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Background: Surfactant Protein D (SP-D) is a pattern recognition molecule belonging to the collectin family expressed in multiple human organ systems including the lungs. Previous studies have shown that SP-D concentrations in bronchoalveolar lavage samples decreases and serum concentrations increases in patients with asthma possibly attributable to a combination of induced SP-D synthesis and decreased air-blood barrier integrity. The aims of this study were to investigate if the serum level of SP-D and common variations in the SP-D gene were associated to asthma in adolescents and young adults. Methods: Prospective observational study including 449 adolescents and young adults (age 11-27 years) previously diagnosed with asthma during a two-year period from 2003 to 2005 (0-16 years). At follow-up from 2016 to 2017 314 healthy controls with no medical history of asthma were recruited. Serum SP-D was analyzed on samples obtained at baseline as well as samples obtained at follow-up. SP-D genotyping was performed for rs721917, rs2243639 and rs3088308. Results: No differences were found in mean levels of sSP-D and SFTPD genotype among subjects with current asthma, no current asthma and controls. Serum SP-D and SFTPD genotype were not associated to any clinical parameters of asthma. Furthermore, baseline sSP-D was not associated to asthma at follow-up. Conclusion: Serum surfactant protein D and common SP-D gene variants were not associated with asthma in Danish adolescents and young adults with mild to moderate asthma. Serum surfactant protein D did not demonstrate any value as a clinical biomarker of asthma.

Background Asthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children. Methods We studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex. Results Among the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23). Conclusion Our findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.

Purpose: The present study assessed the role of an amino acid-based formula (AAF) in the growth of infants with cow's milk protein allergy (CMPA). Methods: Non-breastfed, term infants aged 0-6 months with symptoms suggestive of CMPA were recruited from 10 pediatric centers in China. After enrollment, infants were started on AAF for two weeks, followed by an open food challenge (OFC) with cow's milk-based formula (CMF). Infants with confirmed CMPA remained on AAF until 9 months of age, in conjunction with a cow's milk protein-free complementary diet. Body weight, length, and head circumference were measured at enrollment and 9 months of age. Measurements were converted to weight-for-age, length-for-age, and head circumference-for-age Z scores (WAZ, LAZ, HCAZ), based on the World Health Organization growth reference. Results: Of 254 infants (median age 16.1 weeks, 50.9% male), 218 (85.8%) were diagnosed with non-IgE-mediated CMPA, 33 (13.0%) tolerated CMF, and 3 (1.2%) did not complete the OFC. The mean WAZ decreased from 0.119 to -0.029 between birth and enrollment (p=0.067), with significant catch-up growth to 0.178 at 9 months of age (p=0.012) while being fed the AAF. There were no significant changes in LAZ (0.400 vs. 0.552; p=0.214) or HCAZ (-0.356 vs. -0.284; p=0.705) from the time of enrollment to age 9 months, suggesting normal linear and head growth velocity. Conclusion: The amino acid-based study formula, in conjunction with a cow's milk protein-free complementary diet, supported normal growth till 9 months of age in a cohort of Chinese infants with challenge-confirmed non-IgE-mediated CMPA.

Background: Previous studies have investigated the natural course of cow's milk allergy (CMA) and development of atopic diseases into adolescence. Studies with long-term follow-up into adulthood are lacking. The aim of this study was to investigate (a) the natural course of CMA in a 1-year birth cohort of Danish children from birth until 15 and 26 years of age and (b) the development of atopic diseases in a group of children with CMA (group A) compared to a random sample of 276 children from the same birth cohort (group B). Methods: A birth cohort of 1749 newborns was investigated prospectively for the development of CMA and atopic diseases. During the first year of life and at 18 months and 3, 5, 10, 15, and 26 years of age, questionnaire-based interviews, physical examination, skin prick tests, and specific IgE testing, and from 10 years also spirometry, were carried out. Results: Thirty-nine (2.2%) were diagnosed with CMA. The recovery rate was 87%, 92%, and 97% at 3, 5, and 26 years of age. Compared to group B, group A had significantly (P

Background Prenatal phthalate exposure has been suggested to alter immune responses and increase the risk of asthma, eczema and rhinitis. However, few studies have examined the effects in prospective cohorts and only one examined rhinitis. We therefore studied associations between maternal urinary concentrations of phthalate metabolites and asthma, eczema and rhinitis in offspring aged 5 years. Methods From 552 pregnant women in the Odense Child Cohort, we quantified urinary concentrations of 12 phthalate metabolites in third trimester. We assessed asthma, rhinitis and eczema in their offspring at age 5 years with a questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC), and conducted logistic regression adjusting for relevant confounders. Results 7.4% of the children had asthma, 11.7% eczema and 9.2% rhinitis. Phthalate exposure was low compared to previous cohorts. No significant associations between prenatal phthalate exposure and asthma were found. Odds ratios (ORs) of child rhinitis with a doubling in ΣDiNPm and di-2-ethylhexyl phthalate metabolite (ΣDEHPm) concentrations were, respectively, 1.15 (95% confidence interval (CI) 0.97,1.36) and 1.21 (CI 0.93,1.58). The OR of eczema when doubling ΣDiNPm was 1.24 (CI 1.00,1.55), whereas the OR of using medicine against eczema when doubling a di-ethyl phthalate (DEP) metabolite was 0.81 (CI 0.68,0.96). Conclusion The lack of association between maternal phthalate exposure and asthma in the offspring may be due to low exposure and difficulties in determining asthma in 5-year-olds. The higher odds of rhinitis may raise public concern but further research in larger cohorts of older children is warranted.

