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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Background and Aims: Smokeless tobacco is a heterogeneous product group with diverse composition and prevalence globally. Tobacco use during pregnancy is concerning due to the risk of adverse pregnancy outcomes and effects on child health. Nicotine may mediate several of these effects. This systematic review measured health outcomes from Swedish smokeless tobacco (snus) use during pregnancy. Method: Literature search was conducted by an information specialist in May 2022. We included human studies of snus use during pregnancy compared with no tobacco use, assessed risk of bias, conducted a meta-analysis and assessed confidence in effectestimates using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Results: We included 18 cohort studies (42 to 1 006 398 participants). Snus use during pregnancy probably (moderate confidence in risk estimates) increase the risk of neonatal apnea, adjusted odds ratio 95% confidence interval [aOR (95% CI)] 1.96 (1.30 to 2.96). Snus use during pregnancy possibly (low confidence in risk estimates) increase the risk of stillbirths aOR 1.43 (1.02 to 1.99), extremely premature births aOR 1.69 (1.17 to 2.45), moderately premature birth aOR 1.26 (1.15 to 1.38), SGA aOR 1.26 (1.09 to 1.46), reduced birth weight mean difference of 72.47 g (110.58 g to 34.35 g reduction) and oral cleft malformations aOR 1.48 (1.00 to 2.21). It is uncertain (low confidence in risk estimates, CI crossing 1) whether snus use during pregnancy affects risk of preeclampsia aOR 1.11 (0.97 to 1.28), antenatal bleeding aOR 1.15 (0.92 to 1.44) and very premature birth aOR 1.26 (0.95 to 1.66). Risk of early neonatal mortality and altered heart rate variability is uncertain, very low confidence. Snus using mothers had increased prevalence of caesarean sections, low confidence. Conclusions: This systematic review reveals that use of smokeless tobacco (snus) during pregnancy may adversely impact the developing child.

Copyright © 2022 Allergy and respiratory disorders are common in young athletic individuals. In the context of elite sport, it is essential to secure an accurate diagnosis in order to optimize health and performance. It is also important, however, to consider the potential impact or consequences of these disorders, in recreationally active individuals engaging in structured exercise and/or physical activity to maintain health and well-being across the lifespan. This EAACI Task Force was therefore established, to develop an up-to-date, research-informed position paper, detailing the optimal approach to the diagnosis and management of common exercise-related allergic and respiratory conditions. The recommendations are informed by a multidisciplinary panel of experts including allergists, pulmonologists, physiologists and sports physicians. The report is structured as a concise, practically focussed document, incorporating diagnostic and treatment algorithms, to provide a source of reference to aid clinical decision-making. Throughout, we signpost relevant learning resources to consolidate knowledge and understanding and conclude by highlighting future research priorities and unmet needs. European Academy of Allergy and Clinical Immunology

Background: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods: From the Scandinavian antenatally recruited PreventADALL mother–child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA/L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA/L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Results: Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16–0.81 kUA/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53–8.68). Conclusion: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and

Aims To identify maternal food-avoidance diets and dietary supplement use during breastfeeding, and to explore factors associated with food avoidance diets. Design A prospective mother–child birth cohort study. Methods Electronic questionnaires were answered by 1,462 breastfeeding mothers 6 months postpartum in the Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) study from 2014–2016. Demographic and antenatal factors were analysed for associations with food avoidance diets in 1,368 women by multiple logistic regression. Results Overall, 289 breastfeeding women (19.8%) avoided at least one food item in their diet, most commonly cow's milk in 99 women (6.8%). Foods were most often avoided due to conditions in the child, maternal factors or lifestyle choice. The odds for food avoidance diets were 2.1 (95% CI: 1.3, 3.4) for food allergy (presumed or diagnosed) and 19.4 (5.4, 70.1) for celiac disease in the mother. Dietary supplements were reported by nearly 80%, most commonly cod liver oil. Maternal food-avoidance diets and dietary supplements during breastfeeding

Background: Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy. Methods: This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to

