Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma: Results from the SysPharmPediA Study.

RATIONALE: Early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to identify prognostic and diagnostic biomarkers in pediatric asthma. OBJECTIVES: To assess the accuracy of gas chromatography-mass spectrometry based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma. METHODS: This study encompassed a discovery (SysPharmPediA) and validation phase (U-BIOPRED, PANDA). Firstly, exhaled VOCs that discriminated asthma control levels were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled, based on asthma control test scores and number of severe attacks in the past year. Additionally, potential of VOCs in predicting two or more future severe asthma attacks in SysPharmPediA was evaluated. MEASUREMENTS AND MAIN RESULTS: Complete data were available for 196 children (SysPharmPediA=100, U-BIOPRED=49, PANDA=47). In SysPharmPediA, after randomly splitting the population into training (n=51) and test sets (n=49), three compounds (acetophenone, ethylbenzene, and styrene) distinguished between uncontrolled and controlled asthmatics. The area under the receiver operating characteristic curve (AUROCC) for training and test sets were respectively: 0.83 (95% CI: 0.65-1.00) and 0.77 (95% CI: 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ±0.06 (UBIOPRED) and 0.68 ±0.05 (PANDA). Attacks prediction tests, resulted in AUROCCs of 0.71 (95% CI 0.51-0.91) and 0.71 (95% CI 0.52-0.90) for training and test sets. CONCLUSIONS: Exhaled metabolites analysis might enable asthma control classification in children. This should stimulate further development of exhaled metabolites-based point-of-care tests in asthma.

Maternal mental health disorders and offspring asthma and allergic diseases: The role of child mental health.

BACKGROUND: Maternal psychological stress during pregnancy and postnatally has been shown to be associated with offspring atopic diseases (asthma, atopic dermatitis and allergic rhinitis). The aim of this study was to assess whether this association may be attributable to the child's own mental health disorders. METHOD: The study population included 15,092 twin children born 2002-2010 in Sweden. Questionnaire data at age 9 years was linked to national patient- and prescription registers. Maternal mental health during pregnancy and 3 years postnatally were identified from diagnosis and medication data (depression, anxiety and stress disorders). Atopic diseases in children were identified from questionnaires, diagnosis and medication data. Child mental health status (depression and anxiety) was identified from questionnaires. Three-way decomposition methods tested for mediation or interaction by child mental health disorders. RESULTS: Maternal mental health disorders were associated with most child atopic diseases including asthma aRR1.36 (95% CI 1.12, 1.60), and child mental health disorders, aRR1.73 (95% CI 1.56, 1.92). Children with mental health disorders were comorbid for atopic diseases with only asthma reaching statistical significance, aRR1.29 (95% CI 1.14, 1.47). Three-way decomposition found that mediation or interaction by child mental health disorders did not account for the mother mental health and child atopy associations except in parent-report asthma, where child mental health disorders mediated 13.4% (95% CI 2.1, 24.7) of the effect, but not for objectively defined (diagnosis and medication) asthma. CONCLUSION: The associations between maternal mental health and child asthma and allergic diseases do not appear to be attributable to child mental health disorders.

Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms.

It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.

Preterm birth reduces the risk of IgE sensitization up to early adulthood: A population-based birth cohort study.

BACKGROUND: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens. OBJECTIVE: To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood. METHODS: Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE ≥0.35 kUA /L to fx5 and/or Phadiatop at each time point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA. RESULTS: In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks) and 330 (9.4%) post-term (≥42 weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR = 0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR = 0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR = 0.71 (95% CI: 0.54-0.94). CONCLUSIONS: Our study suggests an inverse association between preterm birth and long-term IgE sensitization.

Ambient air pollution and inflammation-related proteins during early childhood.

BACKGROUND AND AIM: Experimental studies show that short-term exposure to air pollution may alter cytokine concentrations. There is, however, a lack of epidemiological studies evaluating the association between long-term air pollution exposure and inflammation-related proteins in young children. Our objective was to examine whether air pollution exposure is associated with inflammation-related proteins during the first 2 years of life. METHODS: In a pooled analysis of two birth cohorts from Stockholm County (n = 158), plasma levels of 92 systemic inflammation-related proteins were measured by Olink Proseek Multiplex Inflammation panel at 6 months, 1 year and 2 years of age. Time-weighted average exposure to particles with an aerodynamic diameter of <10 µm (PM10), <2.5 µm (PM2.5), and nitrogen dioxide (NO2) at residential addresses from birth and onwards was estimated via validated dispersion models. Stratified by sex, longitudinal cross-referenced mixed effect models were applied to estimate the overall effect of preceding air pollution exposure on combined protein levels, "inflammatory proteome", over the first 2 years of life, followed by cross-sectional protein-specific bootstrapped quantile regression analysis. RESULTS: We identified significant longitudinal associations of inflammatory proteome during the first 2 years of life with preceding PM2.5 exposure, while consistent associations with PM10 and NO2 across ages were only observed among girls. Subsequent protein-specific analyses revealed significant associations of PM10 exposure with an increase in IFN-gamma and IL-12B in boys, and a decrease in IL-8 in girls at different percentiles of proteins levels, at age 6 months. Several inflammation-related proteins were also significantly associated with preceding PM10, PM2.5 and NO2 exposures, at ages 1 and 2 years, in a sex-specific manner. CONCLUSIONS: Ambient air pollution exposure influences inflammation-related protein levels already during early childhood. Our results also suggest age- and sex-specific differences in the impact of air pollution on children's inflammatory profiles.

