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  • 1.
    Abelius, Martina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Jedenfalk, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Janefjord, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Pregnancy modulates the allergen-induced cytokine production differently in allergic and non-allergic women2017Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 28, nr 8, s. 818-824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The immunological environment during pregnancy may differ between allergic and non-allergic women. This study investigates the effect of maternal allergy on the allergen-induced cytokine and chemokine levels and whether pregnancy modulates these immune responses differently in allergic and non-allergic women. Methods: The birch-, cat-, phytohemagglutinin- and tetanus toxoid-induced interferon-gamma(IFN-gamma), interleukin (IL)-4, IL-5, IL-10, IL-13, the T-helper 1 (Th1)-associated chemokine CXCL10 and the Th2-associated chemokine CCL17 levels were quantified in 20 women with allergic symptoms (sensitized, n=13) and 36 women without allergic symptoms (non-sensitized, n=30) at gestational weeks 10-12, 15-16, 25, 35 and 2 and 12months post-partum. Results: Birch-, but not cat-induced, IL-5, IL-13 and CCL17 levels were increased during pregnancy as compared to post-partum in the sensitized women with allergic symptoms. In contrast, cat-, but not birch-induced, IL-5 and IL-13 levels were increased during pregnancy as compared to post-partum in the non-sensitized women without allergic symptoms. Furthermore, IFN-gamma secretion was increased in the first and decreased in the second and third trimesters in response to birch and decreased in the third trimester in response to cat as compared to post-partum in the non-sensitized women without allergic symptoms. Increased allergen-induced IL-4, IL-5 and IL-13 levels were associated with allergic symptoms and sensitization. Conclusions: Pregnancy had a clear effect on the allergen-induced IL-5, IL-13, CCL17, IFN-gamma and CXCL10 production, with distinct enhanced Th2-responses to birch in the allergic group and to cat in the non-allergic group.

  • 2.
    Abelius, Martina S
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lempinen, Esma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lindblad, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy2014Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, nr 4, s. 387-393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

    Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

    Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

    Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

  • 3.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Ted
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Oldaeus, Göran
    County Hospital Ryhov, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, nr 6, s. 556-561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

    Objective

    To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.

    Methods

    A randomized, placebo-controlled trial with oral supplementation with Lreuteri ATCC 55730 (1 × 108 CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.gov ID NCT01285830).

    Results

    The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.

    Conclusion

    The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect of L. reuteri on the immune system seems to be transient. Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

  • 4.
    Benn, CS
    et al.
    Dept of Epidemiology Köpenhamn, Danmark.
    Fagerås Böttcher, Malin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Pedersen, BV
    Dept of Epidemiology Köpenhamn, Danmark.
    Filteau, SM
    Centre of International Child Health London, UK.
    Duchén, Karel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Mammary epithelial paracellular permeability in atopic and non-atopic mothers versus childhood atopy2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, nr 2, s. 123-126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sodium/potassium (Na/K) ratios are considered to be a marker of mammary epithelial paracellular permeability. The aim of the present study was to investigate the association between maternal atopy and Na/K ratios in breast milk and the association between Na/K ratios in breast milk and the development of atopy in the offspring. Early and mature milk samples were obtained from 30 atopic and 43 non-atopic women. We found no differences in the Na/K ratios between atopic and non-atopic women. At 18 months of age, 22 (30%) of the children had a positive skin prick test (SPT) and 26 (36%) had symptoms of atopic diseases. Overall, high levels of Na/K compared with low and slightly raised levels of Na/K in the maternal milk tended to be associated with a positive SPT and atopic disease. However, if the mother was atopic, high levels of Na/K in early or mature milk were associated with a significantly increased risk of a positive SPT or atopic disease in the offspring [RR = 4.8 (1.9-12)] whereas no such association was observed in non-atopic mothers [RR = 0.8 (0.4-1.7), p for interaction = 0.001]. Thus, high Na/K levels in the breast milk may be associated with the development of atopy and atopic diseases in the offspring of atopic mothers.

