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Peralta GP, Fuertes E, Granell R, et al., 2019, Childhood body composition trajectories and adolescent lung function: Findings from the ALSPAC study, American Journal of Respiratory and Critical Care Medicine, Vol: 200, Pages: 75-83, ISSN: 1073-449X
RATIONALE: Body composition changes throughout life may explain the inconsistent associations reported between body mass index (BMI) and lung function in children. OBJECTIVES: To assess the associations of body weight and composition trajectories from 7 to 15 years with lung function at 15 years and lung function growth between 8 and 15 years. METHODS: Sex-specific BMI, lean body mass index (LBMI) and fat mass index (FMI) trajectories were developed using Group-Based Trajectory Modeling on data collected at least twice between 7 and 15 years from 6,964 children (49% boys) in the UK Avon Longitudinal Study of Parents and Children birth cohort. Associations of these trajectories with post-bronchodilation lung function parameters at 15 years and with lung function growth rates from 8 to 15 years were assessed using multivariable linear regression models, stratified by sex, in a subgroup with lung function data (n=3,575). MEASUREMENTS AND MAIN RESULTS: For all body mass measures we identified parallel trajectories that increased with age. There was no consistent evidence of an association between the BMI trajectories and lung function measures. Higher LBMI trajectories were associated with higher levels and growth rates of FVC, FEV1, and FEF25-75 in both sexes (e.g. boys in the highest LBMI trajectory had on average a 0.62L [95%CI: 0.44; 0.79, p-trend<0.0001] higher FVC at 15 years than boys in the lowest trajectory). Increasing FMI trajectories were associated with lower levels and growth rates of FEV1 and FEF25-75 only in boys and lower levels of FEV1/FVC in both sexes. CONCLUSIONS: Higher lean body mass during childhood and adolescence is consistently associated with higher lung function at 15 years in both sexes, whereas higher fat mass is associated with lower levels of only some lung function parameters.
Keidel D, Maria Anto J, Basagana X, et al., 2019, The role of socioeconomic status in the association of lung function and air pollution - A pooled analysis of three adult ESCAPE cohorts, International Journal of Environmental Research and Public Health, Vol: 16, ISSN: 1660-4601
Ambient air pollution is a leading environmental risk factor and its broad spectrum ofadverse health effects includes a decrease in lung function. Socioeconomic status (SES) is knownto be associated with both air pollution exposure and respiratory function. This study assesses therole of SES either as confounder or effect modifier of the association between ambient air pollutionand lung function. Cross-sectional data from three European multicenter adult cohorts were pooledto assess factors associated with lung function, including annual means of home outdoor NO2.Pre-bronchodilator lung function was measured according to the ATS-criteria. Multiple mixedlinear models with random intercepts for study areas were used. Three different factors (education,occupation and neighborhood unemployment rate) were considered to represent SES. NO2 exposurewas negatively associated with lung function. Occupation and neighborhood unemployment rateswere not associated with lung function. However, the inclusion of the SES-variable education improvedthe models and the air pollution-lung function associations got slightly stronger. NO2 associationswith lung function were not substantially modified by SES-variables. In this multicenter Europeanstudy we could show that SES plays a role as a confounder in the association of ambient NO2 exposurewith lung function.
Rastogi S, Shastry J, Kong B, et al., 2019, Association of atopic dermatitis, ultraviolet radiation and climate factors: a systematic review and ecological meta-analysis, Society-for-Investigative-Dermatology (SID) Meeting, Publisher: ELSEVIER SCIENCE INC, Pages: S32-S32, ISSN: 0022-202X
Carsin AE, Fuertes E, Schaffner E, et al., 2019, Restrictive spirometry pattern is associated with low physical activity levels. A population based international study, Respiratory Medicine, Vol: 146, Pages: 116-123, ISSN: 0954-6111
Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry. Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC ≥ Lower Limit of Normal and a FVC<80% predicted in two population-based studies (ECRHS-III and SAPALDIA3). Physical activity was measured using the International Physical Activity Questionnaire. The odds of having low physical activity (<1st study-specific tertile) was evaluated using adjusted logistic regression models. Results: Subjects with a restrictive spirometry pattern (n = 280/4721 in ECRHS, n = 143/3570 in SAPALDIA) reported lower levels of physical activity than those with normal spirometry (median of 1770 vs 2253 MET·min/week in ECRHS, and 3519 vs 3945 MET·min/week in SAPALDIA). Subjects with a restrictive spirometry pattern were more likely to report low physical activity (meta-analysis odds ratio: 1.41 [95%CI 1.07–1.86]) than those with a normal spirometry. Obesity, respiratory symptoms, co-morbidities and previous physical activity levels did not fully explain this finding. Conclusion: Adults with a restrictive spirometry pattern were more likely to report low levels of physical activity than those with normal spirometry. These results highlight the need to identify and act on this understudied but prevalent condition.
