the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk. The aim of the study was to assess the tolerance and safety of a formula ...containing an innovative mixture of oligosaccharides in early infancy.
this study was performed as a multi-center, randomized, double-blind, placebo-controlled trial including healthy term infants. Infants were recruited before the age of 8 weeks, either having started with formula feeding or being fully breast-fed (breastfeeding group). Formula-fed infants were randomized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Growth, tolerance and adverse events were assessed at 8, 16, 24 and 52 weeks of age. The prebiotic and control groups showed similar mean weight, length and head circumference, skin fold thicknesses, arm circumference gains and stool frequency at each study point. As far as the anthropometric parameters are concerned, the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point. The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants, whereas at 52 weeks were strikingly smaller. The stool consistency in the prebiotic group was softer than in the control group at 8, 16 and 24 weeks (p<0.001) and closer to that of the breastfeeding group. There was no difference in the incidence of adverse events between the two formula groups.
our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants.
drks-neu.uniklinik-freiburg.de DRKS 00000201.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zusammenfassung
Die Global Initiative for Asthma (GINA) hat in den Jahren 2019–2021 einige substanzielle Änderungen für das Management von Patienten mit Asthma empfohlen, die auch Schulkinder und ...Jugendliche betreffen. Eine sehr wesentliche neue Empfehlung ist, dass kurzwirksame Betamimetika (SABA) aus Sicherheitsgründen nur mehr in Kombination mit inhalativen Steroiden (ICS) gegeben werden sollten. Bei Jugendlichen werden GINA-Stufe 1 und 2 zusammengezogen und bei Asthmaproblemen eine Bedarfsinhalation mit niedrig dosierter ICS-Formoterol-Kombination empfohlen. Als Alternative wird die Trennung in Stufe 1 mit Inhalation von SABA und einem ICS bei Bedarf und in Stufe 2 wie bisher die tägliche Inhalation eines ICS und SABA bei Bedarf empfohlen. Dieser Weg wird auch als der bevorzugte bei Kindern von 6 bis 11 Jahren vorgeschlagen. Diese neuen GINA-Empfehlungen wurden jedoch nicht von allen nationalen oder internationalen Leitlinien übernommen, da vor allem für Kinder die Evidenz dafür gering ist. Tiotropium, Mepolizumab und Dupilumab wurden in die Therapie des schweren Asthmas aufgenommen.
Kinder mit Asthma erkranken nicht häufiger oder schwerer an COVID-19 als Kinder ohne Asthma. Verschiedene Mechanismen wie ein möglich protektiver Effekt der Typ-2-Inflammation, die antivirale und immunmodulierende Wirkung von ICS und die Niederregulierung von ACE2-Rezeptoren durch die allergische Sensibilisierung könnten dafür verantwortlich sein.
Retinoid acid receptor-related Orphan Receptor Alpha (RORA) was recently identified as a susceptibility gene for asthma in a genome-wide association study. To investigate the impact of RORA on asthma ...susceptibility, we performed a genetic association study between RORA single nucleotide polymorphisms (SNPs) in the vicinity of the asthma-associated SNP (rs11071559) and asthma-related traits. Because the regulatory region of a previously implicated asthma susceptibility gene, Neuropeptide S receptor 1 (NPSR1), has predicted elements for RORA binding, we hypothesized that RORA may interact biologically and genetically with NPSR1. 37 RORA SNPs and eight NPSR1 SNPs were genotyped in the Swedish birth cohort BAMSE (2033 children) and the European cross-sectional PARSIFAL study (1120 children). Seven RORA SNPs confined into a 49 kb region were significantly associated with physician-diagnosed childhood asthma. The most significant association with rs7164773 (T/C) was driven by the CC genotype in asthma cases (OR = 2.0, 95%CI 1.36-2.93, p = 0.0003 in BAMSE; and 1.61, 1.18-2.19, p = 0.002 in the combined BAMSE-PARSIFAL datasets, respectively), and strikingly, the risk effect was dependent on the Gln344Arg mutation in NPSR1. In cell models, stimulation of NPSR1 activated a pathway including RORA and other circadian clock genes. Over-expression of RORA decreased NPSR1 promoter activity further suggesting a regulatory loop between these genes. In addition, Rora mRNA expression was lower in the lung tissue of Npsr1 deficient mice compared to wildtype littermates during the early hours of the light period. We conclude that RORA SNPs are associated with childhood asthma and show epistasis with NPSR1, and the interaction between RORA and NPSR1 may be of biological relevance. Combinations of common susceptibility alleles and less common functional polymorphisms may modify the joint risk effects on asthma susceptibility.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Austria, newborns have been screened for cystic fibrosis (CF) by analyzing immunoreactive trypsinogen (IRT) from dried blood spots (DBS)s for nearly 20 years. Recently, pancreatitis-associated ...protein (PAP) analysis was introduced as a second-tier test with the aim of reducing recalls for second DBS cards while keeping sensitivity high. For 28 months, when IRT was elevated (65-130 ng/mL), PAP was measured from the first DBS (
= 198,927) with a two-step cut-off applied. For the last 12 months of the observation period (
= 85,421), an additional IRT×PAP cut-off was introduced. If PAP or IRT×PAP were above cut-off, a second card was analyzed for IRT and in case of elevated values identified as screen-positive. Above 130 ng/mL IRT in the first DBS, newborns were classified as screen-positive. IRT analysis of first DBS resulted in 1961 (1%) tests for PAP. In the first 16 months, 26 of 93 screen-positive were confirmed to have CF. Two false-negatives have been reported (sensitivity = 92.8%). Importantly, less than 30% of families compared to the previous IRT-IRT screening scheme had to be contacted causing distress. Adding IRT×PAP caused a marginally increased number of second cards and sweat tests to be requested during this period (15 and 3, respectively) compared to the initial IRT-PAP scheme. One case of confirmed CF was found due to IRT×PAP, demonstrating an increase in sensitivity. Thus, the relatively simple and economical algorithm presented here performs effectively and may be a useful model for inclusion of CF into NBS panels or modification of existing schemes.