  • 5.
    Benson, Mikael
    et al.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strannegård, Inga-Lisa
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Wennergren, Göran
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strannegård, Örjan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Cytokines in nasal fluids from school children with seasonal allergic rhinitis1997Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 8, nr 3, s. 143-149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allergic rhinitis is a particularly good model for studies of cytokine production in vivo. In this study the occurrence of the cytokines IL-4, IL-5, IL-10 and IFN-gamma as well as the soluble receptor for IL-4 in nasal lavage fluids were assayed in 38 school children, with seasonal allergic rhinitis, and 19 healthy age-matched, non-atopic controls, using highly sensitive enzyme immunoassays. IL-4 levels in patients with seasonal allergic rhinitis were markedly increased in comparison with those in non-atopic controls or in atopic patients before the start of the pollen season. In controls, but not in the atopic patients, levels of IFN-gamma and IL-5 were significantly higher in specimens obtained during the pollen season than in those obtained outside the season. The IL-4/IFN-gamma ratios were significantly higher in atopic than in non-atopic subjects and further increased in atopic patients during the season. In addition to IL-4, elevated levels of IL-10 were observed in association with seasonal rhinitis. Following treatment with a topical steroid (budesonide) there was a statistically significant increase of the levels of soluble IL-4 receptor. These findings indicate that nonatopic and atopic individuals react to pollen exposure with distinct cytokine patterns in agreement with the Th1/Th2 concept. Topical steroids may possibly decrease inflammation by increasing the formation of soluble IL-4 receptor.

  • 6.
    Benson, Mikael
    et al.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strannegård, Inga-Lisa
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Wennergren, Göran
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strannegård, Örjan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Interleukin-5 and interleukin-8 in relation to eosinophils and neutrophils in nasal fluids from school children with seasonal allergic rhinitis1999Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 10, nr 3, s. 178-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objectives of this study were to measure interleukins 5 and 8 (IL-5 and IL-8) in relation to eosinophils and neutrophils, in nasal lavage fluids from 60 school children with allergic rhinitis, and to determine the influence of treatment with a topical steroid (budesonide) on the levels of the two cytokines. Highly sensitive enzyme immunoassays were used to analyze IL-5 and IL-8. IL-5 levels and relative eosinophil counts in nasal lavage fluid increased significantly in patients with allergic rhinitis during the pollen season, compared with values obtained before the start of the season, and decreased significantly after treatment with budesonide. By contrast, no significant changes in IL-8 or neutrophils were found during the pollen season, nor did they decrease following treatment. In the untreated patients, IL-5 levels correlated significantly with eosinophil counts but not with neutrophil counts, whereas IL-8 levels correlated with neutrophil counts but not with eosinophil counts. After budesonide treatment, the correlation between IL-8 and neutrophils remained, and a correlation between IL-8 and eosinophils emerged. These findings support the concepts that IL-5 has a key role in regulating eosinophils and that IL-8 is important for the regulation of neutrophils. Whereas IL-5 and relative eosinophil counts are profoundly affected by topical steroid treatment, IL-8 and neutrophils are not demonstrably affected by such treatment. It is possible that neutrophils, through the release of IL-8, could be chemotactic for eosinophils in steroid-treated patients.