Background Sensitization to both inhalant and food allergens has been shown to be risk factors for development of asthma and rhinoconjunctivitis (RC). However, few studies have addressed the role of transient or persistent IgE sensitization to specific allergens in early life for later development of allergic diseases. The aim of this study was to explore the association between transient and persistent sensitization in early life and the development of asthma and RC at 6 and 14 years. Methods The Danish Allergy Research Center (DARC) cohort is a prospective non-interventional birth cohort study comprising 562 children. For the purpose of this study, we examined a subgroup of the original cohort with specific IgE measured at, at least 3 of 4 follow-ups between 3 and 18 months of age (n = 366). Multiple logistic regression models were used to investigate the association between transient and persistent early-life sensitization to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. Results Both transient early-life sensitization and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99[1.41-11.32] and 5.95[1.78-19.92]) and RC (aOR 2.94[1.19-7.28] and 6.18[1.86-20.53]) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to house dust mite (HDM) had increased risk of asthma (aOR 3.80[1.17-12.41]) at 14 years. Conclusions Early transient IgE sensitization and persistent IgE sensitization to hen's egg were associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years.

Background: Allergic diseases are common and represent a considerable health and economic burden worldwide. We aimed to examine the effect of a combination of two probiotic strains administered in late infancy and early childhood on the development of allergic diseases and sensitization.Methods: In this double-blind, placebo-controlled intervention trial, participants were randomized to receive a daily mixture of Lactobacillus rhamnosus and Bifidobacterium animalis subsp lactis or placebo-starting prior to attending day care. The intervention period was 6 months, and the parents answered web-based questionnaires on allergic symptoms and doctor's diagnosed allergic disease monthly. IgE was measured at baseline and follow-up.Results: A total of 290 participants were randomized: 144 in the probiotic group and 146 in the placebo group. Mean age at intervention start was 10.1 months. At follow-up (mean age 16.1 months), the incidence of eczema was 4.2% in the probiotic group and 11.5% in the placebo group (P = 0.036). The incidence of asthma and conjunctivitis did not differ between groups, and no children presented with rhinitis. Sensitization was equal in the two groups at intervention start (7.5% and 9.5%, respectively), and two children in each group were sensitized during the intervention.Conclusions: We observed a significantly lower incidence of eczema in the probiotic group compared to the placebo group. The probiotics were administered in late infancy-prior to attending day care-suggesting a broader window of opportunity using probiotics in the prevention of eczema. The incidence of asthma, rhinitis, conjunctivitis, and sensitization did not differ.

BACKGROUND: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily, which plays multifaceted roles in innate immunity and normal endothelial function. It has been proposed that MFAP4 promotes the development of asthma in vivo and proasthmatic pathways of bronchial smooth muscle cells in vitro. The aim of this study was to investigate the significance of serum MFAP4 in adolescents and young adolescents with persistent asthma.METHODS: Prospective, observational study including adolescents and young adults (age 11-27 years) previously diagnosed with asthma during childhood 2003 to 2005 (0-15 years) at the four pediatric outpatient clinics in the Region of Southern Denmark (n = 449). Healthy controls were recruited at follow-up (n = 314). Detection of serum MFAP4 was performed by AlphaLISA technique.RESULTS: Current asthma was associated to a 14% higher mean level of serum MFAP4 compared with controls (expβ 1.14, 95% confidence intervals [CI], 1.05-1.23) and a 6% higher mean level compared with subjects with no current asthma (expβ 1.06, 95% CI, 0.99-1.13). No association was found at follow-up between serum MFAP4 and self-reported atopic symptoms (other than asthma), Asthma Control Test-score, fractional exhaled nitric oxide (FeNO), nor to flow rate at 1 second, forced vital capacity, and forced expiratory flow 25% to 75%, response to short-acting beta 2 agonist or mannitol.CONCLUSIONS: We found a significantly higher mean level of serum MFAP4 in adolescent and young adults with mild to moderate asthma compared with healthy controls but no association to FeNO and lung function nor to the response to short-acting beta 2 agonist or mannitol. The result supports the hypothesis that MFAP4 plays a role in the pathogenesis of asthma although the marker did not demonstrate any obvious potential as an asthma biomarker in adolescents and young adults with asthma. To understand the possible proasthmatic functions of MFAP4, further investigation in specific asthma phenotypes and the underlying molecular mechanisms is warranted.

Introduction: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that have resulted in global environmental exposures. Previous epidemiological studies have reported possible effects on the immune system after developmental PFAS exposure, but the possible impact on childhood infectious disease is unclear. Objectives: To investigate the association between prenatal exposure to PFAS and symptoms of infections at age 1–4 years. Methods: The Odense Child Cohort is an on-going prospective study on children's health, where serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in 649 pregnant women before gestational week 16. Of these women, 359 reported on symptoms of infection in their child every two weeks for a one-year period. The association between prenatal exposure to PFAS and the symptoms was estimated using a logistic regression model and a negative binomial regression model. For the latter, the outcome was reported as an incidence rate-ratio (IRR), and all models were adjusted for maternal age, educational level, parity and child age. Results: On average, the children experienced symptoms of infection 23% of the time during one year. PFOS exposure in the high tertile compared to the low tertile was associated with a statistically significant increased proportion of days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), P-trend

Background Atopic diseases are among the most common chronic diseases in adolescents and it is uncertain whether the prevalence of atopic diseases has reached a plateau or is still increasing. The use of the ISAAC (International Study of Asthma and Allergy in Childhood) questionnaire has provided comparable prevalence rates from many countries; whereas studies including clinical examinations and strict diagnostic criteria are scarce. We aimed to investigate the prevalence of atopic diseases, the pattern of sensitization and comorbidities at 14 years in a prospective birth cohort. Methods The children were examined eight times from birth to 14 years. Visits included questionnaire-based interviews, clinical examination, skin prick test and specific IgE. Results Follow-up rate at 14-years was 66.2%. The 12-month prevalence of any atopic disease was high (40.3%) mostly due to a high prevalence of rhinoconjunctivitis (32.8%) whereas the prevalence of asthma was 12.9% and of atopic dermatitis 8.1%. In children with at least one atopic disease 60% were sensitized while only 16% of those without atopic diseases were sensitized. The frequency of sensitization depended on the phenotype. Among children with rhinoconjunctivitis only, rhinoconjunctivitis with concomitant astma or atopic dermatitis or both 62.5%, 81.5%, 70% and 100% respectively were sensitized, whereas it was 7.7% and 33.3% of children with only asthma or atopic dermatitis. Conclusion The prevalence of rhinoconjunctivitis was high in adolescence. Children with rhinoconjunctivitis with and without comorbidities were frequently sensitized. Children with asthma without concomitant allergic rhinoconjunctivitis were rarely sensitized. This article is protected by copyright. All rights reserved.

