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Rationale Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods In the prospective BILD-birth-cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter (PM10) and nitrogen dioxide with lung function at 44 weeks postconceptional age and exhaled markers of inflammation and oxidative stress response (fraction of exhaled nitric oxide (FeNO)) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results Significant associations of PM10 during the second trimester of pregnancy with lung function and FeNO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32 - 36 weeks), with an increase of [184.9 (79.1, 290.7) mL/min] minute ventilation per 10 ��g/m3 increase in PM10 than in term infants [75.3 (19.7, 130.8) mL/min] (pprematurity �� PM10 interaction = 0.04, after multiple comparison adjustment padj = 0.09). Associations of PM10 and FeNO differed between moderate to late preterm [3.4 (-0.1, 6.8) ppb] and term [-0.3 (-1.5, 0.9) ppb] infants, the interaction with prematurity was significant (pprematurity �� PM10 interaction = 0.006, padj = 0.036). Conclusion Preterm infants showed significant higher susceptibility even to low-to-moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. FeNO results further elucidate differences in inflammatory/oxidative stress response comparing preterms to terms.

In 2014, drug-induced enterocolitis syndrome (DIES) was described for the first time. It is still a poorly known disease with symptoms that typically resemble those of food protein-induced enterocolitis syndrome (FPIES). To date, six more cases of DIES have been described and new clinical diagnostic criteria have been proposed based on those in the international guidelines for FPIES. In this paper, the authors describe three more cases of DIES. In addition, similarities and differences with FPIES have been deeply analyzed. To date, several unanswered questions need to be addressed, but clinicians must be instructed how to identify DIES, in order to make an allergy workup and give definite therapeutic indications to patients, especially in children where DIES seems to be more frequent.

