Publications by authors named "Ulrike Gehring"

173 Publications

Residential PM exposure and the nasal methylome in children.

Environ Int 2021 Aug 16;153:106505. Epub 2021 Apr 16.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Rationale: PMinduced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known.

Objectives: We aimed to study associations of fine particulate matter PM exposure with DNA methylation in nasal cells.

Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA).

Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM.

Conclusion: We observed wide-spread DNAm variability associated with average past year PM exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.
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http://dx.doi.org/10.1016/j.envint.2021.106505DOI Listing
August 2021

Green space, air pollution, traffic noise and saliva cortisol in children: The PIAMA study.

Environ Epidemiol 2021 Apr 2;5(2):e141. Epub 2021 Apr 2.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.

Green space, air pollution, and traffic noise exposure may be associated with stress levels in children. A flattened diurnal cortisol slope (the decline in cortisol concentrations from awakening to evening) is an indicator of chronic stress. We examined associations of green space, ambient air pollution, and traffic noise with the diurnal cortisol slope in children 12 years of age.

Methods: At age 12 years, 1,027 participants of the Dutch PIAMA birth cohort collected three saliva samples during 1 day. We estimated residential exposure to green space (i.e., the average Normalized Difference Vegetation Index [NDVI] and percentages of green space in circular buffers of 300 m and 3,000 m), air pollution, and traffic noise. Associations of these exposures with the diurnal cortisol slope (in nmol/L per hour) were assessed by multiple linear regression, adjusting for potential confounders.

Results: Higher average NDVI and total percentage of green space in a 3,000 m buffer were associated with a larger diurnal decrease in cortisol levels (adjusted difference [95% confidence interval] = -0.11 nmol/L/hr [-0.21, 0.00 nmol/L/hr] per interquartile range increase in the average NDVI; -0.13 nmol/L/hr [-0.26, 0.00 nmol/L/hr] per interquartile range increase in the total percentage of green space). These associations were largely driven by associations with the percentage of agricultural green space and by associations in children living in nonurban areas. We observed no relationships between air pollution or traffic noise and the diurnal cortisol slope.

Conclusions: Residential exposure to green space in a buffer of 3,000 m may be associated with lower stress levels in children 12 years of age.
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http://dx.doi.org/10.1097/EE9.0000000000000141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043724PMC
April 2021

Modelling nationwide spatial variation of ultrafine particles based on mobile monitoring.

Environ Int 2021 Apr 15;154:106569. Epub 2021 Apr 15.

Institute for Risk Assessment Sciences (IRAS), Division of Environmental Epidemiology, Utrecht University, 3584 CK Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands.

Background: Large nation- and region-wide epidemiological studies have provided important insights into the health effects of long-term exposure to outdoor air pollution. Evidence from these studies for the long-term effects of ultrafine particles (UFP), however is lacking. Reason for this is the shortage of empirical UFP land use regression models spanning large geographical areas including cities with varying topographies, peri-urban and rural areas. The aim of this paper is to combine targeted mobile monitoring and long-term regional background monitoring to develop national UFP models.

Method: We used an electric car to monitor UFP concentrations in selected cities and towns across the Netherlands over a 14-month period in 2016-2017. Routes were monitored 3 times and concentrations were averaged per road segment. In addition, we used kriging maps based on regional background monitoring (20 sites; 3 × 2 weeks) over the same period to assess annual average regional background concentrations. All road segments were used to model spatial variation of UFP with three different land-use (regression) approaches: supervised stepwise regression, LASSO and random forest. For each approach, we also tested a deconvolution method, which segregates the average concentration at each road segment into a local and background signal. Model performance was evaluated with short-term (400 sites across the Netherlands; 3 × 30 minutes) and external longer-term measurements (42 sites in two major cities; 3 × 24 hours). We also compared predictions of all six models at 1000 random addresses spread over the country.

Results: We found similar predictive performance for the six models, with validation R values from 0.25 to 0.35 for short-term measurements and 0.52 to 0.60 for longer-term external measurements. Models with and without deconvolution had similar predictive performance. All models based on the deconvolution method included a regional background kriging map as important predictor. Correlations between predictions at random addresses were high with Pearson correlations from 0.84 to 0.99. Models overestimated exposure at the short-term and long-term sites by about 20-30% in all cases, with small differences between regions and road types.

Conclusion: We developed robust nation-wide models for long-term UFP exposure combining mobile monitoring with long-term regional background monitoring. Minor differences in predictive performance between different algorithms were found, but the deconvolution approach is considered more physically realistic. The models will be applied in Dutch nation-wide health studies.
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http://dx.doi.org/10.1016/j.envint.2021.106569DOI Listing
April 2021

Early childhood infections and body mass index in adolescence.

Int J Obes (Lond) 2021 May 26;45(5):1143-1151. Epub 2021 Mar 26.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: The incidence of childhood overweight and obesity is rising. It is hypothesized that infections in early childhood are associated with being overweight. This study investigated the association between the number of symptomatic infections or antibiotic prescriptions in the first 3 years of life and body mass index (BMI) in adolescence.

