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BACKGROUND: A genetic defect in the epidermal barrier protein filaggrin plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in the filaggrin gene (FLG) contribute to the development and persistence of food allergies.OBJECTIVE: We tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. METHODS: We recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the four most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as control population. RESULTS: FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. CONCLUSION: Using the gold standard for food allergy diagnosis, we demonstrate that FLG LOF mutations confer a risk of any food allergy independent of eczema. They predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.

Background Primary hazelnut allergy is a common cause of anaphylaxis in children, as compared to birch-pollen associated hazelnut allergy. Population-based data on hazelnut and concomitant birch-pollen allergy in children are lacking. We aimed to investigate the prevalence of primary and pollen-associated hazelnut allergy and sensitization profiles in school-aged children in Berlin, Germany. Methods 1570 newborn children were recruited in Berlin in 2005–2009. The school-age follow-up (2014–2017) was based on a standardized web-based parental questionnaire and clinical evaluation by a physician including skin prick tests, allergen specific immunoglobulin E serum tests and placebo-controlled double-blind oral food challenges, if indicated. Results 1004 children (63.9% response) participated in the school-age follow-up assessment (52.1% male). For 1.9% (n = 19, 95%-confidence interval 1.1%–2.9%) of children their parents reported hazelnut-allergic symptoms, for half of these to roasted hazelnut indicating primary hazelnut allergy. Symptoms of birch-pollen allergy were reported for 11.6% (n = 116 95%-CI 9.7%–13.7%) of the children. Both birch-pollen allergy and hazelnut allergy associated symptoms affected 0.6% (n = 6, 95%-CI 0.2%–1.3%) of children. Assessment of allergic sensitization was performed in 261 participants and showed that almost 20% of these children were sensitized to hazelnut, being the most frequent of all assessed food allergens, or birch-pollen, the majority to both. Conclusions Based on parental reports hazelnut-allergic symptoms were far less common than sensitization to hazelnut. This needs to be considered by physicians to avoid unnecessary changes in diet due to sensitization profiles only, especially when there is a co-sensitization to hazelnut and birch-pollen.

Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS.COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742).In Kiel-I (PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions.The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).

In Myasthenia Gravis (MG) thymic pathologies are often present and thymectomy is used as treatment. By flow cytometry we elucidated alterations of naive CD4+ T cell homeostasis in MG patients and patients with thymoma. MG patients showed increased absolute numbers of CD31- centralnaive CD4+ T cells. Thymoma patients displayed a significantly higher fraction of peripheral blood CD31+ thymicnaive T cells. We show an altered naive CD4+ T cell homeostasis in MG patients that might predispose to autoimmunity. Aberrant generation of T cells in thymoma can be detected by an increased frequency of CD31+ thymicnaive CD4+ T cells in the periphery.

Urbanization and biodiversity loss are linked to chronic disorders, in particular allergic diseases. The aim of this scoping review was to provide a synopsis of intervention studies specifically examining the influence of exposure to natural environments on human microbiota as well as immunological markers as suggested interlink between natural environment and the development of allergic diseases.We searched PubMed (MEDLINE®) and all references cited in the included studies following the PRISMA statement guidelines. No restrictions regarding age and sex of study participants, language or publication date were made. The protocol was registered at OSF REGISTRIES (https://osf.io/musgr).After screening, eight intervention studies were included. The interventions reported were mainly of pilot character and various, ranging from nature-related educational programs, biodiversity interventions in day-cares to short-term contact with soil- and sand-preparations. Most of the studied interventions appeared to increase human microbiota richness and diversity in specific taxa groups in the short-time. Immunological markers were assessed in only two studies. In these, their associations with human microbiota richness were pre-dominantly reported.There is some evidence that the so-called biodiversity interventions have the potential to diversify human microbiota, at least over a short period. Adequately powered randomized controlled trials with long term follow-up are required to examine sustainable effects on microbiota and immune system.

