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Abstract Background Numerous studies have investigated links between body mass index (BMI) trajectories and cardiovascular risk, yet discrepancies in BMI measurement duration and timing of the cardiovascular-related outcome evaluation have led to inconsistent findings. Methods We included participants from the Swedish birth cohort (BAMSE) and applied latent class mixture modeling to identify BMI trajectories using data of multiple BMI measures (≥ 4 times) from birth until 24-year follow-up (n = 3204). Subsequently, we analyzed the associations of BMI trajectories with lipids (n = 1974), blood pressure (n = 2022), HbA1c (n = 941), and blood leukocytes (n = 1973) using linear regression. We also investigated the circulating levels of 92 inflammation-related proteins (n = 1866) across BMI trajectories. Results Six distinct BMI groups were identified, denoted as increasing—persistent high (n = 74; 2.3%), high—accelerated increasing (n = 209; 6.5%), increasing—accelerated resolving (n = 142; 4.4%), normal—above normal (n = 721; 22.5%), stable normal (n = 1608; 50.2%), and decreasing—persistent low (n = 450; 14.1%) BMI groups. The increasing—persistent high and high—accelerated increasing BMI groups had higher levels of total cholesterol [mean difference (95% confidence intervals): 0.30 (0.04–0.56) and 0.16 (0.02–0.31) mmol/L], triglyceride, low-density lipoprotein, hemoglobin A1C [3.61 (2.17–5.54) and 1.18 (0.40–1.98) mmol/mol], and low-density lipoprotein/high-density lipoprotein ratios, but a lower level of high-density lipoprotein than the stable normal BMI group. These two groups also had higher leukocyte cell counts and higher circulating levels of 28 inflammation-related proteins. No increased cardiometabolic markers were observed in the increasing—accelerated resolving BMI group. Conclusions Participants with persistently high or accelerated increasing BMI trajectories from birth to young adulthood have elevated levels of cardiometabolic risk markers at young adulthood than those with stable normal BMI. However, a raised BMI in childhood may not be inherently harmful to cardiometabolic health, provided it does not persist into adulthood.

Background Both depression and respiratory disease are common today in young populations. However, little is known about the relationship between them. Aims This study aims to explore the association between depression in childhood to early adulthood and respiratory health outcomes in early adulthood, and the potential underlying mechanisms. Method A prospective study was conducted based on the Swedish BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi [Children, Allergy, Milieu, Stockholm, Epidemiology]) birth cohort (n = 4089). We identified clinically diagnosed depression through the dispensation of antidepressants, using national register data confirmed by self-reported diagnosis. At the 24-year follow-up, respiratory health was assessed via questionnaires and clinical evaluation. Metabolic and inflammatory profiles were analysed to explore potential mechanisms. Results Among the 2994 participants who provided study data, 403 (13.5%) had depression at any time point from around age 10 to 25 years. Depression was associated with higher risks of any chronic bronchitis symptoms (odds ratio = 1.58, 95% CI 1.21–2.06) and respiratory symptoms (odds ratio = 1.41, 95% CI 1.11–1.80) in early adulthood, independent of body mass index (BMI) and smoking status. Compared to individuals without depression, those with depression had a higher fat mass index (FMI (β = 0.48, 95% CI 0.22–0.74)) and increased blood levels of fibroblast growth factor 21 and Interleukin-6 in early adulthood. These markers together with FMI were found to partly mediate the association between depression and respiratory symptoms (total mediation proportion: 19.8 and 15.4%, respectively, P < 0.01). Conclusions Depression in childhood to early adulthood was associated with an increased risk of respiratory ill-health in early adulthood, independently of smoking. Metabolic and inflammatory dysregulations may underlie this link.

Background: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE). Objective: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings. Methods: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding. Results: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51). Conclusions: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.

Background: Children with severe asthma suffer from recurrent symptoms and impaired quality of life despite advanced treatment. Underlying causes of severe asthma are not completely understood, although genetic mechanisms are known to be important. Objective: The aim of this study was to identify gene regulatory enhancers in leukocytes, to describe the role of these enhancers in regulating genes related to severe and mild asthma in children, and to identify known asthma-related SNPs situated in proximity to enhancers. Methods: Gene enhancers were identified and expression of enhancers and genes were measured by Cap Analysis Gene Expression (CAGE) data from peripheral blood leukocytes from children with severe asthma (n = 13), mild asthma (n = 15), and age-matched controls (n = 9). Results: From a comprehensive set of 8,289 identified enhancers, we further defined a robust sub-set of the high-confidence and most highly expressed 4,738 enhancers. Known single nucleotide polymorphisms, SNPs, related to asthma coincided with enhancers in general as well as with specific enhancer-gene interactions. Blocks of enhancer clusters were associated with genes including TGF-beta, PPAR and IL-11 signaling as well as genes related to vitamin A and D metabolism. A signature of 91 enhancers distinguished between children with severe and mild asthma as well as controls. Conclusions: Gene regulatory enhancers were identified in leukocytes with potential roles related to severe and mild asthma in children. Enhancers hosting known SNPs give the opportunity to formulate mechanistic hypotheses about the functions of these SNPs.