Subjects: The current study is part of the Prevention and Incidence of Asthma and Mite Allergy population-based birth cohort study. Weight and height were measured by trained research staff at ages 12 and 16 years. The 3015 active participants at age 18 years were asked for informed consent for general practitioner (GP) data collection and 1519 gave written informed consent. Studied exposures include (1) GP-diagnosed infections, (2) antibiotic prescriptions, and (3) parent-reported infections in the first 3 years of life. Generalized estimating equation analysis was used to determine the association between each of these exposures and BMI z-score.

Results: Exposure data and BMI measurement in adolescence were available for 622 participants. The frequencies of GP-diagnosed infections and antibiotic prescriptions were not associated with BMI z-score in adolescence with estimates being 0.14 (95% CI -0.09-0.37) and 0.10 (95% CI -0.14-0.34) for the highest exposure categories, respectively. Having ≥6 parent-reported infections up to age 3 years was associated with a 0.23 (95% CI 0.01-0.44) higher BMI z-score compared to <2 parent-reported infections.

Conclusions: For all infectious disease measures an increase in BMI z-score for the highest childhood exposure to infectious disease was observed, although only statistically significant for parent-reported infections. These results do not show an evident link with infection severity, but suggest a possible cumulative effect of repeated symptomatic infections on overweight development.
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http://dx.doi.org/10.1038/s41366-021-00806-5DOI Listing
May 2021

Mental Well-being and General Health in Adolescents with Asthma: The Prevention and Incidence of Asthma and Mite Allergy Birth Cohort Study.

J Pediatr 2021 Jun 4;233:198-205.e2. Epub 2021 Feb 4.

Center for Prevention and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Objectives: To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma.

Study Design: Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental well-being and perceived general health using generalized estimating equations.

Results: At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages.

Conclusions: The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health.
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http://dx.doi.org/10.1016/j.jpeds.2021.01.074DOI Listing
June 2021

A widening gap between boys and girls in musculoskeletal complaints, while growing up from age 11 to age 20 - the PIAMA birth Cohort study.

Eur J Pain 2021 04 29;25(4):902-912. Epub 2021 Jan 29.

Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

Introduction: The adolescent years represent a key period for the development of musculoskeletal complaints (MSC) and the differences between boys and girls. We evaluated the prevalence and course of MSC and factors associated with MSC while growing up from age 11 to age 20.

Methods: Questionnaire-based data at age 11 (n = 2,638), age 14 (n = 2,517), age 17 (n = 2,094) and at age 20 (n = 2,206) from the ongoing Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort were analyzed. MSC refers to pain of lower back, upper- and/or lower extremities. A multivariable logistic regression analysis was used to evaluate a number of factors in relation to persistent pain (pain reported at three out of four measurements).

Results: Prevalence of MSC increased from 14.2% at age 11 to 22.1% at age 20 for boys, and from 17.4% at age 11 to 37.9% at age 20 for girls. Persistent pain was found among 5.1% of the boys and 16.5% of the girls. Being bullied, sleeping problems and tiredness during the day were significantly associated with persistent pain, in both boys and girls, while the latter two were more prevalent among girls. Self-reported (sports-) accidents, and among girls also early onset of puberty, were also significantly associated with persistent pain, but lifestyle factors, such as physical activity and smoking, were not.

Conclusion: The prevalence of MSC increases during adolescence, with a widening gap between boys and girls. The factors associated with MSC are similar in boys and girls, though the prevalence of some of these differ by sex.

Significance: Measuring a group of youngsters 4 times between age 11 and 20 shows an increase in the percentage reporting musculoskeletal complaints (MSC) with a widening gap between girls and boys, with more pain among girls. Boys and girls do hardly differ with respect to factors associated with MSC, being mainly psychosocial factors and (sports) accidents.
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http://dx.doi.org/10.1002/ejp.1719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048429PMC
April 2021

Blood eosinophils associate with reduced lung function growth in adolescent asthmatics.

Clin Exp Allergy 2021 Apr 16;51(4):556-563. Epub 2021 Jan 16.

Department of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands.

Background And Objective: Some children with asthma have low lung growth, putting them at increased risk for COPD later in life. However, it is currently not clear who will experience this adverse growth pattern. We therefore investigated the predictive role of blood eosinophils as a type 2 inflammation marker in lung growth, focusing on the presence and severity of asthma.

Methods: We investigated blood eosinophils and lung function growth (percentage of predicted values) using linear mixed models in children and adolescents from two longitudinal cohorts. One cohort was hospital-based and consisted of asthmatic children at their first outpatient clinic visit after referral by the general practitioner (n = 133, mean age 9.8), while the second was a general population-based birth cohort (PIAMA, asthma n = 52 and non-asthma n = 433, mean age 8.1). The hospital-based cohort had not been treated with inhaled corticosteroids (ICS) before referral.