Fuertes E, Carsin AE, Garcia-Larsen V, et al., 2018, IS THE ASSOCIATION OF PHYSICAL ACTIVITY WITH FEV1 AND FVC PARTIALLY MEDIATED BY C-REACTIVE PROTEIN LEVELS?: THE ECRHS STUDY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A229-A230, ISSN: 0040-6376
Fuertes EI, Markevych I, Jarvis D, et al., 2018, Residential air pollution does not modify the positive association between physical activity and lung function in current smokers in the ECRHS study, Environment International, Vol: 120, Pages: 364-372, ISSN: 0160-4120
BackgroundVery few studies have examined whether a long-term beneficial effect of physical activity on lung function can be influenced by living in polluted urban areas.ObjectiveWe assessed whether annual average residential concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters < 2.5 μm (PM2.5) and <10 μm (PM10) modify the effect of physical activity on lung function among never- (N = 2801) and current (N = 1719) smokers in the multi-center European Community Respiratory Health Survey.MethodsAssociations between repeated assessments (at 27–57 and 39–67 years) of being physically active (physical activity: ≥2 times and ≥1 h per week) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated using adjusted mixed linear regression models. Models were conducted separately for never- and current smokers and stratified by residential long-term NO2, PM2.5 mass and PM10 mass concentrations (≤75th percentile (low/medium) versus >75th percentile (high)).ResultsAmong current smokers, physical activity and lung function were positively associated regardless of air pollution levels. Among never-smokers, physical activity was associated with lung function in areas with low/medium NO2, PM2.5 mass and PM10 mass concentrations (e.g. mean difference in FVC between active and non-active subjects was 43.0 mL (13.6, 72.5), 49.5 mL (20.1, 78.8) and 49.7 mL (18.6, 80.7), respectively), but these associations were attenuated in high air pollution areas. Only the interaction term of physical activity and PM10 mass for FEV1 among never-smokers was significant (p-value = 0.03).ConclusionsPhysical activity has beneficial effects on adult lung function in current smokers, irrespective of residential air pollution levels in Western Europe. Trends among never-smokers living in high air pollution areas are less clear.
Russell M, Dharmage S, Fuertes E, et al., 2018, The association of vigorous physical activity with 10-year adult asthma incidence, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Carsin A-E, Keidel D, Fuertes E, et al., 2018, Physical activity and incidence of restrictive spirometry pattern in adults, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Fuertes E, Carsin A-E, Larsen VG, et al., 2018, Mediation analysis of CRP on the association of physical activity with FEV1 and FVC: the ECRHS study., 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Peralta GP, Fuertes E, Carsin A-E, et al., 2018, Body mass index trajectories during adult life and lung function decline, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Hüls A, Klümper C, MacIntyre EA, et al., 2018, Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2 & TLR4 and air pollution in early life, Pediatric Allergy and Immunology, Vol: 29, Pages: 596-605, ISSN: 1399-3038
BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, were assessed using parental-reported questionnaires in six birth cohorts (N=5,685). Associations of nitrogen dioxide (NO2) estimated at the home address of each child at birth, and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (p(interaction)=0.029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4 SNPs and its interaction with air pollution supports the role of oxidative stress & inflammation in AD. This article is protected by copyright. All rights reserved.
