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BACKGROUND Pollen exposure is associated with respiratory symptoms in children and adults. However, the association of pollen exposure with respiratory symptoms during infancy, a particularly vulnerable period, remains unclear. We examined whether pollen exposure is associated with respiratory symptoms in infants and if maternal atopy, infant's sex or air pollution modify this association. METHODS We investigated 14,874 observations from 401 healthy infants of a prospective birth cohort. The association between pollen exposure and respiratory symptoms, assessed in weekly telephone interviews, was evaluated using generalized additive mixed models (GAMM). Effect modification by maternal atopy, infant's sex and air pollution (NO2 , PM2.5 ) was assessed with interaction terms. RESULTS Per infant 37��2 (mean��SD) respiratory symptom scores were assessed during the analysis period (January through September). Pollen exposure was associated with increased respiratory symptoms during the daytime (RR [95% CI] per 10% pollen/m3 : combined 1.006 [1.002, 1.009]; tree 1.005 [1.002, 1.008]; grass 1.009 [1.000, 1.23]) and nighttime (combined 1.003 [0.999, 1.007]; tree 1.003 [0.999, 1.007]; grass 1.014 [1.004, 1.024]). While there was no effect modification by maternal atopy and infant's sex, a complex crossover interaction between combined pollen and PM2.5 was found (p-Value 0.002). CONCLUSION Even as early as during the first year of life, pollen exposure was associated with an increased risk of respiratory symptoms, independent of maternal atopy and infant's sex. Because infancy is a particularly vulnerable period for lung development, the identified adverse effect of pollen exposure may be relevant for the evolvement of chronic childhood asthma.

Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype.Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort.Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration.Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment.

BACKGROUND Improvement of paediatric healthcare is hampered by inefficient processes for 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 standardised between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality. AIMS SwissPedData 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 set of common data elements (CDEs) that covers all processes of routine paediatric care in hospitals. METHODS A 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 digitalisation. We then used a modified Delphi method to reach a broad consensus on a national EHR-based set of CDEs. RESULTS All Swiss children's hospitals use EHR to document some or all aspects of care. One hundred and nineteen paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national set of CDEs that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 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. CONCLUSION SwissPedData is a set of CDEs 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.

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4th and 12th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52–28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2–56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation., publishedVersion

Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in ealthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project “Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)” was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland.

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.