Zusammenfassung Die stetige steigende Anzahl von Notaufnahmepatient*innen geht auf Personen mit zwar akutem, aber nicht notfallmedizinischem Behandlungsbedarf zuruck sowie auf multimorbide Menschen mit komplexem Versorgungsbedarf. Trotz der wachsenden Inanspruchnahme von Notaufnahmen durch so genannte ambulant sensitive Krankheitsfalle (ASK) wird ihrer wichtigen Schnittstellenfunktion zwischen ambulantem, stationaren und Pflegesektor in der offentlichen Auseinandersetzung unzureichend Rechnung getragen. Uber Zusammensetzung und Charakteristika von Notaufnahmepatient*innen liegen bislang kaum aussagekraftige Daten vor. Diese sind jedoch erforderlich, um bedarfsorientierte Interventionen zur Reduktion der Inanspruchnahme von Notaufnahmen durch Patient*innen mit ASK zu entwickeln. Zur Erlangung reprasentativer Daten wurde deshalb das vom Bundesministerium fur Bildung und Forschung (BMBF) geforderte Versorgungsforschungsnetzwerk EMANet initiiert. EMANet zielt u.a. darauf ab, systematisch Versorgungsverlaufe ambulant und stationar behandelter Notaufnahmepatient*innen mit ASK an allen acht Notaufnahmen des Berliner Bezirks Mitte zu untersuchen. Der vorliegende Artikel prasentiert den konzeptionellen Hintergrund der Forschungsaktivitaten des EMANet-Netzwerks wahrend der Forderphase 01.12.2016 - 31.11.2019 und skizziert einen wesentlichen Bestandteil der Netzwerkarbeit. In EMANet werden exemplarisch a) kardial erkrankte Menschen mit moglichen psychischen Komorbiditaten, b) ambulant versorgte Personen mit akuten oder chronischen Atemwegserkrankungen und c) geriatrische Patient*innen mit Oberschenkelhalsfraktur untersucht. Mit den erhobenen Daten uber Muster der Inanspruchnahme und subjektiver Zufriedenheit sollen Risikofaktoren fur potentiell vermeidbare Krankheiten bzw. Verschlechterungen chronischer Erkrankungen und Optimierungspotenziale fur die Versorgung identifiziert werden. Das „mixed methods“-Projekt erhebt sowohl quantitative Primardaten zu zwei Zeitpunkten von 1.650 Patient*innen als auch Sekundardaten aus den Krankenhausinformationssystemen. Erganzend werden qualitative Interviews mit Patient*innen und Mitarbeiter*innen zum Versorgungsbedarf gefuhrt. Das Erkenntnisinteresse besteht darin, Informationen zum Inanspruchnahmeverhalten zu gewinnen, welche die Uberlastung von Notaufnahmen substanziell erklaren und zu strukturellen Veranderungen des Gesundheitswesens beitragen konnen.

Although myasthenia gravis (MG) is a classic autoantibody-mediated disease, T cells are centrally involved in its pathogenesis. In recent years a number of studies have analyzed the role of CD4+ FoxP3+ regulatory T cells (Treg) in the disease with contradictory results. Here, the generation of Treg was significantly reduced in thymoma as compared to thymic hyperplasia and normal thymus tissue (p=0.0002). In the peripheral blood, Treg subsets classified according to CD49d, HELIOS and CD45RA expression changed after thymectomy and in the long-term course of immunosuppression. Compared to healthy volunteers the frequency of CD45RA+FoxP3low Treg was reduced in MG patients in general (p=0.037) and in particular in patients without immunosuppression (p=0.036). In our study, thymectomy and immunosuppressive treatment were associated with changes in Treg subpopulations. The reduced frequency of CD45RA+FoxP3low Treg we observed in MG patients might play a role in MG pathogenesis.