Abstract Background Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown. Objective To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD. Methods Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry. Results The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p

BackgroundMany studies reported associations between long-term exposure to environmental factors and mortality; however, little is known on the combined effects of these factors and health. We aimed to evaluate the association between external exposome and all-cause mortality in large administrative and traditional adult cohorts in Europe.MethodsData from six administrative cohorts (Catalonia, Greece, Rome, Sweden, Switzerland and the Netherlands, totaling 27,913,545 subjects) and three traditional adult cohorts (CEANS-Sweden, EPIC-NL-the Netherlands, KORA–Germany, totaling 57,653 participants) were included. Multiple exposures were assigned at the residential addresses, and were divided into three a priori defined domains: (1) air pollution [fine particulate matter (PM2.5), nitrogen dioxide (NO₂), black carbon (BC) and warm-season Ozone (warm-O3)]; (2) land/built environment (Normalized Difference Vegetation Index—NDVI, impervious surfaces, and distance to water); (3) air temperature (cold- and warm-season mean and standard deviation). Each domain was synthesized through Principal Component Analysis (PCA), with the aim of explaining at least 80% of its variability. Cox proportional-hazards regression models were applied and the total risk of the external exposome was estimated through the Cumulative Risk Index (CRI). The estimates were adjusted for individual- and area-level covariates.ResultsMore than 205 million person-years at risk and more than 3.2 million deaths were analyzed. In single-component models, IQR increases of the first principal component of the air pollution domain were associated with higher mortality [HRs ranging from 1.011 (95% CI: 1.005–1.018) for the Rome cohort to 1.076 (1.071–1.081) for the Swedish cohort]. In contrast, lower levels of the first principal component of the land/built environment domain, pointing to reduced vegetation and higher percentage of impervious surfaces, were associated with higher risks. Finally, the CRI of external exposome increased mortality for almost all cohorts. The associations found in the traditional adult cohorts were generally consistent with the results from the administrative ones, albeit without reaching statistical significance.DiscussionVarious components of the external exposome, analyzed individually or in combination, were associated with increased mortality across European cohorts. This sets the stage for future research on the connections between various exposure patterns and human health, aiding in the planning of healthier cities.

Background: Asthma was initially described as a risk factor for severe coronavirus disease 2019 (COVID-19), but the uptake of COVID-19 vaccine among young adults with asthma is not well studied. Objective: The aims were to assess COVID-19 vaccine uptake among young adults in general and to explore potential determinants including sociodemographic factors and asthma. Methods: Participants from the population-based birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) were included: 4,064 in the study population, 3,064 in a follow-up at age 24 years, and 2,049 in a COVID-19 follow-up (mean age, 26.5 years). Asthma and asthma-associated characteristics were assessed through questionnaires and clinical data. Data on all COVID-19 vaccines registered between January 1, 2021, and February 15, 2023, were extracted from the National Vaccination Register. Results: In the study population (n = 4,064), 53.9% had ≥3 COVID-19 vaccine doses registered. In the 24-year follow-up population (n = 3,064), vaccine uptake differed in relation to education (P < .001). Among the participants with university/college education, 65.7% had an uptake of ≥3 doses of vaccine, compared to 54.1% among the participants with elementary school/high school education. Participants with asthma had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.62; 95% confidence interval, 0.41-0.92) and ≥2 compared to peers without asthma. Those with uncontrolled disease also had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.30; 95% confidence interval, 0.13-0.66) and ≥2 compared to participants with controlled asthma. Conclusions: COVID-19 vaccine uptake among young adults is lower in individuals from households with lower socioeconomic status and among those with asthma, including uncontrolled asthma.

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

Abstract Background Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1–11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. Results We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values

Abstract The concept of “one-airway-one-disease”, coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases.

Abstract Post coronavirus disease-19 (post COVID-19) is mainly studied in clinical populations and less is known about post COVID-19 in a young general population. The aim of the study is to investigate the prevalence and symptoms of post COVID-19 and its potential risk factors in young adults. Participants from the Swedish population-based birth cohort BAMSE were included (n = 2022, mean age 26.5 years). Post COVID-19 was assessed through a questionnaire and defined as symptoms after confirmed COVID-19 (registry-based or self-reported positive test) lasting for ≥ 2 months. In total, 681 participants had had confirmed COVID-19. Among them, 112 (16.5%) fulfilled the definition of post COVID-19 (17.8% in females, 14.5% in males, p = 0.26). The most common post COVID-19 symptoms were altered smell and taste (68.8%), dyspnea (33.7%) and fatigue (30.4%). Overall, no major risk factors for post COVID-19 were identified except for being bedbound during COVID-19. However, asthma and rhinitis were associated with the post COVID-19 symptom dyspnea, migraine with altered smell and taste, and lower self-rated health with fatigue. In conclusion, post COVID-19 symptoms are common, also among young adults in the general population. Although not life-threatening, it could have a considerable impact on public health due to the high prevalence and long-term symptoms.