Butland BK, Anderson HR, van Donkelaar A, et al., 2018, Ambient air pollution and the prevalence of rhinoconjunctivitis in adolescents: A worldwide ecological analysis, Air Quality, Atmosphere and Health, Vol: 11, Pages: 755-764, ISSN: 1873-9326
Whether exposure to outdoor air pollution increases the prevalence of rhinoconjunctivitis in children is unclear. Using data from Phase Three of the International Study of Asthma and Allergies in childhood (ISAAC) we investigated associations of rhinoconjunctivitis prevalence in adolescents with model-based estimates of ozone, and satellite-based estimates of fine (diameter <2.5µm) particulate matter (PM2.5) and nitrogen dioxide (NO2). Information on rhinoconjunctivitis (defined as self-reported nose symptoms without a cold or flu accompanied by itchy watery eyes in the past 12 months) was available on 505,400 children aged 13-14 years, in 183 centres in 83 countries. Centre-level prevalence estimates were calculated and linked geographically with estimates of long-term average concentrations of NO2, ozone and PM2.5. Multi-level models were fitted adjusting for population density, climate, sex and Gross National Income. Information on parental smoking, truck traffic and cooking fuel was available for a restricted set of centres (77 in 36 countries). Between-centres within-countries, the estimated change in rhinoconjunctivitis prevalence per 100 children, was 0.171 (95% Confidence Interval; -0.013, 0.354) per 10% increase in PM2.5, 0.096 (-0.003, 0.195) per 10% increase in NO2 and -0.186 (-0.390, 0.018) per 1 ppbV increase in ozone. Between-countries, rhinoconjunctivitis prevalence was significantly negatively associated with both ozone and PM2.5. In the restricted dataset, the latter association became less negative following adjustment for parental smoking and open fires for cooking. In conclusion, there were no significant within-country associations of rhinoconjunctivitis prevalence with study pollutants. Negative between-country associations with PM2.5 and ozone require further investigation.
Marcon A, Locatelli F, Keidel D, et al., 2018, Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study, Thorax, Vol: 73, Pages: 825-832, ISSN: 1468-3296
BACKGROUND: It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. OBJECTIVE: We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. METHODS: We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st-3rd quartiles: 29-44) by their level of airway responsiveness using quintiles of methacholine dose-response slope at the first examination (1991-1994). Then, we excluded subjects with airflow obstruction at the second examination (1999-2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010-2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. RESULTS: We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose-response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. CONCLUSIONS: Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression.
Fuertes EI, Carsin A-E, Antó JM, et al., 2018, Leisure-time vigorous physical activity is associated with better lung function: the prospective ECRHS study, Thorax, Vol: 73, Pages: 376-384, ISSN: 1468-3296
Objective We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort.Methods FEV1 and FVC were measured in 3912 participants at 27–57 years and 39–67 years (mean time between examinations=11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity ≥2 times and ≥1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV1 and FVC.Results Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline.Conclusion Leisure-time vigorous physical activity was associated with higher FEV1 and FVC over a 10-year period among current smokers, but not with FEV1 and FVC decline.
Fuertes EI, Standl M, Markevych I, et al., 2018, Is the association between pet ownership and indoor endotoxin levels confounded or modified by outdoor residential greenspace?, Science of the Total Environment, Vol: 625, Pages: 716-721, ISSN: 0048-9697
BackgroundPet ownership is consistently associated with higher indoor endotoxin concentrations, but may also be related to the amount of greenspace around the home. This study examined whether the association between pet ownership and higher indoor endotoxin concentrations is confounded or modified by residential greenspace.MethodsInformation on pet ownership was collected at the time of recruitment of the German LISA birth cohort. Endotoxin levels were measured in settled house dust sampled from mothers' mattresses (N = 1197) and living room floors (N = 390). Greenspace around the home was assessed as the mean Normalized Difference Vegetation Index in 100 m, 500 m and 1000 m buffers around the home, and as the distance to the nearest urban and natural green space. Linear regression models assessed cross-sectional associations between pet ownership and log-transformed endotoxin levels, adjusted for known predictors of endotoxin levels. Confounding by greenspace was assessed by additionally adjusting the models for each greenspace variable. Effect modification was assessed by including interaction terms between pet ownership and each greenspace variable, and by model stratification.ResultsDog and cat ownership were associated with higher endotoxin levels in mothers' mattresses, whereas only dog ownership was associated with endotoxin levels in the floor samples. All associations were highly robust to further adjustment for greenspace, and there was little evidence to suggest any effect modification (interaction terms had p-values > 0.05).ConclusionsResidential greenspace did not confound or modify the association between pet ownership and indoor endotoxin levels. Studies should continue investigating whether pets influence the indoor environment only by their presence, or also by acting as transmission vectors of the outdoors.