The medical challenges caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) pose a tremendous burden on the healthcare system. This study aimed to analyze the effects of a SARS-CoV‑2 infections or disease progression on inpatient mortality of geriatric patients after proximal femoral fracture surgery.A retrospective analysis was conducted in all patients with a proximal femoral fracture surgically treated in an urban regional trauma center from 01/01/2020 to 01/31/2021. According to PCR test results detecting SARS-CoV‑2, the patients were divided into two groups (SARS-CoV‑2 positive vs. SARS-CoV‑2 negative). Patient data, disease progression data, and treatment-related information were evaluated for all patients. Statistical data analysis was performed using unpaired Student's t test or non-parametric Mann-Whitney U test.A total of 311 patients (women: 70.4%, age: 82.0 ± 11.0 years) were included in this study. Of these 3.9% (12/311) had a positive test result for SARS-CoV‑2. Significantly more deceased patients were found in the group tested positive for SARS-CoV‑2 (SARS-CoV‑2 positive: 41.7%, SARS-CoV‑2 negative: 5.4%, p 0.001). In addition, the number of proximal femoral fracture associated deaths correlated with the number of positive test results performed in the Clinic. The length of stay of SARS-CoV‑2 COVID-19 survivors tended to be greater than in those who were tested negative (SARS-CoV‑2 COVID-19 positive: 15.6 ± 13.1 days, SARS-CoV‑2 COVID-19 negative: 11.5 ± 6.5 days, p = 0.683). Furthermore, a significant difference in age was found in SARS-CoV‑2 survivors and SARS-CoV‑2 decedents (deceased: 95.5 ± 7.5 years, alive: 83.5 ± 7.3 years, p = 0.020).The study was conducted before the introduction of SARS-CoV‑2 vaccination. The results therefore refer to immune naive (unvaccinated) patients. In our study, more than 40% of all patients with proximal femoral fractures who tested positive for SARS-CoV‑2 died during hospitalization. An additional, critical factor in this respect was the age of the infected patients. Nonetheless, a positive correlation was demonstrated between the mortality rate and the number of positive SARS-CoV‑2 detections. Regarding the greater length of stay of patients tested positive for SARS-CoV‑2, the limited transfer options (further rehabilitation, skilled nursing facility) of the infected ones can be considered as causal. Particularly the vulnerable older patients are increasingly endangered by a combination of proximal femoral fracture and SARS-CoV‑2.HINTERGRUND: Die medizinischen Herausforderungen, die durch das Schwere Akute Respiratorische Syndrom durch Coronavirus 2 (SARS-CoV‑2) verursacht werden, stellen eine enorme Belastung für das deutsche Gesundheitssystem dar. Ziel dieser Studie war es, die Auswirkungen einer SARS-CoV‑2-Infektion oder eines asymptomatischen Krankheitsverlaufs auf die stationäre Mortalität geriatrischer Patienten nach einer proximalen Femurfraktur zu analysieren.Es erfolgte eine retrospektive Analyse aller Patienten mit proximaler Femurfraktur, die vom 1. Januar 2020 bis zum 31.01.2021 in einem städtischen regionalen Traumazentrum operiert wurden. Anhand der PCR-Testergebnisse zum Nachweis von SARS-CoV‑2 wurden die Patienten in zwei Gruppen eingeteilt (SARS-CoV‑2 positiv vs. SARS-CoV‑2 negativ). Für alle Patienten wurden Patientendaten, Daten zum Krankheitsverlauf und Informationen zur Behandlung ausgewertet. Die statistische Datenanalyse wurde mit dem ungepaarten Student’s t-Test oder dem nichtparametrischen Mann-Whitney-U-Test durchgeführt.Insgesamt wurden 311 Patienten (Frauen: 70,4 %, Alter: 82,0 ± 11,0 Jahre) in die Studie aufgenommen. Von diesen hatten 3,9 % (12/311) ein positives Testergebnis für SARS-CoV‑2. In der positiv auf SARS-CoV‑2 getesteten Gruppe befanden sich signifikant mehr verstorbene Patienten (SARS-CoV‑2 positiv: 41,7 %, SARS-CoV‑2 negativ: 5,4 %, p 0,001). Darüber hinaus korrelierte die Zahl der Todesfälle im Zusammenhang mit proximalen Femurfrakturen mit der Zahl der positiven Testergebnisse in der Klinik . Die Verweildauer der Überlebenden von SARS-CoV‑2 COVID-19 war tendenziell länger als bei denjenigen, die negativ getestet wurden (SARS-CoV‑2 COVID-19 positiv: 15,6 ± 13,1 Tage, SARS-CoV‑2 COVID-19 negativ: 11,5 ± 6,5 Tage, p = 0,683). Darüber hinaus wurde ein signifikanter Altersunterschied zwischen den Überlebenden von SARS-CoV‑2 und den Verstorbenen von SARS-CoV‑2 festgestellt (verstorben: 95,5 ± 7,5 Jahre, lebend: 83,5 ± 7,3 Jahre, p = 0,020).Die Studie wurde vor der Einführung der COVID-19-SARS-CoV‑2-Impfung durchgeführt. Die Ergebnisse beziehen sich daher auf immun-naive (nicht geimpfte) Patienten. In unserer Studie starben mehr als 40 % aller Patienten mit proximalen Femurfrakturen, die positiv auf SARS-CoV‑2 getestet wurden, während des Krankenhausaufenthalts. Ein zusätzlicher, kritischer Faktor in dieser Hinsicht war das Alter der infizierten Patienten. Dennoch wurde eine positive Korrelation zwischen der Sterblichkeitsrate und der Anzahl der positiven SARS-CoV‑2- nachgewiesen. Hinsichtlich der längeren Verweildauer der positiv auf SARS-CoV‑2 getesteten Patienten können die eingeschränkten Verlegungsmöglichkeiten (Weiterrehabilitation, Fachpflegeeinrichtung) der Infizierten als ursächlich angesehen werden. Insbesondere die vulnerablen älteren Patienten sind durch eine Kombination aus proximaler Femurfraktur und SARS-CoV‑2 zunehmend gefährdet.

RationaleIn adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.ObjectivesTo define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.MethodsIn the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults)) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with lipopolysaccharide (LPS) or anti-CD3/CD28.Measurements and main resultsBased on blood eosinophil counts and allergen-specific serum IgE antibodies, patients were categorised into four mutually exclusive phenotypes: “atopy-only”, “eosinophils-only”, “T2-high” (eosinophilia + atopy) and “T2-low” (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset, suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (pConclusionsUsing easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at a younger age.

Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models.Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgAWith this study we demonstrate for the first time a significant association of increased IgA

Background Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children. Methods Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development.

BackgroundImprovement of paediatric healthcare is hampered by inefficient processes of generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardized between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality.AimsSwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based common data model (CDM) that covers all processes of routine paediatric care in hospitals.MethodsA taskforce of paediatricians from large Swiss children’s hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalization. We then used a modified Delphi method to reach a broad consensus on a national EHR-based CDM.ResultsAll Swiss children’s hospitals use EHR to document some or all aspects of care. 119 paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national CDM that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 common data elements (CDEs): 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional.ConclusionSwissPedData is a CDM for information to be collected in EHR of Swiss children’s hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

Introduction: COL4A3 degradation is significantly increased in severe, exacerbating type 2 asthmatics and correlates with increased chymase positive mast cells (mouse model of asthma). However, whether chymase is sufficient/necessary for COL4A3 degradation and if this mode of action is responsive to therapeutic intervention, is unknown. We hypothesized, that mast cell chymase is necessary for COL4A3 degradation and that treatment with anti-IgE reduces COL4A3 degradation. Methods: The COL4A3 fibrolysis marker C4Ma3 (Nordic Bioscience, Denmark) was measured in female 6-8 week old Balb/C mice, which were sensitized (OVA i.p., day 1, 14, 21) and challenged with aerosol (OVA i.n., day 26, 27, 28) to induce acute allergic airway inflammation. Acute exacerbations were provoked by instillation of poly(cytidylic-inosinic, i.n. day 28) and Chymase was inhibited with Fulacimstat (i.t.). Allergic, uncontrolled asthmatics (n=19, Omalizumab treatment), were monitored over six months. Treatment response was set as Asthma Control Test (ACT) improvement of g3 points. Serum levels of C4Ma3 were determined at baseline, 3 and 6 months. Results: Chymase inhibition prevented OVA-challenge induced C4Ma3 increase. Recombinant chymase alone did not induce elevated C4Ma3 level. Ten out of 19 patients had ACT score increases of g3 points after treatment. Responders mean level of circulating C4Ma3 was 8.87 ng/mL (confidence interval (CI): 7.02-10.72ng/mL), which decreased to 6.57 ng/mL (CI: 4.95-8.1ng/mL, pl0.01) after six months treatment. Non-responders did not show any change in serum levels of after treatment. Conclusion: COL4A3 degradation depends on mast cell chymase in vivo and monitoring serum C4Ma3, may afford a novel avenue to stratify and monitor anti-IgE therapy in severe, allergic asthma.

Introduction: Remodeling of the airway wall is a hallmark feature of asthma. Under physiological conditions, a finely tuned balance maintains a functional state of the extracellular matrix. This balance is disrupted in asthma. COL4A3 is reduced 18-fold in lung tissue from asthmatics, however, the mechanism leading to the diminished levels of COL4A3 has remained elusive. Methods: The COL4A3 fibrolysis marker C4Ma3 (Nordic Bioscience, Denmark) was measured in the ALLIANCE cohort study participants (Fuchs et al. 2018). Pediatric controls/cases: 34/134; Adult control/cases 31/149. C4Ma3 data was correlated with clinical data, serum cytokine profiles (27-Bioplex, Biorad). Female 6-8 week old Balb/C mice were sensitized (OVA i.p., day 1, 14, 21) and challenged with aerosol (OVA i.n., day 26, 27, 28) to induce acute allergic airway inflammation. Acute exacerbations were provoked by instillation of poly(cytidylic-inosinic, i.n. day 28). Murine precision cut lung slices (PCLS) were used to elucidate the role of sensitisation for COL4A3 degradation. Results: Increased C4Ma3 correlated with asthma exacerbation (pl0.01) and elevated levels of Th2/Th9 cytokines in the ALLIANCE cohort. Serum levels of C4Ma3 were elevated in OVA challenged mice (pl0.0001) and correlated with lung tissue levels of mast cell chymase (pl0.01), but not with neutrophils or matrix-metallo-proteinase 9. C4MA3 was elevated in PCLS of allergic, HDM challenged mice (pl0.05) with no further increase after PolyIC. Conclusion: COL4A3 degradation (circulating C4Ma3), is elevated in severe, exacerbating type 2 asthmatics. C4Ma3 levels correlate with chymase positive mast cells in a mouse model of asthma exacerbation. These data highlight that the degradation of COL4A3 is a central part of the pathology of asthma.