Background Moderate-to-late preterm birth (32 to

BackgroundWe evaluated the independent and joint effects of air pollution, land/built environment characteristics, and ambient temperature on all-cause mortality as part of the EXPANSE project.MethodsWe collected data from six administrative cohorts covering Catalonia, Greece, the Netherlands, Rome, Sweden, and Switzerland and three traditional cohorts in Sweden, the Netherlands, and Germany. Participants were linked to spatial exposure estimates derived from hybrid land use regression models and satellite data for: air pollution [fine particulate matter (PM2.5), nitrogen dioxide (NO₂), black carbon (BC), warm season ozone (O3)], land/built environment [normalized difference vegetation index (NDVI), distance to water, impervious surfaces], and ambient temperature (the mean and standard deviation of warm and cool season temperature). We applied Cox proportional hazard models accounting for several cohort-specific individual and area-level variables. We evaluated the associations through single and multiexposure models, and interactions between exposures. The joint effects were estimated using the cumulative risk index (CRI). Cohort-specific hazard ratios (HR) were combined using random-effects meta-analyses.ResultsWe observed over 3.1 million deaths out of approximately 204 million person-years. In administrative cohorts, increased exposure to PM2.5, NO2, and BC was significantly associated with all-cause mortality (pooled HRs: 1.054, 1.033, and 1.032, respectively). We observed an adverse effect of increased impervious surface and mean season-specific temperature, and a protective effect of increased O3, NDVI, distance to water, and temperature variation on all-cause mortality. The effects of PM2.5 were higher in areas with lower (10th percentile) compared to higher (90th percentile) NDVI levels [pooled HRs: 1.054 (95% confidence interval (CI) 1.030–1.079) vs. 1.038 (95% CI 0.964–1.118)]. A similar pattern was observed for NO2. The CRI of air pollutants (PM2.5 or NO2) plus NDVI and mean warm season temperature resulted in a stronger effect compared to single-exposure HRs: [PM2.5 pooled HR: 1.061 (95% CI 1.021–1.102); NO2 pooled HR: 1.041 (95% CI 1.025–1.057)]. Non-significant effects of similar patterns were observed in traditional cohorts.DiscussionThe findings of our study not only support the independent effects of long-term exposure to air pollution and greenness, but also highlight the increased effect when interplaying with other environmental exposures.

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value

Abstract Background The COVID-19 pandemic has impacted on public health in several ways. The aim of the study was to investigate changes in lifestyle, adiposity, and cardiometabolic markers among young adults in Sweden during the COVID-19 pandemic and their determinants. Methods The study included 1 004 participants from the population-based birth cohort BAMSE. Anthropometrics, body composition (bioelectric impedance analyses), pulse, and blood pressure were measured before (December 2016–May 2019; mean age 22.6 years) and during (October 2020–June 2021; mean age 25.7 years) the COVID-19 pandemic. Lifestyle changes during the pandemic were assessed through a questionnaire. Results All measures of adiposity (weight, BMI, body fat percentage, trunk fat percentage) and cardiometabolic markers (blood pressure, pulse) increased during the study period (e.g., body fat percentage by a median of + 0.8% in females, p

Introduction: The complex interplay of multiple environmental factors and cardiovascular has scarcely been studied. Within the EXPANSE project, we evaluated the association between long-term exposure to multiple environmental indices and stroke incidence across Europe. Methods: Participants from three traditional adult cohorts (Germany, Netherlands and Sweden) and four administrative cohorts (Catalonia [region Spain], Rome [city-wide], Greece and Sweden [nationwide]) were followed until incident stroke, death, migration, loss of follow-up or study end. We estimated exposures at residential addresses from different exposure domains: air pollution (nitrogen dioxide (NO2), particulate matter

Abstract Background During the transition from paediatric to adult healthcare there is a gap between asthma guidelines and actual management with decreased healthcare consultations and dispensations of asthma medications after the transition to adult healthcare among young people with asthma. How health-related quality of life (HRQoL) develops during the transition from adolescence to young adulthood is unclear. Our aim was therefore to investigate HRQoL among young people with asthma during the transition to adulthood. Further, to assess if level of asthma control and physical activity influence any potential association between asthma and HRQoL. Methods The study population consisted of 2268 participants from the ongoing Swedish population-based prospective birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology). HRQoL was measured using the instrument EQ-5D-3 L and three general questions. The EQ-5D-3 L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3 L instrument and questions on general health, symptoms and treatment of asthma, and lifestyle factors were based on data from follow-ups at 16 and 24 years. Cross-sectional analyses were made. Results At the 24-year follow-up, the adjusted median values of EQ VAS were lower compared with at the 16-year follow-up; among both participants with asthma (80 vs. 85, p

