Accelerometry-assessed sleep clusters and cardiometabolic risk factors in adolescents.

OBJECTIVE: This study aimed to identify sleep clusters based on objective multidimensional sleep characteristics and test their associations with adolescent cardiometabolic health. METHODS: The authors included 1090 participants aged 14.3 to 16.4 years (mean = 15.2 years) who wore 7-day accelerometers during the 15-year follow-up of the German Infant Study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development (GINIplus) and the Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany (LISA) birth cohorts. K-means cluster analysis was performed across 12 sleep characteristics reflecting sleep quantity, quality, schedule, variability, and regularity. Cardiometabolic risk factors included fat mass index (FMI), blood pressure, triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and insulin resistance (n = 505). Linear and logistic regression models were examined. RESULTS: Five sleep clusters were identified: good sleep (n = 337); delayed sleep phase (n = 244); sleep irregularity and variability (n = 108); fragmented sleep (n = 313); and prolonged sleep latency (n = 88). The "prolonged sleep latency" cluster was associated with increased sex-scaled FMI (ß = 0.39, 95% CI: 0.15-0.62) compared with the "good sleep" cluster. The "sleep irregularity and variability" cluster was associated with increased odds of high triglycerides only in male individuals (odds ratio: 9.50, 95% CI: 3.22-28.07), but this finding was not confirmed in linear models. CONCLUSIONS: The prolonged sleep latency cluster was associated with higher FMI in adolescents, whereas the sleep irregularity and variability cluster was specifically linked to elevated triglycerides (≥1.7 mmol/L) in male individuals.

The Influence of Short-Term Weather Parameters and Air Pollution on Adolescent Airway Inflammation.

Fraction of exhaled Nitric Oxide (FeNO) is a marker of airway inflammation. We examined the main effects and interactions of relative humidity (RH) and air pollution on adolescents' FeNO. Two thousand and forty-two participants from the 15-year follow-up of the German GINIplus and LISA birth cohorts were included. Daily meteorological (maximum [Tmax], minimum [Tmin] and mean [Tmean] temperatures and RH) and air pollution [Ozone (O3), nitrogen dioxide (NO2) and particulate matter < 2.5 µm (PM2.5)] were assessed. Linear models were fitted with Ln(FeNO) as the outcome. Increases in FeNO indicate an increase in lung inflammation. Increased FeNO was associated with an increase in temperature, PM2.5, O3 and NO2. A 5% increase in RH was associated with a decrease in FeNO. Interactions between RH and high (p = 0.007) and medium (p = 0.050) NO2 were associated with increases in FeNO; while interactions between RH and high (p = 0.042) and medium (p = 0.040) O3 were associated with decreases in FeNO. Adverse effects were present for male participants, participants with low SES, participants with chronic respiratory disease, and participants from Wesel. Short-term weather and air pollution have an effect on lung inflammation in German adolescents. Future research should focus on further assessing the short-term effect of multiple exposures on lung inflammation in adolescents.

Full Breastfeeding and Allergic Diseases-Long-Term Protection or Rebound Effects?

A previous follow-up of the GINIplus study showed that breastfeeding could protect against early eczema. However, effects diminished in adolescence, possibly indicating a "rebound effect" in breastfed children after initial protection. We evaluated the role of early eczema until three years of age on allergies until young adulthood and assessed whether early eczema modifies the association between breastfeeding and allergies. Data from GINIplus until 20-years of age (N = 4058) were considered. Information on atopic eczema, asthma, and rhinitis was based on reported physician's diagnoses. Adjusted Odds Ratios (aOR) were modelled by using generalized estimating equations. Early eczema was associated with eczema (aORs = 3.2-14.4), asthma (aORs = 2.2-2.7), and rhinitis (aORs = 1.2-2.7) until young adulthood. For eczema, this association decreased with age (p-for-interaction = 0.002-0.006). Longitudinal models did not show associations between breastfeeding and the respective allergies from 5 to 20 years of age. Moreover, early eczema generally did not modify the association between milk feeding and allergies except for rhinitis in participants without family history of atopy. Early eczema strongly predicts allergies until young adulthood. While preventive effects of full breastfeeding on eczema in infants with family history of atopy does not persist until young adulthood, the hypothesis of a rebound effect after initial protection cannot be confirmed.

Gene-environment interaction in the association of residential greenness and 25(OH) vitamin D.