Background Globally, the number of children born by cesarean delivery is constantly increasing. However, hormonal and physiological changes associated with labor and vaginal delivery are considered necessary for lung maturation. Objective We aimed to assess whether the mode of delivery is associated with changes in respiratory and atopic outcomes during infancy and at school age. Study Design We included 578 children, born at ≥37 weeks of gestation, from a prospective birth cohort study. We compared weekly respiratory symptoms throughout the first year of life and infant lung function (tidal breathing and multiple-breath washout) at 5 weeks of age between children born by cesarean delivery (N=114) and those born by vaginal delivery (N=464) after term pregnancy in healthy women. At a follow-up visit conducted at 6 years of age (N=371, of which 65 were delivered by cesarean delivery), we assessed respiratory, atopic, and lung function outcomes (spirometry, body plethysmography, and multiple-breath washout). We performed adjusted regression analyses to examine the association between cesarean delivery and respiratory and atopic outcomes. To account for multiple testing, we used the Bonferroni correction, which led to an adapted significance level of P Results During infancy, children born by cesarean delivery did not have more respiratory symptoms than those born by vaginal delivery (median, 4 weeks; interquartile range, 7 weeks vs median, 5 weeks; interquartile range, 7 weeks; adjusted incidence rate ratio, 0.8; 95% confidence interval, 0.6–1.0; P=.02). Infant lung function was similar between the groups. Children born by cesarean delivery did not have a higher incidence of “ever wheezing” (adjusted odds ratio, 0.9; 95% confidence interval, 0.5–1.8; P=.78) or current asthma (adjusted odds ratio, 0.4; 95% confidence interval, 0.0–3.5; P=.42) at school age than those born by vaginal delivery. There was no difference in the lung function parameters between the groups. Conclusion Cesarean delivery was not associated with respiratory symptoms in the first year of life, nor with different respiratory or atopic outcomes at school age, when compared with vaginal delivery. Our results indicate that there are no long-term consequences on the respiratory health of the child associated with cesarean delivery.

“Breathomics” in asthma is a rapidly growing area of significant scientific interest, as indicated by a recently published review, two research articles, and their accompanying editorials in high impact pneumology journals [1–5]. The repeatedly observed associations between breath volatile organic compounds (VOCs) and sputum or blood inflammatory cells [2, 3] suggest that breathomics are on the brink of introduction as a valuable clinically tool. However, there are also major concerns about unresolved methodological issues and a general paucity of high-quality data [1, 6]. In this letter we detail our concerns with breathomics based on data from a cohort of adult asthma patients with a broad spectrum of clinical phenotypes., Despite recent publications, we are not close to finding a clinically valuable breath VOC biomarker for asthma or asthma phenotypes https://bit.ly/3heTgtK

RationaleAsthma in pregnancy is associated with respiratory diseases in the offspring.ObjectiveTo investigate if maternal asthma is associated with lung function in early life.MethodsData on lung function measured at 5–6 weeks of age were combined from two large birth cohorts: the Bern Infant Lung Development (BILD) and the Australian Breathing for Life Trial (BLT) birth cohorts conducted at three study sites (Bern, Switzerland; Newcastle and Sydney, Australia). The main outcome variable was time to reach peak tidal expiratory flow as a percentage of total expiratory time(tPTEF:tE%). Bayesian linear hierarchical regression analyses controlling for study site as random effect were performed to estimate the effect of maternal asthma on the main outcome, adjusting for sex, birth order, breast feeding, weight gain and gestational age. In separate adjusted Bayesian models an interaction between maternal asthma and sex was investigated by including an interaction term.Measurements and main resultsAll 406 BLT infants were born to mothers with asthma in pregnancy, while 193 of the 213 (91%) BILD infants were born to mothers without asthma. A significant interaction between maternal asthma and male sex was negatively associated with tPTEF:tE% (intercept 37.5; estimate: –3.5; 95% credible interval –6.8 to –0.1). Comparing the model posterior probabilities provided decisive evidence in favour of an interaction between maternal asthma and male sex (Bayes factor 33.5).ConclusionsMaternal asthma is associated with lower lung function in male babies, which may have lifelong implications on their lung function trajectories and future risk of wheezing and asthma.

