Sachs Childrens Hospital

Stockholm, Sweden

Sachs Childrens Hospital

Stockholm, Sweden

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Vereda A.,Mount Sinai School of Medicine | Vereda A.,Hospital Infantil Universitario Nino Jesus | Van Hage M.,Karolinska Institutet | Ahlstedt S.,Karolinska Institutet | And 6 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

Background: Peanut allergy affects persons from various geographic regions where populations are exposed to different dietary habits and environmental pollens. Objective: We sought to describe the clinical and immunologic characteristics of patients with peanut allergy from 3 countries (Spain, the United States, and Sweden) using a molecular component diagnostic approach. Methods: Patients with peanut allergy from Madrid (Spain, n = 50), New York (United States, n = 30), Gothenburg, and Stockholm (both Sweden, n = 35) were enrolled. Clinical data were obtained either from a specific questionnaire or gathered from chart reviews. IgE antibodies to peanut extract and the peanut allergens rAra h 1, 2, 3, 8 and 9, as well as to cross-reactive birch (rBet v 1) and grass (rPhl p 1, 5, 7, and 12) pollen allergens, were analyzed. Results: American patients frequently had IgE antibodies to rAra h 1 to 3 (56.7% to 90.0%) and often presented with severe symptoms. Spanish patients recognized these 3 recombinant peanut allergens less frequently (16.0% to 42.0%), were more often sensitized to the lipid transfer protein rAra h 9 (60.0%), and typically had peanut allergy after becoming allergic to other plant-derived foods. Swedish patients detected rAra h 1 to 3 more frequently than Spanish patients (37.1% to 74.3%) and had the highest sensitization rate to the Bet v 1 homologue rAra h 8 (65.7%), as well as to rBet v 1 (82.9%). Spanish and Swedish patients became allergic to peanut at 2 years or later, whereas the American children became allergic around 1 year of age. Conclusions: Peanut allergy has different clinical and immunologic patterns in different areas of the world. Allergen component diagnostics might help us to better understand this complex entity. © 2010 American Academy of Allergy, Asthma and Immunology.


Vogt H.,Linköping University | Lindstrom K.,Sachs Childrens Hospital | Braback L.,Sundsvall Hospital | Braback L.,Umeå University | And 2 more authors.
Pediatrics | Year: 2011

OBJECTIVE: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of school-children grouped according to degree of immaturity expressed as completed gestational weeks at birth. METHODS: This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators. RESULTS: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks' gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08-1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96-2.64) for children born in weeks 23 to 28, after adjustment for confounders. The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age. CONCLUSION: Preterm birth increased the risk of ICS use in these 6- to 19-year-olds by degree of immaturity, from extremely preterm to early term birth. Copyright © 2011 by the American Academy of Pediatrics.


Lieberman J.A.,Mount Sinai School of Medicine | Lieberman J.A.,University of Memphis | Glaumann S.,Sachs Childrens Hospital | Glaumann S.,Karolinska Institutet | And 6 more authors.
Journal of Allergy and Clinical Immunology: In Practice | Year: 2013

Background: Increasing data suggest that analysis of IgE to peanut components can be clinically helpful and possibly more accurate than IgE to whole peanut. Not all studies examining this topic, however, have used prospective samples, multiple components, and peanut challenges. Objective: We sought to determine the utility of peanut component testing, using a standardized, commercially available test done before oral peanut challenge in various populations of patients with suspected peanut allergy from 2 different countries. Methods: IgE to whole peanut and the recombinant allergen components Ara h 1, 2, 3, and 8 were analyzed from serum samples drawn before double-blind peanut challenge from 4 distinct cohorts of patients with suspected peanut allergy from 2 nations (United States and Sweden). Results: Patients (n = 167; median age, 11.7 years; interquartile range, 7.0-15.0 years) had serum analyzed for peanut components and completed an oral food challenge to peanut. Although IgE to peanut was the most sensitive test (0.93), Ara h 2 was the most specific (0.92) and provided the best positive predictive value (0.94) of all the tests. Ara h 2 was also the best overall diagnostic test by receiver operating characteristic analysis (area under the curve, 0.84; P < .05). Conclusions: In patients with suspected peanut allergy, IgE to peanut is a sensitive test but is not specific. IgE to Ara h 2 is a more specific and more accurate diagnostic test in this sampling of patients with suspected peanut allergy. Given each tests attributes, a stepwise approach to testing may provide clinicians with a way to minimize the need for peanut challenges. © 2013 American Academy of Allergy, Asthma & Immunology.


