkyl phosphoric acid esters (PAPs) and fluorotelomer alcohols (FTOHs) (highest medians: 53.9 ng/g for 6:2 diPAP and 45.7 ng/g for 8:2 FTOH). Several significant and strong correlations (up to ρ = 0.95) were found among different PFASs in dust as well as between PFASs in dust and air samples (previously published) from the same rooms. The logarithm of dust to air concentrations (log K dust/air) plotted against the logarithm of the octanol-air partition coefficient (log K oa) resulted in a significant linear regression line with R2 > 0.88. Higher dust levels of PFOS were detected in rooms with plastic flooring material in comparison to wood (p < 0.05). Total estimated daily intakes via dust (EDI dust) and air (EDI air) of perfluoroalkyl acids (PFAA), including biotransformation of precursors to PFAAs, were calculated for 10.5-year-old children. The total EDI dust for PFOA and PFOS were estimated to be 0.007 ng/kg bw/day and 0.006 ng/kg bw/day, respectively, in an intermediate exposure scenario. The sum of the total EDIs for all PFAAs was slightly higher for dust than air (0.027 and 0.019 ng/kg bw/day). Precursor biotransformation was generally important for total PFOS intake, while for the PFCAs, FTOH biotransformation was estimated to be important for air, but not for dust exposure. Graphical abstract Unlabelled Image Highlights • PAPs and FTOHs were the predominant PFASs in children's bedroom floor dust. • Linear regression was obtained between log K dust/air and log K oa (r = 0.94, R2 > 0.88). • PFOS dust levels were higher in rooms with plastic than wooden floor material. • PFCA intake via dust was driven by direct intake and not by precursor intake. • 53 PFASs were detected in the dust standard reference material (SRM) 2585. [ABSTRACT FROM AUTHOR]

Background Although epidemiological studies have reported associations between mortality and both ambient air pollution and air temperature, it remains uncertain whether the mortality effects of air pollution are modified by temperature and vice versa. Moreover, little is known on the interactions between ultrafine particles (diameter ≤ 100 nm, UFP) and temperature. Objective We investigated whether the short-term associations of particle number concentration (PNC in the ultrafine range (≤100 nm) or total PNC ≤ 3000 nm, as a proxy for UFP), particulate matter ≤ 2.5 μm (PM 2.5 ) and ≤ 10 μm (PM 10 ), and ozone with daily total natural and cardiovascular mortality were modified by air temperature and whether air pollution levels affected the temperature-mortality associations in eight European urban areas during 1999–2013. Methods We first analyzed air temperature-stratified associations between air pollution and total natural (nonaccidental) and cardiovascular mortality as well as air pollution-stratified temperature-mortality associations using city-specific over-dispersed Poisson additive models with a distributed lag nonlinear temperature term in each city. All models were adjusted for long-term and seasonal trend, day of the week, influenza epidemics, and population dynamics due to summer vacation and holidays. City-specific effect estimates were then pooled using random-effects meta-analysis. Results Pooled associations between air pollutants and total and cardiovascular mortality were overall positive and generally stronger at high relatively compared to low air temperatures. For example, on days with high air temperatures (>75th percentile), an increase of 10,000 particles/cm 3 in PNC corresponded to a 2.51% (95% CI: 0.39%, 4.67%) increase in cardiovascular mortality, which was significantly higher than that on days with low air temperatures (<25th percentile) [−0.18% (95% CI: −0.97%, 0.62%)]. On days with high air pollution (>50th percentile), both heat- and cold-related mortality risks increased. Conclusion Our findings showed that high temperature could modify the effects of air pollution on daily mortality and high air pollution might enhance the air temperature effects. [ABSTRACT FROM AUTHOR]