Objectives Studies on health effects of tobacco often rely on self-reported exposure data, which is subjective and can lead to misclassification. The aim of this study was to describe the prevalence of cigarette smoking, snus and e-cigarette use, as well as to validate self-reported tobacco use among young adults in Sweden.Method Participants of a population-based Swedish cohort (n=3052), aged 22–25 years, assessed their tobacco use in a web questionnaire. Urinary cotinine was analysed in a subsample of the study population (n=998). The agreement between self-reported tobacco use and urinary cotinine was assessed using Cohen’s Kappa coefficient (κ) at a cut-off level of 50 ng/mL.Results Patterns of tobacco use differed between men and women. Among men, 20.0% reported daily snus use, 5.8% daily cigarette smoking and 5.6% any e-cigarette use. In contrast, 3.2% of the women reported daily snus use, 9.0% daily cigarette smoking and 2.4% any e-cigarette use. Among the tobacco use categories, daily snus users had the highest levels of cotinine. Of reported non-tobacco users, 3.5% had cotinine levels above the cut-off, compared with 68.0% among both occasional cigarette smokers and snus users, 67.5% among all e-cigarette users and 94.7% and 97.8% among daily cigarette smokers and snus users, respectively. Agreement between self-reported tobacco use and urinary cotinine was classified as strong for daily use of cigarettes (κ=0.824) and snus (κ=0.861), while moderate to weak for occasional smoking (κ=0.618), occasional snus use (κ=0.573) and any e-cigarette use (κ=0.576).Conclusions We found high validity of self-reported tobacco use in our study population, particularly for daily tobacco use. Further, we found that daily snus users were exposed to high levels of cotinine. Together with previous findings, our results indicate good validity of self-reported tobacco use among young adults.

Background Epidemiological studies suggest beneficial associations between dietary fibre intake, lung function and chronic respiratory symptoms in adults. Our aim was to investigate the association between dietary fibre intake in childhood and respiratory health up to adulthood. Methods The individual fibre intake of 1956 participants from the Swedish population-based birth cohort BAMSE was estimated from 98- and 107-item food frequency questionnaires at ages 8 and 16 years, respectively. At 8, 16 and 24 years, lung function was measured by spirometry. Respiratory symptoms (cough, mucus production, breathing difficulties/wheeze) were assessed by questionnaires, and airway inflammation by exhaled nitric oxide fraction (FENO) (≥25 ppb) at 24 years. Longitudinal associations with lung function were analysed by mixed-effects linear regression; associations with respiratory symptoms and airway inflammation were analysed by logistic regression, adjusting for potential confounders. Results There were no associations between fibre intake at 8 years, as total and from different sources, spirometry measurements and respiratory symptoms at 24 years. Higher fruit fibre intake tended to be inversely associated with airway inflammation at 24 years (OR 0.70, 95% CI 0.48–1.00), which became non-significant after exclusion of participants with food-related allergic symptoms (OR 0.74, 95% CI 0.49–1.10). No associations between fibre intake at 8 and 16 years as an updated lagged exposure and spirometry measurements up to 24 years were observed. Conclusion In this longitudinal study, we observed no consistent association between dietary fibre intake in childhood and lung function or respiratory symptoms up to adulthood. Further research on dietary fibre in relation to respiratory health across the life course is needed.

Climate change is one of the major public health emergencies with already unprecedented impacts on our planet, environment and health. Climate change has already resulted in substantial increases in temperatures globally and more frequent and extreme weather in terms of heatwaves, droughts, dust storms, wildfires, rainstorms and flooding, with prolonged and altered allergen and microbial exposure as well as the introduction of new allergens to certain areas. All these exposures may have a major burden on patients with respiratory conditions, which will pose increasing challenges for respiratory clinicians and other healthcare providers. In addition, complex interactions between these different factors, along with other major environmental risk factors (e.g. air pollution), will exacerbate adverse health effects on the lung. For example, an increase in heat and sunlight in urban areas will lead to increases in ozone exposure among urban populations; effects of very high exposure to smoke and pollution from wildfires will be exacerbated by the accompanying heat and drought; and extreme precipitation events and flooding will increase exposure to humidity and mould indoors. This review aims to bring respiratory healthcare providers up to date with the newest research on the impacts of climate change on respiratory health. Respiratory clinicians and other healthcare providers need to be continually educated about the challenges of this emerging and growing public health problem and be equipped to be the key players in solutions to mitigate the impacts of climate change on patients with respiratory conditions. Educational aims To define climate change and describe major related environmental factors that pose a threat to patients with respiratory conditions. To provide an overview of the epidemiological evidence on climate change and respiratory diseases. To explain how climate change interacts with air pollution and other related environmental hazards to pose additional challenges for patients. To outline recommendations to protect the health of patients with respiratory conditions from climate-related environmental hazards in clinical practice. To outline recommendations to clinicians and patients with respiratory conditions on how to contribute to mitigating climate change.