BACKGROUND Improved quality of life (QoL) after oral immunotherapy (OIT) in peanut allergic children is often reported by their parents, while the child's perspective is less clear. OBJECTIVE We aimed to explore whether 2 years of OIT improved QoL in children with peanut allergy and to identify factors influencing change in QoL. METHODS In the open-labeled TAKE-AWAY peanut OIT trial including children with anaphylaxis to peanuts, 57 were randomized to OIT and 20 to observation. The Pediatric Quality of Life Inventory Version 4.0 was completed by parents and children at enrollment (Y0 ), after 1 year (end of updosing; Y1 ) and after 2 years (Y2 ) of OIT. Minimally clinically important difference (MCID) is ≥5.3. Perceived treatment burden was recorded by visual analogue scales, including adverse events (AEs). An open food challenge (OFC) was performed at Y2 . RESULTS At Y2 , 18 children had discontinued OIT and 2 of 39 OIT children refused OFC, while 35 of 37 were desensitized to 7500 mg peanut protein. From Y0 to Y2, the mean change (95% confidence intervals) in QoL was 4.4 (0.5, 8.3) among child self-reports and twice as large among parental proxy reports (9.3 [4.3, 14.3]; both P

The nutritional drivers for mother-child sharing of bacteria and the corresponding longitudinal trajectory of the infant gut microbiota development are not yet completely settled. We therefore aimed to characterize the mother-child sharing and the inferred nutritional utilization potential for the gut microbiota from a large unselected cohort. We analyzed in depth gut microbiota in 100 mother-child pairs enrolled antenatally from the general population-based Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) cohort. Fecal samples collected at gestational week 18 for mothers and at birth (meconium), 3, 6, and 12 months for infants were analyzed by reduced metagenome sequencing to determine metagenome size and taxonomic composition. The nutrient utilization potential was determined based on the Virtual Metabolic Human (VMH, www.vmh.life) database. The estimated median metagenome size was ∼150 million base pairs (bp) for mothers and ∼20 million bp at birth for the children. Longitudinal analyses revealed mother-child sharing (P 25% for all age groups). In a multivariate analysis of variance (ANOVA), the mother-child-shared Bacteroides were associated with vaginal delivery (1.7% explained variance, P = 0.0001). Both vaginal delivery and mother-child sharing were associated with host-derived mucins as nutrient sources. The age-related increase in metagenome size corresponded to an increased diversity in nutrient utilization, with dietary polysaccharides as the main age-related factor. Our results support host-derived mucins as potential selection means for mother-child sharing of initial colonizers, while the age-related increase in diversity was associated with dietary polysaccharides. IMPORTANCE The initial bacterial colonization of human infants is crucial for lifelong health. Understanding the factors driving this colonization will therefore be of great importance. Here, we used a novel high-taxonomic-resolution approach to deduce the nutrient utilization potential of the infant gut microbiota in a large longitudinal mother-child cohort. We found mucins as potential selection means for the initial colonization of mother-child-shared bacteria, while the transition to a more adult-like microbiota was associated with dietary polysaccharide utilization potential. This knowledge will be important for a future understanding of the importance of diet in shaping the gut microbiota composition and development during infancy.

BACKGROUND Physical activity during pregnancy is important for maternal and offspring health. Optimal conditions during pregnancy may help reduce the burden of noncommunicable diseases. National and international guidelines recommend at least 150 minutes of physical activity of at least moderate intensity per week. To optimize physical activity in pregnant women, it is important to identify factors associated with higher levels of physical activity. OBJECTIVE This study aimed to explore types and levels of physical activity in midpregnancy in Norway and Sweden and to identify factors associated with higher levels of physical activity. MATERIALS AND METHODS From the population-based mother-child cohort Preventing Atopic Dermatitis and Allergies in Children study recruiting 2697 women in Norway and Sweden from 2014 to 2016, we included 2349 women who answered an electronic questionnaire at enrollment in midpregnancy. Women were asked about regular physical activity in the last 2 weeks of pregnancy and afterward for types and levels of physical activity in pregnancy and before pregnancy and socioeconomic status, lifestyle, and maternal health. Logistic regression analyses were used to identify factors associated with higher levels of physical activity in pregnancy, defined as >30 minutes per session of ≥2 times per week of moderate- or high-intensity brisk walking, strength training, jogging, and bicycling. RESULTS No regular physical activity during the last 2 weeks before answering the questionnaire at midpregnancy was reported by 689 women (29%). In this study, 1787 women (76%) reported weekly strolling during pregnancy. Regular physical activity at least twice weekly in the first half of pregnancy was reported as brisk walking by 839 women (36%), bicycling by 361 women (15%), strength training by 322 women (14%), and other activities by

Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to identify the nutrient utilization- and short-chain fatty acid (SCFA) production potential of gut microbes in infants during the first year of life. Stool samples were obtained from mothers at 18 weeks of pregnancy and from infants at birth (first stool) at 3, 6, and 12-months of age from the general population-based PreventADALL cohort. We identified the taxonomic and SCFA composition in 100 mother-child pairs. The SCFA production and substrate utilization potential of gut microbes were observed by multiomics (shotgun sequencing and proteomics) on six infants. We found a four-fold increase in relative butyrate levels from 6 to 12 months of infant age. The increase was correlated to Eubacterium rectale and its bacterial network, and Faecalibacterium prausnitzii relative abundance, while low butyrate at 12 months was correlated to Ruminococcus gnavus and its associated network of bacteria. Both E. rectale and F. prausnitzii expressed enzymes needed for butyrate production and enzymes related to dietary fiber degradation, while R. gnavus expressed mucus-, fucose, and human milk oligosaccharides (HMO)-related degradation enzymes. Therefore, we believe that the presence of E. rectale, its network, and F. prausnitzii are key bacteria in the transition from an infant- to an adult-like gut microbiota with respect to butyrate production. Our results indicate that the transition from an infant- to an adult-like gut microbiota with respect to butyrate producing bacteria, occurs between 6 and 12 months of infant age. The bacteria associated with the increased butyrate ratio/levels were E. rectale and F. prausnitzii, which potentially utilize a variety of dietary fibers based on the glycoside hydrolases (GHs) expressed. R. gnavus with a negative association to butyrate potentially utilizes mucin, fucose, and HMO components. This knowledge could have future importance in understanding how microbial metabolites can impact infant health and development.

Background and Aim: Impaired lung function in early infancy is associated with later wheeze and asthma, while fetal thoracic circumference (TC) may predict severity of neonatal lung hypoplasia. To explore fetal origins of aberrant lung development we aimed to determine if mid-pregnancy fetal TC was associated with lung function in healthy 3-month old infants. Methods: From the Scandinavian general population-based PreventADALL birth cohort (n=2701), 716 infants had ultrasound measures of TC at around 18 weeks gestational age (GA) and tidal flow volume measures in the awake state at three months of age. Fetal TC correlates strongly with fetal age, estimated by head circumference (HC). Thus, the association between the ratio TC/HC and infant time to Peak Tidal Expiratory Flow to Expiratory time (tPTEF/tE) was analyzed, by linear regression. Maternal asthma, infant sex, GA at birth, birthweight, postnatal age in days, weight, length, respiratory rate, time since last feeding and if the infant had ever been examined for respiratory symptoms were included as covariates. Outcomes were a tPTEF/tE Results: The infants were 47.5% girls. The mean (min, max) GA at birth was 40.2 (35.3, 42.4) weeks and weight at three months 6.3 (4.4, 8.9) kg. The mean (min, max) TC/HC was 0.75 (0.61, 0.93) and tPTEF/tE 0.39 (0.19, 0.60). Five infants had a tPTEF/tE Conclusion: Fetal TC/HC in mid-pregnancy was not associated with tPTEF/tE in healthy awake 3-month old infants.