Genetic effects of allergen-specific IgE levels on exhaled nitric oxide in schoolchildren with asthma: The STOPPA twin study.

BACKGROUND: Exhaled nitric oxide and blood eosinophils are clinical asthma T-helper type 2 markers in use. Immunoglobulin E (IgE) is often involved in the inflammation associated with atopic asthma. The effect of both blood eosinophils and allergen-specific IgE on exhaled nitric oxide levels is not completely understood. Twin-design studies can improve understanding of the underlying contribution of genetically and/or environmentally driven inflammation markers in asthma. Our aim was to disentangle the covariance between asthma and exhaled nitric oxide into genetic and environmental contributions that can account for inflammation markers in a paediatric population. METHODS: This population-based, cross-sectional twin study enrolled 612 monozygotic (MZ) and same-sex dizygotic (DZ) schoolchildren. Multivariate structural equation modelling was utilized to separate the covariance between asthma and exhaled nitric oxide into genetic and/or environmental effects, taking allergen-specific IgE level and blood eosinophil count into account while controlling for confounding factors. RESULTS: The cross-twin/cross-trait correlations had a higher magnitude in the MZ twins than in the DZ twins, indicating that genes affect the association. The likelihood ratio test for model fitting resulted in the AE model (ie additive genetic effects, A, and non-shared environmental effects, E) as the most parsimonious. A majority, 73%, of the phenotypic correlation between asthma and exhaled nitric oxide, r = .19 (0.05-0.33), was attributable to genetic effects which mainly was due to the allergen-specific IgE level. CONCLUSIONS: This study indicates that the association between asthma and exhaled nitric oxide in children is to a large extent explained by genetics via allergen-specific IgE level and not blood eosinophils. This might partly explain the clinical heterogeneity in this group. A next step could be to include allergen-specific IgE level in multivariate omic studies.

Agreement between asthma questionnaire and health care register data.

PURPOSE: Risk factors and consequences of asthma can be studied by using validated questionnaires. The overall objective of this study was to assess the agreement of parental-reported asthma-related questions regarding their children against Swedish health care registers. METHODS: We linked a population-based twin cohort of 27 055 children aged 9 to 12 years to the Swedish Prescribed Drug Register, National Patient Register, and the primary care register. Parent-reported asthma was obtained from questionnaires, and diagnoses and medication were retrieved from the registers. For the agreement between the questionnaire and the registers, Cohen's kappa was estimated. RESULTS: The kappa of the "reported ever asthma" against a "register-based ever asthma" was 0.69 and 0.57 between the parental-"reported doctor's diagnosis" and "register-based doctor's diagnosis." The highest agreement between "reported current asthma" and "register-based current asthma" with at least 1 dispensed medication or a diagnosis applied to different time windows was seen for an 18-month window (kappa = 0.70). CONCLUSIONS: We found that parent-reported asthma-related questions showed on average good agreement with the Swedish health care registers. This implies that in-depth questionnaires with rich information on phenotypes are suitable proxies for asthma in general and can be used for health care research purposes.

Limited association between markers of stress during pregnancy and fetal growth in 'Born into Life', a new prospective birth cohort.

AIMS: We aimed to investigate the associations between perceived maternal stress or salivary cortisol levels during pregnancy and birthweight. METHODS: In 2010-2012, we recruited 92 women living in Stockholm, Sweden, and followed them from before conception and through pregnancy and childbirth. Their Perceived Stress Scale (PSS) scores and salivary cortisol levels were collected at 26-28 gestational weeks. Birthweight was collected from medical records. Linear regression analyses and Pearson correlations were performed between the PSS scores or cortisol levels and birthweight, respectively, adjusted for gestational age. RESULTS: No significant associations were found between PSS scores or cortisol levels and birthweight. There was a trend towards higher salivary cortisol levels among infants with lower birthweights, and this effect was attenuated after adjusting for gestational age. Morning cortisol levels (r = -0.31, p = 0.01), the decline in cortisol levels (r = -0.26, p = 0.03) and evening cortisol levels (r = -0.21, p = 0.09) were negatively correlated with PSS scores. CONCLUSION: Maternal stress during pregnancy was not associated with birthweight. The inverse correlation between PSS scores and cortisol levels may indicate other mechanisms for maternal stress on child outcomes than the previous explanation of hypothalamic-pituitary-adrenal axis activity.