Background and Aims: When investigating and treating asthma in children, diagnosing must be precise and valid. There is a need for studies researching asthma in children showing how to use registry-based, epidemiological data. We examined the feasibility and validity of using anti-asthmatic drug prescription data to identify children with asthma and assessed medication patterns in children with and without confirmed asthma.Methods: We used population-based Danish prescription data and hospital discharge registries to identify all children aged 0 to 14 years who had redeemed at least one prescription for an inhaled anti-asthmatic drug. Individual asthma cases were validated by hospital discharge information and by their treating general practitioners according to international asthma guidelines.Results: In total, 2053 children, out of a population of 20181, had redeemed at least one prescription of any inhaled anti-asthmatic drug. The positive predictive value (PPV) of having two different asthma medications prescribed in 1 year was 80.2% for presence of true asthma, with a sensitivity of 59%. Corresponding estimates of PPV/sensitivity of at least one prescription for an inhaled corticosteroid (ICS) were 79% and 58%, respectively, while the true asthma PPV with at least one LABA prescription increased to 97%. Among children with confirmed asthma, one-third had not used Beta2-agonist therapy as part of their treatment. Conversely, among children without confirmed asthma, 40% were prescribed a minimum of two prescriptions for any kind of inhaled anti-asthmatic drug, and 12% and 9% used an ICS or Leukotriene receptor antagonist, respectively.Conclusions: Anti-asthmatic drug prescription data could be used to identify children with true asthma, with reasonable accuracy. The observed pattern of anti-asthmatic medication usage among children with and without confirmed asthma suggests that there is room for therapeutic improvement.

INTRODUCTION: The symptoms of cow's milk protein allergy (CMPA) in infancy can be non-specific which may delay a correct diagnosis and cause adverse clinical outcomes. The diagnosis of non-IgE-mediated CMPA is particularly complex as it involves a 2 to 4 week elimination diet followed by oral food challenge (OFC). The Cow's Milk-related Symptom Score (CoMiSS) is a clinical resource for primary healthcare providers which aims to increase awareness of CMPA symptoms to facilitate an earlier diagnosis. The aim of the present study is to assess if the CoMiSS can be used as a potential diagnostic tool in infants with suspected CMPA.METHODS AND ANALYSIS: Exclusively formula-fed infants aged 0-6 months presenting with symptoms suggestive of CMPA will be included in this prospective, multicentre trial which will be conducted in 10 centres in China. All infants will commence a 2-week trial of an amino acid-based formula (AAF) while eliminating all cow milk protein from their diets. After the AAF treatment period, infants will undergo an open OFC in hospital with standard cow's milk formula, followed by an open home challenge for another 2 weeks. Clinical symptoms will be documented on standardised symptom scorecards. The CoMiSS will be determined at study entry (CoMiSS 1, before the start of the AAF), after 2 weeks (CoMiSS 2, before the OFC) and after a further period of 2 weeks or when symptoms suggestive of CMPA reappear (CoMiSS 3). Weight and length will be measured at each visit. The difference between CoMiSS 1 and 2 as a predictor of the OFC outcome will also be assessed. The diagnostic accuracy of the baseline CoMiSS will be calculated.ETHICS AND DISSEMINATION: The study was approved by the Hunan Children's Hospital Medical Ethics Committee, Hunan, China. The findings of this trial will be submitted for publication in a peer-reviewed journal in paediatric nutrition or gastroenterology. Abstracts will be submitted to the relevant national and international conferences.TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Clinicians with expertise in managing children with gastrointestinal problems and/or atopic diseases attended a workshop in Brussels in September 2014 to review the literature and determine whether a clinical score derived from symptoms associated with the ingestion of cow's milk proteins could help primary healthcare providers. The Cow's Milk-related Symptom Score (CoMiSS), which considers general manifestations, dermatological, gastrointestinal and respiratory symptoms, was developed as an awareness tool for cow's milk-related symptoms. It can also be used to evaluate and quantify the evolution of symptoms during therapeutic interventions, but does not diagnose cow's milk protein allergy and does not replace a food challenge. Its usefulness needs to be evaluated by a prospective randomised study. Conclusion The CoMiSS provides primary healthcare clinicians with a simple, fast and easy-to-use awareness tool for cow's milk-related symptoms.

Background: Rhinoconjunctivitis is a global health problem and one of the most common chronic conditions in children. Development of rhinoconjunctivitis depends on both genetic and environmental factors. Many studies have investigated rhinoconjunctivitis, but only few studies have evaluated the risk factors for non-allergic rhinoconjunctivitis in children finding family history of atopic diseases and gender to be of importance. The aim of this study was to investigate possible risk factors in early life for rhinoconjunctivitis, allergic as well as non-allergic, in adolescence. Methods: The children in the Danish Allergy Research Center cohort were examined eight times from birth to 14 years of age. Visits included questionnaire-based interview, clinical examination, skin prick test and specific IgE. We used univariate and multivariate logistic regression to investigate the relationship between early-life risk factors and the development of rhinoconjunctivitis, allergic as well as non-allergic, in adolescence. Results: Follow-up rate at 14-years was 66.2%. The prevalence of rhinoconjunctivitis was 32.8%. Family history of atopic diseases (aOR 2.25), atopic dermatitis (aOR 3.24), food allergy (aOR 3.89), early sensitization to inhalant and food allergens (aOR 2.92 and aOR 3.13) and male gender (aOR 1.90) were associated with allergic rhinoconjunctivitis but not with non-allergic rhinoconjunctivitis. Early environmental tobacco exposure was inversely associated with rhinoconjunctivitis (aOR 0.42), allergic (aOR 0.47) as well as non-allergic (aOR 0.43). Conclusion: Different patterns of associations were revealed when stratifying rhinoconjunctivitis in allergic and non-allergic suggesting that allergic rhinoconjunctivitis and non-allergic-rhinoconjunctivitis are different phenotypes.