Nanopore sequencing is rapidly becoming more popular for use in various microbiota-based applications. Major limitations of current approaches are that they do not enable de novo species identification and that they cannot be used to verify species assignments. This severely limits applicability of the nanopore sequencing technology in taxonomic applications. Here, we demonstrate the possibility of de novo species identification and verification using hexamer frequencies in combination with k-means clustering for nanopore sequencing data. The approach was tested on the human infant gut microbiota of 3-month-old infants. Using the hexamer k-means approach we identified two new low abundant species associated with vaginal delivery. In addition, we confirmed both the vaginal delivery association for two previously identified species and the overall high levels of bifidobacteria. Taxonomic assignments were further verified by mock community analyses. Therefore, we believe our de novo species identification approach will have widespread application in analyzing microbial communities in the future.

Rationale: The tobacco harm reduction literature is replete with vague language, far-reaching claims, and unwarranted certainty. The American Thoracic Society has increasingly recognized the need for a framework for reliably making such claims. Evidence-based standards improving the scientific value and transparency of harm reduction claims are expected to improve their trustworthiness, clarity, and consistency. Methods: Experts from relevant American Thoracic Society committees identified key topic areas for discussion. Literature search strategy included English language articles across Medline, Google Scholar, and the Cochrane Collaborative databases, with expanded search terms including tobacco, addiction, smoking, cigarettes, nicotine, and harm reduction. Workgroup members synthesized their evidentiary summaries into a list of candidate topics suitable for inclusion in the final report. Breakout groups developed detailed content maps of each topic area, including points to be considered for suggested recommendations. Successive draft recommendations were modified using an iterative consensus process until unanimous approval was achieved. Patient representatives ensured the document’s relevance to the lay public. Results: Fifteen recommendations were identified, organized into four framework elements dealing with: estimating harm reduction among individuals, making claims on the basis of population impact, appropriately careful use of language, and ethical considerations in harm reduction. Discussion: This statement clarifies important principles guiding valid direct and inferential harm reduction claims. Ideals for effective communication with the lay public and attention to unique ethical concerns are also delineated. The authors call for formal systems of grading harm reduction evidence and regulatory assurances of longitudinal surveillance systems to document the impact of harm reduction policies.

Background There are limited data on the feasibility, efficacy and safety of high-dose oral immunotherapy (OIT) in children highly allergic to peanuts. Objective In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000 mg peanut protein or, alternatively, a lower individual maintenance dose (IMD), by OIT up-dosing. Secondarily, we aimed to identify adverse events (AEs) and determine factors associated with reaching a maintenance dose. Methods The TAKE-AWAY peanut OIT trial enrolled 77 children 5-15 years old, with a positive oral peanut challenge. Fifty-seven were randomized to OIT with biweekly dose step-up until reaching MMD or IMD and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocol deviations were explored for associations with reaching maintenance dose. Results All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s-IgG4 /s-IgE ratio (OR [95% CI]: 1.02 [1.00, 1.04]) was associated with reaching MMD. Conclusion Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25-5 g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited the feasibility of reaching MMD.

AIM: In infants with acute bronchiolitis, the precision of parental disease severity assessment is unclear. We aimed to determine if parental assessment at the time of hospitalisation predicted the use of supportive care, and subsequently determine the likelihood that the infant with acute bronchiolitis would receive supportive care. METHODS: From the Bronchiolitis ALL south-east Norway study, we included all 267, 0-12 month old, infants with acute bronchiolitis whose parents at the time of hospitalisation completed a three-item visual analogue scale (VAS) concerning Activity, Feeding and Illness. Respiratory rate, oxygen saturation (SpO2 ) and use of supportive care were recorded daily. By multivariate logistic regression analyses we included significant predictors available at hospital admission to predict the use of supportive care. RESULTS: The parental Activity, Feeding and Illness VAS scores significantly predicted supportive care with odds ratios of 1.23, 1.26 and 1.36, respectively. The prediction algorithm included parental Feeding and Illness scores, SpO2 , gender and age, with an area under the curve of 0.76 (95% CI 0.69, 0.81). A positive likelihood ratio of 2.1 gave the highest combined sensitivity of 81% and specificity of 61%. CONCLUSION: Parental assessment at hospital admission moderately predicted supportive care treatment in infants with acute bronchiolitis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00817466. Funding source: The study received support in part by Medicines for Children, Pediatric department, Haukeland University hospital, Norway.