Background Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma. Methods We searched four bibliographic databases from inception to 15 March 2021. Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken. Results 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated “very low” to “low” for quality of measurement properties and none met all quality standards. Conclusions This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

Abstract Background Obese asthma is a complex phenotype and further characterization of the pathophysiology is needed. This study aimed to explore inflammation‐related plasma biomarkers in lean and overweight/obese asthmatics. Methods We elucidated levels of inflammation‐related plasma proteins in obese asthma phenotypes in the population‐based cohort BAMSE (Swedish: Children, Allergy, Milieu, Stockholm, Epidemiology) using data from 2069 24‐26‐year‐olds. Subjects were divided into lean asthma (n = 166), lean controls (n = 1440), overweight/obese asthma (n = 73) and overweight/obese controls (n = 390). Protein levels (n = 92) were analysed using the Olink Proseek Multiplex Inflammation panel. Results Of the 92 included proteins, 41 were associated with lean and/or overweight/obese asthma. The majority of proteins associated with overweight/obese asthma also associated with overweight/obesity among non‐asthmatics. Beta‐nerve growth factor (BetaNGF), interleukin 10 (IL‐10), and matrix metalloproteinase 10 (MMP10) were associated only with lean asthma while C‐C motif chemokine 20 (CCL20), fibroblast growth factor 19 (FGF19), interleukin 5 (IL‐5), leukemia inhibitory factor (LIF), tumor necrosis factor ligand superfamily member 9 (TNFRSF9), and urokinase‐type plasminogen activator (uPA) were associated only with overweight/obese asthma. Overweight/obesity modified the association between asthma and 3 of the proteins: fibroblast growth factor 21 (FGF21), interleukin 4 (IL‐4), and urokinase‐type plasminogen activator (uPA). In the overweight/obese group, interleukin‐6 (IL‐6) was associated with non‐allergic asthma but not allergic asthma. Conclusion These data indicate distinct plasma protein phenotypes in lean and overweight/obese asthmatics which, in turn, can impact upon therapeutic approaches.

Residential relocation is increasingly used as a natural experiment in epidemiological studies to assess the health impact of changes in environmental exposures. Since the likelihood of relocation can be influenced by individual characteristics that also influence health, studies may be biased if the predictors of relocation are not appropriately accounted for. Using data from Swedish and Dutch adults (SDPP, AMIGO), and birth cohorts (BAMSE, PIAMA), we investigated factors associated with relocation and changes in multiple environmental exposures across life stages.We used logistic regression to identify baseline predictors of moving, including sociodemographic and household characteristics, health behaviors and health. We identified exposure clusters reflecting three domains of the urban exposome (air pollution, grey surface, and socioeconomic deprivation) and conducted multinomial logistic regression to identify predictors of exposome trajectories among movers.On average, 7 % of the participants relocated each year. Before relocating, movers were consistently exposed to higher levels of air pollution than non-movers. Predictors of moving differed between the adult and birth cohorts, highlighting the importance of life stages. In the adult cohorts, moving was associated with younger age, smoking, and lower education and was independent of cardio-respiratory health indicators (hypertension, BMI, asthma, COPD). Contrary to adult cohorts, higher parental education and household socioeconomic position were associated with a higher probability of relocation in birth cohorts, alongside being the first child and living in a multi-unit dwelling. Among movers in all cohorts, those with a higher socioeconomic position at baseline were more likely to move towards healthier levels of the urban exposome.We provide new insights into predictors of relocation and subsequent changes in multiple aspects of the urban exposome in four cohorts covering different life stages in Sweden and the Netherlands. These results inform strategies to limit bias due to residential self-selection in epidemiological studies using relocation as a natural experiment.

Abstract MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® is a Good Practice of DG Santé on digitally‐enabled, patient‐centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co‐operation and Development). MASK‐air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK‐air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as‐needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom‐medication score (ARIA‐EAACI‐CSMS) has been validated for clinical practice and trials. The implications of the novel MASK‐air® results should lead to change management in rhinitis and asthma.

Abstract Background This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms. Methods Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA). Results The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA. Conclusions We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.

Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data.

Abstract Background Dietary fibre may reduce the risk of allergy. Our aim was to investigate the association between fibre intake in childhood, asthma, allergic rhinitis and IgE sensitization up to adulthood. Methods The individual fibre intake of 2285 participants from the Swedish population‐based birth cohort BAMSE was estimated between 98‐ and 107‐item food frequency questionnaires at ages 8 and 16 years, respectively. At 8, 16 and 24 years, asthma and allergic rhinitis symptoms were assessed by questionnaires, and sensitization to common allergens by serum IgE. Longitudinal associations were analysed by generalized estimating equations, adjusting for potential confounders. Results An inverse overall association was indicated between fibre intake at 8 years and allergic rhinitis symptoms up to 24 years (OR per 5 g/d 0.86; 95% CI 0.77–0.96), particularly in combination with airborne (0.74; 0.62–0.89) and food (0.69; 0.54–0.88) allergen sensitization. Higher fibre intake was also associated with specific allergen sensitization, for example, birch (0.77; 0.67–0.88) and soy (0.68; 0.53–0.87). No association was observed with asthma. Regarding sources, fruit (0.79; 0.67–0.94) and other (potatoes, chips/popcorn, legumes, and nuts, 0.71; 0.50–0.99), but not cereal or vegetable fibre were associated with allergic rhinitis. In additional analyses, including long‐term fibre intake at 8 and 16 years, excluding participants with food‐related allergic symptoms to examine reverse causation, as well as adjusting for antioxidant intake, associations were attenuated and became non‐significant. Conclusion Higher fibre intake in mid‐childhood may be inversely associated with allergic rhinitis and sensitization to specific allergens up to adulthood. However, avoidance of food triggers of allergic symptoms in allergic rhinitis patients may contribute to the protective associations.