There is increasing awareness for beneficial health effects of green space surrounding the home, but the underlying mechanisms are not yet fully understood and challenging to study given the correlation with other exposures. Here, the association of residential greenness and vitamin D including a gene-environment interaction is investigated. 25-hydroxyvitamin D (25(OH)D) was measured by electrochemiluminescence at ages 10 and 15 years in participants of two German birth cohorts GINIplus and LISA. Greenness was measured using the Landsat-derived Normalized Difference Vegetation Index (NDVI) in a 500 m buffer surrounding the home. Linear and logistic regression models were applied at both time points adjusted for several covariates (N10Y = 2,504, N15Y = 2,613). In additional analyses vitamin D-related genes, physical activity, time spent outdoors, supplements, and measurement season were investigated as potential confounders or effect modifiers. A 1.5-SD increase in NDVI was significantly associated with increased 25(OH)D values at ages 10 and 15 years (ß10y = 2.41 nmol/l, p=<0.01; ß15y = 2.03 nmol/l, p = 0.02). In stratified analyses, the associations were not seen in participants spending more than 5 h/day outside in summer, having a high physical activity level, taking supplements, or being examined during the winter season. In a subset (n = 1,732) with genetic data, a significant gene-environment interaction of NDVI with CYP2R1, an upstream gene in 25(OH)D synthesis, was observed at age 10 years. When investigating 25(OH)D sufficiency, defined as values above 50 nmol/l, a 1.5-SD increase in NDVI was associated with significantly higher odds of having sufficient 25 (OH)D levels at age 10 years (OR = 1.48, 1.19-1.83). In conclusion, robust associations between residential greenness and 25 (OH)D levels were observed in children and adolescents independent of other confounders and additionally supported by the presence of a gene-environment interaction. Effects of NDVI were stronger in those having lower vitamin D levels at age 10 years due to their covariate profile or genetically lower 25(OH)D synthesis.

Dietary digestible carbohydrates are associated with higher prevalence of asthma in humans and with aggravated lung allergic inflammation in mice.

BACKGROUND: Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. METHODS: Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. RESULTS: We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. CONCLUSION: High consumption of digestible carbohydrates is associated with an increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms.

Allergic disease trajectories up to adolescence: Characteristics, early-life, and genetic determinants.

BACKGROUND: Allergic diseases often develop jointly during early childhood but differ in timing of onset, remission, and progression. Their disease course over time is often difficult to predict and determinants are not well understood. OBJECTIVES: We aimed to identify trajectories of allergic diseases up to adolescence and to investigate their association with early-life and genetic determinants and clinical characteristics. METHODS: Longitudinal k-means clustering was used to derive trajectories of allergic diseases (asthma, atopic dermatitis, and rhinitis) in two German birth cohorts (GINIplus/LISA). Associations with early-life determinants, polygenic risk scores, food and aeroallergen sensitization, and lung function were estimated by multinomial models. The results were replicated in the independent Swedish BAMSE cohort. RESULTS: Seven allergic disease trajectories were identified: "Intermittently allergic," "rhinitis," "early-resolving dermatitis," "mid-persisting dermatitis," "multimorbid," "persisting dermatitis plus rhinitis," and "early-transient asthma." Family history of allergies was more prevalent in all allergic disease trajectories compared the non-allergic controls with stronger effect sizes for clusters comprising more than one allergic disease (e.g., RRR = 5.0, 95% CI = [3.1-8.0] in the multimorbid versus 1.8 [1.4-2.4] in the mild intermittently allergic cluster). Specific polygenic risk scores for single allergic diseases were significantly associated with their relevant trajectories. The derived trajectories and their association with genetic effects and clinical characteristics showed similar results in BAMSE. CONCLUSION: Seven robust allergic clusters were identified and showed associations with early life and genetic factors as well as clinical characteristics.

Ambient ozone exposure and bone turnover markers in children: Results from the GINIplus and LISA birth cohorts.