Background Consumption of farm milk in early life is associated with less asthma and allergies. Objective We hypothesized that genetic variation in the innate immunity receptor CD14 might modify the ...association between farm milk consumption and asthma and atopy. Methods Questionnaire data, serum IgE levels, and genotypes for 4 single nucleotide polymorphisms in CD14 were assessed in farmers' and nonfarmers' children from 2 European populations (Allergy and Endotoxin study, n = 576; Prevention of Allergy Risk factors for Sensitization in children related to Farming and Anthroposophic Lifestyle study, n = 1539). In a subsample (n = 222) CD14 gene expression was measured in peripheral blood leukocytes. The effects of farm milk and CD14 genotypes on asthma, allergies, and CD14 expression and their interactions were investigated. Results We found a significant interaction between genetic variation in CD14/−1721 and farm milk consumption. Adjusted odds ratios for the association between farm milk and asthma varied between the genotypes: AA, 0.18 (95% CI, 0.07-0.47); AG, 0.47 (95% CI, 0.26-0.86); and GG, 0.98 (95% CI, 0.46-2.08). Similar patterns were observed for symptoms of allergic rhinoconjunctivitis and pollen sensitization. CD14/−1721 also modified the association between farm milk and CD14 gene expression (adjusted geometric means ratios: AA, 1.61 (95% CI, 0.98-2.66); AG, 1.11 (95% CI, 0.71-1.72); and GG, 0.76 (95% CI, 0.39-1.48). Conclusion The protective effect of farm milk consumption on allergic diseases is stronger in children carrying the A allele in CD14/−1721 than in children homozygous for the G allele. This might be mediated through farm milk–induced upregulated CD14 gene expression. Clinical implications Our results support the hypothesis that the inverse association between farm milk consumption and allergic diseases is mediated by CD14 -activated innate immune mechanisms.
Background It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants. Objective To investigate the ...relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences. Methods As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-γ, IL-10, and TNF-α. Results Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-γ production, but not with IL-5 and IL-10. Conclusion Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-γ production.
The children with the highest fecal butyrate levels had a significantly reduced risk of becoming sensitized to inhalant allergens, with a similar directional trend for asthma, atopic dermatitis and ...sensitization to food allergens.
Both genetic and environmental factors are important for the development of allergic diseases. However, a detailed understanding of how such factors act together is lacking. To elucidate the ...interplay between genetic and environmental factors in allergic diseases, we used a novel bioinformatics approach that combines feature selection and machine learning. In two materials, PARSIFAL (a European cross-sectional study of 3113 children) and BAMSE (a Swedish birth-cohort including 2033 children), genetic variants as well as environmental and lifestyle factors were evaluated for their contribution to allergic phenotypes. Monte Carlo feature selection and rule based models were used to identify and rank rules describing how combinations of genetic and environmental factors affect the risk of allergic diseases. Novel interactions between genes were suggested and replicated, such as between ORMDL3 and RORA, where certain genotype combinations gave odds ratios for current asthma of 2.1 (95% CI 1.2-3.6) and 3.2 (95% CI 2.0-5.0) in the BAMSE and PARSIFAL children, respectively. Several combinations of environmental factors appeared to be important for the development of allergic disease in children. For example, use of baby formula and antibiotics early in life was associated with an odds ratio of 7.4 (95% CI 4.5-12.0) of developing asthma. Furthermore, genetic variants together with environmental factors seemed to play a role for allergic diseases, such as the use of antibiotics early in life and COL29A1 variants for asthma, and farm living and NPSR1 variants for allergic eczema. Overall, combinations of environmental and life style factors appeared more frequently in the models than combinations solely involving genes. In conclusion, a new bioinformatics approach is described for analyzing complex data, including extensive genetic and environmental information. Interactions identified with this approach could provide useful hints for further in-depth studies of etiological mechanisms and may also strengthen the basis for risk assessment and prevention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IgE synthesis by human B cells results from allergen-dependent, T(H)2-mediated isotype switching. Exposure to a farming environment protects against IgE responses.
We reconstructed allergen-dependent ...switching patterns in vivo to identify the level or levels at which farm exposure acts to protect against atopy.
Serum IgG1 to IgG4 and IgE to grass (rPhl p 1 and rPhl p 5), cat (rFel d 1), and mite (rDer p 2) were assessed by means of ELISA in the Allergy and Endotoxin study population (812 children). Farm exposure was defined as currently living on a farm, exposure to stables/farm milk in the first year of life, or both.
Farm exposure did not affect allergen-specific IgG2 and IgG3 levels but had complex allergen-specific effects on IgG1, IgG4, and IgE levels. Exposure protected against grass-specific responses at every step along the IgG1/IgG4/IgE switching pathway but had no significant effect on mite responses. Protection from cat responses was concentrated at the IgG1 level. For all allergens, failure to express IgG1 was associated with low prevalence of IgG4 or IgE responses. Notably, coexpression of IgG1, IgG4, and IgE to grass was associated with increased risk of allergic disease and higher IgE levels compared with production of IgG1 and IgE without IgG4, suggesting IgG4 coexpression marks stronger activation of T(H)2-dependent events.
The protective effects of farm exposure were confined to T(H)2-dependent IgG1, IgG4, and IgE expression and were allergen and switch stage specific, suggesting that distinct mechanisms regulate individual steps within allergen-induced class switching in vivo.
Environmental interventions to prevent IgE expression might need to be tailored to specific allergens.
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