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p

Purpose Asthma is frequently reported in endurance athletes. The aim of the present study was to assess the long-term airway inflammatory response to endurance exercise in high-level athletes with and without asthma. Methods In a cross-sectional design, 20 asthmatic athletes (10 swimmers and 10 cross-country skiers), 19 athletes without asthma (10 swimmers and 9 cross-country skiers), and 24 healthy nonathletes completed methacholine bronchial challenge, lung function tests, and sputum induction on two separate days. All athletes competed on a national or international level and exercised ≥10 h·wk-1. The nonathletes exercised ≤5 h·wk-1 and reported no previous lung disease. Bronchial hyperresponsiveness (BHR) was defined as a methacholine provocation dose causing 20% decrease in the forced expiratory volume in 1 s of ≤8 μmol. Results BHR was present in 13 asthmatic athletes (62%), 11 healthy athletes (58%), and 8 healthy nonathletes (32%), and the prevalence differed among groups (P = 0.005). Sputum inflammatory and epithelial cell counts did not differ between groups and were within the normal range. Median (25th to 75th percentiles) sputum interleukin-8 was elevated in both asthmatic (378.4 [167.0-1123.4]) and healthy (340.2 [175.5-892.4]) athletes as compared with healthy nonathletes (216.6 [129.5-314.0], P = 0.02). No correlations were found between provocation dose causing 20% decrease and sputum cell counts. Conclusion Independent of asthma diagnosis, a high occurrence of BHR and an increased sputum interleukin-8 were found in athletes as compared with nonathletes. Airway inflammation or epithelial damage was not related to BHR. (Less)

Background Prenatal exposure to perfluoralkyl substances (PFASs) has been reported to be associated with immunosuppression in early childhood, but with contradictory findings related to atopic and lung diseases. Aim We aimed to determine if prenatal exposure to PFASs is associated with asthma or other allergic diseases or respiratory tract infections in childhood. Methods Nineteen PFASs were measured in cord blood available from 641 infants in the Environment and Childhood Asthma (ECA) prospective birth cohort study. The six most abundant PFASs were perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonamide (PFOSA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA). Health outcomes were assessed at two and ten years of age, and included reported obstructive airways disease (wheeze by 10 years; asthma by 2 and 10 years; reduced lung function at birth; allergic rhinitis by 10 years), atopic dermatitis (AD) by 2 and 10 years, allergic sensitization by 10 years, and episodes of common respiratory tract infections (common cold by 2 years, lower respiratory tract infections (LRTI) by 10 years). The associations between exposure and health outcomes were examined using logistic and Poisson regression. Results The number of reported airways infections were significantly associated with cord blood concentrations of PFAS; common colds by two years with PFUnDA (β = 0.11 (0.08–0.14)) and LRTIs from 0 to 10 years of age with PFOS (β = 0.50 (0.42–0.57)), PFOA (β = 0.28 (0.22–0.35)), PFOSA (β = 0.10 (0.06–0.14)), PFNA (β = 0.09 (0.03–0.14)) and PFUnDA (β = 0.18 (0.13–0.23)) concentrations. Neither reduced lung function at birth, asthma, allergic rhinitis, AD nor allergic sensitization were significantly associated with any of the PFASs. Conclusion Although prenatal exposure to PFASs was not associated with atopic or lung manifestations by 10 years of age, several PFASs were associated with an increased number of respiratory tract infections in the first 10 years of life, suggesting immunosuppressive effects of PFASs.

The evidence of exercise-induced bronchoconstriction (EIB) without asthma (EIBwA ) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms is of major importance as EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby, we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads toward better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.