BACKGROUND Current in vitro allergen-specific IgE (sIgE) detection assays measure IgE against allergen extracts or molecules in a single- or multiplex approach. Direct comparisons of the performance of such assays among young children with common presentations of allergic diseases regardless of sensitization status are largely missing. OBJECTIVES The aim of this study was a comparison of the analytical and diagnostic performance for common clinical questions of three commonly used technologies which rely upon different laboratory methodologies among children of the All Age Asthma (ALLIANCE) cohort (clinicaltrials.gov: NCT02496468). METHODS Sera from 106 paediatric study participants (mean age 4 years) were assessed for the presence of sIgE by means of the ImmunoCAP™ sx1 and fx5 mixes, the ImmunoCAP ISAC™ 112 microarray and a Euroline™ panel. RESULTS Total and negative concordance was high (>82%->89%), while positive concordance varied considerably (0%-100%) but was also >50% for the most common sensitizations analysed (house dust mite and birch). All three test systems showed good sensitivity and specificity (AUC consistently > 0.7). However, no significant differences with regard to identifying sIgE sensitizations associated with symptoms in children with suspected pollen- or dust-triggered wheeze or presenting with symptoms of allergic rhinoconjunctivitis or food allergy were detected. Extending the number of allergens did not change the similar performance of the three assay systems. CONCLUSION AND CLINICAL RELEVANCE Among young children, the three sIgE assays showed good analytical and diagnostic concordance. Our results caution that the identification of larger numbers of sensitizations by more comprehensive multiplex approaches may not improve the clinical utility of sIgE testing in this age group.

BackgroundAsthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3).ObjectiveTo delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response.MethodsThe serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (paediatric cases/controls: n=134/n=35; adult cases/controls: n=149/n=31). Exacerbation of allergic airway disease in mice was induced by sensitising to ovalbumin (OVA), challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor; Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (n=14) and cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA; n=9) as well as patients with severe allergic uncontrolled asthma (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed using the Asthma Control Test.ResultsSerum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in cystic fibrosis plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic OR 31.5).ConclusionC4Ma3 levels depend on lung mast cell chymase and are increased in a severe, exacerbating allergic asthma phenotype. C4Ma3 may serve as a novel biomarker to predict anti-IgE therapy response.

BackgroundIn recent years, YouTube has become a recognized source of medical information for health care consumers. Although YouTube has advantages in this context, there are potential dangers as videos may contain nonscientific, misleading, or even harmful information.ObjectiveAs little is known about YouTube as a source of information on atopic dermatitis (AD), we investigated the content-related quality of AD videos and their perception among YouTube users.MethodsThe quality of the 100 most viewed AD videos was assessed by using the Global Quality Scale (GQS) and the DISCERN instrument. Videos were classified as “useful,” “misleading,” and “potentially harmful,” and the correlations of viewers’ ratings (likes) with the GQS and DISCERN scores were assessed.ResultsAmong the 100 videos, 68.0% (68/100) and 62.0% (62/100) were of poor and very poor scientific quality, respectively. Additionally, 32.0% (32/100) of the videos were classified as useful, 48.0% (48/100) were classified as misleading, and 34.0% (34/100) were classified as potentially harmful. Viewers’ ratings did not correlate with the GQS and DISCERN scores. Overall, 50.0% (50/100) of the videos were posted by private individuals and promoters of complementary/alternative treatments, 42.0% (42/100) by therapeutical advertisers, and only 8.0% (8/100) by nonprofit organizations/universities.ConclusionsOur study demonstrated that two-thirds of the videos analyzed were below acceptable medical quality standards and that many videos were disseminating misleading or even dangerous content. Subjective and anecdotal content was overrepresented, and viewers did not appear to be able to distinguish between high- and low-quality videos. Health promotion strategies by professional medical organizations are needed to improve their presence and visibility on YouTube.