BACKGROUND: Multiple environmental factors can regulate bone metabolism, and it is hypothesized that air pollution may be deleteriously involved in this regulation. However, only a few studies considered bone turnover markers (BTMs) - sensitive and specific markers of bone metabolism - as outcomes, and no study investigated the exposure to ambient ozone. Here, we intended to explore the associations between long-term exposure to ambient ozone and concentrations of two BTMs, osteocalcin and ß-isomer of C-terminal telopeptide of type I collagen (CTx), amongst 10-year-old children. METHODS: Based on the GINIplus and LISA birth cohorts, our cross-sectional analysis included 1848 children aged 10 years from Munich and Wesel. Serum osteocalcin and CTx concentrations were measured. We estimated ozone exposures by optimal interpolation, assessed nitrogen dioxide and particulate matter with an aerodynamic diameter <10 µm concentrations by land use regression models, and assigned the exposures to home addresses. Linear regression models were built and adjusted for covariates as well as co-pollutants. RESULTS: The mean concentrations were 93.09 ng/mL and 663.66 ng/L for osteocalcin and CTx, respectively. In general, higher levels of ozone were associated with decreased concentrations of both BTMs. This held true for the two areas and different exposure metrics. The number of days per year with a maximum 8-h average concentration exceeding 120 µg/m³ showed consistent results across different models. Specifically, models adjusted for co-pollutants illustrated that the beta estimates and 95% confidence intervals on osteocalcin and CTx were -2.51 (-3.78, -1.14) and -44.53 (-57.12, -31.93), respectively, for an increase of 10 days. CONCLUSIONS: We found that long-term exposure to ambient ozone was associated with decreased concentrations of BTMs in German children. This association might potentially affect bone metabolism. Nevertheless, unless other prospective studies confirm our results, the detrimental effects of ambient ozone on bone development in children should be interpreted cautiously.

Psychopathological symptoms as precursors of depressive symptoms in adolescence: a prospective analysis of the GINIplus and LISA birth cohort studies.

INTRODUCTION: Depressive symptoms are highly prevalent in adolescence, highlighting the need for early identification of precursors. Research into psychopathological symptoms predicting depressive psychopathology in adolescents is therefore of great relevance. Moreover, given that the prevalence of depressive symptomatology in adolescence shows marked differences between girls and boys, insight into potential sex-specific differences in precursors is important. METHODS: This study examined the relationships between emotional problems, conduct problems, hyperactivity/inattention, peer problems, and difficulties in prosocial behaviour at age 10 (Strengths and Difficulties Questionnaire), and the presence of depressive symptoms at age 15 (Depression Screener for Teenagers). Using data from 2824 participants of the GINIplus and LISA birth cohorts, the association of each SDQ subscale at age 10 years with the presence of depressive symptoms at age 15 years was analyzed using sex-specific logistic regression, adjusting for potential confounders. RESULTS: Emotional problems [odds ratio (OR) 1.99, p = 0.002 for boys and OR 1.77, p < 0.001 for girls] and peer problems (OR 2.62, p < 0.001 for boys, OR 1.91, p = 0.001 for girls) at age 10 showed an increased risk for the presence of depressive symptoms at age 15. Additionally, boys with conduct problems at age 10 were at greater risk of showing depressive symptoms in adolescence (OR 2.50, p < 0.001). DISCUSSION: Based on the identified prospective relationships in our study, it might be of particular importance to tailor prevention approaches during childhood to peer and emotional problems to reduce the risk of depressive psychopathology in adolescence. Moreover, particularly in boys, it seems important to also target conduct problems in childhood as a precursor of depressive symptoms in the adolescent period.

Obesogenic eating behaviour and dietary intake in German children and adolescents: results from the GINIplus and LISA birth cohort studies.

BACKGROUND/OBJECTIVES: The transition to adolescence is characterised by considerable behavioural changes, including diet. This study describes the level of obesogenic eating behaviours in 10- and 15-year-olds, and their association with dietary intake. SUBJECTS/METHODS: Participants of the 10- and 15-year follow-ups of the German GINIplus and LISA birth cohort studies were included (N10 = 2257; N15 = 1880). Eating behaviours and dietary intake were assessed via self-report questionnaires. Sex-stratified, cross-sectional associations of "external eating", "emotional eating" and "dietary restraint" (the latter at age 15 years only) with dietary intake (17 food groups-categorised into tertiles, macronutrients, and total energy) were assessed using multinomial logistic or multiple linear regression as required, adjusting for covariates and correcting for multiple testing. RESULTS: Reported levels of eating behaviours were low in both age-groups. External eating was higher in 10-year-old males than females, while all eating behaviours were most pronounced in 15-year-old females. At 10 years, emotional eating was associated with medium vegetable intake in females (Relative Risk Ratio (RRR) = 1.84, p = 0.0017). At 15 years, external eating was associated with total energy (kJ) in females (ß = 718, p = 0.0002) and high butter intake in males (RRR = 1.96, p = 0.0019). Dietary restraint in females was inversely associated with total energy (ß = -967, p < 0.0001) and omega-3 fatty acids (Means Ratio (MR) = 0.94, p = 0.0017), and positively associated with high fruit (RRR = 2.20, p = 0.0003) and whole grains (RRR = 1.94, p = 0.0013). CONCLUSION: Obesogenic eating behaviour scores are low among children and adolescents of a predominantly high socioeconomic status population and present only few associations with specific aspects of diet, mainly among adolescent females.