  • 7.
    Benson, Mikael
    et al.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strannegård, Inga-Lisa
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Wennergren, Göran
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strannegård, Örjan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Low levels of interferon-gamma in nasal fluid accompany raised levels of T-helper 2 cytokines in children with ongoing allergic rhinitis2000Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, nr 1, s. 20-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The T-helper 2 (Th2) cytokines interleukin-(IL-) 4, IL-5, IL-6, IL-10 and the Th1 cytokine IFN-gamma and their associations with eosinophil, eosinophil cationic protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from 60 school children with allergic seasonal rhinitis and 36 nonatopic healthy controls, before and during the pollen season. Eosinophil differential counts and IgE increased significantly in the patients during the pollen season. The eosinophil differential counts, ECP and IgE were all significantly higher during the season than in specimens simultaneously obtained from the nonatopic controls. Before season, the levels of ECP and IgE, but not eosinophils, were significantly higher in the patients than in the controls. During the season the nasal lavage fluid levels of IFN-gamma were significantly lower and the IL-4/IFN-gamma quotients significantly higher in the allergic than in the control children. In the allergic children, but not in the controls, the nasal fluid levels of the Th2 cytokines IL-4, IL-5 and IL-10 increased during the season, and together with IL-6, were correlated with the differential counts of eosinophils, and with the levels of ECP and IgE. These findings are compatible with the hypothesis that a deficient release of the Th1 cytokine IFN-gamma plays an important role in the pathogenesis of allergic inflammation. Regardless of whether the defective IFN-gamma secretion is primary or a consequence of suppression by other cytokines, it will in the atopic subjects enhance the release of Th2 cytokines, which in turn will facilitate the development of allergic inflammation.

  • 8.
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    The gastrointestinal flora and the skin. Is there a link?2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, s. 51-56Artikel i tidskrift (Refereegranskat)
  • 9. Bråbäck, Lennart
    et al.
    Kjellman, N-I.Max
    Sandin, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Atopy among schoolchildren in northern and southern Sweden in relation to pet ownership and early life events2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern. Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren. (n=2108) aged 10-11 years from Link÷ping in southern Sweden and ╓stersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in ╓stersund and in Link÷ping. A higher prevalence of sensitization to animal dander among children in ╓stersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Link÷ping (adjusted odds ratio 2.1, 95% confidence interval 1.1-4.0) and in ╓stersund (adjusted odds ratio 2.0, 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Link÷ping, whereas current smoking was associated with a decreased risk of sensitization in -stersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.

  • 10.
    Böttcher, Malin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Bjurström, Jenny
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Mai, Xiaomei
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children2003Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, nr 5, s. 345-350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.

  • 11.
    Böttcher, Malin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fredriksson, Jenny
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Hellquist, Anna
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production2003Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, nr 1, s. 27-34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-γ and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-γ production was to some extent caused by TGF-β, as the effect was modified when an anti-TGF-β antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-γ production, which was partly due to the high levels of TGF-β, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-β in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.

  • 12.
    Böttcher, Malin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Center for Allergy Research and Institute of Environmental Medicine, Karolinska Institute, Karolinska, Sweden.
    Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants2003Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, nr 1, s. 35-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.

  • 13.
    Böttcher, Malin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Jenmalm, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Garofalo, R
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy2000Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, nr 1, s. 29-39Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and ▀-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6 : total n-3 and the arachidonic acid, C20:4 n-6 (AA) : EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA:EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low a-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

  • 14.
    Casas, Rosaura
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, nr 2, s. 59-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

  • 15.
    Devenney, Irene
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Norrman, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forslund, Tony
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Fälth-Magnusson, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Sundqvist, Tommy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Urinary nitric oxide excretion in infants with eczema2010Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 21, nr 1, s. e229-e234Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.