Results: Subjects in the hospital-based asthma cohort had more severe asthma compared with the asthmatic subjects in the population-based cohort, defined by lower lung function levels and a higher prevalence of bronchial hyper-responsiveness. In the asthma cohort, higher blood eosinophil numbers were associated with less growth in FEV (estimated change in lung function per 1 unit increase in ln blood eosinophils (B): -0.66%/year (95% confidence interval (CI): -1.11 to -0.20, p < .01)) and FVC (B: -0.40%/year (95% CI: -0.75 to -0.05), p = .025)) during follow-up in adolescence (min 7, max 17 years). These associations were not observed in the general population-based birth cohort, regardless of asthma status during follow-up (age 8-16).

Conclusions And Clinical Relevance: Blood eosinophil counts in children with asthma not treated with ICS at referral were predictive of lower growth in FEV and FVC during follow-up in adolescence. Our findings indicate that this association is dependent on the degree of asthma severity. Future studies should address whether anti-eosinophilic treatments preserve lung function growth in children with asthma.
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http://dx.doi.org/10.1111/cea.13818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048657PMC
April 2021

Spatial and Spatiotemporal Variability of Regional Background Ultrafine Particle Concentrations in the Netherlands.

Environ Sci Technol 2021 01 30;55(2):1067-1075. Epub 2020 Dec 30.

Institute for Risk Assessment Sciences (IRAS), Division of Environmental Epidemiology, Utrecht University, 3584 CK Utrecht, The Netherlands.

Studies of the health effects of ultrafine particles (UFPs) in large nationwide cohorts are currently hampered by a lack of knowledge about spatial and spatiotemporal variations in regional background UFPs. We measured the UFP (10-300 nm) at 20 regional background locations (3 × 2 weeks) across the Netherlands and a reference site continuously over a total period of 14 months in 2016-2017. We compared the overall averages for each site and used kriging to create a regional background spatial map of the Netherlands. Spatiotemporal variability was analyzed by correlating time-series of 2 and 24 h average concentrations. The overall average measured UFP concentrations at the 20 locations ranged from 3814 to 7070 particles/cm. We found the spatial correlation in the UFP concentrations up to 180 km and clear differences between the north and the more populated southern parts of the country. The average temporal correlation between 2 and 24 h average UFP concentrations was 0.50 (IQR: 0.36-0.61) and 0.58 (IQR: 0.44-0.75), respectively. Temporal correlation declined weakly with a distance between sites, from 0.58 for sites within 80 km of each other to 0.47 for sites farther away. The substantial spatial variation in the regional background UFP concentrations suggests that regional variation may contribute importantly to exposure contrast in nationwide health studies of UFP.
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http://dx.doi.org/10.1021/acs.est.0c06806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818655PMC
January 2021

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

J Allergy Clin Immunol 2021 Mar 15;147(3):1031-1040. Epub 2020 Dec 15.

Centre for Individualized Infection Medicine, CiiM, a joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.

Objective: We sought to identify DNA methylation profiles associated with childhood allergy.

Methods: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses.

Results: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium.

Conclusion: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.
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http://dx.doi.org/10.1016/j.jaci.2020.11.044DOI Listing
March 2021

Headache in girls and boys growing up from age 11 to 20 years: the Prevention and Incidence of Asthma and Mite Allergy birth cohort study.

Pain 2021 05;162(5):1449-1456

Centre for Nutrition, Prevention, and Health Services, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

Abstract: The striking difference between men and women in headache prevalence is suggested to develop in adolescence. Although headaches are common and affect quality of life and daily functioning, the evidence needed to develop effective counselling and preventive approaches is still limited. Using data collected at age 11, 14, 17, and 20 years in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study (n = 3064 with ≥ 1 questionnaire), we assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health, and psychosocial factors. Associations were analysed longitudinally with generalized linear mixed models and discrete time hazard models. From age 11 to 20 years, the prevalence of headache increased from 9.4% to 19.8% in girls and hardly changed in boys (7.6%-6.1%). Headache commonly co-occurred with other unfavorable health and psychosocial conditions. Eighty-eight percent of the girls and 76% of boys with headache also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health, or worrying. Results suggest higher headache prevalence in adolescents following lower educational tracks, in those who skip breakfast ≥2 days per week, and in boys exposed to tobacco smoke in infancy. In girls, sleeping problems and musculoskeletal complaints were associated with higher odds of incident headache and residential greenness with lower odds of incident headache. The high prevalence and strong female predominance of headache, already in adolescence and often with comorbidities, deserve recognition by professionals in (preventive) health care settings and schools.
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http://dx.doi.org/10.1097/j.pain.0000000000002141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054541PMC
May 2021

Air pollution and IgE sensitization in 4 European birth cohorts-the MeDALL project.

J Allergy Clin Immunol 2021 Feb 11;147(2):713-722. Epub 2020 Sep 11.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden. Electronic address:

Background: Whether long-term exposure air to pollution has effects on allergic sensitization is controversial.

Objective: Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years.

Methods: A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM absorbance (a measurement of the blackness of PM filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021).

Results: Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-μg/m increase in NO exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-μg/m increase in exposure).

Conclusion: Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.
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http://dx.doi.org/10.1016/j.jaci.2020.08.030DOI Listing
February 2021

House dust endotoxin, asthma and allergic sensitization through childhood into adolescence.

Clin Exp Allergy 2020 09 23;50(9):1055-1064. Epub 2020 Jul 23.

Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.

Background: House dust endotoxin may have beneficial effects on allergic sensitization and asthma in children. Evidence is scarce for adolescents and most studies so far have been cross-sectional and limited to a single exposure measurement.

Objective: We assessed associations of house dust endotoxin with asthma and allergic sensitization from birth to age 17 years longitudinally taking into account exposure early in life and at primary school age.

Methods: We used data of 854 participants of the prospective Dutch PIAMA birth cohort study with house dust endotoxin measurements at 3 months and/or 5-6 years and data on asthma and/or allergic sensitization from at least one of 11 follow-ups until age 17. We assessed overall and age-specific associations of the prevalence of asthma and sensitization with mattress and living room floor dust concentrations (per gram of dust) and loads (per m of sampling surface).

Results: Higher living room floor dust endotoxin concentrations at 3 months were associated with lower odds of asthma until age 4 [odds ratio (95% confidence interval) ranging from 0.70 (0.51-0.97) at age 1 to 0.76 (0.57-1.00) at age 3 per interquartile range increase], but not thereafter in children of allergic mothers. Higher living room floor dust endotoxin at 5-6 years was associated with higher odds of sensitization at 8-16 years [eg odds ratio (95% confidence interval) 1.70 (1.17-2.47) per interquartile range increase in endotoxin load].

Conclusions And Clinical Relevance: House dust endotoxin may have beneficial effects on asthma in preschool children of allergic mothers, which do not persist into adolescence. Beneficial associations with allergic sensitization could not be confirmed.
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http://dx.doi.org/10.1111/cea.13705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540017PMC
September 2020

House dust mites: Does a clean mattress mean Der p 1-free breastmilk?

Pediatr Allergy Immunol 2020 11 13;31(8):990-993. Epub 2020 Jul 13.

School of Molecular Sciences, University of Western Australia, Perth, WA, Australia.

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http://dx.doi.org/10.1111/pai.13311DOI Listing
November 2020

Dynamic prediction model to identify young children at high risk of future overweight: Development and internal validation in a cohort study.

Pediatr Obes 2020 09 13;15(9):e12647. Epub 2020 May 13.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: Primary prevention of overweight is to be preferred above secondary prevention, which has shown moderate effectiveness.

Objective: To develop and internally validate a dynamic prediction model to identify young children in the general population, applicable at every age between birth and age 6, at high risk of future overweight (age 8).

Methods: Data were used from the Prevention and Incidence of Asthma and Mite Allergy birth cohort, born in 1996 to 1997, in the Netherlands. Participants for whom data on the outcome overweight at age 8 and at least three body mass index SD scores (BMI SDS) at the age of ≥3 months and ≤6 years were available, were included (N = 2265). The outcome of the prediction model is overweight (yes/no) at age 8 (range 7.4-10.5 years), defined according to the sex- and age-specific BMI cut-offs of the International Obesity Task Force.

Results: After backward selection in a Generalized Estimating Equations analysis, the prediction model included the baseline predictors maternal BMI, paternal BMI, paternal education, birthweight, sex, ethnicity and indoor smoke exposure; and the longitudinal predictors BMI SDS, and the linear and quadratic terms of the growth curve describing a child's BMI SDS development over time, as well as the longitudinal predictors' interactions with age. The area under the curve of the model after internal validation was 0.845 and Nagelkerke R was 0.351.

Conclusions: A dynamic prediction model for overweight was developed with a good predictive ability using easily obtainable predictor information. External validation is needed to confirm that the model has potential for use in practice.
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http://dx.doi.org/10.1111/ijpo.12647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507129PMC
September 2020

Air pollution and the development of asthma from birth until young adulthood.

Eur Respir J 2020 07 2;56(1). Epub 2020 Jul 2.

Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.

Background: Air pollution is associated with asthma development in children and adults, but the impact on asthma development during the transition from adolescence to adulthood is unclear. Adult studies lack historical exposures and consequently cannot assess the relevance of exposure during different periods of life. We assessed the relevance of early-life and more recent air pollution exposure for asthma development from birth until early adulthood.

Methods: We used data of 3687 participants of the prospective Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort and linked asthma incidence until age 20 years to estimated concentrations of nitrogen dioxide (NO), particulate matter with a diameter <2.5 μm (PM), <10 μm (PM), and 2.5-10 μm, and PM absorbance ("soot") at the residential address. We assessed overall and age-specific associations with air pollution exposure with discrete time-hazard models, adjusting for potential confounders.

Results: Overall, we found higher incidence of asthma until the age of 20 years with higher exposure to all pollutants at the birth address (adjusted odds ratio (95% CI) ranging from 1.09 (1.01-1.18) for PM to 1.20 (1.10-1.32) for NO) per interquartile range increase) that were rather persistent with age. Similar associations were observed with more recent exposure defined as exposure at the current home address. In two-pollutant models with particulate matter, associations with NO persisted.

Conclusions: Exposure to air pollution, especially from motorised traffic, early in life may have long-term consequences for asthma development, as it is associated with an increased risk of developing asthma through childhood and adolescence into early adulthood.
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http://dx.doi.org/10.1183/13993003.00147-2020DOI Listing
July 2020

The joint effect of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants' term birth weight.

