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Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs migh

Background: The persistently high prevalence of allergic diseases in Western industrial nations and the limited possibilities of causal therapy make evidence-based recommendations for primary prevention necessary. Methods: The recommendations of the S3 guideline Allergy Prevention, published in its last version in 2014, were revised and consulted on the basis of a current systematic literature search. The evidence search was conducted for the period 06/2013 - 11/2020 in the electronic databases Cochrane and MEDLINE, as well as in the reference lists of current reviews and through references from experts. The literature found was screened in two filtering processes, first by title and abstract, and the remaining papers were screened in the full text for relevance. The studies included after this were sorted by level of evidence, and the study quality was indicated in terms of potential bias (low/high). The revised recommendations were formally agreed and consented upon with the participation of representatives of the relevant professional societies and (self-help) organizations (nominal group process). Of 5,681 hits, 286 studies were included and assessed. Results: Recommendations on maternal nutrition during pregnancy and breastfeeding as well as on infant nutrition in the first months of life again play an important role in the updated guideline: Many of the previous recommendations were confirmed by the current data. It was specified that breastfeeding should be exclusive for the first 4 - 6 months after birth, if possible, and that breastfeeding should continue with the introduction of complementary foods. A new recommendation is that supplementary feeding of cow's milk-based formula should be avoided in the first days of life if the mother wishes to breastfeed. Furthermore, it was determined that the evidence for a clear recommendation for hydrolyzed infant formula in non-breastfed infants at risk is currently no longer sufficient. It is therefore currently reco

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. 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.

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 increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related

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 (N-10 = 2257; N-15 = 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 (beta = 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 (beta = -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.

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.

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.

AIM: To gather the current evidence and to offer recommendations for follow-up and management.METHODS: The Special Interest Group on Coeliac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010 - March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all co-authors. Recommendations were voted upon: joint agreement was set as at least 85%.RESULTS: Publications (n=2775) were identified and 164 were included. Using evidence and/or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anaemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential coeliac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from paediatric to adult health-care.CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with coeliac disease and highlight gaps that should be investigated to further improve management.

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BackgroundAssociations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined.ObjectiveWe assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data.MethodsDietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13–80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI.ResultsThe replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with –3.91 mg/dL (95% CI: –6.98, –0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically signi

Background Lipid mediators derived from omega-6 and omega-3 polyunsaturated fatty acids (PUFA) contribute to the regulation of inflammatory processes in the lung. Adolescence represents an important stage of lung growth, and modifying the availability of PUFA through diet might hold potential for improved lung function. However, effects may depend on individual differences in PUFA metabolism. We assessed the association of rich sources of dietary PUFA with lung function in adolescents, and evaluated the modifying role of 17 single nucleotide polymorphisms (SNP) in the FADS gene cluster involved in PUFA metabolism.Methods 1931 participants of the 15-year follow-up of the GINIplus and LISA birth cohort studies, with data on dietary intake (food-frequency questionnaire), spirometry, and genotyped SNPs of the FADS cluster, were included. Cross-sectional associations of rich dietary sources of omega-6 (margarine) and omega-3 (oily fish) PUFA with lung function z-scores (FVC and FEV1), were assessed by linear regression, adjusting for covariates (sex, age, height, BMI, parental education, asthma, daily calories). Genotypes were coded following an additive model (minor allele count: 0/1/2). Interactions between dietary PUFA and each SNP were independently tested. Following a significant interaction, analyses were additionally stratified by the relevant SNP genotype. Correction for multiple testing was performed according to Nyholt.Results Mean GLI z-scores of FVC and FEV1 were -0.51 and -0.54, respectively. Margarine and oily fish each represented <1% of daily caloric intake. No significant cross-sectional associations were observed between these sources of PUFA and lung function. Although a single nominal effect was found for the interaction between oily fish and rs174449, with respect to FVC (see figure 1 for the association of oily fish and FVC stratified by genotype), it was no longer significant after correction for multiple testing.

Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD’s National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children’s school attendance and parents’ productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. Conclusions: The review of the economic literature on ADA for the treatment of patients

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregula

INTRODUCTION: Patients with paediatric-onset inflammatory bowel disease (PIBD) may develop a complicated disease course, including growth failure, bowel resection at young age and treatment-related adverse events, all of which can have significant and lasting effects on the patient's development and quality of life. Unfortunately, we are still not able to fully explain the heterogeneity between patients and their disease course and predict which patients will respond to certain therapies or are most at risk of developing a more complicated disease course. To investigate this, large prospective studies with long-term follow-up are needed. Currently, no such European or Asian international cohorts exist. In this international cohort, we aim to evaluate disease course and which patients are most at risk of therapy non-response or development of complicated disease based on patient and disease characteristics, immune pathology and environmental and socioeconomic factors. METHODS AND ANALYSIS: In this international prospective observational study, which is part of the PIBD Network for Safety, Efficacy, Treatment and Quality improvement of care (PIBD-SETQuality), children diagnosed with inflammatory bowel disease <18 years are included at diagnosis. The follow-up schedule is in line with standard PIBD care and is intended to continue up to 20 years. Patient and disease characteristics, as well as results of investigations, are collected at baseline and during follow-up. In addition, environmental factors are being assessed (eg, parent's smoking behaviour, dietary factors and antibiotic use). In specific centres with the ability to perform extensive immunological analyses, blood samples and intestinal biopsies are being collected and analysed (flow cytometry, plasma proteomics, mRNA expression and immunohistochemistry) in therapy-naïve patients and during follow-up. ETHICS AND DISSEMINATION: Medical ethical approval has been obtained prior to patient recruitment for all si

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.

Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring’s birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.

© Copyright © 2020 Benítez-Páez, Olivares, Szajewska, Pieścik-Lech, Polanco, Castillejo, Nuñez, Ribes-Koninckx, Korponay-Szabó, Koletzko, Meijer, Mearin and Sanz. Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring’s birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.

Background: Assessing high-sensitivity C-reactive protein (hs-CRP) in relation to allergic endpoints can shed light on both the mechanisms of allergic disease development and early non-communicable disease prevention. However, only a few epidemiological studies so far have investigated the relationship in children and adolescents, and the results were mixed. Objectives: We sought to examine the interrelation between hs-CRP levels and allergic outcomes using a larger population size and a longitudinal study design. Methods: Complete data were available on 1,955 participants from the 15-years follow-up of the 2 large population-based German birth cohorts – GINIplus and LISA. Serum hs-CRP concentrations were measured using the immunoturbidimetric high-sensitive assay. Six allergic endpoints were used – doctor-diagnosed asthma, doctor-diagnosed eczema, doctor-diagnosed allergic rhinitis, food sensitization, aeroallergen sensitization, and any sensitization. We used generalized estimation equation models to assess the associations between hs-CRP levels and allergic endpoints. Results: Our longitudinal analyses did not detect any significant association between hs-CRP levels and any of the studied allergic outcomes (e.g., asthma, eczema, allergic rhinitis, food sensitization, aeroallergen sensitization, and any sensitization). The results were consistent in a series of sensitivity analyses. Conclusions: Our study suggests that there is no association between hs-CRP levels and any of the allergic endpoints in German adolescents. However, whether allergic diseases are inflammatory conditions and which markers might be most sensitive, remain to be confirmed in future studies.