Tischer C, Dadvand P, Basagana X, et al., 2017, Urban upbringing and childhood respiratory and allergic conditions: A multi-country holistic study., Environmental Research, Vol: 161, Pages: 276-283, ISSN: 0013-9351
OBJECTIVE: We integratively assessed the effect of different indoor and outdoor environmental exposures early in life on respiratory and allergic health conditions among children from (sub-) urban areas. METHODS: This study included children participating in four ongoing European birth cohorts located in three different geographical regions: INMA (Spain), LISAplus (Germany), GINIplus (Germany) and BAMSE (Sweden). Wheezing, bronchitis, asthma and allergic rhinitis throughout childhood were assessed using parental-completed questionnaires. We designed "environmental scores" corresponding to different indoor, green- and grey-related exposures (main analysis, a-priori-approach). Cohort-specific associations between these environmental scores and the respiratory health outcomes were assessed using random-effects meta-analyses. In addition, a factor analysis was performed based on the same exposure information used to develop the environmental scores (confirmatory analysis, data-driven-approach). RESULTS: A higher early exposure to the indoor environmental score increased the risk for wheezing and bronchitis within the first year of life (combined adjusted odds ratio: 1.20 [95% confidence interval: 1.13-1.27] and 1.28 [1.18-1.39], respectively). In contrast, there was an inverse association with allergic rhinitis between 6 and 8 years (0.85 [0.79-0.92]). There were no statistically significant associations for the outdoor related environmental scores in relation to any of the health outcomes tested. The factor analysis conducted confirmed these trends. CONCLUSION: Although a higher exposure to indoor related exposure through occupants was associated with an increased risk for wheezing and bronchitis within the 1st year, it might serve as a preventive mechanism against later childhood allergic respiratory outcomes in urbanized environments through enhanced shared contact with microbial agents.
Markevych I, Schoierer J, Hartig T, et al., 2017, Exploring pathways linking greenspace to health: Theoretical and methodological guidance, Environmental Research, Vol: 158, Pages: 301-317, ISSN: 0013-9351
BACKGROUND: In a rapidly urbanizing world, many people have little contact with natural environments, which may affect health and well-being. Existing reviews generally conclude that residential greenspace is beneficial to health. However, the processes generating these benefits and how they can be best promoted remain unclear. OBJECTIVES: During an Expert Workshop held in September 2016, the evidence linking greenspace and health was reviewed from a transdisciplinary standpoint, with a particular focus on potential underlying biopsychosocial pathways and how these can be explored and organized to support policy-relevant population health research. DISCUSSIONS: Potential pathways linking greenspace to health are here presented in three domains, which emphasize three general functions of greenspace: reducing harm (e.g. reducing exposure to air pollution, noise and heat), restoring capacities (e.g. attention restoration and physiological stress recovery) and building capacities (e.g. encouraging physical activity and facilitating social cohesion). Interrelations between among the three domains are also noted. Among several recommendations, future studies should: use greenspace and behavioural measures that are relevant to hypothesized pathways; include assessment of presence, access and use of greenspace; use longitudinal, interventional and (quasi)experimental study designs to assess causation; and include low and middle income countries given their absence in the existing literature. Cultural, climatic, geographic and other contextual factors also need further consideration. CONCLUSIONS: While the existing evidence affirms beneficial impacts of greenspace on health, much remains to be learned about the specific pathways and functional form of such relationships, and how these may vary by context, population groups and health outcomes. This Report provides guidance for further epidemiological research with the goal of creating new evidence upon which to develop polic
Fuertes E, Markevych I, Jarvis D, et al., 2017, Residential PM2.5 and greenness may modify the effect of physical activity on lung function, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Luzak A, Fuertes E, Flexeder C, et al., 2017, Which early life events or current environmental and lifestyle factors influence lung function in adolescents? results from the GINIplus & LISAplus studies, RESPIRATORY RESEARCH, Vol: 18, ISSN: 1465-993X
BackgroundVarious factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds.MethodsBest subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF25–75)) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis.ResultsA higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF25–75. Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2–22.4%), but these events were consistently negatively associated with airway function.ConclusionsAlthough the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.