BMC Pregnancy Childbirth 2020 Feb 27;20(1):132. Epub 2020 Feb 27.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, STR 6.118, Utrecht, 3508, GA, The Netherlands.

Background: It is well known that maternal smoking during pregnancy and maternal pre-pregnancy overweight have opposite effects on the infants' birth weight. We report on the association of the combination between both risk factors and the infants' birth weight.

Methods: We studied 3241 infants born at term in the PIAMA birth cohort. Maternal smoking during pregnancy and pre-pregnancy height and weight were self-reported. Multivariable regression analysis was performed to assess the associations between infants of mothers who only smoked during pregnancy, who only had pre-pregnancy overweight and who had both risk factors simultaneously, on term birth weight and the risk of being SGA or LGA.

Results: Of 3241 infants, 421 infants (13%) were born to smoking, non-overweight mothers, 514 (15.8%) to non-smoking, overweight mothers, 129 (4%) to smoking and overweight mothers and 2177 (67%) to non-smoking, non-overweight mothers (reference group). Infants of mothers who smoked and also had pre-pregnancy overweight had similar term birth weight (- 26.6 g, 95%CI: - 113.0, 59.8), SGA risk (OR = 1.06, 95%CI: 0.56, 2.04), and LGA risk (OR = 1.09, 95%CI: 0.61, 1.96) as the reference group.

Conclusions: Our findings suggested that the effects of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants' birth weight cancel each other out. Therefore, birth weight may not be a good indicator of an infant's health status in perinatal practice because it may mask potential health risks due to these maternal risk factors when both present together.
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http://dx.doi.org/10.1186/s12884-020-2816-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047372PMC
February 2020

Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma: A meta-analysis of European birth cohorts.

Environ Int 2020 03 18;136:105474. Epub 2020 Jan 18.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; INSERM, U1168, VIMA: Aging and Chronic Diseases, Epidemiological and Public Health Approaches, Villejuif, France; Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, F-78180 Montigny le Bretonneux, France; Université Rennes, INSERM, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.

Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades.

Objective: We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries.

Methods: Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrogen dioxide (NO), nitrogen oxides, mass of particulate matter with an aerodynamic diameter <10 μm (PM), 10-2.5 μm (PM) and <2.5 μm (PM), and PM absorbance were assigned to the birth, four- and eight-year home addresses using highly defined spatial air pollution exposure models. Cohort-specific cross-sectional associations were assessed using logistic regression models adjusted for demographic and environmental covariates and combined in a random effects meta-analysis.

Results: The overall prevalence of pediatric eczema, rhinoconjunctivitis and asthma at four years was 15.4%, 5.9% and 12.4%. We found no increase in the prevalence of these outcomes at four or eight years with increasing air pollution exposure. For example, the meta-analysis adjusted odds ratios (95% confidence intervals) for eczema, rhinoconjunctivitis and asthma at four years were 0.94 (0.81, 1.09), 0.90 (0.75, 1.09), and 0.91 (0.74, 1.11), respectively, per 10 μg/m increase in NO at the birth address, and 1.00 (0.81, 1.23), 0.70 (0.49, 1.00) and 0.88 (0.54, 1.45), respectively, per 5 μg/m increase in PM at the birth address.

Discussion: In this large meta-analysis of five birth cohorts, we found no indication of adverse effects of long-term air pollution exposure on the prevalence of current pediatric eczema, rhinoconjunctivitis or asthma.
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http://dx.doi.org/10.1016/j.envint.2020.105474DOI Listing
March 2020

Nasal DNA methylation profiling of asthma and rhinitis.

J Allergy Clin Immunol 2020 06 14;145(6):1655-1663. Epub 2020 Jan 14.

Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Gronigen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address:

Background: Epigenetic signatures in the nasal epithelium, which is a primary interface with the environment and an accessible proxy for the bronchial epithelium, might provide insights into mechanisms of allergic disease.

Objective: We aimed to identify and interpret methylation signatures in nasal epithelial brushes associated with rhinitis and asthma.

Methods: Nasal epithelial brushes were obtained from 455 children at the 16-year follow-up of the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Epigenome-wide association studies were performed on children with asthma, rhinitis, and asthma and/or rhinitis (AsRh) by using logistic regression, and the top results were replicated in 2 independent cohorts of African American and Puerto Rican children. Significant CpG sites were related to environmental exposures (pets, active and passive smoking, and molds) during secondary school and were correlated with gene expression by RNA-sequencing (n = 244).

Results: The epigenome-wide association studies identified CpG sites significantly associated with rhinitis (n = 81) and AsRh (n = 75), but not with asthma. We significantly replicated 62 of 81 CpG sites with rhinitis and 60 of 75 with AsRh, as well as 1 CpG site with asthma. Methylation of cg03565274 was negatively associated with AsRh and positively associated with exposure to pets during secondary school. DNA methylation signals associated with AsRh were mainly driven by specific IgE-positive subjects. DNA methylation related to gene transcripts that were enriched for immune pathways and expressed in immune and epithelial cells. Nasal CpG sites performed well in predicting AsRh.