The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders.

OBJECTIVE: In 2015, the Academy for Eating Disorders collaborated with international patient, advocacy, and parent organizations to craft the 'Nine Truths About Eating Disorders'. This document has been translated into over 30 languages and has been distributed globally to replace outdated and erroneous stereotypes about eating disorders with factual information. In this paper, we review the state of the science supporting the 'Nine Truths'. METHODS: The literature supporting each of the 'Nine Truths' was reviewed, summarized and richly annotated. RESULTS: Most of the 'Nine Truths' arise from well-established foundations in the scientific literature. Additional evidence is required to further substantiate some of the assertions in the document. Future investigations are needed in all areas to deepen our understanding of eating disorders, their causes and their treatments. CONCLUSIONS: The 'Nine Truths About Eating Disorders' is a guiding document to accelerate global dissemination of accurate and evidence-informed information about eating disorders. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Topology of genetic associations between regional gray matter volume and intellectual ability: Evidence for a high capacity network.

Intelligence is associated with a network of distributed gray matter areas including the frontal and parietal higher association cortices and primary processing areas of the temporal and occipital lobes. Efficient information transfer between gray matter regions implicated in intelligence is thought to be critical for this trait to emerge. Genetic factors implicated in intelligence and gray matter may promote a high capacity for information transfer. Whether these genetic factors act globally or on local gray matter areas separately is not known. Brain maps of phenotypic and genetic associations between gray matter volume and intelligence were made using structural equation modeling of 3T MRI T1-weighted scans acquired in 167 adult twins of the newly acquired U-TWIN cohort. Subsequently, structural connectivity analyses (DTI) were performed to test the hypothesis that gray matter regions associated with intellectual ability form a densely connected core. Gray matter regions associated with intellectual ability were situated in the right prefrontal, bilateral temporal, bilateral parietal, right occipital and subcortical regions. Regions implicated in intelligence had high structural connectivity density compared to 10,000 reference networks (p=0.031). The genetic association with intelligence was for 39% explained by a genetic source unique to these regions (independent of total brain volume), this source specifically implicated the right supramarginal gyrus. Using a twin design, we show that intelligence is genetically represented in a spatially distributed and densely connected network of gray matter regions providing a high capacity infrastructure. Although genes for intelligence have overlap with those for total brain volume, we present evidence that there are genes for intelligence that act specifically on the subset of brain areas that form an efficient brain network.

Heritability of brain volume change and its relation to intelligence.

Human brain volumes change throughout life, are highly heritable, and have been associated with general cognitive functioning. Cross-sectionally, this association between volume and cognition can largely be attributed to the same genes influencing both traits. We address the question whether longitudinal changes in brain volume or in surface area in young adults are under genetic control and whether these changes are also related to general cognitive functioning. We measured change in brain volume and surface area over a 5-year interval in 176 monozygotic and dizygotic twins and their non-twin siblings aged 19 to 56, using magnetic resonance imaging. Results show that changes in volumes of total brain (mean = -6.4 ml; 0.5% loss), cerebellum (1.4 ml, 1.0% increase), cerebral white matter (4.4 ml, 0.9% increase), lateral ventricles (0.6 ml; 4.8% increase) and in surface area (-19.7 cm(2),1.1% contraction) are heritable (h(2) = 43%; 52%; 29%; 31%; and 33%, respectively). An association between IQ (available for 91 participants) and brain volume change was observed, which was attributed to genes involved in both the variation in change in brain volume and in intelligence. Thus, dynamic changes in brain structure are heritable and may have cognitive significance in adulthood.

Heritability of structural brain network topology: a DTI study of 156 twins.

Individual variation in structural brain network topology has been associated with heritable behavioral phenotypes such as intelligence and schizophrenia, making it a candidate endophenotype. However, little is known about the genetic influences on individual variation in structural brain network topology. Moreover, the extent to which structural brain network topology overlaps with heritability for integrity and volume of white matter remains unknown. In this study, structural network topology was examined using diffusion tensor imaging at 3T. Binary connections between 82 structurally defined brain regions per subject were traced, allowing for estimation of individual topological network properties. Heritability of normalized characteristic path length (λ), normalized clustering coefficient (γ), microstructural integrity (FA), and volume of the white matter were estimated using a twin design, including 156 adult twins from the newly acquired U-TWIN cohort. Both γ and λ were estimated to be under substantial genetic influence. The heritability of γ was estimated to be 68%, the heritability estimate for λ was estimated to be 57%. Genetic influences on network measures were found to be partly overlapping with volumetric and microstructural properties of white matter, but the largest component of genetic variance was unique to both network traits. Normalized clustering coefficient and normalized characteristic path length are substantially heritable, and influenced by independent genetic factors that are largely unique to network measures, but partly also implicated in white matter directionality and volume. Thus, network measures provide information about genetic influence on brain structure, independent of global white matter characteristics such as volume and microstructural directionality.