Depression and diet quality appear to be associated in the general population. Nevertheless, little is known about their relationship among pregnant females. The aims of this study were first, to investigate longitudinally whether or not diet quality is associated with depressive symptoms during pregnancy; second, to examine whether or not variation in diet quality during pregnancy predicts variation in depressive symptoms; and third, to explore how individual dietary components are associated with depressive symptoms. A longitudinal secondary analysis of the Kuopio Birth Cohort Study in eastern Finland was conducted. Data were collected from pregnant females during the first and third trimesters of pregnancy. The participants were 1,362 pregnant females who entered the study between 2012 and 2017. Depressive symptoms, as measured with the Edinburgh Postnatal Depressive Scale during the first and third trimesters of pregnancy were used as continuous variables. The main analyses consisted of linear mixed model analyses adjusted for potential confounders to longitudinally assess the association between diet quality as measured by the Healthy Eating Index-2015, calculated using data from a food frequency questionnaire completed during the first trimester and third trimester, and depressive symptoms during the study period. An exploratory set of linear mixed models was also used to longitudinally assess the associations between selected individual food frequency questionnaire food groups and depressive symptoms. Descriptive analyses revealed that 12.3% of the participants had clinically relevant levels of depressive symptoms (ie, Edinburgh Postnatal Depressive Scale score ≥10) during either the first or third trimester. Longitudinal modeling suggested that depressive symptoms in pregnant females tend to remain stable throughout pregnancy. Females with a poorer quality diet already displayed higher levels of depressive symptoms during the first trimester of pregnancy (β = –.038 ±.016; P = 0.022). Variation in diet quality did not predict variation in depressive symptoms over the course of pregnancy (β = –9.741 × 10–5 ±.001; P = 0.869). Females entering pregnancy with a poorer quality diet also displayed higher levels of depressive symptoms compared with females with a higher quality diet at the beginning of pregnancy, and this association remained constant throughout pregnancy. Further research is needed to assess the direction and the potential causality of the observed associations between diet quality and depressive symptoms. [ABSTRACT FROM AUTHOR]

Ambient particles (PM2.5) are estimated to be the leading source of environmental burden of disease. Modern populations spend more than 80%, often over 90% of their time indoors, where the exposures to ambient particles are modified by the building and ventilation system. The health risks, however, are routinely evaluated and controlled using only outdoor concentration measurements. The objective of the current work is to integrate a number of previously developed methods for estimation of the particle size distribution changes caused by infiltration of particles from outdoor air. The model is evaluated against population-based measurements conducted in 45 homes in Helsinki, Finland, with 3–5 repeated daily measurements. In comparison with previous sulphur-based estimation of PM2.5 infiltration rate, the aerosol model using 12-channel particle number size distribution from an electrical aerosol spectrometer (EAS) as input, was capable of capturing 85% of variance of indoor PM2.5 originating from outdoors. The estimated residential PM2.5 infiltration factor in Helsinki was 0.55±0.13 (mean±sd), while the corresponding values from the previously used elemental marker method were 0.58±0.15. These results demonstrate the importance of the particle size dependent aerosol processes in forming actual human exposures and doses, especially in showing that the exposures and doses are not equally modified by infiltration. [ABSTRACT FROM AUTHOR]

Abstract: Farming environment and environmental exposure to microbial agents have been suggested to promote favorable development of immune system in children and protect against allergic diseases. However, effects of farm exposure on adult immune responses are less clear. Aim of the present study was to examine associations of farm related factors and measured microbial exposure with stimulated production of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in peripheral blood samples among farming women. Whole peripheral blood samples were obtained from 112 women living on farms and stimulated with phorbol myristate acetate/ionomycin, lipopolysaccharide and staphylococcal enterotoxin B. Following 24h stimulation, protein levels of IFN-γ and IL-4 in the supernatants were measured by ELISA. From house dust, concentrations of 3-hydroxy fatty acids (C10:0–C14:0, marker for Gram-negative bacteria), muramic acid (Gram-positive bacteria) and ergosterol (fungal biomass) were analyzed with GC–MS/MS and viable microbes by culturing. Information on farm related factors and allergic diseases were collected from self-administered questionnaires. We found that household pets or other current or childhood farm-related factors had only few associations with stimulated cytokine production among studied farming women. Similarly, no strong associations were observed between markers of microbial exposure measured in house dust and cytokine levels. Atopic sensitization, allergic rhinitis and recent respiratory infections were, however, associated with reduced IFN-γ production. Our results suggest that the capacity of the studied environmental factors to modulate immune system is relatively weak in adulthood. [Copyright &y& Elsevier]

