Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

BACKGROUND: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children. METHODS: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. RESULTS: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors. CONCLUSION: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies.

Frequency of food allergy in school-aged children in eight European countries-The EuroPrevall-iFAAM birth cohort.

BACKGROUND: The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. METHODS: A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). RESULTS: A total of 6105 children participated in this school-age follow-up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow-up) and 3.8% (88 related to 2289 with completed eligibility assessment). INTERPRETATION: In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.

The Montreal Cognitive Assessment (MoCA) in a population-based sample of Turkish migrants living in Germany.

OBJECTIVES: Data on cognitive testing in migrants in Germany are scarce. We aimed to evaluate the Montreal Cognitive Assessment (MoCA) in Turkish migrants in Berlin and its association with demographics and health-related variables. METHOD: For this cross-sectional study, a random sample of persons with Turkish names was drawn from the registration-office. Cognitive function was assessed using the MoCA; 0 = worst, 30 = best total score. Multivariable linear regression models were calculated to determine associated factors with the total MoCA-score. RESULTS: In our analyses we included 282 participants (50% female), mean age 42.3 ± 11.9 years (mean ± standard deviation (SD)). The mean ± SD MoCA score was 23.3 ± 4.3. In the multivariable analysis, higher education (ß = 2.68; p < 0.001), and chosing the German version of the MoCA (ß = -1.13; p = 0.026), were associated with higher MoCA-scores, whereas higher age (ß = -0.08; p = 0.002) was associated with lower MoCA scores. CONCLUSION: In our study, a higher educational level, lower age, and German as the preferred test language (as compared to Turkish) were positively associated with the cognitive performance of Berliners with Turkish roots. To examine neurocognitive health of migrants, longitudinal population-based and clinical cohort studies that specifically compare migrants and their descendants with the original population of their home countries are required.

Physician's appraisal vs documented signs and symptoms in the interpretation of food challenge tests: The EuroPrevall birth cohort.

BACKGROUND: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges. METHODS: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician's appraisal were compared to documented signs and symptoms. RESULTS: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen's kappa spanning from 0.42 to 0.84. CONCLUSIONS: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data.

Live Cell Therapy as Potential Risk Factor for Q Fever.

During an outbreak of Q fever in Germany, we identified an infected sheep flock from which animals were routinely used as a source for life cell therapy (LCT), the injection of fetal cells or cell extracts from sheep into humans. Q fever developed in 7 LCT recipients from Canada, Germany, and the United States.

Sex-Related Allergic Rhinitis Prevalence Switch from Childhood to Adulthood: A Systematic Review and Meta-Analysis.

BACKGROUND: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. METHODS: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self- or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. RESULTS: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. CONCLUSIONS: The male predominance of rhinitis prevalence in childhood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms.

Prediction and prevention of allergic rhinitis: A birth cohort study of 20 years.

BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases, usually starting in the first 2 decades of life. Information on predictors, risk, and protective factors is missing because of a lack of long-term prospective studies. OBJECTIVE: Our aim was to examine early-life environmental and lifestyle determinants for AR up to age 20 years. METHODS: In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated at 19 time points. A Cox regression model examined the associations between 41 independent early-life factors and onset of AR (as the primary outcome), including sensitization against aeroallergens and the secondary outcomes of nonallergic rhinitis and AR plus asthma. RESULTS: Two hundred ninety subjects had AR within 13,179 person years observed. The risk of AR was higher with a parental history of AR (adjusted hazard ratio [aHR], 2.49; 95% CI, 1.93-3.21), urticaria (aHR, 1.32; 95% CI, 1.00-1.74), or asthma (aHR, 1.29; 95% CI, 0.95-1.75). Early allergic sensitization (aHR, 4.53; 95% CI, 3.25-6.32), eczema within the first 3 years of life (aHR, 1.83; 95% CI, 1.38-2.42), male sex (aHR, 1.28; 95% CI, 1.02-1.61), and birthday in summer or autumn (aHR, 1.26; 95% CI, 1.00-1.58) were independent predictors of AR up to age 20 years. None of the other socioeconomic, environmental, lifestyle, pregnancy, and birth-related factors were associated with AR. CONCLUSION: Only nonmodifiable factors, particularly early allergic sensitization or eczema and parental AR, predicted AR up to age 20 years. No modifiable aspects of early-life environment or lifestyle were identified as targets for primary prevention.