Rosenlund H.,Karolinska Institutet | Kull I.,Karolinska Institutet | Pershagen G.,Karolinska Institutet | Wolk A.,Karolinska Institutet | And 3 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

Background: Previous largely cross-sectional studies suggest that fruit and vegetable consumption reduces the risk of allergic disease in children, but results are conflicting. Objective: To investigate the association between current fruit or vegetable intake and allergic disease in 8-year-old Swedish children, and to evaluate the potential effect of disease-related modification of consumption. Methods: Cross-sectional data were obtained from a Swedish birth cohort study. Information on fruit and vegetable consumption as well as symptoms and diagnoses of allergic diseases was obtained by parental questionnaires at the 8-year follow-up. Allergen-specific IgE levels against food and inhalant allergens were obtained from blood samples collected at age 8 years. In total, 2447 children were included. Data were analyzed with logistic regression. Results: An inverse relation was observed between total fruit consumption and rhinitis (odds ratio, highest vs lowest quartile, 0.62; 95% CI, 0.45-0.86; P for trend, .002), whereas no association was observed for total vegetable intake. In analyses of individual foods, intake of apples/pears and carrots was inversely associated with rhinitis, asthma, and atopic sensitization. Fifty percent of the children with rhinitis were sensitized against birch pollen, which may cross-react with apples and carrots. After exclusion of children who reported food-related allergic symptoms, most of the observed inverse associations moved toward the null and became nonsignificant. Conclusion: We confirm the inverse associations between fruit intake and allergic disease in children observed in earlier studies. However, our data also indicate that disease-related modification of consumption contributed to this association. © 2011 American Academy of Allergy, Asthma & Immunology.


Glaumann S.,Sachs Childrens Hospital | Nopp A.,Karolinska Institutet | Johansson S.G.O.,Karolinska Institutet | Rudengren M.,Thermo Fisher Scientific | And 3 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2012

Background: Immunoglobulin E (IgE)-sensitization to peanut is common and can indicate an allergy. A positive test needs to be confirmed by a double-blind, placebo-controlled food challenge (DBPCFC), which is regarded as 'the gold standard'. The aim of the study was to evaluate the basophil allergen threshold sensitivity (CD-sens) and antibodies to peanut allergen components in relation to DBPCFC in the diagnoses of peanut allergy in children. Methods: Thirty-eight children with suspected peanut allergy underwent a DBPCFC. CD-sens to peanut and Ara h 2 were analysed as well as IgE-antibody to peanut and some of its allergen components (Ara h 1, 2, 3, 8 and 9). Results: Twenty-five children had a positive DBPCFC, and 92% of these were positive in CD-sens to peanut and Ara h 2. Two children with a positive DBPCFC were classified as 'low-responders' and were not further evaluated. Children positive in DBPCFC had higher CD-sens values to peanut (median 1.3; range 0.4-29, n = 21) compared with children negative in DBPCFC (median 0; range 0-0.5, n = 13) (P < 0.0001). A positive DBPCFC correspond with increased levels of IgE-antibody to Ara h 1, 2 and 3 compared with those with a negative challenge (P < 0.0001 for all). All children with a negative CD-sens were negative in DBPCFC. Conclusion: In this study, a negative CD-sens to peanut excluded peanut allergy. Both tests, CD-sens to peanut and immunoassay for IgE-antibody to the peanut components, appear to be safe, time saving and cost-effective complements to DBPCFC. © 2011 John Wiley & Sons A/S.


Magnusson J.O.,Karolinska Institutet | Kull I.,Institute of Clinical Research and Education | Kull I.,Karolinska Institutet | Mai X.-M.,Norwegian University of Science and Technology | And 3 more authors.
Pediatrics | Year: 2012

OBJECTIVES: Our aim was to examine the associations between high BMI and changes in BMI status during the first 7 years of life and asthma and allergic sensitization at age 8 years. METHODS: A birth cohort of newborn infants was followed for 8 years. Repeated parental questionnaires provided information on environmental exposures and health outcomes. Information on height and weight during childhood was retrieved from preschool and school health care records. The analyses included the 2075 children for whom information was available on weight and height, as well as on asthma, at age 8 years. RESULTS: A high BMI (≥85th percentile) at age 1, 4, and/or 7 years was associated with an increased risk of asthma at age 8 years. However, no significant association was observed among children with high BMI at age 12 and/or 18 months (early age) or at age 4 years who developed a normal BMI by age 7 years. The risk was increased among children with high BMI at age 7 years, regardless of their earlier weight. Moreover, we observed an increased risk of sensitization to inhalant allergens among children with high BMI at age 7 years. CONCLUSIONS: Our study indicates that high BMI during the first 4 years does not increase the risk of asthma at school age among children who have developed a normal weight by age 7 years. However, high BMI at age 7 years is associated with an increased risk of asthma and sensitization to inhalant allergens. Copyright © 2012 by the American Academy of Pediatrics.


Gruzieva O.,Karolinska Institutet | Merid S.K.,Karolinska Institutet | Melen E.,Karolinska Institutet | Melen E.,Sachs Childrens Hospital
Paediatric Respiratory Reviews | Year: 2014

Epigenetic mechanisms, defined as changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence, have been proposed to constitute a link between genetic and environmental factors that affect complex diseases. Recent studies show that DNA methylation, one of the key epigenetic mechanisms, is altered in children exposed to air pollutants and environmental tobacco smoke early in life. Several candidate gene studies on epigenetics have been published to date, but it is only recently that global methylation analyses have been performed for respiratory disorders such as asthma and chronic obstructive pulmonary disease. However, large-scale studies with adequate power are yet to be presented in children, and implications for clinical use remain to be evaluated. In this review, we summarize the recent advances in epigenetics and respiratory disorders in children, with a main focus on methodological challenges and analyses related to phenotype and exposure using global methylation approaches. © 2014 Elsevier Ltd.