Background: Exhaled nitric oxide (eNO) is a biomarker of airway inflammation and seems to precede respiratory symptoms, such as asthma, in childhood. Identifying genetic determinants of postnatal eNO levels might aid in unraveling the role of eNO in epithelial function or airway inflammation and disease. Objective: We sought to identify genetic determinants of early postnatal eNO levels and subsequent respiratory symptoms during the first year of life. Methods: Within a population-based birth cohort, eNO levels were measured in healthy term infants aged 5 weeks during quiet tidal breathing in unsedated sleep. We assessed associations of single nucleotide polymorphisms with eNO levels in a genome-wide association study and subsequent symptoms of lower respiratory tract infections during the first year of life and asked whether this was modified by prenatal and early-life environmental factors. Results: We identified thus far unknown determinants of infant eNO levels: rs208515 (P = 3.3 x 10(-8)), which is located at 6q12, probably acting in "trans'' and explaining 10.3% of eNO level variance, and rs1441519 (P = 1.6 x 10(-6)), which is located at 11p14, potentially affecting nitric oxide synthase 3 (NOS3) expression, as shown by means of in vitro functional analyses. Moreover, the 6q12 locus was inversely associated with subsequent respiratory symptoms (P < .05) and time to recovery after first respiratory symptoms during the first year of life (P < .05). Conclusion: The identification of novel genetic determinants of infant eNO levels might implicate that postnatal eNO metabolism in healthy infants before first viral infections and sensitization is related to mechanisms other than those associated with asthma, atopy, or increased risk thereof later in life.

Ein 14-jahriger Junge wird bei uns nach zweimaliger Anaphylaxie in der Folge von Hymenopterenstichen mit der Frage nach einer spezifischen Immuntherapie (SIT) vorgestellt. Ein Notfallset war zwar vorhanden, jedoch unvollstandig, und der Junge war nicht geschult!

Background: miRNAs are critically involved in asthma and are actively secreted in extracellular vesicles (EV) for inter-cell communication. We have previously shown that total extracellular miRNAs in plasma can distinguish between asthma and healthy controls (Milger, Allergy, 2017). Thus, we now aimed to investigate if miRNA profiles from plasma EVs are altered in patients with asthma. Methods: We isolated EVs from 1 mL plasma of adult subjects from the ALLIANCE cohort with mild-to-moderate (AM) or severe asthma (AS), and healthy controls (HC) (n=15/group) by size exclusion chromatography (Izon). EVs were characterized by nanoparticle-tracking analysis and flow cytometry. EV RNA was isolated and subjected to small RNA-seq (Illumina). We correlated sequencing data with clinical characteristics and confirmed candidate miRNAs in a new set of EV isolates by RT-qPCR. Results: Isolated EVs had a median size of 131.5 nm and a median concentration of 8.6x10^9 particles/mL in HC, with no significant differences among the groups. RNA-seq detected 139 EV-miRNAs, 35 of which were expressed at moderate to high levels. miR-122-5p was significantly higher in EVs from AS patients compared to HC (log2FC=1.77, padj=0.019) and we observed a trend for miR-191-5p (log2FC=0.39, padj=0.11). Both findings were confirmed by RT-qPCR. Further, miR-191-5p significantly correlated with FEV1%pred (R=-0.38 p=0.013), eosinophil (R=0.45, p=0.0056) and neutrophil (R=-0.37, p=0.027) counts in blood. Conclusion: miR-122-5p and miR-191-5p are increased in EVs from subjects with asthma, and miR-191-5p correlates with lung function impairment and inflammation. Therefore, EV miRNAs might qualify for disease subphenotyping in asthma.