Abstract: Background: Children from farming families have less allergies than their peers. Consumption of farm milk or unpasteurized milk has been shown to explain (part of) the farming effect or protect against allergies independent of farming status. Objectives: We investigated whether the protective effect of farm milk consumption can be explained by higher levels of bacterial endotoxin in milk. Methods: We measured endotoxin in approximately 400 farm milk and shop milk samples from farming and non-farming families, respectively, with the kinetic chromogenic Limulus Amebocyte Lysate test and compared endotoxin levels between groups defined by farming status and type of milk (farm milk/shop milk). Results: Endotoxin levels were significantly higher in milk samples from non-farming families compared to farming families [adjusted geometric means ratio (95% confidence interval)=2.61 (1.53–4.43)]. No significant difference in endotoxin levels was found between shop milk and farm milk samples [adjusted geometric means ratio (95% confidence interval)=1.56 (0.94–2.58)]. The difference between farming and non-farming families could be explained completely for farm milk and partially for shop milk by storage conditions and temperature during transportation to the fieldworker''s home. Conclusion: The farming effect and the effect of farm milk consumption cannot be explained by higher levels of endotoxin in milk from farmers and farm milk, respectively. [Copyright &y& Elsevier]

Abstract: The number of ultrafine particles in urban air may be more health relevant than the usually measured mass of particles smaller than 2.5 or 10μm. Epidemiological studies typically assess exposure by measurements at a central site. Limited information is available about how well measurements at a central site reflect exposure to ultrafine particles. The goals of this paper are to assess the relationships between particle number (PN) and mass concentrations measured outdoors at a central site, right outside and inside the study homes. The study was conducted in four European cities: Amsterdam, Athens, Birmingham and Helsinki. Particle mass (PM10 and PM2.5), PN, soot and sulfate concentrations were measured at these sites. Measurements of indoors and outdoors near the home were made during 1 week in 152, mostly non-smoking, homes. In each city continuous measurements were also performed at a central site during the entire study period. The correlation between 24-h average central site outdoor and indoor concentrations was lower for PN (correlation among cities ranged from 0.18 to 0.45) than for PM2.5 (0.40–0.80), soot (0.64–0.92) and sulfate (0.91–0.99). In Athens, the indoor–central site correlation was similar for PN and PM2.5. Infiltration factors for PN and PM2.5 were lower than for sulfate and soot. Night-time hourly average PN concentrations showed higher correlations between indoor and central site, implying that indoor sources explained part of the low correlation found for 24-h average concentrations. Measurements at a central site may characterize indoor exposure to ambient particles less well for ultrafine particles than for fine particle mass, soot and sulfate. [Copyright &y& Elsevier]