  • 16.
    Ferdousi, Hosne Ara
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Munir, Abdul Kashem Mohamma
    Linköpings universitet, Institutionen för medicin och vård, Lungmedicin. Linköpings universitet, Hälsouniversitetet.
    Zetterström, Olle
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Dreborg, Sten
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, nr 5, s. 238-246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Variations in peak expiratory flow (PEF) and serum eosinophil mediators were studied in healthy adolescents. Twenty-five boys and 31 girls, 11–16 years of age (mean age 14.3 years), were selected and investigated during the birch pollen season of 1995; 45 were also investigated during the autumn of the same year. The PEF was measured twice daily and eosino-phil mediators in serum and in urine were measured by radioimmunoassay (RIA) once during the birch pollen season and once in autumn. The type values of the daily PEF variation, expressed in amplitude percentage mean, were 6.4 and 3.9%, mean values were 7.35 and 6.74%, and the 95th percentiles were 18 and 14%, during the birch pollen season and autumn, respectively. The 95th percentiles were 41 and 38 µg/l for serum eosinophil cationic protein (s-ECP), 74 and 62 µg/l for serum eosinophil protein X (s-EPX), 987 and 569 µg/l for serum myeloperoxidase (s-MPO), and 165 and 104 µg/mmol for urinary eosinophil protein X/urinary creatinine (u-EPX/u-creatinine), during the birch pollen season and autumn, respectively. The levels of the eosinophil mediators decreased significantly from May (n = 56) to November (n = 45), for s-ECP from a median value of 14 µg/l to 7 µg/l (p= 0.001), for s-EPX from a median value of 28 µg/l to 20 µg/l (p= 0.001), and for the neutrophil mediator, s-MPO, from a median value of 440 g/l to 292 g/l (p< 0.001). The PEF variability decreased significantly (p= 0.037), from spring (n = 55; median 8%, 95% confidence interval [CI] 7.8–10.19) to autumn (n = 44; median 6%, 95% CI 6.1–8.9). A significant correlation was found between the levels of s-ECP and s-EPX (rs = 0.7, p< 0.001), between s-ECP and s-MPO (rs = 0.6, p< 0.001), between s-EPX and s-MPO (rs = 0.4, p< 0.005), and between s-EPX and u-EPX/u-creatinine (rs = 0.6, p< 0.0001), in the birch pollen season (n = 56) and in the autumn (n = 45). There was a positive correlation found in PEF variability between the two seasons (n = 43; rs = 0.5, p= 0.0006). No other correlation was found between PEF variability and any other parameters. The difference in the levels of eosinophil mediators between seasons in non-atopic, healthy children is unexplained. Normal limits for mediators were higher and PEF variability was almost the same as has been reported in adults. When using normal values, seasonal influences should be considered.

  • 17.
    Ferdousi, Hosne Ara
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Zetterström, Olle
    Linköpings universitet, Institutionen för medicin och vård, Lungmedicin. Linköpings universitet, Hälsouniversitetet.
    Dreborg, Sten
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever2005Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, nr 6, s. 478-486Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65–80%) and the MBPT test (79–85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.

  • 18.
    Furuhjelm, Catrin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Warstedt, Kristina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fagerås Böttcher, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fälth-Magnusson, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Larsson, Johanna
    Pediatric Clinic, Ryhov Hospital, Jönköping, Sweden.
    Fredriksson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Duchén, Karel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Allergic disease in infants up to 2 yr of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation inpregnancy and lactation2011Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 22, nr 5, s. 505-514Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (x-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of x-3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. Thecumulative incidence of IgE-associated disease was lower in the x-3-supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p = 0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p = 0.01–0.05) in a dose-dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p < 0.05) regardless of sensitization. In summary, the x-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype.

  • 19.
    Fälth-Magnusson, Karin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Franzen, Lennart
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Jansson, Gunnar
    Department of Pediatrics, Motala, Sweden.
    Laurin, Pia
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Stenhammar, Lars
    Department of Pediatrics, Norrköping, Sweden.
    Infant feeding history shows distinct differences between Swedish celiac and reference children1996Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 7, nr 1, s. 1-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Infant feeding history was investigated in 72 celiac and 288 age-matched reference children in a retrospective questionnaire study. The reply rate was 100% in celiac and 91. 6% in reference children. The celiac children were breast-fed for a significantly shorter time than reference children, and they were less often breast-fed at the introduction of gluten. The age of the children at gluten introduction was similar, but the cellac children were significantly more often introduced by a gluten-containing follow-up formula, while the reference children more often started on a gluten-containing porridge. The results can be interpreted in two ways. First, it could be argued that breast milk per se protects against symptoms of celiac disease in childhood. It could, however, also be claimed that breast-feeding merely modulates the gluten introduction, causing a less abrupt introduction of gluten in the baby diet and thereby fewer overt symptoms of the disease.