Background: Hen's egg is one of the commonest causes of food allergy, but there are little data on its risk factors. Objective: To assess the risk factors, particularly eczema, for hen's egg allergy in the EuroPrevall birth cohort. Methods: In the pan-European EuroPrevall birth cohort, questionnaires were undertaken at 12 and 24 months or when parents reported symptoms. Children with suspected egg allergy were invited for skin prick testing, specific IgE assessment, and double-blind, placebo-controlled food challenge (DBPCFC) as indicated. Each egg allergy case (positive DBPCFC or egg-induced anaphylaxis) was allocated up to 2 age- and country-matched controls. Results: A total of 12,049 infants were recruited into the EuroPrevall birth cohort, and 9,336 (77.5%) were followed until 2 years. A total of 86 infants had egg allergy (84 by DBPCFC) and were matched with 140 controls. Independently associated with egg allergy were past/current eczema (adjusted odds ratio, 9.21; 95% CI, 2.65-32.04), Scoring Atopic Dermatitis (1.54 per 5 units; 1.28-1.86), antibiotics in the first week of life (6.17; 1.42-26.89), and current rhinitis (3.02; 1.04-8.78). Increasing eczema severity was associated with an increasing likelihood of egg allergy. Eczema was reported to have started 3.6 (SE, 0.5) months before egg allergy. Age of introduction of egg into the diet was not associated with egg allergy. Conclusions: Similar to peanut allergy, eczema was strongly associated with egg allergy development and the association increased with increasing eczema severity. The age of introduction of dietary egg was not a risk factor. The potential role of antibiotics in early life as a risk factor for egg allergy needs further examination.

Whether there is a general perturbation of B and plasma cell subsets in myasthenia gravis (MG) has not been investigated so far. Here we performed a detailed flow cytometric analysis of blood and if available thymic tissue in order to detect MG-specific and therapy-induced changes. We observed significant differences in the distribution of B cell subsets in MG patients, yet these were mainly attributable to medical treatment. Furthermore MG is associated with significantly increased frequencies of plasma cells that were especially activated in purely ocular disease manifestation. In contrast to thymoma, B cell subset distribution in hyperplastic thymus could be distinguished from peripheral blood, however both tissues were not significantly enriched with plasma cells. Thus B cell differentiation in general is not defective in MG, but modified by therapy and enhanced frequencies of plasma cells can be detected in MG patients.

This systematic review aims to evaluate the effects of dance (movement) therapy and ballroom dances as therapeutic interventions for adults with physical and mental illnesses in comparison to other interventions or care as usual. A systematic literature search for randomized controlled trials examining dance therapy and ballroom dances published between 1995 and 2011 was carried out in the electronic databases MEDLINE and PsycINFO. 13 publications reporting results from 11 randomized trials (predominantly from USA and Scandinavia) were identified with mostly small samples. They examined breast cancer (n = 2), dementia (n = 1), Parkinson's disease (n = 2), heart failure (n = 1), diabetes type 2 (n = 1), depression (n = 3) and fibromyalgia (n = 1). Dance (movement) therapy had a positive impact for patients with breast cancer, improving quality of life, shoulder range of motion and body image. In patients with depression psychological distress was reduced by dance therapy. Ballroom dances improved balance and coordination in patients with Parkinson's disease and disease-specific quality of life in patients with heart failure. Dance (movement) therapy and ballroom dances seem beneficial for patients with breast cancer, depression, Parkinson's disease, diabetes and heart failure. However, further good quality research is needed to gain more profound insight into the efficacy of these treatment options.

Background The prevalence of allergic airway diseases in childhood is higher in boys than in girls but switches toward a female predominance in adolescents and adults. The sex-specific prevalence of allergic sensitization to 1 of the most common allergens worldwide, house dust mite (HDM), has not been examined systematically by age group and species. Objective To systematically review the literature to examine sex-specific differences in the prevalence of allergic sensitization to HDM. Methods On the basis of a systematic MEDLINE search for population-based studies published between 1990 and 2007, we conducted meta-analyses of male to female ratios for sensitization to 2 different species of HDMs ( Dermatophagoides pteronyssinus and Dermatophagoides farinae ) separately for children and adults. Results We included data from 7,822 children and 18,522 adults from 15 studies. The prevalence of sensitization to D pteronyssinus was significantly higher in boys vs girls (male to female ratio, 1.39; 95% confidence interval [CI], 1.13-1.71) and in men vs women (male to female ratio, 1.40; 95% CI, 1.22-1.61). For sensitization to D farinae, the significant male predominance in adults was even more pronounced (male to female ratio, 1.95; 95% CI, 1.37-2.79), but there were no sex-specific differences in children (male to female ratio, 0.90; 95% CI, 0.56-1.46). Conclusions In adults, the male predominance in sensitization to HDM seems to be contrary to the prevalence of allergic airway symptoms, which has a female predominance. The male predominance is even higher in allergic sensitization to D farinae than to D pteronyssinus . Further research is necessary regarding sex-specific differences in allergy and asthma.