Conclusions: We identified replicable DNA methylation profiles of asthma and rhinitis in nasal brushes. Exposure to pets may affect nasal epithelial methylation in relation to asthma and rhinitis.
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http://dx.doi.org/10.1016/j.jaci.2019.12.911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282965PMC
June 2020

Surrounding green, air pollution, traffic noise exposure and non-accidental and cause-specific mortality.

Environ Int 2020 01 26;134:105341. Epub 2019 Nov 26.

National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Background: Most previous studies that investigated associations of surrounding green, air pollution or traffic noise with mortality focused on single exposures.

Objectives: The aim of this study was to evaluate combined associations of long-term residential exposure to surrounding green, air pollution and traffic noise with total non-accidental and cause-specific mortality.

Methods: We linked a national health survey (Public Health Monitor, PHM) conducted in 2012 to the Dutch longitudinal mortality database. Subjects of the survey who were 30 years or older on 1 January 2013 (n = 339,633) were followed from 1 January 2013 till 31 December 2017. We used Cox proportional hazard models to evaluate associations of residential surrounding green (including the average Normalized Difference Vegetation Index (NDVI) in buffers of 300 m and 1000 m), annual average air pollutant concentrations (including particulate matter (PM, PM), nitrogen dioxide (NO)) and traffic noise with non-accidental, circulatory disease, respiratory disease, lung cancer and neurodegenerative disease mortality.

Results: We observed 26,886 non-accidental deaths over 1.627.365 person-years of follow-up. Surrounding green, air pollution and traffic noise exposure were not significantly associated with non-accidental or cause-specific mortality. For non-accidental mortality, we found a hazard ratio (HR) of 0.99 (0.98, 1.01) per IQR increase in NDVI 300 m, a HR of 0.99 (95% CI: 0.97, 1.01) per IQR increase in NO, a HR of 0.98 (0.97, 1.00) per IQR increase in PM and a HR of 0.99 (95% CI: 0.97, 1.01) per IQR increase in road-traffic noise. Analyses restricted to non-movers or excluding subjects aged 85+ years did not change the findings.

Conclusion: We found no evidence for associations of long-term residential exposures to surrounding green, air pollution and traffic noise with non-accidental or cause-specific mortality in a large population based survey in the Netherlands, possibly related to the relatively short follow-up period.
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http://dx.doi.org/10.1016/j.envint.2019.105341DOI Listing
January 2020

Timing of secondhand smoke, pet, dampness or mould exposure and lung function in adolescence.

Thorax 2020 02 20;75(2):153-163. Epub 2019 Nov 20.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands

Background: The relevance of timing of exposure in the associations of secondhand tobacco smoke (SHS), pets, and dampness or mould exposure with lung function is unclear. We investigated the relevance of timing of these exposures for lung function in adolescence.

Methods: We used data from participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort with spirometric measurements at ages 12 and 16 years (n=552). Data on residential exposure to SHS, pets, and dampness or mould were obtained by repeated parental questionnaires. We characterised timing of exposure through longitudinal patterns using latent class growth modelling and assessed associations of these patterns with FEV and FVC at ages 12 and 16 and FEV and FVC growth between ages 12 and 16 using linear regression models.

Results: Childhood SHS exposure was associated with reduced FEV growth/year (95% CI) (-0.34% (-0.64% to -0.04%)). Late childhood and early life pet exposure was associated with increased FEV growth (0.41% (0.14% to 0.67%)) and reduced FVC growth (-0.28% (-0.53% to -0.03%)), respectively, compared with very low exposure. Early life dampness or mould exposure was associated with reduced lung function growth. All time windows of SHS exposure tended to be associated with lower attained lung function and pet exposure tended to be associated with higher FEV.

Conclusion: SHS exposure during childhood could lead to reduced lung function growth and lower attained lung function in adolescence. While pet exposure in late childhood may not adversely affect lung function, early childhood pet exposure may slow down FVC growth in adolescence.
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http://dx.doi.org/10.1136/thoraxjnl-2019-213149DOI Listing
February 2020

Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL.

BMJ Open Respir Res 2019 13;6(1):e000460. Epub 2019 Sep 13.

Institute for Social Medicine, Epidemiology and Health Economics, Charité Universitätsmedizin Berlin, Berlin, Germany.

Introduction: To understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences.

Methods: We used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex-puberty interaction terms and conducted a one-stage individual participant data meta-analysis.

Results: Girls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases.

Discussion: We found an incidence 'sex shift' in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.
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http://dx.doi.org/10.1136/bmjresp-2019-000460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797252PMC
April 2020

Does maternal IgG protect infants from allergen-specific IgE sensitization?

J Allergy Clin Immunol 2019 11 25;144(5):1454-1455. Epub 2019 Sep 25.

Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.jaci.2019.08.011DOI Listing
November 2019

Residential surrounding green, air pollution, traffic noise and self-perceived general health.

Environ Res 2019 12 17;179(Pt A):108751. Epub 2019 Sep 17.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.