Since the 1930's the scientific literature on cow's milk protein allergy (CMPA) has accumulated. Over the last decade new diagnostic tools and treatment approaches have been developed. The diagnosis of reproducible adverse reactions to cow's milk proteins (CMP), i.e. CMPA, still has to be confirmed by controlled elimination and challenge procedures. Advanced diagnostic testing using epitope and microarray technology may in the future improve the diagnostic accuracy of CMPA by determination of specific IgE against specific allergen components of cow's milk protein. The incidence of CMPA in early childhood is approximately 2-3% in developed countries. Symptoms suggestive of CMPA may be encountered in 5-15% of infants emphasizing the importance of controlled elimination/milk challenge procedures. Reproducible clinical reactions to CMP in human milk have been reported in 0.5% of breastfed infants. Most infants with CMPA develop symptoms before 1 month of age, often within 1 week after inter introduction of CMP-based formula. The majority has two or more symptoms from two or more organ systems. Approximately 50-70% have cutaneous symptoms, 50-60% gastrointestinal symptoms and 20-30% respiratory symptoms. Symptoms may occur within 1 hour after milk intake (immediate reactions) or after 1 hour (late reactions). The prognosis of CMPA is good with a remission rate of approximately 45 to 50% at 1 year, 60 to 75% at 2 years and 85 to 90% at 3 years. Associated adverse reactions to other foods develop in up to 50% and allergy against inhalants in 50 to 80%. The basic treatment of CMPA is avoidance of CMP. In early childhood a milk substitute is needed. Documented extensively hydrolysed formulas are recommended, whereas partially hydrolysed formulas should not be used because of a high degree of antigenicity and allergenicity associated with adverse reactions. In case of intolerance to extensively hydrolysed formulas and multiple food allergies a formula based on aminoacids is recommended. Alternative milk substitutes such as sheep's and goat's milk should not be used because of a high degree of cross reactivity with CMP. Milk from other mammals such as mare and donkey may be tolerated by some children with CMPA. Soy protein is as allergenic as CMP and soy formula is not recommended for young children with CMPA because of a great risk of development of allergy to soy, whereas soymilk is normally tolerated in older children with CMPA. Recent treatment modalities are oral immunotherapy (OIT) involving the ingestion of increasing amounts of milk allergen on a regular basis to desensitize and potentially permanently tolerize patients to CMP. OIT can increase the reaction thresholds to CMP, but questions about safety and long-term efficacy remain. Anti-IgE therapy with Omalizumab may improve the safety and efficacy of OIT and may provide benefit in monotherapy.

BACKGROUND: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults.METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized.RESULTS: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults.CONCLUSIONS: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.

BACKGROUND: Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts.METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized.RESULTS: Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration.CONCLUSIONS: Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority.

Allergic diseases are common in childhood and can cause a significant morbidity and impaired quality-of-life of the children and their families. Adequate allergy testing is the prerequisite for optimal care, including allergen avoidance, pharmacotherapy and immunotherapy. Children with persisting or recurrent or severe symptoms suggestive for allergy should undergo an appropriate diagnostic work-up, irrespective of their age. Adequate allergy testing may also allow defining allergic trigger in common symptoms. We provide here evidence-based guidance on when and how to test for allergy in children based on common presenting symptoms suggestive of allergic diseases.

Background We have previously reported patch test reactivity to nickel sulphate in a cohort of unselected infants tested repeatedly at 3–18 months of age. A reproducible positive reaction at 12 and 18 months was selected as a sign of nickel sensitivity provided a patch test with an empty Finn chamber was negative. A reproducible positive reaction was seen in 8.6% of the infants. The objective of this study is to follow-up on infants with alleged nickel sensitivity. Methods A total of 562 infants were included in the cohort and patch tested with nickel sulphate (ICDRG guidelines). The 26 children with a positive patch test reaction to nickel sulphate at 12 and 18 months were offered repeated patch tests at 3 and 6 yr. Results Among the 21 children tested at both 12 months, 18 months and at 3 and 6 yr only 2 of 21 had reproducible nickel reactions (one clinically relevant), 13 of 21 were negative and 6 of 21 were negative at 3 or 6 yr. Conclusions Only 9.5% of the children had reproducible nickel sulphate reactivity, while 62% became negative. The results are noteworthy and can be interpreted in different ways: Repeated nickel patch tests did not cause patch test sensitization. The test reactions in infancy are probably of irritant or non-specific nature. Hence, nickel patch tests should only be performed in small children if there is a clinical suspicion of nickel-induced allergic contact dermatitis.

Background It is questionable how repeated patch tests with nickel sulfate in infancy affect nickel patch test reactivity at a later age. Methods The Danish Allergy Research Center (DARC) cohort encompasses 562 infants invited to a clinical examination including patch tests with nickel sulfate six times during the first 36 months of life. At the follow-up investigation at 14 years of age (2013–2014), participants were offered re-patch tests with nickel sulfate. The Odense Adolescence Cohort Study TOACS cohort encompasses 1501 schoolchildren evaluated for the first time at 14 years of age (1995–1996) including clinical examination and nickel sulfate patch tests. The prevalence of nickel sensitization in the DARC cohort was compared to the prevalence in the TOACS cohort at 14 years of age. Results Nickel sulfate sensitization was found in 1.2% of the participants from the DARC cohort tested repeatedly with nickel sulfate in early childhood and retested at 14 years of age compared to 8.6% of the participants from the TOACS cohort patch-tested for the first time at 14 years of age using the same patch test system and test concentration. Conclusion The significant difference in nickel patch test reactivity comparing the two cohorts may reflect an immunologic effect or the effect of nickel regulation.