Mai X.-M.,Norwegian University of Science and Technology | Mai X.-M.,Sintef | Kull I.,Karolinska Institutet | Wickman M.,Karolinska Institutet | And 2 more authors.
Clinical and Experimental Allergy | Year: 2010

Background Early antibiotic use has been postulated to increase the development of allergic disease. Antibiotic use results from infection. Early infection may play a confounding role in the relationship between antibiotic use and allergic disease. Objective We aimed to investigate the relationship between antibiotic use during the first year of life and the development of allergic diseases in a birth cohort study, and also to carefully address the confounding effect of early respiratory infection. Methods Three thousand three hundred and six children were included in this study who participated in investigations at all occasions of 2 months, 1, 4 and 8 years of age. Data on antibiotic use and respiratory infections were collected at the age of 1 year. Diagnoses of allergic diseases at 4 and 8 years of age were derived from the follow-up questionnaires. Results During the first year of life, 43% (n=1420) of the children received antibiotics and 32% (n=1046) of the children had at least one type of respiratory infection among pneumonia, bronchitis and otitis. In univariate logistic regression analysis and after adjustment for early life factors, antibiotic use during the first year of life was associated with wheeze, asthma, eczema and food hypersensitivity at 4 years of age. After adjustment for the above respiratory infections during the first year of life, only the associations with wheeze and asthma at age 4 years remained statistically significant. These associations became non-significant in a subgroup analysis in children without early allergic signs. At age 8 years, antibiotic use during the first year of life was significantly associated with wheeze and eczema after adjustment for early life factors. The significant associations at age 8 years faded away following further adjustment for the respiratory infections. Conclusion Our study indicated that the association between early antibiotic use and later allergic disease could at least partially be explained by early respiratory infection. © 2010 Blackwell Publishing Ltd.


Rathsman B.,Sachs Childrens Hospital | Donner M.,Karolinska Institutet | Ursing C.,Karolinska Institutet | Nystrom T.,Karolinska Institutet
Diabetic Medicine | Year: 2016

Aims: To investigate the incidence of all-cause mortality, composite mortality and morbidity in people with Type 1 diabetes formerly randomized in the Stockholm Diabetes Intervention Study. Methods: A total of 102 people with Type 1 diabetes were randomized in the period 1982-1984 to intensified conventional treatment or standard treatment with insulin for a mean of 7.5 years. We prospectively re-evaluated this cohort for the period until 2011 with regard to all-cause mortality and composite mortality, which consisted of myocardial infarction, stroke and end-stage renal disease as primary endpoints. Secondary endpoints were first-time hospitalization for myocardial infarction and stroke or end-stage renal disease. Data on HbA1c levels (mean of 22 values/person) were retrospectively collected between 1996 and 2011. Results: During the median follow-up of 28 years, 22 people died: seven in the intensified conventional insulin group compared with 15 in the standard treatment group (P = 0.30). With regard to composite mortality, six people in the intensified conventional insulin group died compared with 11 in the standard treatment group (P = 0.56). For the secondary endpoints, 11 people in the intensified conventional insulin group developed myocardial infarction or stroke compared with 17 in the standard treatment group (P = 0.72), and one person in the intensified conventional insulin compared with seven people in the standard treatment group developed end-stage renal disease (P = 0.09). Mean HbA1c levels did not differ between groups during the follow-up years. Conclusions: All-cause mortality, cardiovascular morbidity and progression to end-stage renal disease did not differ in people with Type 1 diabetes earlier randomized to intensified insulin treatment. © 2015 Diabetes UK.


Berntson L.,Uppsala University | Hedlund-Treutiger I.,Sachs Childrens Hospital | Alving K.,Uppsala University
Clinical and Experimental Rheumatology | Year: 2016

Objective There is extensive evidence for an influence of gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN), which may change the gut microbiota, is an effective anti-inflammatory treatment for Crohn's disease in children. We wanted to explore the immediate anti-inflammatory effect of EEN in children with juvenile idiopathic arthritis (JIA). Methods Thirteen patients with JIA (7-17 years of age), in a disease flare-up, were included in the study. Six children dropped out within 1.5-2.0 weeks of treatment, and seven patients continued, constituting the study cohort. EEN was given for three to eight weeks, with clinical and laboratory status assessed before and after treatment periods. In addition to conventional laboratory tests, 92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience). Results EEN had a significant anti-inflammatory effect on active joints (p=0.031), JADAS27 (p=0.016) and morning stiffness (p=0.031). In the multiplex analysis of inflammatory proteins, MMP-1 (matrix metalloproteinase), involved in the degradation of collagens in chondrocytes, decreased significantly (p=0.047), as did MCP-4 (p=0.031) and 4E-BP1 (p=0.031). Conclusion Exclusive enteral nutrition for three to eight weeks had anti-inflammatory effect in all children with JIA that continued with EEN for more than two weeks. The study is only exploratory but the result supports an immunologically important role for the intestinal canal in these patients. © Clinical and Experimental Rheumatology 2016.

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