  • 20.
    Giampietro, P.G.
    et al.
    Department of Paediatrics, University La Sapienza, Rome, Italy.
    Kjellman, N.-I.M.
    Oldaeus, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Wouters-Wesseling, W.
    Numico Research, Wageningen, Netherlands.
    Businco, L.
    Department of Paediatrics, University La Sapienza, Rome, Italy.
    Hypoallergenicity of an extensively hydrolyzed whey formula2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, nr 2, s. 83-86Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow's milk allergy (CMA). Accepting that none of the hydrolysate-based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85-100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75-100%) tolerated Profylac, and 64% (95% CI: 37-81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctor's supervision. However, the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested.

  • 21. Grüber, C
    et al.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Do early childhood immunizations influence the development of atopy and do they cause allergic reactions?2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, nr 6, s. 296-311Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Concerns about allergic side-effects of vaccines and about a possible promotion of allergic diseases contribute to incomplete vaccination rates in childhood. This article reviews the current understanding of these issues. There is evidence that pertussis and diphtheria/tetanus antigens elicit immunoglobulin E (IgE) antibody formation as part of the immune response. In murine models, pertussis toxin is an effective adjuvant for IgE formation against simultaneously administered antigens. In children, however, sensitization to unrelated antigens or development of allergic diseases do not seem to be augmented. In contrast, bacille Calmette-GuΘrin (BCG) and measles vaccination have been proposed as suppressors of allergy because of their T helper 1 (Th1)-fostering properties. In the murine system, BCG inhibits allergic sensitization and airway hyper-reactivity. Some epidemiological studies in humans suggest an inhibitory effect of tuberculosis on allergy. BCG vaccination in children, however, has no or merely a marginal suppressive effect on atopy. Other vaccine components such as egg proteins, gelatin, and antibiotics are a potential hazard to children with severe clinical reactions to these allergens. These rare children should be vaccinated under special precautions. In conclusion, vaccination programs do not explain the increasing prevalence of allergic diseases, but individual children may uncommonly develop an allergic reaction to a vaccine. The risks of not vaccinating children, however, far outweigh the risk for allergy. Therefore, childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed for allergy.

  • 22.
    Gustafsson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Barn- och ungdomspsykiatri. Östergötlands Läns Landsting, CPS - Centrum för psykiatri och samhällsmedicin, BUP - Barn- och ungdomspsykiatri.
    Kjellman, N-IM
    Björkstén, B
    Family interaction and a supportive social network as salutogenic factors in childhood atopic illness2002Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 13, nr 1, s. 51-57Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of psycho-social factors in the development of allergy was studied prospectively in 82 infants with a family history of atopy. The family participated in a standardized family test when the children were 18 months old. The ability to adjust to demands of the situation ('adaptability'), and the balance between emotional closeness and distance ('cohesion'), were assessed from videotapes by independent raters. Families rated as functional in both of these aspects were classified as 'functional', otherwise as 'dysfunctional'. The social network, life events, atopic symptoms (based on postal inquiries regarding symptoms answered by the parents, and on physical examinations), psychiatric symptoms, and socio-economic circumstances of the families were evaluated when the children were 18 months and 3 years of age. The children were classified as atopic (asthmatic symptoms or eczema) or as non-atopic. All but two children with atopic disease at 3 years of age had atopic disease before 18 months of age, while 32 of 60 children with atopic disease at 18 months of age had no problems by 3 years of age. An unbalanced family interplay at 18 months was associated with a relative risk (RR) of 1.99 for continuing atopic illness at 3 years of age (1.18

  • 23.
    Hansson, L. Å.
    et al.
    Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
    Silfverdal, Sven-Arne
    Departments of Paediatrics, Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden.
    Strömbäck, L.
    Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
    Erling, V.
    Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
    Zaman, S.
    Department of Social and Preventive Pediatrics, King Edward Medical College, Lahore, Pakistan.
    Olcén, Per
    Departments of Paediatrics, Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden.
    Telemo, E.
    Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
    The immunological role of breast feeding2001Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, nr s14, s. 15-19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    No abstract available.