Improved management of childhood atopic dermatitis after individually tailored nurse consultations: A pilot study.

BACKGROUND: For optimal therapy of atopic dermatitis (AD) in children, parent education for treatment strategies that consider the episodic course and multiple triggers is essential. Regular consultations with doctors often cannot appropriately provide this. Therefore, supplemental patient education tools have been established. We evaluate single nurse consultations, assessing their global benefit, parents' self-confidence, and children's symptoms and sleep disturbance. METHODS: Parents of children with AD were invited for an individually tailored nurse consultation by the doctor initially consulted in cases where difficulties in implementing care recommendations were detected and established therapeutic patient education (TPE) group programmes were impracticable. Parents' estimation of their own self-confidence, current disease severity and its treatment was assessed by a questionnaire at the consultation and by telephone 14 days later. RESULTS: Parents of 1628 children (mean age 1.7 yr) attended consultations in 22 centres (317-6 patients; median 38). At follow-up parents indicated a significantly increased self-confidence to handle the recommendations and >90% rated the consultation highly supportive. The frequency of severe symptoms was significantly lower (20% of initial cases), as of moderate symptoms (50%). Median scores for sleep disruption and pruritus decreased by >50%. CONCLUSIONS: Individually tailored single nurse consultations for AD are associated with a significant benefit for the families after 14 days. We recommend these in addition to the usual medical care in cases where participation in TPE programmes is impossible or a short-time follow-up is required. To substantiate their effect, studies with a long-term follow-up and a control group are warranted.

Is immunoglobulin E to Staphylococcus aureus enterotoxins associated with asthma at 20 years?

BACKGROUND: In adults, subjects sensitized to Staphylococcus aureus enterotoxins (SE) seem to have an increased risk of asthma, whereas this association is less clear in childhood and adolescence. The primary aim of the present analysis was to examine the association between sensitization to SE and asthma at the age of 20 years. METHODS: The German Multicentre Allergy Study recruited 1314 healthy newborns in 1990. We analyzed data from 61 asthmatics (based on at least two criteria: physician diagnosed asthma ever, wheezing in the last 12 months, asthma medication in the last 12 months) and 122 healthy study participants at age 20. In serum, specific Immunoglobulin E (IgE) to SE and common aeroallergens were measured. The association between asthma at age 20 and sensitization to SE was estimated by logistic regression models considering allergic, socio-demographic, and lifestyle factors as potential confounders. RESULTS: Fifty-five percent of the included participants were female. At age 20, subjects sensitized to SE were more likely to have asthma than not-sensitized subjects: raw odds ratio (OR) 2.5, 95%-confidence interval (95%CI) [1.3-4.7]; adjusted OR 1.6, 95%CI [0.8-3.4]. CONCLUSION: Asthmatics at age 20 were more often sensitized to SE compared to controls. Our study may indicate a moderate relationship between SE-sensitization and asthma; however, this association attenuated after adjusting for potential confounders and was no longer statistically significant. Longitudinal investigations with SE-IgE measurements at different time points in larger samples are needed to explore the temporal manner of this relationship.

Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS.