Background There are phenotypic differences in asthma in males and females. Differences in lung function between the sexes at the peak lung function level in young adulthood are so far not directly addressed. The aim of the present study was to assess lung function in early adulthood in males and females depending on asthma onset and remission. Methods Participants were included from the population-based birth cohort BAMSE and classified as having: never asthma, childhood asthma in remission, adolescent onset asthma or persistent asthma. Pre- and post-bronchodilator lung function (in Z-score) and lung clearance index (LCI) were measured at age 24 years. Lung function was compared stratified for sex between the never asthma and asthma groups univariately and in multiple linear regression analyses adjusted for maternal and paternal asthma, maternal smoking during pregnancy, secondary smoking, daily smoking, early respiratory syncytial virus infection, traffic pollution, childhood allergic sensitisation, and body mass index at age 24 years. Results All asthma phenotypes were associated with a lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) post-bronchodilation at 24 years. This was most pronounced in males with persistent asthma compared to males with never asthma (regression coefficient: −0.503; 95% CI: −0.708– −0.298). Childhood asthma (in remission or persistent) was associated with a lower FEV1. After adjustment, the associations remained significant for males. For females, the significant associations with lower FEV1 and FEV1/FVC remained only for subjects with asthma in remission. Persistent asthma was associated with higher LCI in females. Conclusions In females, in contrast to males, the association between asthma and lower lung function was attenuated after adjustment for known risk factors.

Abstract Obesity-related inflammation is associated with cardiovascular, metabolic, and pulmonary diseases. The aim of this study was to demonstrate associations between adiposity measurements and levels of inflammation-related plasma proteins in a population of young adults. Subjects from a population-based birth cohort with a mean age of 22.5 years were included in the study population (n = 2074). Protein levels were analyzed using the Olink Proseek Multiplex Inflammation panel. Percentage body fat (%BF) and visceral fat rating (VFR) measurements were collected using Tanita MC 780 body composition monitor. Linear regression of standardized values was used to investigate associations. Potential effect modifications by sex and BMI category were assessed. Of 71 investigated proteins, 54 were significantly associated with all adiposity measurements [%BF, body mass index (BMI), VFR and waist circumference]. Among proteins associated with %BF, seven showed a larger or unique association in overweight/obese subjects and three showed a significant effect modification by sex. Fourteen proteins more strongly associated with VFR in females compared to males. Adipose-associated systemic inflammation was observed in this young adult population. Sex and adiposity localization influenced some of the associations. Our results highlight specific proteins as suitable biomarkers related to adiposity.

Most studies of health-related quality of life (HRQoL) and atopic dermatitis are based on data from dermatology clinics. The aim of this study was to determine whether atopic dermatitis affects HRQoL in adolescence and young adulthood, based on data from the population-based cohort BAMSE (Children, Allergy, Environmental, Stockholm, Epidemiology). A further aim was to determine if the use of topical corticosteroids and healthcare contacts affect HRQoL. Participants with data from birth to young adulthood (n=3,064) were included. Two generic instruments were used to measure HRQoL:General Health at age 12, 16 and 24 years and EQ-5D-3L, including EQ-visual analogue scale (EQ-VAS) at age 24 years. In addition, the disease-specific Dermatology Quality Life Index (DLQI) was used at 24 years. Healthcare consultations for atopic dermatitis were obtained from Stockholm Regional Healthcare Data Warehouse (n = 1,944). Participants with atopic dermatitis had an increased odds ratio (OR) of not feeling completely healthy (adjusted OR 1.50; 95% confidence interval (95% CI): 1.30–1.73). Participants with persistent atopic dermatitis, fulfilling atopic dermatitis criteria in the 12- and/or 16- and 24-year follow-ups reported worse EQ-VAS value 70.0 (95% CI 67.3–72.7) in the 25th percentile, than peers without atopic dermatitis. Over an 8-year period, contact with healthcare was limited (mean number 0.96). In conclusion, atopic dermatitis had a negative impact on HRQoL in young adults from adolescence to adulthood and healthcare consultations were few.