Biological age is increased by stress and restored upon recovery.

Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. At epigenetic, transcriptomic, and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

Medication use in uncontrolled pediatric asthma: Results from the SysPharmPediA study.

BACKGROUND: Uncontrolled pediatric asthma has a large impact on patients and their caregivers. More insight into determinants of uncontrolled asthma is needed. We aim to compare treatment regimens, inhaler techniques, medication adherence and other characteristics of children with controlled and uncontrolled asthma in the: Systems Pharmacology approach to uncontrolled Paediatric Asthma (SysPharmPediA) study. MATERIAL AND METHODS: 145 children with moderate to severe doctor-diagnosed asthma (91 uncontrolled and 54 controlled) aged 6-17 years were enrolled in this multicountry, (Germany, Slovenia, Spain, and the Netherlands) observational, case-control study. The definition of uncontrolled asthma was based on asthma symptoms and/or exacerbations in the past year. Patient-reported adherence and clinician-reported medication use were assessed, as well as lung function and inhalation technique. A logistic regression model was fitted to assess determinants of uncontrolled pediatric asthma. RESULTS: Children in higher asthma treatment steps had a higher risk of uncontrolled asthma (OR (95%CI): 3.30 (1.56-7.19)). The risk of uncontrolled asthma was associated with a larger change in FEV1% predicted post and pre-salbutamol (OR (95%CI): 1.08 (1.02-1.15)). Adherence and inhaler techniques were not associated with risk of uncontrolled asthma in this population. CONCLUSION: This study showed that children with uncontrolled moderate-to-severe asthma were treated in higher treatment steps compared to their controlled peers, but still showed a higher reversibility response to salbutamol. Self-reported adherence and inhaler technique scores did not differ between controlled and uncontrolled asthmatic children. Other determinants, such as environmental factors and differences in biological profiles, may influence the risk of uncontrolled asthma in this moderate to severe asthmatic population.

Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma.

Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10-8 were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10-9) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.

Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies.

There is consistent evidence that brain volume changes in early and late life. Most longitudinal studies usually only span a few years and include a limited number of participants. In this review, we integrate findings from 56 longitudinal magnetic resonance imaging (MRI) studies on whole brain volume change in healthy individuals. The individual longitudinal MRI studies describe only the development in a limited age range. In total, 2,211 participants were included. Age at first measurement varied between 4 and 88 years of age. The studies included in this review were performed using a large range of methods (e.g., different scanner protocols and different acquisition parameters). We applied a weighted regression analysis to estimate the age dependency of the rate of relative annual brain volume change across studies. The results indicate that whole brain volume changes throughout the life span. A wave of growth occurs during childhood/adolescence, where around 9 years of age a 1% annual brain growth is found which levels off until at age 13 a gradual volume decrease sets in. During young adulthood, between ∼18 and 35 years of age, possibly another wave of growth occurs or at least a period of no brain tissue loss. After age 35 years, a steady volume loss is found of 0.2% per year, which accelerates gradually to an annual brain volume loss of 0.5% at age 60. The brains of people over 60 years of age show a steady volume loss of more than 0.5%. Understanding the mechanisms underlying these plastic brain changes may contribute to distinguishing progressive brain changes in psychiatric and neurological diseases from healthy aging processes. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

Development of gut microbiota during the first 2 years of life.

Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.

A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma.

There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the "Systems Pharmacology Approach to Uncontrolled Pediatric Asthma" (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.

Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study.

The maternal immune system is going through considerable changes during pregnancy. However, little is known about the determinants of the inflammatory proteome and its relation to pregnancy stages. Our aim was to investigate the plasma inflammatory proteome before, during and after pregnancy. In addition we wanted to test whether maternal and child outcomes were associated with the proteome. A cohort of 94 healthy women, enrolled in a longitudinal study with assessments at up to five time points around pregnancy, ninety-two inflammatory proteins were analysed in plasma with a multiplex Proximity Extension Assay. First, principal components analysis were applied and thereafter regression modelling while correcting for multiple testing. We found profound shifts in the overall inflammatory proteome associated with pregnancy stage after multiple testing (p < .001). Moreover, maternal body mass index (BMI) was associated with inflammatory proteome primarily driven by VEGFA, CCL3 and CSF-1 (p < .05). The levels of most inflammatory proteins changed substantially during pregnancy and some of these were related to biological processes such as regulation of immune response. Maternal BMI was significantly associated with higher levels of three inflammation proteins calling for more research in the interplay between pregnancy, inflammation and BMI.