  • 24.
    Host, A.
    et al.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Halken, S.
    Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Muraro, A.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI, Lerum, Sweden.
    Niggemann, B.
    Department of Pneumology and Immunology, University Children's Hospital Charité, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St. Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Abt. für Kinderheilkunde, Marien-Hospital, Wesel, Germany.
    Carlsen, K.-H.
    Voksentoppen National Centre of Asthma, Allergy and Chronic, Lung Diseases in Children, Oslo, Norway.
    Duchen, Karel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Eigenmann, P.A.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, VIC, Australia.
    Jones, C.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Department of Dermatology and Venerology, ErasmusMC-University Medical Center, Sophia Children's Hospital Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hospital Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Wahn, U.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Warner, J.A.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Vandenplas, Y.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children: Amendment to previous published articles in Pediatric Allergy and Immunology 2004, by an expert group set up by the Section on Pediatrics, European Academy of Allergology and Clinical Immunology2008Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 19, nr 1Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    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. © 2008 The Authors.

  • 25.
    Jenmalm, Maria
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Aniansson Zdolsek, Helena
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Holt, Patrocl G.
    TVW Telethon Institute for Child Health Research, Division of Cell Biology, Perth, Western Australia .
    Björkstén, Bengt
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Expression of and responses to CD2 and CD3 in 18-month-old children with and without atopic dermatitis2000Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, nr 3, s. 175-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We hypothesize that atopy is associated with a reduced T-cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by 3H-thymidine incorporation in phytohaemagglutinin (PHA)- and anti-CD3-stimulated peripheral blood mononuclear cells (PBMC) of 18-month-old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)-2 was added to compensate for possible functional differences in accessory cells. Anti-CD3-induced secretion of IL-4, IL-5, IL-6, IL-10, IL-13, and interferon-γ (IFN-γ) was analyzed by enzyme-linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2+ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti-CD3-induced proliferation declined more rapidly with antibody dilution in the allergic than in the non-allergic children. Atopic dermatitis was associated with high levels of anti-CD3-stimulated IL-5 secretion. The IL-4/IL-10 and IL-4/IFN-γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test-negative children with eczema produced higher levels of IL-10 than skin prick test-positive children. In conclusion, atopic children have a reduced T-cell function. Atopic dermatitis is associated with increased IL-5 production, while high total IgE levels are associated with high IL-4/IFN-γ and IL-4/IL-10 ratios.