Self-perceived general health (SGH) is one of the most inclusive and widely used measures of health status and a powerful predictor of mortality. However, only a limited number of studies evaluated associations of combined environmental exposures on SGH. Our aim was to evaluate associations of combined residential exposure to surrounding green, air pollution and traffic noise with poor SGH in the Netherlands. We linked data on long-term residential exposure to surrounding green based on the Normalized Difference Vegetation Index (NDVI) and a land-use database (TOP10NL), air pollutant concentrations (including particulate matter (PM, PM), and nitrogen dioxide (NO)) and road- and rail-traffic noise with a Dutch national health survey, resulting in a study population of 354,827 adults. We analyzed associations of single and combined exposures with poor SGH. In single-exposure models, NDVI within 300 m was inversely associated with poor SGH [odds ratio (OR) = 0.91, 95% CI: 0.89, 0.94 per IQR increase], while NO was positively associated with poor SGH (OR = 1.07, 95% CI: 1.04, 1.11 per IQR increase). In multi-exposure models, associations with surrounding green and air pollution generally remained, but attenuated. Joint odds ratios (JOR) of combined exposure to air pollution, rail-traffic noise and decreased surrounding green were higher than the odds ratios of single-exposure models. Studies including only one of these correlated exposures may overestimate the risk of poor SGH attributed to the studied exposure, while underestimating the risk of combined exposures.
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http://dx.doi.org/10.1016/j.envres.2019.108751DOI Listing
December 2019

Associations of Combined Exposures to Surrounding Green, Air Pollution, and Road Traffic Noise with Cardiometabolic Diseases.

Environ Health Perspect 2019 08 8;127(8):87003. Epub 2019 Aug 8.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands.

Background: Surrounding green, air pollution, and noise have been associated with cardiometabolic diseases, but most studies have assessed only one of these correlated exposures.

Objectives: We aimed to evaluate associations of combined exposures to green, air pollution, and road traffic noise with cardiometabolic diseases.

Methods: In this cross-sectional study, we studied associations between self-reported physician-diagnosed diabetes, hypertension, heart attack, and stroke from a Dutch national health survey of 387,195 adults and residential surrounding green, annual average air pollutant concentrations [including particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]), PM with aerodynamic diameter [Formula: see text] ([Formula: see text]), nitrogen dioxide ([Formula: see text]), and oxidative potential (OP) with the dithiothreitol (DTT) assay ([Formula: see text])] and road traffic noise. Logistic regression models were used to analyze confounding and interaction of surrounding green, air pollution, and noise exposure.

Results: In single-exposure models, surrounding green was inversely associated with diabetes, while air pollutants ([Formula: see text], [Formula: see text]) and road traffic noise were positively associated with diabetes. In two-exposure analyses, associations with green and air pollution were attenuated but remained. The association between road traffic noise and diabetes was reduced to unity when adjusted for surrounding green or air pollution. Air pollution and surrounding green, but not road traffic noise, were associated with hypertension in single-exposure models. The weak inverse association of surrounding green with hypertension attenuated and lost significance when adjusted for air pollution. Only [Formula: see text] was associated with stroke and heart attack.

Conclusions: Studies including only one of the correlated exposures surrounding green, air pollution, and road traffic noise may overestimate the association of diabetes and hypertension attributed to the studied exposure. https://doi.org/10.1289/EHP3857.
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http://dx.doi.org/10.1289/EHP3857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792364PMC
August 2019

Detrimental effects of air pollution on adult lung function.

Eur Respir J 2019 Jul 25;54(1). Epub 2019 Jul 25.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands

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http://dx.doi.org/10.1183/13993003.01122-2019DOI Listing
July 2019

Role of timing of exposure to pets and dampness or mould on asthma and sensitization in adolescence.

Clin Exp Allergy 2019 10 18;49(10):1352-1361. Epub 2019 Aug 18.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.

Background: Pet and dampness or mould exposure are considered risk factors for asthma and sensitization. It is unclear whether timing of exposure to these factors is differentially associated with asthma risk and sensitization in adolescence.

Objective: We investigated the role of timing of pet and dampness or mould exposure in asthma and sensitization in adolescence. Understanding this role is essential to build targeted prevention strategies.

Methods: We used data from 1871 participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. Residential exposure to pets, dampness or mould was assessed by repeated parental questionnaires. We used asthma data from the 17-year questionnaire and sensitization data from the 16-year medical examination. We characterized timing using longitudinal exposure patterns from pregnancy till age 17 using longitudinal latent class growth modelling. We used logistic regression models to analyse associations of exposure patterns with asthma at age 17 and sensitization at age 16.

Results: For none of the time windows, exposure to pets and dampness or mould was associated with asthma at age 17, but a lower sensitization risk at age 16 was suggested, for example the odds ratio (95% confidence interval) for sensitization was 0.63 (0.35-1.11) and 0.69 (0.44-1.08) for early life and persistently high pet exposure, respectively, compared with very low exposure. An inverse association was also suggested for sensitization and moderate early childhood dampness or mould exposure (0.71 [0.42-1.19]).