Background Asthma prediction in early infancy is essential for the development of new preventive strategies. Loss-of-function mutations in the filaggrin gene (FLG) were identified as risk factors for eczema and associated asthma. Objective We evaluated the utility of the FLG mutations for the prediction of asthma. Methods Eight hundred seventy-one individuals of the prospective German Multicenter Allergy Study cohort were genotyped for 3 FLG mutations. Information on asthma, eczema, and food sensitization was available from birth to 13 years of age. Pulmonary function was measured from 7 to 13 years of age. The predictive value of the FLG mutations and of atopic phenotypes in infancy was assessed for asthma. Results In infants with eczema and sensitization to food allergens, the FLG mutations predicted childhood asthma with a positive predictive value of 100% (95% CI, 65.5% to 100%). This subgroup was characterized by a significant decrease in pulmonary function until puberty and represented 8.1% of all asthmatic children and 19.1% of patients with asthma after infantile eczema. We found a strong synergistic interaction between the FLG -null alleles and early food sensitization in the disease transition from eczema to asthma (relative excess risk due to interaction, 2.64; 95% CI, 1.70-3.98; P = .00040). Conclusion FLG mutations and food sensitization represent 2 distinct mechanisms interacting in the pathogenesis of asthma. In infants with eczema and food sensitization, genotyping of the FLG mutations allows the prediction of asthma before the onset of symptoms. Our findings might facilitate the development of early subgroup-specific interventions to prevent the progression from eczema to asthma.

Summary Objectives To assess, over a period of 12 months, whether homoeopathic treatment could influence eczema signs/symptoms and quality of life (QoL) compared with conventional treatment. Design Prospective multi-centre cohort study. Setting Children with eczema aged 1–16 years were recruited from primary care practices. Interventions Conventional versus homoeopathic treatment. Outcome measures Patients (or parents) assessed eczema symptoms by numerical rating scales as well as disease-specific Atopie Lebensqualitaets-Fragebogen (ALF) and general quality of life (KINDL, KITA) at 0, 6 and 12 months. Results A total of 118 children were included: 54 from homoeopathic (mean age±S.D. was 5.1±3.3 years; 56% boys) and 64 from conventional practices (6.2±3.8 years; 61% boys). Eczema symptoms (assessed by patients or their parents) improved from 0 to 12 months for both treatment options, but did not differ between the two groups: 3.5–2.5 versus 3.4–2.1; p =0.447 (adjusted). Disease-related quality of life improved in both groups similarly. In the subgroup of children aged 8–16 years the general quality of life showed a better trend for conventional treatment compared with homoeopathic treatment ( p =0.030). Conclusions This observational study is the first long-term prospective investigation to compare homoeopathic and conventional treatment of eczema in children. Over a period of 12 months, both therapy groups improved similarly regarding perception of eczema symptoms (assessed by patients or parents) and disease-related quality of life.

Background Childhood eczema often precedes the development of asthma and allergic rhinitis in the so-called atopic march . Recently, 2 loss-of-function mutations in the gene encoding the epidermal barrier protein filaggrin were reported to be predisposing factors for eczema and concomitant asthma, suggesting a possible role in disease transition. Objective We aimed to assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes. Methods The filaggrin mutations were genotyped and tested for association with allergic disorders in 2 large European populations including 1092 children with eczema. Results Highly significant association of the filaggrin null mutations with eczema and concomitant asthma was replicated. Moreover, we found that these mutations predispose to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. We show that the presence of 2 filaggrin null alleles is an independent risk factor for asthma in children with eczema, and that the 2 investigated mutations account for about 11% of eczema cases in the German population. Conclusion These results lend strong support to the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization highlights the importance of the epidermal barrier in the pathogenesis of these disorders. Clinical implications Our results suggest that the maintenance and repair of the epidermal barrier in infants with eczema may prevent the subsequent development of allergic airways disease.