Tischer C, Gascon M, Fernandez-Somoano A, et al., 2017, Urban green and grey space in relation to respiratory health in children, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
We assessed the effect of three different indices of urban built environment on allergic and respiratory conditions.This study involved 2472 children participating in the ongoing INMA birth cohort located in two bio-geographic regions (Euro-Siberian and Mediterranean) in Spain. Residential surrounding built environment was characterised as 1) residential surrounding greenness based on satellite-derived normalised difference vegetation index (NDVI), 2) residential proximity to green spaces and 3) residential surrounding greyness based on urban land use patterns. Information on wheezing, bronchitis, asthma and allergic rhinitis up to age 4 years was obtained from parent-completed questionnaires. Logistic regression and generalised estimating equation modelling were performed.Among children from the Euro-Siberian region, higher residential surrounding greenness and higher proximity to green spaces were negatively associated with wheezing. In the Mediterranean region, higher residential proximity to green spaces was associated with a reduced risk for bronchitis. A higher amount of residential surrounding greyness was found to increase the risk for bronchitis in this region.Associations between indices of urban residential greenness and greyness with respiratory diseases differ by region. The pathways underlying these associations require further exploration.
Fuertes E, Flohr C, Silverberg JI, et al., 2017, Global Associations between UVR Exposure and Current Eczema Prevalence in Children from ISAAC Phase Three, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 137, Pages: 1248-1256, ISSN: 0022-202X
We sought to examine the relationship globally between UVR dose exposure and current eczema prevalences. ISAAC Phase Three provided data on eczema prevalence for 13- to 14-year-olds in 214 centers in 87 countries and for 6- to 7-year-olds in 132 centers in 57 countries. Linear and nonlinear associations between (natural log transformed) eczema prevalence and the mean, maximum, minimum, standard deviation, and range of monthly UV dose exposures were assessed using linear mixed-effects regression models. For the 13- to 14-year-olds, the country-level eczema prevalence was positively and linearly associated with country-level monthly mean (prevalence ratio = 1.31 [95% confidence interval = 1.05–1.63] per kJ/m2) and minimum (1.25 [1.06–1.47] per kJ/m2) UVR dose exposure. Linear and nonlinear associations were also observed for other metrics of UV. Results were similar in trend, but nonsignificant, for the fewer centers with 6- to 7-year-olds (e.g., 1.24 [0.96–1.59] per kJ/m2 for country-level monthly mean UVR). No consistent within-country associations were observed (e.g., 1.05 [0.89–1.23] and 0.92 [0.71–1.18] per kJ/m2 for center-level monthly mean UVR for the 13- to 14- and 6- to 7-year-olds, respectively). These ecological results support a role for UVR exposure in explaining some of the variation in global childhood eczema prevalence.
Gref A, Merid SK, Gruzieva O, et al., 2017, Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 195, Pages: 1373-1383, ISSN: 1073-449X
Rationale: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors.Objectives: To identify gene–environment interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels.Methods: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctors’ diagnoses of asthma up to 8 years in three European birth cohorts (n = 1,534) with look-up for interaction in two separate North American cohorts, CHS (Children’s Health Study) and CAPPS/SAGE (Canadian Asthma Primary Prevention Study/Study of Asthma, Genetics and Environment) (n = 1,602 and 186 subjects, respectively). We assessed expression quantitative trait locus effects in human lung specimens and blood, as well as associations among air pollution exposure, methylation, and transcriptomic patterns.Measurements and Main Results: In the European cohorts, 186 SNPs had an interaction P < 1 × 10−4 and a look-up evaluation of these disclosed 8 SNPs in 4 loci, with an interaction P < 0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within adenylate cyclase 2 (ADCY2) showed the same direction of the interaction effect and were found to influence ADCY2 gene expression in peripheral blood (P = 4.50 × 10−4). One other SNP with P < 0.05 for interaction in CHS, rs686237, strongly influenced UDP-Gal:betaGlcNAc β-1,4-galactosyltransferase, polypeptide 5 (B4GALT5) expression in lung tissue (P = 1.18 × 10−17). Air pollution exposure was associ
Kreiner E, Waage J, Standl M, et al., 2017, Shared genetic variants suggest common pathways in allergy and autoimmune diseases., Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 771-781, ISSN: 1097-6825
BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed 2 genome-wide association studies on self-reported allergy and sensitization comprising a total of 62,330 subjects. These results were used to calculate enrichment for single nucleotide polymorphisms (SNPs) previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites and characterized commonalities in variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DNase-hypersensitive site data. Finally, we compared the allergy data with those of all known diseases. RESULTS: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (P = 1.4e-17) encompassing 29 loci at a false discovery rate of less than 0.05. Such enrichment seemed to be a general characteristic for autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in patients with autoimmune diseases but not those with other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms. Further studies of these shared genetic mechanisms might help in understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.