Residential green space and age at menarche in German and Australian adolescent girls: A longitudinal study.

BACKGROUND: A large multicentre European study reported later onset of menopause among women residing in greener areas. This influence on the timing of a reproductive event like menopause, raises the question whether similar associations can be observed with timing of menarche. We investigated whether exposure to residential green space was related to the age at menarche in German and Australian adolescent girls. METHODS: The analytic samples comprised of 1706 German and 1474 Australian adolescent girls. Percentage of green space was calculated in 1000 m buffers around a residential address or its surrogate at the previous follow-up. Mixed effects Cox proportional hazard models were used to explore the associations. The survival object was the occurrence of menarche at the time of follow-up (15-year follow-up of the German cohorts and the study wave at 14-15 years in the Australian cohort) and number of years since baseline (10-year follow-up in the German cohort and the study wave at 10-11 years in the Australian cohort). Participants who did not reach menarche were included as censored observations. RESULTS: A greener residence was not associated with the age at menarche. Null findings were consistent in the general population and in analyses stratified by socioeconomic status or urbanicity in both countries. Urban residents were more likely to have earlier menarche, and this association was consistent across Germany and Australia. CONCLUSION: The results of our analysis do not support the hypothesis that residing in places with more green space can influence timing of menarche. However, given the limitations of our study, researchers should not be discouraged to further explore environmental risk factors of early menarche.

Outdoor air pollution and hormone-assessed pubertal development in children: Results from the GINIplus and LISA birth cohorts.

BACKGROUND: Air pollution is hypothesized to affect pubertal development. However, the few studies on this topic yielded overall mixed results. These studies did not consider important pollutants like ozone, and none of them involved pubertal development assessed by estradiol and testosterone measurements. We aimed to analyze associations between long-term exposure to four pollutants and pubertal development based on sex hormone concentrations among 10-year-old children. METHODS: These cross-sectional analyses were based on the 10-year follow-up medical examinations of 1945 children from the Munich and Wesel centers of the GINIplus and LISA German birth cohorts. Female and male pubertal development was assessed by dichotomizing the concentration of hormones in serum at 18.4 pmol/L and 0.087 nmol/L using the lower limits of quantification for estradiol and testosterone, respectively. Land-use regression models derived annual average concentrations of particulate matter with an aerodynamic diameter < 2.5 and 10 µm (PM2.5 and PM10), as well as spatial models assessed yearly average concentrations of nitrogen dioxide (NO2) and ozone, were calculated at the 10-year residential addresses. To evaluate associations, we utilized logistic regressions adjusted for potential covariates. The analyses were stratified by area and sex. RESULTS: Around 73% of the 943 females and 25% of the 1002 males had a high level of hormones and had already started puberty at the age of 10. Overall, we found no statistically significant associations between exposure to particles (PM2.5 or PM10) and pubertal development. Results on NO2 and ozone were not significant as well; for instance, per 10 µg/m3 increase in ozone concentration, odds ratios and 95% confidence intervals were 0.900 (0.605, 1.339) and 0.830 (0.573, 1.203) for females and males, respectively. Stratified by area, the aforementioned results did not reveal any associations either. CONCLUSIONS: Our study did not observe the associations between ambient air pollutants and pubertal development determined by estradiol and testosterone levels in children. However, due to the current limited number of studies on this topic, our results should be cautiously interpreted. Future longitudinal studies are needed to assess the association.

Long-term Air Pollution Exposure Under European Union Limits and Adolescents' Lung Function: Modifying Effect of Abnormal Weight in the GINIplus and LISA Birth Cohorts.