BACKGROUND: The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population-based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow-up data from two decades of a birth cohort study. METHODS: In 1990, we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population-based MAS birth cohort study. The sample was purposely risk-enriched by increasing the proportion of children at high allergy risk (i.e. at least 2 allergic family members among parents and siblings) from 19% in the source population to 38% in the final sample. The remaining 62% of all MAS children had a low or no allergy risk. Symptoms, medication and doctor's diagnoses of allergic diseases have been assessed using standardized questionnaires including validated ISAAC questions in 19 follow-up assessments up to age 20. Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant: asthma, allergic rhinitis and eczema. RESULTS: Response at age 20 was 72% (n = 942) of all recruited participants. At age 20, 18.5% (95% CI, 15.0-22.5%) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3% (95% CI, 4.3-9.0%) of those with non-allergic parents. At this age, allergic multimorbidity was similar in women and men (12.7% (95% CI, 9.7-16.2%) vs. 11.6% (95% CI, 8.9-14.8%)), whereas single allergic diseases were slightly more common in women than men (24.2% (95% CI, 20.2-28.5%) vs. 20.1% (95% CI, 16.6-24.0%)). Asthma occurred more frequently with coexisting allergic rhinitis and/or eczema than as a single entity from pre-puberty to adulthood. CONCLUSION: Having parents with allergies is not only a strong predictor to develop any allergy, but it strongly increases the risk of developing allergic multimorbidity. In males and females alike, coexisting allergies were increasingly common throughout adolescence up to adulthood. Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity.

Early-life determinants of asthma from birth to age 20 years: a German birth cohort study.

BACKGROUND: The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. OBJECTIVE: We aimed to determine early-life predictors of asthma incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. METHODS: In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). RESULTS: Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95% CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR, 1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]), had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]), had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. CONCLUSION: Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.

Implementation of a Surveillance System for Severe Acute Respiratory Infections at a Tertiary Care Hospital in Austria: Protocol for a Retrospective Longitudinal Feasibility Study.

BACKGROUND: The risk of a large number of severe acute respiratory infection (SARI) cases emerging is a global concern. SARI can overwhelm the health care capacity and cause several deaths. Therefore, the Austrian Agency for Health and Food Safety will explore the feasibility of implementing an automatic electronically based SARI surveillance system at a tertiary care hospital in Austria as part of the hospital network, initiated by the European Centre for Disease Prevention and Control. OBJECTIVE: We aim to investigate the availability of routinely collected health record data pertaining to respiratory infections and the optimal approach to use such available data for systematic surveillance of SARI in a real-world setting, describe the characteristics of patients with SARI before and after the beginning of the COVID-19 pandemic, and investigate the feasibility of identifying the risk factors for a severe outcome (intensive care unit admission or death) in patients with SARI. METHODS: We will test the feasibility of a surveillance system, as part of a large European network, at a tertiary care hospital in the province of Lower Austria (called Regional Hospital Wiener Neustadt). It will be a cross-sectional study for the inventory of the electronic data records and implementation of automatic data retrieval for the period of January 2019 through the end of December 2022. The analysis will include an exploration of the database structure, descriptive analysis of the general characteristics of the patients with SARI, estimation of the SARI incidence rate, and assessment of the risk factors and different levels of severity of patients with SARI using logistic regression analysis. RESULTS: This will be the first study to assess the feasibility of SARI surveillance at a large 800-bed tertiary care hospital in Austria. It will provide a general overview of the potential for establishing a hospital-based surveillance system for SARI. In addition, if successful, the electronic surveillance will be able to improve the response to early warning signs of new SARI, which will better inform policy makers in strengthening the surveillance system. CONCLUSIONS: The findings will support the expansion of the SARI hospital-based surveillance system to other hospitals in Austria. This network will be of use to Austria in preparing for future pandemics. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47547.

Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort.