Introduction: A breath test that provides information about the inflammatory phenotype of asthma patients could be a valuable tool in daily clinical practice. We analyzed breath in the adult arm of the ALLIANCE cohort to evaluate if breath VOC patterns differ between asthma phenotypes. Methods: We included 111 patients of three phenotypes: active smokers with asthma (n=29), non-smokers with severe asthma (n=36; ERS/ATS guidelines), and non-smokers with mild-to-moderate asthma (n=46). Patients inhaled pre-cleaned room air and exhaled into an aluminum reservoir tube. The breath was loaded onto two adsorption tubes for the analysis by GC-MS. 134 different VOCs were assessed. Results: The high comparability between simultaneously loaded adsorption tubes and the differences between actively smoking and non-smoking patients (44/134 VOCs with p Conclusion: Breath VOCs appear to be closer related to the clinical than the inflammatory asthma phenotype. One breath VOC might have a clinical relevance as it could support other readily accessible markers like blood eosinophils and exhaled NO to predict the level of eosinophilic airway inflammation.

Background: A protective effect of breastfeeding on lung functional growth has been demonstrated in cohorts of children with asthma or risk for asthma; however it is unclear whether this effect is mediated by inflammation or by a direct effect on lung growth. We assessed the impact of breastfeeding on lung function and symptoms at the age of six years in an unselected, healthy birth cohort. Methods: We prospectively studied 377 healthy term infants from the Bern-Basel Infant Lung Development (BILD) cohort from birth up to 6 years. Any breastfeeding was assessed weekly during the 1st year of life. Risk factors (e.g. smoking exposure, parental atopy, and education) were obtained using standardized questionnaires. The primary outcomes were lung function parameters measured at 6 years of age by spirometry (FEV1, FVC, FEV1/FVC, and FEF25-75) and body plethysmography (FRC, TLC and Reff) and FeNO. Secondary outcomes included ever wheeze, wheeze in the past 12 months, asthma, atopy, atopic dermatitis, allergic rhinitis, and allergic sensitization. Results: We found no evidence that breastfeeding could influence any lung function parameters and FeNO. After adjustment for confounders we found no associations of breastfeeding with respiratory symptoms or sensitization. However, a protective effect of breastfeeding on atopic dermatitis was observed only in girls (odds ratio (OR) per each week of breastfeeding 0.96; 95% confidence interval (CI) 0.92-0.99). Conclusion: This study suggests that breastfeeding has no effect on lung function in unselected healthy children with low risk for asthma, our findings do not support our hypothesis that breastfeeding might have a direct impact on lung function at 6 years.

BACKGROUND A positive effect of breastfeeding on lung function has been demonstrated in cohorts of children with asthma or risk for asthma. We assessed the impact of breastfeeding on lung function and symptoms at the age of 6 years in an unselected, healthy birth cohort. METHODS We prospectively studied healthy term infants from the Bern-Basel Infant Lung Development (BILD) cohort from birth up to 6 years. Any breastfeeding was assessed by weekly phone calls during the first year of life. Risk factors (eg, smoking exposure, parental history of allergic conditions, and education) were obtained using standardized questionnaires. The primary outcomes were lung function parameters measured at 6 years of age by spirometry forced expiratory volume in 1 second, body plethysmography (functional residual capacity [FRCpleth ], the total lung capacity [TLCpleth ], and the effective respiratory airway resistance [Reff ]) and fractional exhaled nitric oxide (FeNO). Secondary outcomes included ever wheeze (between birth and 6 years), wheeze in the past 12 months, asthma, presence of allergic conditions, atopic dermatitis, rhinitis, and positive skin prick test at the age of 6 years. RESULTS In 377 children the mean breastfeeding duration was 36 weeks (SD 14.4). We found no association of breastfeeding duration with obstructive or restrictive lung function and FeNO. After adjustment for confounders, we found no associations of breastfeeding duration with respiratory symptoms or the presence of allergic conditions. CONCLUSION This study found no evidence of an association between breastfeeding and comprehensive lung function in unselected healthy children with long-term breastfeeding. Our findings do not support the hypothesis that the duration of breastfeeding has a direct impact on lung function in a healthy population with low asthmatic risk.