Outdoor levels of fine particles (PM2. 5; particles <2. 5μm) have been associated with cardiovascular health. Persons with existing cardiovascular disease have been suggested to be especially vulnerable. It is unclear, how well outdoor concentrations of PM2. 5 and its constituents measured at a central site reflect personal exposures in Southern European countries. The objective of the study was to assess the relationship between outdoor and personal concentrations of PM2. 5, absorbance and sulphur among post-myocardial infarction patients in Barcelona, Spain. Thirty-eight subjects carried personal PM2. 5 monitors for 24-h once a month (2–6 repeated measurements) between November 2003 and June 2004. PM2. 5 was measured also at a central outdoor monitoring site. Light absorbance (a proxy for elemental carbon) and sulphur content of filter samples were determined as markers of combustion originating and long-range transported PM2. 5, respectively. There were 110, 162 and 88 measurements of PM2. 5, absorbance and sulphur, respectively. Levels of outdoor PM2. 5 (median 17μgm3) were lower than personal PM2. 5 even after excluding days with exposure to environmental tobacco smoke (ETS) (median after exclusion 27μgm3). However, outdoor concentrations of absorbance and sulphur were similar to personal concentrations after exclusion of ETS. When repeated measurements were taken into account, there was a statistically significant association between personal and outdoor absorbance when adjusting for ETS (slope 0. 66, p<0. 001), but for PM2. 5 the association was weaker (slope 0. 51, p=0. 066). Adjustment for ETS had little effect on the respective association of S (slope 0. 69, p<0. 001). Our results suggest that outdoor measurements of absorbance and sulphur can be used to estimate both the daily variation and levels of personal exposures also in Southern European countries, especially when exposure to ETS has been taken into account. For PM2. 5, indoor sources need to be carefully considered. [Copyright &y& Elsevier]

Abstract: Background: Ultrafine particles in urban air represent a potentially important health risk, and are not well characterized by mass concentrations like PM10 or PM2.5. The aerosol particle number concentration (PNC) is dominated by ultrafine particles, but urban PNC measurement campaigns have only recently started in many cities and missing data impedes much research. Hence, reliable estimation techniques are needed. Past estimations of ambient concentrations of particulate matter have focused on mass concentrations. This project developed city-specific models for estimating PNC using available data on other air pollutants and meteorological variables during a period when PNC was measured, and applied them retrospectively to predict daily PNC levels during the Health Effects of Air Pollution on Susceptible Subpopulations (HEAPSS) study period in order to enable epidemiological analyses. Methods: Monitoring of PNC began in April 2001 using condensation particle counters (3022A, TSI) in Augsburg, Barcelona, Helsinki, Rome, and Stockholm. Concurrent measurements of air pollutants and weather were used, as well as selected interactions between the two, to fit a regularized linear model (also called ridge regression). This technique is robust with respect to inclusion of irrelevant explanatory variables and can be modified to be highly tolerant of missing data, two highly beneficial features when there are many explanatory variables. Results: The most important predictor variables were the nitrogen oxides. The models appear to fit PNC data relatively well, with R 2 of 0.77, 0.80, 0.58, 0.84, 0.81 respectively for the five cities. Split-halves analysis (modelling on half of the data with validation on the other half) indicates that the modelling process was fairly reliable. Conclusion: A statistical model can be applied to existing data on traffic-related air pollutants and weather variables in order to predict PNC levels. The retrospective prediction of PNC levels appears to be sufficiently reliable for use in epidemiological research. [Copyright &y& Elsevier]

Problem: To study the production, interrelationships and determinants of maternal and neonatal cytokines (IL-4 and IFN-gamma) in whole blood cultures during labor, after vaginal delivery and at 3 months after delivery. Major results: The concentrations of maternal IFN-gamma and IL-4 in peripheral blood were down-regulated at delivery compared with values 3 months postpartum. The concentrations of neonatal IFN-gamma and IL-4 were down-regulated at birth and were still at a low level 3 months later. The concentrations of IFN-gamma in maternal and umbilical cord blood samples correlated at delivery (r=0.43; P<0.03). Maternal IL-4 concentrations correlated immediately after delivery and 3 months later (r=0.46; P<0.02) as did those of IFN-gamma (r=0.57; P<0.002). Neonates who were delivered at less than 40 weeks of gestation had higher IFN-gamma concentrations 3 months after birth than those who were delivered after a longer duration of gestation (341 vs. 157 pg/ml; P<0.01). Conclusions: Broad immune activation, reflected in increased production of IL-4 and IFN-gamma, can be detected in women during the postpartum period. Labor-related factors had little effect on ranking of mothers in terms of their IL-4 or IFN-gamma levels, since maternal production of these cytokines correlated immediately after delivery and 3 months later. In neonates, the production of IFN-gamma 3 months after birth was dependent on gestational age at delivery. [Copyright &y& Elsevier]