BACKGROUND: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), concomitant depression might have a negative impact on the course of disease and treatment outcomes. The aims of this analysis are to determine the prevalence of depressive symptoms in axSpA and PsA patients in a real-world cohort study and to identify sociodemographic and clinical associated factors for moderate or severe depressive symptoms in both diseases. METHODS: Patients from the RABBIT-SpA cohort with an axSpA or PsA diagnosis and a valid WHO-5 Well-Being Index score at baseline were included. A descriptive analysis of baseline and outcome parameters by category of depressive symptoms was performed and factors associated with the presence of depressive symptoms (moderate or severe) were examined in a logistic regression. RESULTS: Two thousand four hundred seventy patients (1,245 axSpA; 1,225 PsA) were included in the analysis. In both diagnoses, the proportion of patients with moderate depressive symptoms was 8% and 21% with severe symptoms. Patients with moderate or severe depressive symptoms were less likely to engage in sports than those with no or mild depressive symptoms, had more comorbidities and higher scores for disease activity, functional limitations, fatigue, and pain and took more analgesics. In axSpA, patients with a higher disease activity, a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms, while patients with more years in education and engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. PsA patients with a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms while those engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. CONCLUSION: We confirmed a high prevalence of depressive symptoms in both PsA and axSpA. Factors negatively associated with the presence of depressive symptoms were fatigue, not engaging in sports, and greater functional limitations. Depressive symptoms may affect the perception of disease activity / severity by patients. Thus, depressive symptoms are an important condition in axSpA and PsA that should be considered when evaluating disease activity and treatment outcomes.

Voiding dysfunction after the tension-free vaginal tape procedure.

AIM: To assess the incidence of voiding dysfunction in women undergoing a tension-free vaginal tape (TVT) procedure and report our experience with nonsurgical and surgical management. METHODS: Pre- and postoperative introital ultrasonographic measurement of the residual volume was performed in a prospective observational study. Patients' perception of micturition and continence status was assessed by questionnaire. RESULTS: Of 478 women, 4 (0.8%) suffered from micturition disturbance within the first 2 weeks. In the mean of 3 months after surgery, 7.1% of the patients had residual volume between 50 and 100 ml, and 2.6% had residual volume >100 ml. 243 women were investigated after 39 months (range 12-74). The rate of residual volume exceeding 50 ml decreased to 6.5% and was approximated to the preoperative period. CONCLUSION: Incomplete bladder emptying is a possible problem after TVT. In our cohort, 93% of the women had no voiding disturbances or marginally affected voiding after 12-74 months.

Implementing an automated monitoring process in a digital, longitudinal observational cohort study.

BACKGROUND: Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research. METHODS: An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This "conflict catalog" was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried. RESULTS: Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40-64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59-69% were answered. The most common missing values were CRP, ESR, Schober's test, data on systemic glucocorticoid therapy, and presence of enthesitis. CONCLUSION: Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

Influence of bladder volume on pelvic organ prolapse quantification results.

AIMS: To compare the degree of pelvic organ prolapse between examinations performed with full and empty bladder in patients without any prolapse and with pelvic organ prolapse stage I or II using the pelvic organ prolapse quantification (POPQ) system. METHODS: A prospective observational study with 120 consecutive patients with and without symptoms of pelvic organ prolapse was evaluated. All women were examined with full and empty bladder. The data were analyzed by Wilcoxon's signed-rank test. RESULTS: With empty bladder 54% had the same stage, 41% had a one-step higher stage and 5% had a two-step higher stage of prolapse. There was an increase in the extent of prolapse in the empty bladder setting at all six site-specific points (Aa, Ba, C, D, Ap, Bp; p < 0.001) but not in the results of genital hiatus, perineal body and total vaginal length. CONCLUSION: Our results suggest that the full extent of prolapse may be only assessed with an empty bladder.

Risk Factors for Hen's Egg Allergy in Europe: EuroPrevall Birth Cohort.

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.

Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series.

BACKGROUND: In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates. METHODS: A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs. FINDINGS: Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3-4·3) and the median serial interval was 4·0 days (3·0-5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0-99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2-32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6-8·9; 11 of 217) among non-household, high-risk contacts. INTERPRETATION: Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve. FUNDING: All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

Can the use of HEPA cleaners in homes of asthmatic children and adolescents sensitized to cat and dog allergens decrease bronchial hyperresponsiveness and allergen contents in solid dust?

BACKGROUND: Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR). METHODS: In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples. RESULTS: Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV(1) after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR. CONCLUSION: Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study.