Abstract Background Up to half of the population in high-income countries has allergen-specific IgE antibodies. However, data regarding sex differences of IgE-sensitization from childhood to adulthood is limited. Objective To explore IgE-sensitization to common foods and airborne allergens in relation to sex over time in a population-based cohort followed up to young adulthood. Methods The Swedish population-based birth cohort BAMSE includes 4089 subjects who have been followed regularly with questionnaires and clinical investigations. A recent 24-year follow-up included 3069 participants (75%). Sera collected at 4, 8, 16 and 24 years were analyzed for IgE-antibodies to 14 common foods and airborne allergens. Results At 24 years sensitization to foods had decreased compared to previous follow-ups affecting 8.4%, while sensitization to airborne allergens was more common, affecting 42.2%. Male sex was associated with IgE-sensitization to airborne allergens at all ages (overall OR: 1.68, 95% CI 1.46–1.94) while there was no statistically significant association between sex and sensitization to food allergens (overall OR: 1.10, 95% CI 0.93–1.32). Levels of allergen-specific IgE did not differ significantly between males and females for any of the tested foods or airborne allergens at any age, following adjustment for multiple comparisons. Conclusion IgE-sensitization to airborne allergens increases with age up to young adulthood, whereas sensitization to food allergens seems to level off. Male sex is strongly associated with IgE-sensitization to airborne allergens from early childhood up to young adulthood. In contrast, there is little evidence for associations between sex and IgE-sensitization to foods.

Abstract Background Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs. Methods Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped. Results For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development. Conclusions The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

Abstract Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P

At present, there is no cure for asthma, and treatment typically involves therapies that prevent or reduce asthma symptoms, without modifying the underlying disease. A “disease-modifying” treatment can be classed as able to address the pathogenesis of a disease, preventing progression or leading to a long-term reduction in symptoms. Such therapies have been investigated and approved in other indications, e.g. rheumatoid arthritis and immunoglobulin E-mediated allergic disease. Asthma's heterogeneous nature has made the discovery of similar therapies in asthma more difficult, although novel therapies (e.g. biologics) may have the potential to exhibit disease-modifying properties. To investigate the disease-modifying potential of a treatment, study design considerations can be made, including: appropriate end-point selection, length of trial, age of study population (key differences between adults/children in physiology, pathology and drug metabolism) and comorbidities in the patient population. Potential future focus areas for disease-modifying treatments in asthma include early assessments (e.g. to detect patterns of remodelling) and interventions for patients genetically susceptible to asthma, interventions to prevent virally induced asthma and therapies to promote a healthy microbiome. This review explores the pathophysiology of asthma, the disease-modifying potential of current asthma therapies and the direction future research may take to achieve full disease remission or prevention.

Background The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts. Methods We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ≥LLN, and FVC z-score

Introduction Lung function development from childhood to young adulthood is important for lung health later in life. We investigated the association between asthma control and lung function from 8 to 24 years of age. Methods A total of 668 participants from the population-based BAMSE cohort study, with persistent or incidental asthma and between 8 and 24 years of age, were included. Asthma was defined as controlled or uncontrolled at each examination based on the Global Initiative for Asthma (GINA) criteria. Dynamic spirometry was performed at 8, 16 and 24 years of age. Associations between uncontrolled asthma and pre-bronchodilation forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were evaluated with a generalised estimating equation model, as overall associations and at each examination. Unadjusted and adjusted (for sex, current asthma, allergic sensitisation, body mass index, smoking, smoke exposure, inhaled corticosteroid use) analyses were done; and were thereafter stratified by sex, elevated blood eosinophils (≥0.3×109 cells·µL−1), elevated FENO (≥25 ppb), allergic sensitisation and ever/never smoking. Results Uncontrolled asthma was associated with a lower overall FEV1/FVC z-score from 8 to 24 years of age (adjusted regression coefficient −0.11; 95% CI (−0.20 to −0.02; p=0.016). After stratification, this association was primarily seen among females (adjusted regression coefficient −0.170; 95% CI (−0.298 to −0.044; p=0.009) and participants with elevated FENO (regression coefficient −0.207; 95% CI −0.342 to −0.073; p=0.002), in contrast to males and participants with normal FENO. Conclusion Uncontrolled asthma is associated with airflow obstruction from childhood to young adulthood. This highlights the importance of active management of asthma during growth.

Abstract Background MASK‐air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. Methods Daily monitoring VAS data were assessed in MASK‐air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol‐5 Dimensions (EQ‐5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI‐AS) Questionnaire (work and activity impairment scores). Intra‐rater reliability was assessed in users providing multiple daily VASs within the same day. Test–retest reliability was tested in clinically stable users, as defined by the EQ‐5D VAS, CARAT, or “VAS Work” (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ‐5D‐VAS or “VAS Work” indicating clinical change. Results A total of 17,780 MASK‐air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate–high (Spearman correlation coefficient range: 0.437–0.716). Intra‐rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test–retest reliability ICCs ranged between 0.604 and 0.878—“VAS Work” and “VAS asthma” presented the highest ICCs. Moderate/large responsiveness effect sizes were observed—the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness. Conclusion In MASK‐air®, daily monitoring VASs have high intra‐rater reliability and moderate–high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.

Introduction Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. Methods Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. Results We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. Conclusion Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.