The principle objective of the Danish research program ‘Indoor Environment and Children’s Health’ (IECH) was to explore associations between various exposures that children experience in their indoor environments (specifically their homes and daycare centers) and their well-being and health. The targeted health endpoints were allergy, asthma, and certain respiratory symptoms. The study was designed with two stages. In the first stage, a questionnaire survey was distributed to more than 17 000 families with children between the ages of 1 and 5. The questionnaire focused on the children’s health and the environments within the homes they inhabited and daycare facilities they attended. More than 11 000 questionnaires were returned. In the second stage, a subsample of 500 children was selected for more detailed studies, including an extensive set of measurements in their homes and daycare centers and a clinical examination; all clinical examinations were carried out by the same physician. In this study, the methods used for data collection within the IECH research program are presented and discussed. Furthermore, initial findings are presented regarding descriptors of the study population and selected characteristics of the children’s dwellings and daycare centers. Practical Implications This study outlines methods that might be followed by future investigators conducting large-scale field studies of potential connections between various indoor environmental factors and selected health endpoints. Of particular note are (i) the two-stage design – a broad questionnaire-based survey followed by a more intensive set of measurements among a subset of participants who have been selected based on their responses to the questionnaire; (ii) the case–base approach utilized in the stage 2 in contrast to the more commonly used case–control approach; (iii) the inclusion of the children’s daycare environment when conducting intensive sampling to more fully capture the children’s total indoor exposure; and (iv) all clinical examinations conducted by the same physician. We recognize that future investigators are unlikely to fully duplicate the methods outlined in this study, but we hope that it provides a useful starting point in terms of factors that might be considered when designing such a study.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling.

Bjerregaard L., Rubak S., Host A. & Wagner L. (2011) Alcohol consumption patterns among parents of hospitalized children: findings from a brief intervention study. International Nursing Review59, 132–138 Aims: This study aimed to explore parents' perception and experience of a brief intervention (BI), focusing on their alcohol consumption habits to assess the impact on parents of staff members using motivational interviewing (MI) and to gain knowledge of how to reinforce initiatives regarding behavioural changes of lifestyle problems in a clinical setting. Background: Substantial parental alcohol consumption influences children's development negatively. Nursing staff lacks knowledge and training in communicating with parents about alcohol issues. Little is known about parents' attitudes towards, and perception of, nursing staff addressing issues concerning their use of alcohol. Methods: A qualitative approach by use of phenomenological and hermeneutic methods was applied. Through interviews with 15 parents, their opinions and perceptions of a brief alcohol intervention were explored. Results: Three themes emerged from the phenomenological reduction: (1) experiencing respect and genuine interest from the nursing staff, (2) BI causing reflections on own use of alcohol, and (3) reflections continuing and developing over time. Conclusion and practice implications: The parents did not mind having their lifestyle habits discussed in connection with having their child admitted to hospital. The method MI proved effective in getting the parents to talk about and reflect on alcohol consumption habits. The effects of the intervention seemed to last beyond the first months after the intervention took place.

Background: There is no systematic identification of parents with excessive alcohol use who have a child admitted to hospital. Children in families with excessive alcohol issues form a high risk group as substantial alcohol consumption has a damaging influence on a child emotionally, cognitively, socially and physically. Alcohol consumption is a sensitive issue, and health staff needs knowledge, qualifications and adequate training in communicating with parents about this taboo. Aim: To identify specific patterns in subgroups of parents by comparing results from screening and demographic variables • To identify systematic patterns in staff members by demographic variables to decide whether these factors influence the screening results. Methods: During 1 year, screening and brief intervention (SBI) was accomplished, including health staff conducting dialogues with parents of a hospitalized child using motivational interviewing (MI) and screening for risky alcohol behaviour by Cut down, Annoyance from others, feel Guilty, Early-morning Craving (CAGE)-C. Data were analysed by descriptive statistics, and relationships were tested with a statistical significance level of 0.05, using SPSS (version 16.0). Results: Motivational dialogues with 779 parents were conducted by 43 staff members, and 11% of the parents were screened positive for risky alcohol behaviour. Drinking alcohol 4 days a week or more and drinking alcohol outside mealtimes were main risk factors. Parents' gender was the strongest predictor of screening positive and OR was 6.8 for men (CI 4.03-11.74) compared to women, p Language: en

Udgivelsesdato: 2008-Nov BACKGROUND: Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors. AIM: The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies. METHODS: Within the EU-funded network of excellence GA(2)LEN, we performed meta-analyses with data from 12 ongoing European birth cohort studies on asthma and allergy. Each of the birth cohort studies enrolled between 485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis, eczema) of parents and siblings, parental education, access to ground floor, and number of people living at home were assessed by questionnaires. RESULTS: Among the 25 056 families from seven European countries cats (14.9%) were more common than dogs (12.0%). Allergic family history significantly reduced the odds to own a cat (adjusted combined random-effect OR 0.91; 95% CI 0.85-0.99), or dog (0.90; 0.86-0.94). A higher parental educational level had even more pronounced effects on cat (0.84; 0.71-0.98), and dog ownership (0.61; 0.54-0.70). Elder siblings reduced the odds to own cats, but not dogs. Convenient ground access significantly increased the odds, whereas crowding at home was not associated with cat or dog ownership. CONCLUSIONS: The chances to own a cat or dog were significantly reduced in allergic families, in parents with a higher educational level, and in homes without convenient ground access. In addition to parental allergies, social and housing factors should be considered as potential confounders in studies on pet exposure and allergic diseases.