  • 26.
    Jenmalm, Maria
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Björkstén, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Development of immunoglobulin G subclass antibodies to ovalbumin, birch and cat during the first eight years of life in atopic and non-atopic children.  1999Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 10, s. 112-121Artikel i tidskrift (Refereegranskat)
  • 27.
    Jenmalm, Maria
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Björkstén, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Macaubas, C
    Holt, BJ
    Smallacombe, TB
    Holt, PG
    Allergen-induced cytokine secretion in relation to atopic symptoms and immunoglobulin E and immunoglobulin G subclass antibody responses. 1999Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 10, s. 168-177Artikel i tidskrift (Refereegranskat)
  • 28. Juvonen, P
    et al.
    Månsson, M
    Kjellman, Max
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Björkstén, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Jakobsson, I
    Development of immunoglobulin G and immunoglobulin E antibodies to cow's milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow's milk proteins. 1999Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 10, s. 191-198Artikel i tidskrift (Refereegranskat)
  • 29.
    Kallen, Bengt
    et al.
    Lund University, Sweden .
    Finnström, Orvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nygren, Karl-Gosta
    Karolinska Institute, Sweden .
    Otterblad Olausson, Petra
    National Board Health and Welf, Sweden .
    Maternal drug use during pregnancy and asthma risk among children2013Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, nr 1, s. 28-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Maternal use of some drugs, notably paracetamol and drugs for gastroesophageal reflux, has been associated with an increased risk of childhood asthma in the child. We wanted to analyze these associations with consideration to the confounding of maternal asthma. Methods Childhood asthma was identified from the Swedish National Prescription Register and maternal drug use during the latter part of pregnancy from antenatal records, computerized in the Swedish Medical Birth Register. Risks were estimated as odds ratios (OR) with 95% confidence intervals, using MantelHaenszel technique with adjustment for year of birth, maternal age, parity, smoking habits, and BMI. Results A statistical association between maternal use of many different drugs, including paracetamol, and childhood asthma existed but was mainly due to concomitant drug use, related to maternal asthma. The only associations that appeared to be true were with drugs for gastroesophageal reflux (adjusted (OR) = 1.32, 95% CI, 1.181.54) and with opiates (adjusted OR = 1.56 (96% CI, 1.052.34). Conclusions Maternal use of paracetamol did not seem to increase the risk of childhood asthma, but the previously described association with drugs for gastroesophageal reflux was supported. The analysis is complicated by the confounding from maternal asthma.

  • 30.
    Keen, Christina
    et al.
    Department of Pediatrics, Göteborg University, Göteborg, Sweden.
    Johansson, Sofi
    Department of Pediatrics, Göteborg University, Göteborg, Sweden.
    Reinholdt, Jesper
    Department of Oral Biology, Royal Dental College, Aarhus, Denmark.
    Benson, Mikael
    Department of Pediatrics, Göteborg University, Göteborg, Sweden.
    Wennergren, Göran
    Department of Pediatrics, Göteborg University, Göteborg, Sweden.
    Bet v 1-specific IgA increases during the pollen season but not after a single allergen challenge in children with birch pollen-induced intermittent allergic rhinitis2005Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, nr 3, s. 209-216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been found in the nasal fluid of patients with allergic rhinitis. IgA may play a protective role, but there are also data which show that allergen-specific IgA can induce eosinophil degranulation. The aim of this study was to quantitate Bet v 1-specific IgA in relation to total IgA in the nasal fluid of children with birch pollen-induced intermittent allergic rhinitis and healthy controls, after allergen challenge and during the natural pollen season. Eosinophil cationic protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids from 30 children with birch pollen-induced intermittent allergic rhinitis and 30 healthy controls. Samples were taken before the pollen season, after challenge with birch pollen and during the pollen season, before and after treatment with nasal steroids. During the pollen season, but not after nasal allergen challenge, Bet v 1-specific IgA increased in relation to total IgA in children with allergic rhinitis. No change was found in the healthy controls. The ratio of Bet v 1-specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) in the allergic children, p < 0.001. No change was seen after treatment with nasal steroids, although symptoms, ECP and eosinophils were reduced. In conclusion, allergen-specific IgA in relation to total IgA increases in nasal fluids during the pollen season in allergic children but not in healthy controls. These findings are compatible with the hypothesis that allergen-specific IgA plays a role in the allergic inflammation and further studies are needed to clarify the functional role of these allergen-specific antibodies.