Abstract Background Bronchopulmonary dysplasia (BPD) is a risk factor for respiratory disease in adulthood. Despite the differences in underlying pathology, patients with a history of BPD are often treated as asthmatics. We hypothesized that pulmonary outcomes and health-related quality of life (HRQoL) were different in adults born preterm with and without a history of BPD compared to asthmatics and healthy individuals. Methods We evaluated 96 young adults from the LUNAPRE cohort (clinicaltrials.gov/ct2/show/NCT02923648), including 26 individuals born preterm with a history of BPD (BPD), 23 born preterm without BPD (preterm), 23 asthmatics and 24 healthy controls. Extensive lung function testing and HRQoL were assessed. Results The BPD group had more severe airway obstruction compared to the preterm-, (FEV1− 0.94 vs. 0.28 z-scores; p ≤ 0.001); asthmatic- (0.14 z-scores, p ≤ 0.01) and healthy groups (0.78 z-scores, p ≤ 0.001). Further, they had increased ventilation inhomogeneity compared to the preterm- (LCI 6.97 vs. 6.73, p ≤ 0.05), asthmatic- (6.75, p = 0.05) and healthy groups (6.50 p ≤ 0.001). Both preterm groups had lower DLCO compared to healthy controls (p ≤ 0.001 for both). HRQoL showed less physical but more psychological symptoms in the BPD group compared to asthmatics. Conclusions Lung function impairment and HRQoL in adults with a history of BPD differed from that in asthmatics highlighting the need for objective assessment of lung health.

Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p

COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6–12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 μmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.

BackgroundFetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight.Methods and findingsWe performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations.ConclusionsWe observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Information on factors of importance for remission of eczema is scarce. This study explored factors related to the remission and course of preschool eczema (PSE) (eczema at 1, 2 and/or 4 years of age) to 16 years of age (n = 889) in a Swedish cohort. Half of the children were in complete remission by school age (at age 8, 12, and 16 years). In multivariate prognostic models, persistent PSE (eczema at 1, 2 and 4 years of age) (odds ratio 0.27 (95% confidence interval 0.18–0.41)), PSE with sleep disturbance (due to itch at least once a week at 1, 2 and/or 4 years of age) (0.59 (0.43–0.81)), parental allergy (0.73 (0.55–0.96)), parental smoking at child’s birth (0.70 (0.50–0.99)) and filaggrin mutation (R501X, R2447X, 2282del4) (0.47 (0.26–0.85)) were inversely associated with complete remission by school age. Male sex (1.37 (1.03–1.82)) and exclusive breastfeeding ≥4 months (1.44 (1.01–2.05)) were positively associated with complete remission by school age. In conclusion, half of the children with PSE were in complete remission by school age. The most important prognostic factors were persistent PSE and PSE with sleep disturbance due to itch.

Background: Sensitization in early childhood may precede respiratory allergy in adolescence. Methods: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16 years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16 years. Clinically and independent relevant allergen molecules accounting for ≥90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11 years (N = 248) and the outcome was studied at 11 years. Findings: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16 years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16 years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules. Interpretations: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16 years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.

Abstract Background Bronchopulmonary dysplasia (BPD) is a strong risk factor for respiratory morbidity in children born preterm. Our aims were to evaluate lung function in adolescents born preterm with and without a history of BPD, and to assess lung function change over time from school age. Methods Fifty-one individuals born in Stockholm, Sweden between gestational ages 24 to 31 weeks (23 neonatally diagnosed with respiratory distress syndrome (RDS) but not BPD, and 28 graded as mild (n = 17), moderate (n = 7) or severe (n = 4) BPD) were examined in adolescence (13–17 years of age) using spirometry, impulse oscillometry (IOS), plethysmography, and ergospirometry. Comparison with lung function data from school age (6–8 years of age) was also performed. Results Adolescents with a history of BPD had lower forced expiratory volume in 1 s (FEV1) compared to those without BPD (−0.61 vs.-0.02 z-scores, P

BackgroundThe mechanisms explaining multimorbidity between asthma, dermatitis and rhinitis (allergic multimorbidity) are not well known. We investigated these mechanisms and their specificity in distinct cell types by means of an interactome-based analysis of expression data.MethodsGenes associated to the diseases were identified using data mining approaches, and their multimorbidity mechanisms in distinct cell types were characterized by means of an in silico analysis of the topology of the human interactome.ResultsWe characterized specific pathomechanisms for multimorbidities between asthma, dermatitis and rhinitis for distinct emergent non-eosinophilic cell types. We observed differential roles for cytokine signaling, TLR-mediated signaling and metabolic pathways for multimorbidities across distinct cell types. Furthermore, we also identified individual genes potentially associated to multimorbidity mechanisms.ConclusionsOur results support the existence of differentiated multimorbidity mechanisms between asthma, dermatitis and rhinitis at cell type level, as well as mechanisms common to distinct cell types. These results will help understanding the biology underlying allergic multimorbidity, assisting in the design of new clinical studies.