This study presents reference equations for spirometric parameters in 6-year-old children and evaluates the ability of spirometry to discriminate healthy children from children with asthma. Baseline spirometry and respiratory symptoms were assessed in 404 children participating in a longitudinal birth cohort study. Children with known asthma, possible asthma and a control group also performed bronchodilator measurements. At least two acceptable flow-volume curves at baseline were obtained by 368/404 children (91%). The two best values for FEV1 and FVC were within 5% of each other in 88% and 83% of children, respectively. Linear regression analyses for 242 children included in the reference population demonstrated height to be the main predictor of all spirometric indices except FEV1/FVC. FEV1, FEV75, and FVC correlated reasonably to anthropometric data in contrast to flow parameters. Gender differences were found for FEV1, FVC, and FEV75, but not for flow parameters. Asthma was diagnosed in 25/404 children. Baseline lung function in healthy children and children with asthma overlapped, although asthmatic children could be discriminated to some extent. Bronchodilator tests showed a difference in ΔFEV1(mean) between healthy children and children with asthma (3.1% vs. 6.1%, P

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.

Little is known about the health effects of school-related indoor dampness and microbial exposures. In this study, we investigated dampness and dampness-related agents in both homes and schools and their association with allergy and respiratory health effects in 330 Danish pupils. Classroom dampness was identified based on technical inspection and bedroom dampness on parents' self-report. Classroom and bedroom dust was analyzed for seven microbial components. Skin prick testing determined atopic sensitization. Lung function was expressed as z-scores for forced expiratory volume in one-second (zFEV 1), forced vital capacity (zFVC) and the ratio zFEV 1/zFVC using GLI-2012 prediction equations. The parents reported children's allergies, airway symptoms, and doctor-diagnosed asthma. High classroom dampness, but not bedroom dampness, was negatively associated with zFEV 1 (β-coef. −0.71; 95% CI −1.17 to −0.23) and zFVC (β-coef. −0.52; 95% CI −0.98 to −0.06) and positively with wheezing (OR 8.09; 95% CI 1.49 to 43.97). No consistent findings were found between any individual microbial components or combination of microbial components and health outcomes. Among other indoor risk factors, environmental tobacco smoke (ETS) decreased zFEV 1 (β-coef. −0.22; 95% CI −0.42 to −0.02) and zFEV 1/zFVCratio (β-coef. −0.26; 95% CI −0.44 to −0.07) and increased upper airway symptoms (OR 1.66; 95% CI 1.03–2.66). In conclusion, dampness in classrooms may have adverse respiratory health effects in pupils, but microbial agents responsible for this effect remain unknown.

BACKGROUND: Long-term studies of the predictive value of family history and cord blood IgE level until adulthood are few, and their conclusions have been contradictory.METHODS: Screening of total IgE in 1617 cord blood samples was performed in a Danish birth cohort. All infants with cord blood IgE (CB-IgE) ≥0.5 kU/l and a corresponding randomly chosen group with CB-IgE RESULTS: A total of 455 infants were included, 188 with CB-IgE ≥0.5 kU/l and 267 with CB-IgE CONCLUSION: Although family history and elevated CB-IgE were significantly associated with primarily atopic disease until 26 yr, none of these were strong predictors for subsequent sensitization and allergic symptoms from childhood until early adulthood. It appears that the predictive capacity of CB-IgE decreases in adolescence and early adulthood.

Udgivelsesdato: 2006-Dec Longitudinal studies in infant populations using validated diagnostic criteria of atopic dermatitis and sensitization are rarely reported, and disease definitions, testing procedures, age of study population and evaluation of objective markers vary between countries and studies. The objectives of this prospective birth cohort study were to investigate: (i) the prevalence, the cumulative incidence and the pattern of transient and persistent sensitization to common food- and aeroallergens in unselected infants, (ii) the association between sensitization and the development of atopic dermatitis (AD) and (iii) the association between selected perinatal risk factors with respect to AD and post-natal sensitization. During a one-year period a cohort of 562 unselected newborns was established and followed up at the age of 3, 6, 9, 12 and 18 months of age. At all time points infants were examined clinically and by histamine release (HR), total- and specific immunoglobulin E (IgE) and skin prick test (SPT). Sensitization ever to > or =1 allergen at 18 months of age was 59%, 50% and 6% using HR, IgE and SPT, respectively. A transient sensitization to > or =1 allergen was found in 47%, 42% and 4% and a persistent sensitization in 17%, 10% and 3%, respectively. Sensitization to environmental allergens was frequently observed in infancy when testing with HR and IgE. Results of SPT gave much lower frequencies. Reactivity to foods was more frequent than to aeroallergens. The dominant pattern was low-level transient sensitization. This is important to know when sensitization tests are used in the course of examination of infants with eczematous skin diseases. Specific definitions of sensitization like persistent reactivity, high-level sensitization and poly sensitization were clearly associated with AD. A maternal history of AD was a valuable tool in predicting AD in early infancy; a similar finding was less obvious with regard to post-natal sensitization. Cord-specific IgE and cord-HR positive reactivity did not prove better tools than cord-total IgE in predicting AD within the first 18 living months.

The prevalence of asthma and allergic diseases has increased dramatically over the past few decades with the highest incidence occurring in children. Most asthma and related atopic disorders have their origins in early life. Thus, it is imperative to understand the early life origins of the disease in order to identify targets for prevention and early intervention. Although atopic diseases have genetic determinants, the increased incidence of these diseases has occurred far too rapidly for genetic changes to explain the increase. This, most likely, results from changes in environmental influences acting on a pre-existent genetic susceptibility. One of the environmental changes over the last 20–40 years that could have contributed to the recent increase in atopic diseases is diet. Food allergy is often one of the earliest manifestations of atopy, and sensitization to food is a risk factor for the subsequent appearance of respiratory allergy and asthma. However, studies investigating the effects of dietary restrictions on the prevention of allergy have been disappointing. On the other hand, current data suggests that exclusive breastfeeding should be encouraged for at least 4–6 months in infants at both high and low risk of atopy. Increased risk of asthma has also been observed in low birth weight infants, suggesting that under-nutrition can detrimentally alter foetal development. Epidemiological and immunological studies also suggest that dietary modification or supplementation in the foetal and early life could reduce the development of atopic diseases. The current dietary hypotheses relate to antioxidants, lipids, electrolytes and probiotics. The aims of this report are: (i) to assess the best methods to analyse nutrient intake and nutrient status; (ii) to review the existing epidemiological evidence for an association between dietary intake (nutrients and food) and allergic diseases; and (iii) to define the windows of opportunity for nutritional supplementation to be used as a preventative strategy for asthma and allergy.