Markevych I, Maier W, Fuertes E, et al., 2017, Neighbourhood greenness and income of occupants in four German areas: GINIplus and LISAplus, Urban Forestry & Urban Greening, Vol: 21, Pages: 88-95, ISSN: 1618-8667
ObjectiveWe investigated whether families with lower individual-level socioeconomic status (SES) reside in less green neighbourhoods in four areas in Germany.MethodsData were collected within two German birth cohorts – GINIplus and LISAplus. Net equivalent household income was categorized into study area-specific tertiles and used as a proxy for individual-level SES. Neighbourhood greenness was calculated in 500-m buffers around home addresses as: 1) the mean normalized difference vegetation index (NDVI); 2) percent tree cover. Associations between income and neighbourhood greenness were assessed per study area using adjusted linear regression models.ResultsIn the Munich and Leipzig areas, families in the low and medium income tertiles resided in neighbourhoods with lower NDVI compared to those in the high income tertile (mean percent change in NDVI: −4.0 (95% confidence interval = −6.7 to −1.3) and −5.5 (−10.9 to −0.2), respectively). In contrast, in the Wesel area, families in the low income tertile resided in neighbourhoods with higher NDVI (2.9 (0.5–5.3)). Only the association in the Munich area was replicated when using tree cover instead of the NDVI.ConclusionsThis study provides suggestive evidence that the presence and direction of associations between greenness and SES is region-specific in Germany. The degree of urbanization did not clarify this heterogeneity completely.
Fuertes E, Standl M, Forns J, et al., 2016, Traffic-related air pollution and hyperactivity/inattention, dyslexia and dyscalculia in adolescents of the German GINIplus and LISAplus birth cohorts, ENVIRONMENT INTERNATIONAL, Vol: 97, Pages: 85-92, ISSN: 0160-4120
BackgroundFew studies have examined the link between air pollution exposure and behavioural problems and learning disorders during late childhood and adolescence.ObjectivesTo determine whether traffic-related air pollution exposure is associated with hyperactivity/inattention, dyslexia and dyscalculia up to age 15 years using the German GINIplus and LISAplus birth cohorts (recruitment 1995–1999).MethodsHyperactivity/inattention was assessed using the German parent-completed (10 years) and self-completed (15 years) Strengths and Difficulties Questionnaire. Responses were categorized into normal versus borderline/abnormal. Parent-reported dyslexia and dyscalculia (yes/no) at age 10 and 15 years were defined using parent-completed questionnaires. Individual-level annual average estimates of nitrogen dioxide (NO2), particulate matter (PM)10 mass, PM2.5 mass and PM2.5 absorbance concentrations were assigned to each participant's birth, 10 year and 15 year home address. Longitudinal associations between the air pollutants and the neurodevelopmental outcomes were assessed using generalized estimation equations, separately for both study areas, and combined in a random-effects meta-analysis. Odds ratios and 95% confidence intervals are given per interquartile range increase in pollutant concentration.ResultsThe prevalence of abnormal/borderline hyperactivity/inattention scores and parental-reported dyslexia and dyscalculia at 15 years of age was 12.9%, 10.5% and 3.4%, respectively, in the combined population (N = 4745). In the meta- analysis, hyperactivity/inattention was associated with PM2.5 mass estimated to the 10 and 15 year addresses (1.12 [1.01, 1.23] and 1.11 [1.01, 1.22]) and PM2.5 absorbance estimated to the 10 and 15 year addresses (1.14 [1.05, 1.25] and 1.13 [1.04, 1.23], respectively).ConclusionsWe report associations suggesting a potential link between air pollution exposure and hyperactivity/inattention scores, although these findings require replicatio
Heinrich J, Guo F, Fuertes E, 2016, Traffic-Related Air Pollution Exposure and Asthma, Hayfever, and Allergic Sensitisation in Birth Cohorts: A Systematic Review and MetaAnalysis, Geoinformatics and Geostatistics: An Overview, Vol: 4, ISSN: 2327-4581
Fuertes E, Heinrich J, Schultz H, 2016, Re: The effect of air pollution on lung function in children, INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH, Vol: 219, Pages: 476-476, ISSN: 1438-4639
Fuertes E, Markevych I, Bowatte G, et al., 2016, Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts, ALLERGY, Vol: 71, Pages: 1461-1471, ISSN: 0105-4538
BackgroundThe prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort‐specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016).MethodsAllergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6–8 years in six cohorts and 10–12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500‐m buffer around the home address at the time of health assessment. Cohort‐specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random‐effects meta‐analysis.ResultsGreenness in a 500‐m buffer was positively associated with allergic rhinitis at 6–8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta‐analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6–8 years and both outcomes at 10–12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups.ConclusionAlthough residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.