Summary Objectives: To evaluate the effectiveness of homoeopathy versus conventional treatment in routine care. Design: Comparative cohort study. Setting: Patients with selected chronic diagnoses were enrolled in medical practice. Interventions: Conventional treatment or homeopathy. Outcome measures: Severity of symptoms assessed by patients and physicians (visual rating scale, 0–10) at baseline, 6 and 12 months and costs. Results: The analyses of 493 patients (315 adults, 178 children) indicated greater improvement in patients' assessments after homoeopathic versus conventional treatment (adults: homeopathy from 5.7 to 3.2; conventional, 5.9–4.4; p =0.002; children from 5.1 to 2.6 and from 4.5 to 3.2). Physician assessments were also more favourable for children who had received homoeopathic treatment (4.6–2.0 and 3.9–2.7; p p =0.856; children, €1471 versus €786, p =0.137). Conclusion: Patients seeking homoeopathic treatment had a better outcome overall compared with patients on conventional treatment, whereas total costs in both groups were similar.

Strategic technology alliances have received increased attention in the management literature. However, considerably less weight has been given to the study of this phenomenon in different environments and particularly in high velocity environments. This paper analyzes six cases of strategic technology partnerships in the mobile telephone industry. We investigate how, in high velocity environments, firms manage technology partnerships as an integrated element of their technology strategy. Based on the case studies, pointers are identified for the management of relationships in rapidly changing environments. Important pointers include the management of multiple time scales, balancing exploration and exploitation, integrating technology partnering into technology strategy, and managing the balance of continuity and change.

This paper discusses standardization of information and communications technologies. Standardization has become a domain of firm strategizing with information and communication technology standards being increasingly created through semi-open alliances. The paper analyzes the strategic logic of such standardization alliances based on an in-depth case study of the Bluetooth initiative. Similar to other successful standards described in the standardization literature, Bluetooth has been rapidly adopted by a large number of companies. The author argues that at least part of the success is due to the structure and design of the standardization alliance that promoted Bluetooth.

Background Hen's egg is the most common cause of food allergy in early childhood. Objective We investigated the efficacy and safety of early hen's egg introduction at age 4 to 6 months to prevent hen's egg allergy in the general population. Methods This randomized, placebo-controlled trial included 4- to 6-month-old infants who were not sensitized against hen's egg, as determined based on specific serum antibodies (IgE). These infants were randomized to receive either verum (egg white powder) or placebo (rice powder) added to the first weaning food 3 times a week under a concurrent egg-free diet from age 4 to 6 until 12 months. The primary outcome was sensitization to hen's egg (increased specific serum IgE levels) by age 12 months. Hen's egg allergy (secondary outcome) was confirmed by double-blind, placebo-controlled food challenges. Results Among 406 screened infants, 23 (5.7%) had hen's egg–specific IgE before randomization. Seventeen of 23 underwent subsequent double-blind, placebo-controlled food challenges, and 16 were confirmed as allergic, including 11 with anaphylactic reactions. Of the 383 nonsensitized infants (56.7% male), 184 were randomized to verum and 199 to placebo. At 12 months of age, 5.6% of the children in the verum group were hen's egg sensitized versus 2.6% in the placebo group (primary outcome; relative risk, 2.20; 95% CI, 0.68-7.14; P = .24), and 2.1% were confirmed to have hen's egg allergy versus 0.6% in the placebo group (relative risk, 3.30; 95% CI, 0.35-31.32; P = .35). Conclusion We found no evidence that consumption of hen's egg starting at 4 to 6 months of age prevents hen's egg sensitization or allergy. In contrast, it might result in frequent allergic reactions in the community considering that many 4- to 6-month-old infants were already allergic to hen's egg.

Information and communication technologies are in the process of transforming the way business is conducted in a large number of industries. The impact of this change is not well understood. This paper develops a research agenda that helps to investigate the implications of information and communication technology on selected management fields. In particular, the implications are investigated for strategic management, demand and supply chain management, logistics, organization and leadership, and management education. The research agenda is developed by first identifying impacts of information and communication technologies in the domains discussed. From these impacts, research needs are derived.