BACKGROUND: Abnormal weights, eg, obesity, has shown a strong modifying effect on the association between air pollution exposure and lung function impairment in adults. RESEARCH QUESTION: How might weight status modify the effects of long-term air pollution exposure on adolescents' lung function, particularly in areas with pollution levels much lower than the current European Union (EU) air quality standards? STUDY DESIGN AND METHODS: In this observational study, we investigated 2,224 adolescents from the German Infant Study on the Influence of Nutrition Intervention Plus Environmental and Genetic Influences on Allergy Development and the Influence of Life Style Factors on the Development of the Immune System and Allergies in East and West Germany birth cohorts. Lung function was measured at age 15 years. Underweight, normal weight, and overweight or obese were defined using percentiles of BMI. Average concentrations of air pollution were modelled at residential addresses at four exposure windows between 0 and 15 years. Multivariate linear regression models were fitted by weight group on lung function with exposure at each window or cumulative exposure since birth. RESULTS: The median air pollution concentrations were half to two-thirds of the EU standards. Significant associations were observed only for individuals who were underweight and overweight or obese. For example, per interquartile range increase in nitrogen dioxide at the 15-year exposure window, FEV1 declined by -2.9% (95% CI, -5.2% to -0.5%) for the underweight group and -3.4% (95% CI, -5.4% to -1.2%) for the overweight or obese group. Similarly, longer exposure to moderate-level air pollution since birth was associated significantly with lung function impairment for groups with abnormal weight. INTERPRETATION: Exposure to low to moderate levels of air pollution was associated with lung function impairment for adolescents with abnormal weight. Longer exposure aggravated the adverse effect. Whether a critical exposure window since birth exists warrants further exploration.

Air pollution during infancy and lung function development into adolescence: The GINIplus/LISA birth cohorts study.

BACKGROUND: Limited evidence exists on how air pollution exposure during infancy, i.e. the first year of life, may affect lung function development into adolescence. OBJECTIVES: To investigate the association between exposure to air pollution during the first-year of life and lung function development up to the age of 15 in Germany. METHODS: We investigated 915 children from the GINIplus and LISA birth cohorts from Munich (n = 181) and Wesel (n = 734), who had at least two spirometric measurements at ages 6, 10 and 15. Z-scores of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were calculated. Annual average concentrations of nitrogen dioxide, particulate matter with diameters <2.5, <10 and 2.5-10 µm (PM2.5/10/coarse), and PM2.5 absorbance at home addresses during the first-year of life, were estimated by land-use regression models. Associations between infancy exposure and lung function changes were fitted using multivariable linear mixed models with adjustment for potential confounders. RESULTS: For per interquartile range increase in air pollutants during the first-year life, FEV1 z-scores declined annually by -0.012 (95% confidence interval (CI): -0.014, -0.009) for PM2.5 to -0.023 (95%CI: -0.028, -0.018) for PMcoarse. The declines in FVC were lower than FEV1 [-0.006 (95%CI: -0.008, -0.003) to -0.011 (95%CI: -0.019, -0.003)]. In Munich, the attenuations were only significant for FEV1. Effect estimates of infancy exposure for certain air pollutants were higher for groups with asthma, older maternal age, and breastfeeding <12 weeks than their counterparts. DISCUSSION: Infancy exposure to higher air pollution may reduce lung function development up to adolescence, with airway size more affected than lung volume restriction. The potential modifying effects of maternal age, asthmatic status of children and breastfeeding warrant further exploration.

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

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; PM2.5 absorbance (a measurement of the blackness of PM2.5 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/m3 increase in NO2 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 PM2.5 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/m3 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.

Association of early life and acute pollen exposure with lung function and exhaled nitric oxide (FeNO). A prospective study up to adolescence in the GINIplus and LISA cohort.