In a study of 2,978 Danish children aged 5 years from two suburban counties of Copenhagen, carried out in 1998, the authors compared risk factor profiles for wheeze and recurrent cough without wheeze by using polytomous logistic regression to clarify whether the two conditions are likely to have the same etiology. Data were obtained 1) by a mailed parental questionnaire (International Study of Asthma and Allergies in Childhood questions and supplementary questions on cough, sociodemography, perinatal factors, and environmental exposure); 2) through general practitioners (familial allergic disease); and 3) from the National Medical Birth Register (birth weight). Wheeze (WH) was defined as more than one episode of wheeze within the last 12 months (irrespective of cough status) and recurrent cough without WH (RC) as cough occurring outside colds and usually lasting for periods of more than 1 week in children with no more than one attack of wheeze within the last 12 months. Risk factors for comparison were selected as those that, after repeated stepwise logistic regression, remained significant for children with WH or RC. Significant differences were found for gender (p = 0.003), gestational age (p = 0.0002), maternal history of asthma (p = 0.0008), and standard of housing condition (p = 0.04)-all risk factors for WH but not RC. Results may suggest that the two conditions have different etiologies.

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.

Allergy-testing is a prerequisite for specific allergy treatment, including specific allergen avoidance measures, relevant pharmacotherapy and specific allergy vaccination. All children with persisting, recurrent or severe possible "allergic symptoms" or those with a need for continuous treatment should be tested, irrespective of the child's age. Allergy-testing includes a careful case history and a determination of IgE sensitisation by skin prick test or the measurement of allergen-specific IgE in serum by standardised and validated methods. The diagnosis of food allergy cannot usually be based solely on the case history and IgE sensitisation; the diagnosis has to be confirmed by controlled food elimination and food challenge procedures. The diagnosis of inhalant allergic disease requires only confirmatory nasal, conjunctival or bronchial challenges in equivocal cases or before specific allergy treatment such as extensive allergen avoidance measures or allergy vaccination.

BACKGROUND: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers.METHODS: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group.RESULTS: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design.CONCLUSIONS: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.

UNLABELLED: The use of complementary/alternative medicine (CAM) is increasing. The aim was to characterise the use of CAM among patients in a paediatric department. All patients (aged 0-18 years), out-patients or hospitalised, in contact with the Department of Paediatrics, Odense University Hospital during a 2 week period in the autumn of 2001 were asked to participate. In total, 622 (92%) patients participated. The data were collected in an interviewer administered questionnaire during a short structured interview with the patient and parents. CAM was divided into herbal medicine (herbal drugs or dietary supplements) (HM), alternative therapy (AT) (i.e. acupuncture) or chiropractic (CHI). Of all patients, 53% had tried CAM at least once and 23% had tried CAM within the last month (15% HM, 7% AT and 2% CHI). There was no correlation between use of CAM and gender, age or if the patient was out-patient or hospitalised. The users were pre-school children. HM (Bio-Strath and Echinacea) was especially used to strengthen the immune system. Among AT, reflexological treatment was the most popular treatment. The most frequent users of CAM were patients with asthma, eczema or allergy plus patients suffering from gastrointestinal diseases or hospitalised for observation. More than 50% of the users experienced positive effects and 6% had side-effects from AM. Of the CAM users, 11% or 2% of the total paediatric population used CAM instead of conventional medicines.CONCLUSION: Of the paediatric patients, 53% had tried complementary/alternative medicine, which was used as a supplement to conventional medicine although we did not know how long it was used. Paediatric patients should be interviewed about their use of complementary/alternative medicine with regard to side-effects, interactions or lack of compliance with conventional medicine.

Studies in rodents indicate that phthalates can function as adjuvants, increasing the potency of allergens. Meanwhile, epidemiological studies have produced inconsistent findings regarding relationships between phthalate exposures and allergic disease in humans. The present study examined phthalate exposure and allergic sensitization in a large group of 3-5 year old children: 300 random controls and 200 cases with asthma, rhinoconjunctivitis or atopic dermatitis as reported in questionnaires. The children were clinically examined to confirm their health status. Blood samples were analyzed for IgE sensitization to 20 allergens. Adjusted logistic regressions were used to look for associations between phthalate exposure indicators (mass fractions in dust from children's homes and daycares, metabolites in urine, and estimated daily indoor intakes from dust ingestion, inhalation and dermal absorption) and sensitization and allergic disease. No direct associations were found between phthalate exposures and asthma, rhinoconjunctivitis or atopic dermatitis. However, among children with these diseases, there were significant associations between non-dietary exposures to DnBP, BBzP and DEHP in the indoor environment (mass fractions in dust or daily indoor intakes from dust ingestion, inhalation and dermal absorption) and allergic sensitization. Some exposure pathways were more strongly associated with sensitization than others, although the results are not conclusive and require confirmation. A number of the associations depended on accounting for a child's exposure in more than one environment (i.e., daycare facility as well as home). Significant associations were not observed between phthalate metabolites in urine, which reflected exposure from diet as well as indoor pathways, and allergic sensitization.