Conclusion And Clinical Relevance: Different timing of pet and dampness or mould exposure was not associated with asthma, but lower risk of sensitization in adolescence was suggested, which could be partly attributable to reversed causation. Current findings are not sufficient to recommend pet avoidance to prevent allergic disease. More prospective studies are needed to obtain insights that can be used in clinical practice.
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http://dx.doi.org/10.1111/cea.13471DOI Listing
October 2019

Green space, air pollution, traffic noise and cardiometabolic health in adolescents: The PIAMA birth cohort.

Environ Int 2019 10 11;131:104991. Epub 2019 Jul 11.

National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Background: Green space has been hypothesized to improve cardiometabolic health of adolescents, whereas air pollution and traffic noise may negatively impact cardiometabolic health.

Objectives: To examine the associations of green space, air pollution and traffic noise with cardiometabolic health in adolescents aged 12 and 16 years.

Methods: Waist circumference, blood pressure, cholesterol and glycated hemoglobin (HbA1c) were measured in subsets of participants of the Dutch PIAMA birth cohort, who participated in medical examinations at ages 12 (n = 1505) and/or 16 years (n = 797). We calculated a combined cardiometabolic risk score for each participant, with a higher score indicating a higher cardiometabolic risk. We estimated exposure to green space (i.e. the average Normalized Difference Vegetation Index (NDVI) and percentages of green space in circular buffers of 300 m and 3000 m), air pollution (by land-use regression models) and traffic noise (using the Standard Model Instrumentation for Noise Assessments (STAMINA) model) at the adolescents' home addresses at the time of the medical examinations. We assessed associations of these exposures with cardiometabolic health outcomes at ages 12 and 16 by multiple linear regression, adjusting for potential confounders.

Results: We did not observe consistent patterns of associations of green space, air pollution and traffic noise with the cardiometabolic risk score, blood pressure, total cholesterol levels, the total/HDL cholesterol ratio and HbA1c. We found inverse associations of air pollution with waist circumference at both age 12 and 16. These associations weakened after adjustment for region, except for particulate matter with a diameter of <2.5 μm (PM) at age 12. The association of PM with waist circumference at age 12 remained after adjustment for green space and road traffic noise (adjusted difference - 1.42 cm [95% CI -2.50, -0.35 cm] per 1.16 μg/m increase in PM).

Conclusion: This study does not provide evidence for beneficial effects of green space or adverse effects of air pollution and traffic noise on cardiometabolic health in adolescents.
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http://dx.doi.org/10.1016/j.envint.2019.104991DOI Listing
October 2019

Associations of combined exposures to surrounding green, air pollution and traffic noise on mental health.

Environ Int 2019 08 31;129:525-537. Epub 2019 May 31.

National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Background: Evidence is emerging that poor mental health is associated with the environmental exposures of surrounding green, air pollution and traffic noise. Most studies have evaluated only associations of single exposures with poor mental health.

Objectives: To evaluate associations of combined exposure to surrounding green, air pollution and traffic noise with poor mental health.

Methods: In this cross-sectional study, we linked data from a Dutch national health survey among 387,195 adults including questions about psychological distress, based on the Kessler 10 scale, to an external database on registered prescriptions of anxiolytics, hypnotics & sedatives and antidepressants. We added data on residential surrounding green in a 300 m and a 1000 m buffer based on the Normalized Difference Vegetation Index (NDVI) and a land-use database (TOP10NL), modeled annual average air pollutant concentrations (including particulate matter (PM, PM), and nitrogen dioxide (NO)) and modeled road- and rail-traffic noise (Lden and Lnight) to the survey. We used logistic regression to analyze associations of surrounding green, air pollution and traffic noise exposure with poor mental health.

Results: In single exposure models, surrounding green was inversely associated with poor mental health. Air pollution was positively associated with poor mental health. Road-traffic noise was only positively associated with prescription of anxiolytics, while rail-traffic noise was only positively associated with psychological distress. For prescription of anxiolytics, we found an odds ratio [OR] of 0.88 (95% CI: 0.85, 0.92) per interquartile range [IQR] increase in NDVI within 300 m, an OR of 1.14 (95% CI: 1.10, 1.19) per IQR increase in NO and an OR of 1.07 (95% CI: 1.03, 1.11) per IQR increase in road-traffic noise. In multi exposure analyses, associations with surrounding green and air pollution generally remained but attenuated. Joint odds ratios [JOR], based on the Cumulative Risk Index (CRI) method, of combined exposure to air pollution, traffic noise and decreased surrounding green were higher than the ORs of single exposure models. Associations of environmental exposures with poor mental health differed somewhat by age.

Conclusions: Studies including only one of these three correlated exposures may overestimate the influence of poor mental health attributed to the studied exposure, while underestimating the influence of combined environmental exposures.
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http://dx.doi.org/10.1016/j.envint.2019.05.040DOI Listing
August 2019

Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis.

Environ Health Perspect 2019 05 31;127(5):57012. Epub 2019 May 31.

20 Barcelona Institute for Global Health (ISGlobal) , Barcelona, Spain.

Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes.

Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children.

Methods: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression.

Results: Six CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns.

Conclusions: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.
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http://dx.doi.org/10.1289/EHP4522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792178PMC
May 2019