Source apportionment of urban fine particle mass (PM2.5) was done from data collected during two 6-month measurement periods in 1996–97 and 1998–99 in Helsinki, Finland, using absolute principal component analysis and multivariate linear regression. In addition to PM2.5 elemental composition data, 24-h average concentrations of ultrafine particles (diameter <0.1 μm) and accumulation mode particles (diameter 0.1–1.0 μm), as well as absorption coefficients of PM2.5 filters and concentrations of nitrogen oxides (NOx) and sulphur dioxide (SO2) were used as input data to PM2.5 source modelling. Five similar source categories of PM2.5 were identified separately for both measurement periods: local traffic source characterised by NOx, absorption coefficient and ultrafine particle counts; long-range transboundary air pollution characterised by S, K, Zn, Pb and accumulation mode particle counts; crustal source characterised by Si, Al, Ca, Fe and K; oil combustion characterised by V, Ni and SO2; and salt source characterised by Na and Cl. Long-range transboundary air pollution was the major contributor to PM2.5 during both 1996–97 and 1998–99 accounting for 51% and 50%, respectively, of the average PM2.5. Local traffic accounted for 30% and 23%, oil combustion for 3% and 13%, crustal source for 12% and 5%, and salt for 2% and 7% of the average PM2.5 during 1996–97 and 1998–99, respectively. Despite differences in atmospheric concentrations and availability of several elements for statistical analyses in 1996–97 and 1998–99, the estimates of PM2.5 source contributions were both qualitatively and quantitatively comparable for the two measurement periods. Using non-elemental markers proved very useful for both source identification and estimation of source contributions at this measurement site. [Copyright &y& Elsevier]

This study continues to develop a quantitative indicator of moisture damage induced exposure in relation to occupant health in residential buildings. Earlier, we developed a knowledge-based model that links moisture damage variables with health symptoms. This paper presents a statistical model in an effort to improve the knowledge-based model, and formulates a third, simplified model that combines aspects of the both two models. The database used includes detailed information on moisture damage from 164 houses and health questionnaire data from the occupants. Models were formulated using generalized linear model formulation procedures, with 10 moisture damage variables as possible covariates and a respiratory health symptom score as the dependent variable. An 80% random sample of the residences was used for the formulation of models and the remaining 20% were used to evaluate them. Risk ratios (RR) for the respiratory health symptom score among the 80% sample were between 1.32 (1.12–1.55) and 1.48 (1.19–1.83), calculated per 10 points index increase. For the 20% sample, RRs were between 1.71 (1.13–2.58) and 2.34 (1.69–3.23), respectively. Deviance values in relation to degrees of freedom were between 2.00–2.12 (80% sample) and 1.50–1.81 (20% sample). The models developed can be simulated as continuous variables and they all associated significantly with the symptom score, the association being verified with a subset of the database not employed in the model formulation. We concluded that the performance of all models was similar. Therefore, based on the knowledge-based and statistical models, we were able to construct a simple model that can be used in estimating the severity of moisture damage. [Copyright &y& Elsevier]