Dry skin is associated with increased transepidermal water loss (TEWL), which has been found to precede atopic dermatitis (AD) in childhood. Objective We aimed to identify parental, prenatal, and perinatal predictive factors of dry skin, high TEWL, and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months. Methods From the Preventing Atopic Dermatitis and Allergies in children prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL, and eczema were assessed at 3- and 6-month investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL >90th percentile, equaling 11.3 g/m2/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts. Results Significant predictive factors (P < .05) for dry skin at 3 months were delivery >38 gestational weeks and paternal age >37 years; for high TEWL, male sex, birth during winter season, and maternal allergic disease; and for eczema, elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months (adjusted odds ratio: 1.92, 95% confidence interval: 1.21-3.05; P = .005), whereas high TEWL at 3 months was not. Conclusion In early infancy, distinct parental- and pregnancy-related factors were predictive for dry skin, high TEWL, and AD. Dry skin at 3 months of age was predictive for AD 3 months later.

Aim We aimed to determine the prevalence of and factors associated with maternal use of nicotine products in relation to breastfeeding. Methods Nicotine use 3 months postpartum was determined in the Scandinavian PreventADALL mother-child birth cohort study recruiting 1837 women from 2014 to 2016. Electronic questionnaires at 18 weeks pregnancy and 3 months postpartum provided information on snus use, smoking or other nicotine use, infant feeding and socio-economic factors. The risk of nicotine use in relation to breastfeeding was analysed with logistic regression. Results Overall, 5.6% of women used snus (2.9%), smoked (2.7%) or both (n = 2) 3 months postpartum, while one used other nicotine products. Among the 1717 breastfeeding women, 95.1% reported no nicotine use, while 2.4% used snus, 2.5% smoked and one dual user. Compared to 3.7% nicotine use in exclusively breastfeeding women (n = 1242), the risk of nicotine use increased by partly (OR 2.26, 95% CI 1.45-3.52) and no breastfeeding (OR 4.58, 95% CI 2.57-8.21). Nicotine use before (14.5% snus, 16.4% smoking) or in pregnancy (0.2% snus, 0.4% smoking) significantly increased the risk of using nicotine during breastfeeding. Conclusion Few breastfeeding women used snus or smoked 3 months postpartum, with increased risk by nicotine use before or during pregnancy.

Summary Background Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. Methods This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Ostfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov , NCT02449850 . Findings 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI –0·3 to 6·5) for skin intervention and 1·0% (–2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. Interpretation Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Funding The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vardalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council—the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare—FORTE, Oslo University Hospital, the University of Oslo, and Ostfold Hospital Trust.

Background: A woman’s food intake during pregnancy has important implications not only for herself but also for the future health and well-being of her child. Suboptimal dietary quality has been consistently reported in many high-income countries, reflecting poor adherence to dietary guidelines. Objective: This study aimed to explore the intake of food and nutrients in a cohort of pregnant women in Norway and their adherence to Nordic Nutrition Recommendations (NNR) and Norwegian food-based guidelines (NFG). Design: We investigated the dietary intake in 1,674 pregnant women from the mother–child birth cohort, PreventADALL, recruited at approximately 18-week gestational age. Dietary intake was assessed by an electronic validated food frequency questionnaire (PrevFFQ) in the first half of pregnancy. Results: Total fat intake was within the recommended intake (RI) range in most women; however, the contribution of saturated fatty acids to the total energy intake was above RI in the majority (85.2%) of women. Carbohydrate intake was below RI in 43.9% of the women, and 69.5% exceeded the RI of salt. Intakes of fiber, vegetables, and fish were high in a large part of the population. Many women had a high probability of inadequate intakes of the following key micronutrients during pregnancy: folate (54.4%), iron (49.6%), calcium (36.2%), vitamin D (28.7%), iodine (24.4%), and selenium (41.3%). A total of 22.8% women reported an alcohol intake of >1 g/day, and 4.4% reported an alcohol intake of >10 g/day. Women with higher educational levels showed a tendency towards healthier eating habits, except for higher intakes of alcohol and coffee, compared to women with lower educational level. Discussion: Excessive saturated fat intake and limited intake of many important micronutrients during pregnancy were common, potentially increasing the risk for adverse pregnancy and birth outcomes. Conclusions: This study highlights the need for improved nutritional guidance to pregnant women across all educational levels.