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology; American Academy of Pediatrics; American College of Allergy, Asthma & Immunology; Australasian Society of Clinical Immunology and Allergy; Canadian Society of Allergy and Clinical Immunology; European Academy of Allergy and Clinical Immunology; Israel Association of Allergy and Clinical Immunology; Japanese Society for Allergology; Society for Pediatric Dermatology; and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases – sponsored Working Group and the European Academy of Allergy and Clinical Immunology. Keywords: Allergy prevention, Complementary feeding, Peanut allergy

A cohort of 1,749 newborns from the municipality of Odense, born during 1995 at the Odense University Hospital, were followed up prospectively for the development of cow's milk protein allergy/intolerance (CMPA/I) during the first year of life. Once a diagnosis of CMPA/I was confirmed, a milk-free diet was continued until a new milk challenge had shown development of tolerance. All infants with CMPA/I were rechallenged at 12 months of age and, in the event of continued clinical sensitivity to cow's milk protein, controlled rechallenges were performed every 6 months up to 3 years of age; and thereafter every 12 months until the age of 15 years. From the same birth cohort, 276 infants were randomly selected at birth for prospective non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood. Standardized questionnaires on atopic heredity, environmental factors and presence of atopic symptoms were answered at 0, 6, 12 and 18 months and at 5, 10 and 15 years of age. Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months, 5, 10 and 15 years of age. Skin prick test and specific sIgE (Pharmacia CAP) testing were performed at 18 months, 5, 10 and 15 years of age against a panel of inhalant allergens (birch, grass, mugwort, dog, cat, horse, Dermatophagoidespteronyssinus, Dermatophagoides farinae, alternaria and cladosporium herbarum). Furthermore, lung function measurements were performed in children when 10 and 15 years of age. Based on controlled milk elimination and challenge procedures, the diagnosis of CMPA/I was confirmed in 39 out of 117 infants, with symptoms suggestive of CMPA/I, thus resulting in a 1-year incidence of CMPA/I of 2.2%. The overall prognosis of CMPA/I was good, with a total recovery of 56% at 1 year, 77% at 2 years, 87% at 3 years, 92% at 5 and 10 years and 97% at 15 years of age. In children younger than 10 years of age, 41% developed asthma and 31% rhinoconjunctivitis. Children with non-IgE-mediated CMPI had a good prognosis, whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA, development of other food allergies, asthma and rhinoconjunctivitis. During early infancy, recurrent wheezing was the most prevalent disease (20%), followed by atopic dermatitis (14%) and food allergy (7%) at 18 months of age. Physician diagnosed asthma increased from 2% at 1.5 years of age to 9% at 10 years of age. Rhinoconjunctivitis increased from or = class 2; CAP RAST) showed a low rate of sensitization among asymptomatics (3%, 10% and 12%) compared with higher rates of sensitization of 8%, 39% and 30% among symptomatic atopics at 1.5, 5 and 10 years of age respectively. The highest rate of sensitization (53%) was found among children with current asthma at 10 years of age.

OBJECTIVE: The primary objective of this review is to discuss the clinical features, diagnosis, natural history, and prognosis of cow's milk allergy in early childhood and its relationship to development of inhalant allergies.DATA SOURCES: A review of 229 PubMed (National Library of Medicine) articles on cow's milk allergy (CMPA) for the years 1967 through 2001 was performed. In addition, references from other review articles have been included. This review represents a synthesis of these sources and the expert opinion of the author.STUDY SELECTION: The expert opinion of the author was used to select the relevant data for this review.RESULTS: The diagnosis of reproducible adverse reactions to cow's milk protein (CMP), ie, CMPA, has to be confirmed by controlled elimination and challenge procedures. The incidence of CMPA in infancy seems to be approximately 2 to 3% in developed countries. Symptoms suggestive of CMPA may be encountered in approximately 5 to 15% of infants emphasizing the importance of controlled elimination/milk challenge procedures. Reproducible clinical reactions to CMP in human milk have been reported in approximately 0.5% of breastfed infants. Most infants with CMPA develop symptoms before 1 month of age, often within 1 week after introduction of CMP-based formula. The majority has two or more symptoms from two or more organ systems. Approximately 50 to 60% have cutaneous symptoms, 50 to 60% have gastrointestinal symptoms, and approximately 20 to 30% respiratory symptoms. Symptoms may occur within 1 hour after milk intake (immediate reactions) or after 1 hour (late reactions). The prognosis of CMPA is good with a remission rate of approximately 45 to 50% at 1 year, 60 to 75% at 2 years, and 85 to 90% at 3 years. Associated adverse reactions to other foods develop in up to 50% and allergy against inhalants in 50 to 80% before puberty.CONCLUSIONS: CMPA is the most common food allergy in early childhood with an incidence of 2 to 3% in the first year of life. The overall prognosis of CMPA in infancy is good with a remission rate of approximately 85 to 90%. In particular, gastrointestinal symptoms show a good prognosis. An early increased immunoglobulin E-response to CMP is associated with an increased risk of persistent allergy to CMP, development of adverse reactions to other foods, and development of asthma and rhinoconjunctivitis later in childhood.

Asthma and allergic diseases have become one of the epidemics of the 21st century in developed countries. Much of the success of other areas of medicine, such as infectious diseases, lies on preventive measures. Thus, much effort is also being placed lately in the prevention of asthma and allergy. This manuscript reviews the current evidence, divided into four areas of activity. Interventions modifying environmental exposure to allergens have provided inconsistent results, with multifaceted interventions being more effective in the prevention of asthma. Regarding nutrition, the use of hydrolyzed formulas in high-risk infants reduces the incidence of atopic dermatitis, while there is for now not enough evidence to recommend other dietary modifications, pre-biotics, probiotics, or other microbial products. Pharmacologic agents used until now for prevention have not proved useful, while there is hope that antiviral vaccines could be useful in the future. Allergen-specific immunotherapy is effective for the treatment of allergic patients with symptoms; the study of its value for primary and secondary prevention of asthma and allergy is in its very preliminary phases. The lack of success in the prevention of these disorders lies on their complexity, which involves many genetic, epigenetic, and environmental interactions. There is a need to identify target populations, involved mechanisms and interactions, and the best interventions. These must be effective, feasible, implementable, and affordable.

Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3-5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of "allergy friendly" products by parents of children with allergic disease in the current study in contrast to studies conducted earlier.

The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High-risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five-hundred and ninety-five high-risk infants were identified. High-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE)> or =0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively. If breast-feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products. and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to noncompliance. Of 478 infants who completed the study, 232 were exclusively breast-fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not breast-fed at all. The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental-reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p=0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast-fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7%(four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p=0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency ofatopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.