Thiering E, Markevych I, Brueske I, et al., 2016, Associations of Residential Long-Term Air Pollution Exposures and Satellite-Derived Greenness with Insulin Resistance in German Adolescents, ENVIRONMENTAL HEALTH PERSPECTIVES, Vol: 124, Pages: 1291-1298, ISSN: 0091-6765
Background: Epidemiological studies have identified associations between air pollution and green space access with type 2 diabetes in adults. However, it remains unclear to what extent associations with greenness are attributable to air pollution exposure.Objectives: We aimed to investigate associations between long-term exposure to air pollution and satellite-derived greenness with insulin resistance in adolescents.Methods: A total of 837 participants of two German birth cohorts (LISAplus and GINIplus) were included in the analysis. Generalized additive models were used to determine the association of individual satellite-derived greenness defined by the Normalized Difference Vegetation Index (NDVI), long-term air pollution exposure estimated by land-use regression (LUR) models with insulin resistance (HOMA-IR) in 15-year-old adolescents. Models were adjusted for study area, cohort, socioeconomic, and individual characteristics such as body mass index, physical activity, and smoking.Results: Increases of 2 SDs in nitrogen dioxide (NO2; 8.9 μg/m3) and particulate matter ≤ 10 μm in diameter (PM10; 6.7 μg/m3) were significantly associated with 11.4% (95% CI: 4.4, 18.9) and 11.4% (95% CI: 0.4, 23.7) higher HOMA-IR. A 2-SD increase in NDVI in a 1,000-m buffer (0.2 units) was significantly associated with a lower HOMA-IR (–7.4%; 95% CI: –13.3, –1.1). Associations tended to be stronger in adolescents who spent more time outside and in those with lower socioeconomic status. In combined models including both air pollution and greenness, only NO2 remained significantly associated with HOMA-IR, whereas effect estimates for all other exposures attenuated after adjustment for NO2.Conclusions: NO2, often considered as a marker of traffic, was independently associated with insulin resistance. The observed association between higher greenness exposure and lower HOMA-IR in adolescents might thus be attributable mainly to the lower co-exposure to traffi
Gehring U, Wijga AH, Hoek G, et al., 2015, Exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence: a population-based birth cohort study, LANCET RESPIRATORY MEDICINE, Vol: 3, Pages: 933-942, ISSN: 2213-2600
BackgroundPrevious published analyses have focused on the effect of air pollution on asthma and rhinoconjunctivitis throughout early and middle childhood. However, the role of exposure to air pollution in the development of childhood and adolescent asthma and rhinoconjunctivitis remains unclear. We aimed to assess the longitudinal associations between exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence.MethodsWe did a population-based birth cohort study of 14 126 participants from four prospective birth cohort studies from Germany, Sweden, and the Netherlands with 14–16 years of follow-up. We linked repeated questionnaire reports of asthma and rhinoconjunctivitis with annual average air pollution concentrations (nitrogen dioxide [NO2], particulate matter [PM] with a diameter of less than 2·5 μm [PM2·5], less than 10 μm [PM10], and between 2·5 μm and 10 μm [PMcoarse], and PM2·5 absorbance [indicator of soot]) at the participants' home addresses. We analysed longitudinal associations of air pollution exposure at participants' birth addresses and addresses at the time of follow-up with asthma and rhinoconjunctivitis incidence and prevalence in cohort-specific analyses, with subsequent meta-analysis and pooled analyses.FindingsOverall, the risk of incident asthma up to age 14–16 years increased with increasing exposure to NO2 (adjusted meta-analysis odds ratio [OR] 1·13 per 10 μg/m3 [95% CI 1·02–1·25]) and PM2·5 absorbance (1·29 per 1 unit [1·00–1·66]) at the birth address. A similar, albeit non-significant, trend was shown for PM2·5 and incident asthma (meta-analysis OR 1·25 per 5 μg/m3 [95% CI 0·94–1·66]). These associations with asthma were more consistent after age 4 years than before that age. There was no indication of an adverse effect of air pollution
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