Background Acute bronchiolitis during infancy and human rhinovirus (HRV) lower respiratory tract infections increases the risk of asthma in atopic children. We aimed to explore whether specific viruses, allergic sensitisation or cortisol levels during acute bronchiolitis in infancy increase the risk of early asthma, using recurrent wheeze as a proxy. Methods In 294 children with a mean (range) age of 4.2 (0–12) months enrolled during hospitalisation for acute infant bronchiolitis, we analysed virus in nasopharyngeal aspirates, serum specific immunoglobulin E against food and inhalant allergens, and salivary morning cortisol. These factors were assessed by regression analyses, adjusted for age, sex and parental atopy, for risk of recurrent wheeze, defined as a minimum of three parentally reported episodes of wheeze at the 2-year follow-up investigation. Results At 2 years, children with, compared to without, recurrent wheeze had similar rates of respiratory syncytial virus (RSV) (82.9% versus 81.8%) and HRV (34.9% versus 35.0%) at the acute bronchiolitis, respectively. During infancy, 6.9% of children with and 9.2% of children without recurrent wheeze at 2 years were sensitised to at least one allergen (p=0.5). Neither recurrent wheeze nor incidence rate ratios for the number of wheeze episodes at 2 years were significantly associated with specific viruses, high viral load of RSV or HRV, allergic sensitisation, or morning salivary cortisol level during acute bronchiolitis in infancy. Conclusion In children hospitalised with acute infant bronchiolitis, specific viruses, viral load, allergic sensitisation and salivary morning cortisol did not increase the risk of early asthma by 2 years of age., In infants with acute bronchiolitis, specific viruses including human rhinovirus, viral load and/or allergic sensitisation did not increase the risk of asthma by 2 years of age. http://bit.ly/2tCE9Yd

Objective An inverse effect of Helicobacter pylori (H. pylori) on the occurrence of asthma is debated and early acquisition of H. pylori may be important. We analyzed sera from 197 children from Environment and Childhood Asthma (ECA) study in Oslo for Helicobacter pylori (H. pylori) at 2 and 10 years, and symptoms and signs of asthma at 16 years of age. Results While 16.4% of children who were H. pylori negative at 2 and 10 years had current asthma at 16 years, none of the 12 children who were H. pylori positive at 2 years of age had asthma at the age of 16 years, regardless of H. pylori status at 10 years. This trend for less current asthma in children who were H. pylori positive at 2 years compared to persistent or transient negative status at 10 years was not statistically significant, probably due to low number of H. pylori positive children at 2 years of age. Acquisition of H. pylori in school age did not appear to influence the risk of current asthma. Much larger prospective studies are probably required to document whether or not early H. pylori infection may be involved in the risk of asthma development in later childhood.

Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA).The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/mIn the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEVPerceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA.

A high prevalence of asthma and bronchial hyperresponsiveness (BHR) is reported in swimmers and cross-country skiers. It has been suggested that increased parasympathetic nervous activity is involved in asthma development in endurance athletes. We aimed to assess the associations of BHR to parasympathetic activity in healthy and asthmatic swimmers and cross-country skiers and healthy nonathletes.Parasympathetic activity was measured by pupillometry and heart rate variability at the onset of exercise with the cardiac vagal index calculated in 28 cross-country skiers (♂18/♀10), 29 swimmers (♂17/♀12), and 30 healthy nonathlete controls (♂14/♀16) on two different days. All subjects performed a methacholine bronchial challenge with the provocation dose causing 20% decrease in the forced expiratory volume in 1 s calculated (PD20met). Data were analyzed by robust regression analysis and presented as β coefficients with 95% confidence intervals (CI).PD20met was negatively associated with cardiac vagal index (-13.9, 95% CI = -26.8 to -1.0) in all subjects. When adjusted to the type of sport, this association was stronger in swimmers (-8.3, 95% CI = -13.0 to -3.6) as compared with controls and nonsignificant in cross-country skiers. Percent pupil constriction was significantly associated with PD20met in swimmers (-9.4, 95% CI = -15.4 to -3.4) only after adjusting for the type of sport. Fourteen swimmers (48%) and 16 cross-country skiers (57%) had doctor-diagnosed asthma in combination with current BHR and/or current use of asthma drugs. Seventy-two percent swimmers, 44% cross-country skiers, and 39% controls had a PD20met ≤8 μmol (P = 0.015). Fourteen swimmers had a PD20met ≤2 μmol as compared with one cross-country skier (P0.001).Parasympathetic activity measured in the heart is more closely related to BHR as compared with parasympathetic activity measured in the pupils. The type of sport influences BHR severity and its relationship to parasympathetic activity.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