Background The route and dose of exposure are believed to be relevant factors in the sensitization process. Pathogenesis-related group 10 protein (PR-10) molecules are a family of allergenic proteins shared by many pollens (eg, birch and alder) and foods (eg, apple, peach, and soy). Children are exposed to both pollen-derived (inhaled) and food-derived (ingested) PR-10 molecules. Objective We sought to investigate the role of route and dose of exposure in the evolution of IgG and IgE responses to recombinant PR-10 molecules. Methods The German Multicentre Allergy Study examined a birth cohort born in 1990. Blood samples were collected at the ages of 1, 2, 3, 5, 6, 7, 10, and 13 years. Participants were included in the present analysis if they had (1) at least 1 serum sample at each of the 4 age periods or time points (1-3 years, 5-7 years, 10 years, and 13 years) and (2) IgE responses to birch (children with birch atopy) or no IgE response at all to 9 common aeroallergens and food allergens (nonatopic children). Therefore serum IgE antibodies to a panel of 4 airborne and 5 foodborne extracts, as well as to Bet v 1, were measured in singleplex assays, whereas IgG and IgE antibodies to a panel of 3 airborne PR-10 molecules (rBet v 1, rAln g 1, and rCor a 1.0101) and 7 foodborne PR-10 molecules (rCor a 1.0401, rMal d 1, rPru p 1, rGly m 4, rAra h 8, rApi g 1, and rDau c 1) were tested by using a multiplex microarray. Results In the present analyses we included 28 children with birch atopy and randomly selected 28 nonatopic children from the 190 children fulfilling the inclusion criteria. Two different patterns of IgG responses to PR-10 molecules were identified. Among nonatopic subjects, a "default" IgG response was directed mostly against foodborne PR-10, started often before age 2 years, stayed weak, and was mostly transient. Among all atopic subjects, the default IgG response at age 1 year was overwhelmed after age 2 years by an "pre-atopic" IgG response, which started with or shortly before the IgE response and was intense and persistent. This atopic IgG response, as well as the IgE response, involved progressively more foodborne PR-10 proteins with frequencies and levels related to their homology with Bet v 1. Conclusions The results suggest that children have a default antibody response to PR-10 molecules, which is early, weak, and transient; does not involve IgE; and is initiated by foodborne PR-10. By contrast, an atopic antibody response to PR-10 molecules is delayed, strong, and persistent; involves both IgG and IgE; and is initiated by airborne PR-10.

More than 20 years ago, a landmark article by David Strachan showed a striking association between higher numbers of children in households and a lower prevalence of self-reported allergic rhinitis and eczema. A higher frequency of infections in young children and mothers prenatally in larger families was hypothesized to prevent the development of allergic diseases. This thoughtprovoking impulse gave rise to several projects investigating environmental exposures potentially triggering immune responses and their link to allergies, termed the hygiene hypothesis. In addition to remote surrogates, such as day care attendance and family size, immediate parameters, such as number of infections, vaccinations, and use of antibiotics, were repeatedly found to be related to patterns of sensitization and inconsistently associated with allergic diseases. On a more specific level, several microorganisms have been investigated, and the diversity of microbial exposure per se has been linked to childhood asthma recently. Nonetheless, the search for underlying mechanisms mediating the effect of infections and other aspects of hygiene remains unsettled. The farming environment has been used as a setting to study the influence of the joint exposure of several aspects in reference to the hygiene hypothesis. The prevalence of asthma and allergic rhinitis was consistently lower in farming compared with nonfarming populations. Unfortunately, causal pathways are even more concealed by the variety of environmental exposures disparately distributed between farming and nonfarming families, such as direct contact with livestock and its microbial diversity; housing, including dampness and mold formation; or food derived from local production, such as unpasteurized milk, to name but a few. In the current issue of the Journal, Motika et al introduce prevalence data on asthma and allergic sensitization from the remote farming population of the Hutterites in South Dakota, which is located in the Midwest portion of the United States. The results of 2 cross-sectional surveys a decade apart allow the identification of time trends of allergic disorders in this closed community. Originating from Austria, the forerunners of the Hutterites migrated to North America in the 1880s. To date, they have been dedicated to a traditional lifestyle with little influence from modern society.

