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.
We identified seven allergic disease trajectories up to adolescence, which are corresponding to clinical observation in the German GINIplus and LISA studies and replicated the results in the Swedish BAMSE cohort. The clusters can be characterized using polygenic risk scores and early‐life determinants, which support the hygiene hypothesis. The clusters also pose clinical implications for allergic sensitization, increasing with number of present allergic diseases, and lung function.Abbreviations: BAMSE, Barn/Child Allergy Milieu Stockholm Epidemiology; GINIplus, German Infant Study on the Influence of Nutrition Intervention plus Air pollution and Genetics on Allergy Development; LISA, Influence of Life‐style factors on Development of the Immune System and Allergies in East and West Germany study; PRS, polygenic risk score.
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.
We aimed to investigate associations between long-term exposure to air pollution and satellite-derived greenness with insulin resistance in adolescents.
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.
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.
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 traffic-related air pollution.
Thiering E, Markevych I, Brüske I, Fuertes E, Kratzsch J, Sugiri D, Hoffmann B, von Berg A, Bauer CP, Koletzko S, Berdel D, Heinrich J. 2016. Associations of residential long-term air pollution exposures and satellite-derived greenness with insulin resistance in German adolescents. Environ Health Perspect 124:1291-1298; http://dx.doi.org/10.1289/ehp.1509967.
Background
The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross‐sectional studies. We longitudinally analysed the trajectory of ...Der p 23‐specific IgE antibody (sIgE) levels throughout childhood and youth, their early‐life determinants and their clinical relevance for allergic rhinitis and asthma.
Methods
We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months.
Results
Der p 23‐sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23‐sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma.
Conclusions
Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23‐sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.
Background The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. Objectives We sought to characterize the evolutionary patterns of ...the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. Methods We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. Results One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Conclusions Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.
Background
The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a ...population‐based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow‐up data from two decades of a birth cohort study.
Methods
In 1990, we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population‐based MAS birth cohort study. The sample was purposely risk‐enriched by increasing the proportion of children at high allergy risk (i.e. at least 2 allergic family members among parents and siblings) from 19% in the source population to 38% in the final sample. The remaining 62% of all MAS children had a low or no allergy risk. Symptoms, medication and doctor's diagnoses of allergic diseases have been assessed using standardized questionnaires including validated ISAAC questions in 19 follow‐up assessments up to age 20. Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant: asthma, allergic rhinitis and eczema.
Results
Response at age 20 was 72% (n = 942) of all recruited participants. At age 20, 18.5% (95% CI, 15.0–22.5%) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3% (95% CI, 4.3–9.0%) of those with non‐allergic parents. At this age, allergic multimorbidity was similar in women and men (12.7% (95% CI, 9.7–16.2%) vs. 11.6% (95% CI, 8.9–14.8%)), whereas single allergic diseases were slightly more common in women than men (24.2% (95% CI, 20.2–28.5%) vs. 20.1% (95% CI, 16.6–24.0%)). Asthma occurred more frequently with coexisting allergic rhinitis and/or eczema than as a single entity from pre‐puberty to adulthood.
Conclusion
Having parents with allergies is not only a strong predictor to develop any allergy, but it strongly increases the risk of developing allergic multimorbidity. In males and females alike, coexisting allergies were increasingly common throughout adolescence up to adulthood. Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity.
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 TH2‐TH17 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.
Epidemiological study discovers novel associations between high intake of dietary sucrose and starch with current asthma in males and females, respectively. High‐carbohydrate feeding in mice aggravates allergic outcomes: serum IgE, lung inflammatory cell infiltration, TH2‐ or TH2‐TH17 profiles and mucus hypersecretion. Dietary carbohydrate‐driven enhanced pulmonary oxidative stress and decreased systemic anti‐oxidative capacity are involved in this context.Abbreviations: APE, aqueous pollen extract; EOS, eosinophils; GINIplus, German Infant study on the Influence of Nutrition Intervention plus environmental and genetic influences on allergy development; HDM, house dust mite; IgE, immunoglobulin E; LISA, life‐style related factors on the development of the Immune System and Allergies in East and West Germany; M, macrophages; NEU, neutrophils; Th, T helper
Background The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. Objective We aimed to determine early-life predictors of asthma ...incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. Methods In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). Results Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio HR, 0.66 95% CI, 0.47-0.93). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 95% CI, 1.67-3.02), started day care early or late (before 18 months: adjusted HR, 1.79 95% CI, 1.03-3.10; after 3 years: adjusted HR, 1.64 95% CI, 0.96-2.79), had mothers who smoked during pregnancy (adjusted HR, 1.79 95% CI, 1.20-2.67), had poor parents (adjusted HR, 1.55 95% CI, 1.09-2.22), and had parents with asthma (adjusted HR, 1.65 95% CI, 1.17-2.31). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. Conclusion Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.
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 (β = 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.
Summary
Objective
Weight loss during an inpatient obesity treatment is an important predictor of subsequent weight maintenance. However, psychological factors influencing weight loss are not well ...established. Psychological models suggest some importance of executive functioning and emotion regulation strategies. Therefore, this study investigated whether these factors predict weight loss during an inpatient obesity treatment and whether this effect holds after controlling for general personal and treatment characteristics.
Method
A total of 158 adolescents with diagnosed obesity underwent inpatient obesity treatment at a German rehabilitation clinic. Psychological factors (executive functioning and emotion regulation) were measured at admission and used to predict BMI reduction after treatment completion.
Results
More frequent use of reappraisal as an emotion regulation strategy, but not suppression or executive functioning, predicted weight loss at the end of the obesity treatment, even after controlling for age, gender, treatment duration, and BMI at admission.
Conclusion
Functional emotion regulation strategies, like reappraisal, might offer an additional target for obesity treatment programmes, complementary to the more traditional components of psychoeducation, physical activity, and caloric restriction.
PDF