SummaryBackground Epidemiological data and the effect of sun exposure on atopic eczema (AE) suggest that vitamin D (vitD) may be involved in the pathogenesis. Objectives To investigate if vitD levels were associated with the presence or severity of AE in the first 2 years of life in children living in south-east Norway. Methods Infants, recruited to a clinical trial on acute bronchiolitis (n = 404) and from the general population (n = 240), were examined at 1–13 months (first visit) and at 2 years of age (second visit). Caregivers were interviewed using a structured questionnaire. AE was diagnosed clinically, based on well-established criteria. Disease severity was assessed using the SCORing Atopic Dermatitis index. Blood samples were taken for vitD measurements, using liquid chromatography–tandem mass spectrometry and for common filaggrin mutation analyses. Complete data on AE and vitD were available in 596 and 449 children at the first and second visit, respectively. Results Atopic eczema was diagnosed in 67 children (11%) at the first visit and in 103 children (23%) at the second. Mean vitD levels were 58·2 nmol L−1 at the first visit and 66·9 nmol L−1 at the second. Using vitD level tertiles in multivariate regression analysis, there was no association between vitD levels and AE at either visit, regardless of filaggrin mutation. In children without AE at the first visit, vitD levels did not predict AE at the second. Conclusions In this cohort of young children in Norway, we found no association between vitD levels and the presence or severity of AE.

Aim Acute bronchiolitis in infancy increases the risk of later asthma and reduced health-related quality of life (QoL). We aimed to see whether the severity of acute bronchiolitis in the first year of life was associated with QoL nine months later. Methods The parents of 209 of 404 of children hospitalised for acute bronchiolitis in eight paediatric departments in south-east Norway at a mean four months of age (range 0–12 months) completed the Infant/Toddler Quality of Life Questionnaire sent by mail nine months after the acute illness. Disease severity was measured by length of stay and the need for supportive treatment. Interactions with gender, inclusion age, prematurity, maternal ethnicity and maternal education were examined. Results Reduced QoL in four domains was associated with increased length of stay and need for ventilatory support. Physical abilities and general health were associated with both severity markers, whereas bodily pain and discomfort and change in health were associated with length of stay. Ventilatory support was more negatively associated with QoL than atopic eczema and also associated with reduced parental emotions and parental time. Conclusion The severity of acute bronchiolitis in infants was associated with reduced QoL nine months later.

International audience; The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Aim In parallel with falling smoking rates, use of the oral moist tobacco product snus increases among women in reproductive age. We report an update on prevalence and effects of maternal use of snus and nicotine replacement therapy (NRT) during pregnancy and breastfeeding. Methods A literature search of human studies in Medline, PubMed and EMBASE was conducted from September 2016 to May 2018, with stepwise screening of abstracts and subsequent relevant full-text papers for inclusion in Scandinavian and English languages. Results Based on three studies, the prevalence of snus use in pregnancy was up to 3.4% in the first trimester and 2.1% in the third trimester. In 12 studies, we found increased risk of several adverse effects, especially preterm delivery, stillbirth and small for gestational age associated with maternal snus use during pregnancy. Knowledge on effects of NRT during pregnancy was conflicting and inconclusive in 10 studies. We did not identify any studies on prevalence or potential health effects of snus or NRT during breastfeeding. Conclusion Few studies with updated data on the prevalence and adverse health effects of maternal use of snus and NRT during pregnancy were found. No studies during breastfeeding were identified.