BACKGROUND: Pollen exposure has both acute and chronic detrimental effects on allergic asthma, but little is known about its wider effects on respiratory health. This is increasingly important knowledge as ambient pollen levels are changing with the changing global climate. OBJECTIVE: To assess associations of pollen exposure with lung function and fractional exhaled nitric oxide (FeNO) at age 15 in two prospective German birth cohorts, GINIplus and LISA. METHODS: Background city-specific pollen exposure was measured in infancy (during the first three months of life), and contemporary (on the day of and 7 days prior to lung function measurement). Greenness levels within circular buffers (100-3000 m) around the birth and 15-year home addresses were calculated using the satellite-derived Normalized Difference Vegetation Index. Regression models were used to assess the associations of grass and birch pollen with lung function and FeNO, and the modifying effects of residential greenness were explored. RESULTS: Cumulative early life exposure to grass pollen was associated with reduced lung function in adolescence (FEV1: -4.9 mL 95%CI: -9.2, -0.6 and FVC: -5.2 mL 95%CI: -9.8, -0.5 per doubling of pollen count). Acute grass pollen exposure was associated with increased airway inflammation in all children, with higher FeNO increases in children living in green areas. In contrast acute birch pollen exposure was associated with reduced lung function only in children sensitised to birch allergens. CONCLUSION: This study provides suggestive evidence that early pollen exposure has a negative effect on later lung function, which is in turn influenced by acute pollen exposures.

Impact of Residential Green Space on Sleep Quality and Sufficiency in Children and Adolescents Residing in Australia and Germany.

Increasing evidence suggests adults living in greener areas tend to have more favourable sleep-related outcomes, but children and adolescents are under-researched. We hypothesised that children and adolescents living in greener areas would have better quality and more sufficient levels of sleep on average, especially within the context of high traffic noise exposure. These hypotheses were tested using multilevel logistic regressions fitted on samples from the nationally representative Longitudinal Study of Australian Children (10-11 years old, n = 3469, and 14-15 years old, n = 2814) and the GINIplus and LISA cohorts (10 years old, n = 1461, and 15 years old, n = 4172) from the Munich, Wesel, and Leipzig areas of Germany. Questionnaire-based binary indicators of sleep sufficiency and sleep quality in each cohort were assessed with respect to objectively measured green space exposures adjusting for age, sex, and maternal education. Models were augmented with proxy measures of traffic noise and two-way interaction terms to test for effect modification. Cross-tabulations illustrated little convincing evidence of association between green space and insufficient sleep or poor sleep quality in either sample, except for insufficient sleep among 10 year old participants in Germany. These null findings were replicated in adjusted models. The proxy for traffic noise was associated with poor quality sleep in 15 year old participants in Germany, but no convincing evidence of modified association with green space was observed.

Association between objectively assessed physical activity and sleep quality in adolescence. Results from the GINIplus and LISA studies.

STUDY OBJECTIVES: Population-based studies on the association of objectively assessed physical activity (PA) with sleep among adolescents are rare. We examined this association by applying accelerometry and accounting for the day-by-day variability. METHODS: Accelerometers (Actigraph GT3X) were worn for one week by 1223 participants during the 15-year follow-up of the German birth cohorts (German infant study on the Influence of Nutrition Intervention plus air pollution and genetics on allergy development, GINIplus) and (Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany, LISA) to measure PA and sleep. PA was categorised into sedentary, lifestyle and moderate-to-vigorous physical activity (MVPA) referring to Sasaki and Romanzini. Sleep was analysed according to the algorithm developed by Sadeh. Sleep quality was represented by sleep efficiency (SE), sleep onset latency (SOL) and time awake per hour after sleep onset (TAPH). Sleep and activity were additionally reported by diaries. Linear and generalized mixed-effects-models with logit-link with subject specific random intercepts were used stratified by sex and adjusted for confounding variables. RESULTS: Physical activity appears to be associated only with sleep quality the following night. Among female participants, SE improved (ß = 0.12 [95% CI = (0.05; 0.18)]) per 10 minutes increase of MVPA. SOL decreased (OR = 0.83 [95% CI = (0.69; 0.99)]) among male participants with at least 60 min of MVPA per day. Engaging in leisure sport MVPA was associated with higher SE among female (ß = 0.70 [95% CI = (0.22; 1.17)]) and male participants (ß = 0.76 [95% CI = (0.18; 1.34)]). Also, TAPH among female (ß = -0.37 [95% CI = (-0.65; -0.09)]) and SOL among male subjects (OR = 0.70 [95% CI = (0.57; 0.85)]) decreased. Increasing lifestyle activity was related to longer SOL among female (OR = 1.36 [95% CI = (1.15; 1.62)]) and male subjects (OR = 1.32 [95% CI = (1.10; 1.58)]). CONCLUSIONS: In this large population-based sample of German adolescents MVPA and leisure sport improved short term sleep quality, supporting regular PA in adolescents for their health benefit.