• Associations between sources of particle number concentrations and daily deaths. • Time series analysis was carried out for Barcelona, Helsinki, London and Zurich. • Daily photonucleation, fresh traffic, urban, and secondary source contributions. • Inconsistent associations across cities, sources and lags. • Risk increases were stronger for respiratory than for cardiovascular daily mortality. The evidence on the association between ultrafine (UFP) particles and mortality is still inconsistent. Moreover, health effects of specific UFP sources have not been explored. We assessed the impact of UFP sources on daily mortality in Barcelona, Helsinki, London, and Zurich. UFP sources were previously identified and quantified for the four cities: daily contributions of photonucleation, two traffic sources (fresh traffic and urban, with size mode around 30 nm and 70 nm, respectively), and secondary aerosols were obtained from data from an urban background station. Different periods were investigated in each city: Barcelona 2013–2016, Helsinki 2009–2016, London 2010–2016, and Zurich 2011–2014. The associations between total particle number concentrations (PNC) and UFP sources and daily (natural, cardiovascular [CVD], and respiratory) mortality were investigated using city-specific generalized linear models (GLM) with quasi-Poisson regression. We found inconsistent results across cities, sources, and lags for associations with natural, CVD, and respiratory mortality. Increased risk was observed for total PNC and natural mortality in Helsinki (lag 2; 1.3% [0.07%, 2.5%]), CVD mortality in Barcelona (lag 1; 3.7% [0.17%, 7.4%]) and Zurich (lag 0; 3.8% [0.31%, 7.4%]), and respiratory mortality in London (lag 3; 2.6% [0.84%, 4.45%]) and Zurich (lag 1; 9.4% [1.0%, 17.9%]). A similar pattern of associations between health outcomes and total PNC was followed by the fresh traffic source, for which we also found the same associations and lags as for total PNC. The urban source (mostly aged traffic) was associated with respiratory mortality in Zurich (lag 1; 12.5% [1.7%, 24.2%]) and London (lag 3; 2.4% [0.90%, 4.0%]) while the secondary source was associated with respiratory mortality in Zurich (lag 1: 12.0% [0.63%, 24.5%]) and Helsinki (4.7% [0.11%, 9.5%]). Reduced risk for the photonucleation source was observed for respiratory mortality in Barcelona (lag 2, −8.6% [−14.5%, −2.4%]) and for CVD mortality in Helsinki, as this source is present only in clean atmospheres (lag 1, −1.48 [−2.75, −0.21]). We found inconsistent results across cities, sources and lags for associations with natural, CVD, and respiratory mortality. [ABSTRACT FROM AUTHOR]

Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have detrimental health effects. As people are exposed to them mainly through the diet, EU has set maximum food dioxin and PCBs levels. EFSA CONTAM Panel made new risk assessment in 2018 that lowered the tolerable weekly intake (TWI) from 14 pg-TEQ/kg bw/week to 2 pg-TEQ/kg bw/week. Critical effect was decreased semen count at the age of 18–19 years if serum total TEQ at the age of 9 years exceeded the No Observed Adverse Effect Level (NOAEL) of 7 pg/g lipid. However, it is largely unknown to what extent NOAEL is exceed in European boys currently. We thus measured PCBs from small volume of serum in 184 Finnish children 7–10 years of age. To estimate the TEQ levels of children from measured PCB levels, we used our existing human milk PCDD/F and PCB concentrations to create a hierarchical Bayesian regression model that was used to estimate TEQs from measured PCBs. For quality control (QC), three pooled blood samples from 18 to 20 year old males were measured for PCDD/Fs and PCBs, and estimated for TEQs. In QC samples measured and estimated TEQs agreed within 84%–106%. In our estimate for 7–10 year old children, PCDD/F TEQ exceeded NOAEL only in 0.5% and total TEQ in 2.7% of subjects. Risk management following the decreased TWI proposed by the CONTAM Panel should be carefully considered if total TEQ in children is already largely below the NOAEL. • Critical Russian study generated a NOAEL of 7 pg total TEQ/g lipid in 9 year old boys. • Nine major PCBs were measured in serum of 184 Finnish children 7–10 years of age. • Bayes model was used to estimate serum total TEQ concentrations with PCBs. • The model predicted that total TEQ was below the NOAEL in 97.3% of children. • Little health benefits are achieved with further reduction in food maximum levels. [ABSTRACT FROM AUTHOR]