Physical activity (PA) protects against most noncommunicable diseases and has been associated with decreased risk of allergic phenotype, which is increasing worldwide. However, the association is not always present; furthermore it is not clear whether it is strongest for asthma, rhinitis, symptoms of these, or atopic sensitization; which sex is most affected; or whether it can be explained by either avoidance of sport or exacerbation of symptoms by exercise. Interventions are thus difficult to target.

Nocturnal gastroesophageal reflux (nGER) is associated with respiratory symptoms and sleep-disordered breathing (SDB), but the pathogenesis is unclear. We aimed to investigate the association between nGER and respiratory symptoms, exacerbations of respiratory symptoms, SDB and airway inflammation.

There is an ongoing debate about the appropriate spirometric criterion for airway obstruction to detect COPD. Furthermore, the association of different criteria with comorbidity prevalence and inflammatory biomarkers in advanced age is unclear.

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Sporting activities differ in their ability to promote moderate-to-vigorous physical activity (MVPA). To assess adolescents' engagement in sport under field conditions we used accelerometers to measure their MVPA levels during sport. We pay special attention to differences between team and individual sport and between common sports.

Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear.

Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.

Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to the lung during acute allergic airway inflammation. The discovery of a corresponding human mast cell progenitor population in the blood has enabled to study the relation of circulating mast cell progenitors in clinical settings.

The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.

Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed.

The association between the exposure to road traffic noise and the prevalence of hypertension was assessed accounting for background air pollution and the location of rooms with respect to the road.

Several studies have found an association between overweight and asthma, yet the temporal relationship between their onsets remains unclear. We investigated the development of body mass index (BMI) from birth to adolescence among 2,818 children with and without asthma from a Swedish birth cohort study, the BAMSE (a Swedish acronym for "children, allergy, milieu, Stockholm, epidemiology") Project, during 1994-2013. Measured weight and height were available at 13 time points throughout childhood. Asthma phenotypes (transient, persistent, and late-onset) were defined by timing of onset and remission. Quantile regression was used to analyze percentiles of BMI, and generalized estimating equations were used to analyze the association between asthma phenotypes and the risk of high BMI. Among females, BMI development differed between children with and without asthma, with the highest BMI being seen among females with persistent asthma. The difference existed throughout childhood but increased with age. For example, females with persistent asthma had 2.33 times' (95% confidence interval: 1.21, 4.49) greater odds of having a BMI above the 85th percentile at age ≥15 years than females without asthma. Among males, no clear associations between asthma and BMI were observed. In this study, persistent asthma was associated with high BMI throughout childhood among females, whereas no consistent association was observed among males.

Elevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Surveillance of physical activity (PA) is increasingly based on accelerometry. However, data management guidelines are lacking. We propose an approach for combining accelerometry and diary based PA information for assessment of PA in adolescents and provide an example of this approach using data from German adolescents.

Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT₄R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach.

Asthma and allergy are complex disorders influenced by both inheritance and environment, a relationship that might be further clarified by epigenetics. Neuropeptide S Receptor 1 (NPSR1) has been associated with asthma and allergy and a study suggested modulation of the genetic risk by environmental factors. We aimed to study DNA methylation in the promoter region of NPSR1 in relation to asthma and environmental exposures. Electrophoretic Mobility Shift Assay (EMSA) was used to investigate potential functional roles of both genotypes and methylation status in the NPSR1 promoter. DNA methylation was analysed using EpiTYPER in blood samples from two well-characterized cohorts; the BIOAIR study of severe asthma in adults and the Swedish birth cohort BAMSE. We observed that DNA methylation and genetic variants in the promoter influenced the binding of nuclear proteins to DNA, suggesting functional relevance. Significant, although small, differences in methylation were related to both adult severe asthma (p = 0.0001) and childhood allergic asthma (p = 0.01). Furthermore, DNA methylation was associated with exposures such as current smoking in adults for two CpG sites (p = 0.005 and 0.04), parental smoking during infancy in the children (p = 0.02) and in which month the sample was taken (p = 0.01). In summary, DNA methylation levels in the promoter of NPSR1 showed small but significant associations with asthma, both in adults and in children, and to related traits such as allergy and certain environmental exposures. Both genetic variation and the methylated state of CpG sites seem to have an effect on the binding of nuclear proteins in the regulatory region of NPSR1 suggesting complex regulation of this gene in asthma and allergy.

Epidemiologic studies have shown that ambient particulate matter (PM) has adverse effects on cardiovascular health. Effective mitigation of the health effects requires identification of the most harmful PM sources. The objective of our study was to evaluate relative effects of fine PM [aerodynamic diameter0.1 mV, with odds ratios at 2-day lag of 1.53 [95% confidence interval (CI), 1.19-1.97] and 1.11 (95% CI, 1.02-1.20) per 1 microg/m3, respectively. In multipollutant models, where we used indicator elements for sources instead of source-specific PM2.5, only absorbance (elemental carbon), an indicator of local traffic and other combustion, was associated with ST segment depressions. Our results suggest that the PM fraction originating from combustion processes, notably traffic, exacerbates ischemic heart diseases associated with PM mass.