Short-term exposure to ambient ozone and inflammatory biomarkers in cross-sectional studies of children and adolescents: Results of the GINIplus and LISA birth cohorts.

BACKGROUND: While exposure to ambient particulate matter (PM) and nitrogen dioxide (NO2) is thought to be associated with diseases via inflammatory response, the association between exposure to ozone, an oxidative pollutant, and inflammation has been less investigated. AIM: We analyzed associations between short-term exposure to ozone and three inflammatory biomarkers among children and adolescents. METHODS: These cross-sectional analyses were based on two follow-ups of the GINIplus and LISA German birth cohorts. We included 1330 10-year-old and 1591 15-year-old participants. Fractional exhaled nitric oxide (FeNO) and high-sensitivity C-reactive protein (hs-CRP) were available for both age groups while interleukin (IL)-6 was measured at 10 years only. Maximum 8-h averages of ozone and daily average concentrations of NO2 and PM with an aerodynamic diameter <10 µm (PM10) were adopted from two background monitoring stations 0 (same day), 1, 2, 3, 5, 7, 10 and 14 days prior to the FeNO measurement or blood sampling. To assess associations, we utilized linear regression models for FeNO, and logistic regressions for IL-6 and hs-CRP, adjusting for potential covariates and co-pollutants NO2 and PM10. RESULTS: We found that short-term ozone exposure was robustly associated with higher FeNO in adolescents at age 15, but not at age 10. No consistent associations were observed between ozone and IL-6 in children aged 10 years. The relationship between hs-CRP levels and ozone was J-shaped. Relatively low ozone concentrations (e.g., <120 µg/m³) were associated with reduced hs-CRP levels, while high concentrations (e.g., ≥120 µg/m³) tended to be associated with elevated levels for both 10- and 15-year-old participants. CONCLUSIONS: Our study demonstrates significant associations between short-term ozone exposure and FeNO at 15 years of age and a J-shaped relationship between ozone and hs-CRP. The finding indicates that high ozone exposure may favor inflammatory responses in adolescents, especially regarding airway inflammation.

Dietary saturated fat and low-grade inflammation modified by accelerometer-measured physical activity in adolescence: results from the GINIplus and LISA birth cohorts.

BACKGROUND: Saturated fatty acids (SFA) have been reported to promote inflammation. Nevertheless, evidence linking dietary SFA and low-grade inflammation in adolescents is scarce and inconsistent. The modulatory role of physical activity (PA) on fat metabolism and inflammation may provide a potential explanation. Thus, we assessed the association of dietary SFA with high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, in 15-year-olds, and evaluated possible interactions between dietary SFA and different levels of PA. METHODS: Children participating in the 15-year follow-ups of the GINIplus and LISA German birth cohort studies were included (N = 824). SFA intake was estimated by means of a food frequency questionnaire and PA recorded by accelerometers. Average daily minutes of PA were classified into "sedentary", "light" and "moderate-to-vigorous" (MVPA), using Freedson's cut-offs. HsCRP concentrations were measured in serum and categorized into 3 sex-specific levels (below detection limit (I), above 75th percentile (III), in between (II)). Sex-stratified cross-sectional associations between SFA and hsCRP were assessed using multinomial logistic regression, adjusting for potential confounders. Interaction terms were included between SFA and the different PA levels; and if significant interactions were observed, analyses stratified by tertiles of the relevant PA levels were performed. Relative risk ratios (RRR) and 95% confidence intervals (95%CI) were presented for a 1% increase in SFA. RESULTS: An inverse association was observed between SFA intake and hsCRP (II vs. I) in males (RRR = 0.85 [95%CI = 0.76;0.96], p = 0.008), whereas no significant association was observed in females. A significant interaction was observed with "sedentary" and "light" PA but not with MVPA in both sexes (p < 0.05). Stratified analyses indicated a significant inverse association between SFA and medium hsCRP levels in males in the highest light PA tertile (hsCRP II vs. I: 0.67 [0.517;0.858], p = 0.002). CONCLUSION: Our findings do not support a detrimental role of dietary SFA in low-grade inflammation among adolescents. In males, higher dietary SFA was associated with lower hsCRP, although this should be interpreted in the context of possibly correlated nutrients. Children spending the most time in light PA drove the observed inverse association, suggesting a synergistic effect of SFA and lifestyle PA in the resultant inflammatory response.