Rhinitis in older children and adults has been shown to be a predictor for adolescent- and adult-onset asthma. These findings suggest an interaction between the upper and lower airways. Whether rhinitis is a predictor for childhood-onset asthma is unknown.We sought to investigate whether rhinitis in early childhood is an independent predictor for wheezing between the ages of 5 and 13 years in the German Multicentre Allergy Study birth cohort.The German Multicentre Allergy Study cohort initially included 1314 healthy children. They were followed from birth to the age of 13 years with regular questionnaires and interviews. Specific IgE levels were measured at yearly intervals. Airway hyperresponsiveness was assessed at 7 years.Allergic rhinitis until the age of 5 years was found to be a predictor for developing wheezing between the ages of 5 and 13 years, with an adjusted relative risk of 3.82 (P .001). This association was not attributable to the type of sensitization, the severity of sensitization, or atopic dermatitis during the first 2 years of life. In this group of children, 41.5% of all new cases of wheezing occurred among children with preceding allergic rhinitis.The first manifestation of allergic rhinitis occurs in preschool children in whom it is a predictor for subsequent wheezing onset. Preschool children with rhinitis might thus benefit from early assessment of allergic sensitization to identify the children at high risk of wheezing.

Objectives To examine the influence of homoeopathic versus conventional treatment, over a period of 1 year, in children with eczema. Methods In this prospective multi-centre cohort study, children with eczema aged 1–16 years were recruited from primary care practices in Germany. They received either conventional or homoeopathic treatment. Outcome measures were self/parents assessed eczema symptoms by numerical rating scales (0=none; 10=worst symptoms) as well as quality of life at 0, 6 and 12 months. Results We included a total of 118 children: 54 from homoeopathic (mean age±S.D. was 5.1±3.3 years; 56% boys) and 64 from conventional practices (6.2±3.8 years; 61% boys). Eczema symptoms improved from 0 to 12 months for both treatment options. There was no significant difference between the homoeopathic group (3.5–2.5, for 0–12 months) versus the conventional treatment group (3.4–2.1), after adjustment for potential confounders ( p =0.447). Furthermore, disease-related quality of life improved in both groups similarly. In the subgroup of children aged 8–16 years, general quality of life was significantly better for children with conventional compared to those with homoeopathic treatment ( p =0.030). Conclusions This observational study is the first long-term prospective investigation to compare homoeopathic and conventional treatment of eczema in children. Over a period of 1 year, both therapy groups improved similarly regarding patient-oriented outcomes. To resolve current uncertainties surrounding both homoeopathic and conventional treatment for children with eczema, further studies are needed including assessments by raters, who are blinded to treatment. A randomized trial could be designed in a way where both groups of patients—i.e. those seeking conventional and those seeking homoeopathic care—are randomized to either verum or placebo treatment within their preferred type of care.

Rationale Effect of in utero tobacco ( IUT ) and environmental tobacco smoke ( ETS ) exposure on the development of allergic sensitization and airway disorders during the first 10 years of life. Methods In a prospective birth cohort (Multicentre Allergy Study [MAS] with n=1314 newborns), outcome and exposure were annually assessed by questionnaire or interview. Additionally to IUT exposure, four ETS exposure categories were compared: 1.never, 2.by father only, 3.irregularly by mother, and 4.regularly by mother +/-father. Four outcomes were considered: allergic sensitization to inhalant allergens (specific IgE >0.35kU/I), allergic rhinitis, wheezing and respiratory infections. Longitudinal effects of ETS exposure were assessed by generalized estimating equation models (adjusted for education, birth weight, breast feeding, number of siblings, and pets). Results ETS exposure increased with age, 18% had been exposed continuously by maternal ETS and 40% of children had never been exposed to parental ETS. Since genetic predisposition is known to be the most important risk factor for atopy we stratified our analysis by atopic family history. In children with atopic parents ( aP ), combined IUT and regular maternal ETS exposure significantly increased the risk for allergic sensitization (1 aP: OR=1.8 [95% C.I.: 1.1–3.1]; 2 aP: OR=7.0 [1.8–26.7]) and wheezing (1 aP: OR=2.1 [1.3–3.8]; 2 aP: OR=5.7 [2.0–19]). No effect was found in children without aP and for rhinitis and respiratory infections. Conclusions Longterm passive pre- and postnatal tobacco smoke exposure increases the risk for allergic sensitization or wheezing during the first 10 years of life. This effect, however, was only seen in children with a genetic predisposition to allergy.