  • 31.
    Kjellman, Max
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Is allergy prevention realistic and beneficial? 1999Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 10, s. 11-17Artikel i tidskrift (Refereegranskat)
  • 32.
    Lockett, Gabrielle A.
    et al.
    University of Southampton, England.
    Huoman, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Holloway, John W.
    University of Southampton, England; University of Southampton, England.
    Does allergy begin in utero?2015Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, nr 5, s. 394-402Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    It has been recognized for centuries that allergic disease runs in families, implying a role for genetic factors in determining individual susceptibility. More recently, a range of evidence shows that many of these genetic factors, together with in utero environmental exposures, lead to the development of allergic disease through altered immune and organ development. Environmental exposures during pregnancy including diet, nutrient intake and toxin exposures can alter the epigenome and interact with inherited genetic and epigenetic risk factors to directly and indirectly influence organ development and immune programming. Understanding of these factors will be essential in identifying at-risk individuals and possible development of therapeutic interventions for the primary prevention of allergic disease. In this review, we summarize the evidence that suggests allergic disease begins in utero, together with possible mechanisms for the effect of environmental exposures during pregnancy on allergic disease risk, including epigenetics.

  • 33.
    Ludvigsson, Jonas
    et al.
    Barnkliniken Örebro.
    Mostrom, M
    Klinisk Epidemiologi Karolinska Institutet, Stockholm.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Duchén, Karel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Exclusive breastfeeding and risk of atopic dermatitis in some 8300 infants2005Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, nr 3, s. 201-208Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Earlier studies on breastfeeding and atopy in infants have yielded contradictory results. We examined the relationship between exclusive breastfeeding and atopic dermatitis (AD) in a cohort of infants born between 1 October 1997 and 1 October 1999 in south-east Sweden. We evaluated the risk of AD 'at least once' or 'at least three times' during the first year of life in relation to duration of exclusive breastfeeding: < 4 months (short exclusive breastfeeding, SEBF) vs. ≥4 months. All data were obtained through questionnaires. Of 8346 infants with breastfeeding data, 1943 (23.3%) had suffered from AD during the first year of life. Duration of exclusive breastfeeding was not associated with lower risk of AD (p = 0.868). SEBF did not influence the risk of any AD (OR = 1.03, 95% CI OR = 0.91-1.17, p = 0.614) or AD at least three times (OR = 0.97, 95% CI OR = 0.81-1.16, p = 0.755) during the first year of life. Adjustment for confounders did not change these point estimates. Neither was there any link between SEBF and risk of AD among infants with a family history of atopy [adjusted odds ratio (AOR) = 1.16, 95% CI AOR = 0.90-1.48, p = 0.254]. Furred pets at home were linked to a lower risk of AD both among infants with a family history of atopy (AOR = 0.76, 95% CI AOR = 0.60-0.96, p = 0.021) and among infants with no such history (AOR = 0.79, 95% CI AOR = 0.69-0.90, p < 0.001). Infants with no family history of atopy were less prone to develop AD if parents smoked (AOR = 0.76, 95% CI AOR = 0.61-0.95, p = 0.016). This study indicates that exclusive breastfeeding does not influence the risk of AD during the first year of life, while presence of furred pets at home seems to be negatively associated with AD. Copyright © 2005 Blackwell Munksgaard.

  • 34.
    Mai, Xiaomei
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Fagerås Böttcher, Malin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Leijon, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Leptin and asthma in overweight children at 12 years of age2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, nr 6, s. 523-530Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low-birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin-associated cytokines might play roles in overweight-related asthma. Seventy-four VLBW and 64 normal birth weight (NBW) children participated in a 12-yr follow up study assessing asthma and allergy. Twenty-seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)-γ were analyzed by enzyme-linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non-overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non-overweight children. IFN-γ was more often detected in the overweight than in the non-overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN-γ (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non-overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2-27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN-γ might be a pathway in the process of leptin-induced inflammation.

  • 35.
    Mai, Xiaomei
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Gäddlin, Per-Olof
    Central Hospital, Jönköping, Sweden.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Finnström, Orvar
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Centre for Allergy Research and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jenmalm, Maria C.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Leijon, Ingemar
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Asthma, lung function and allergy in 12-year-old children with very low birth weight: a prospective study2003Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, nr 3, s. 184-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We assessed the relationship between very low birth weight (VLBW) (≤1500 g) and the development of asthma, lung function and atopy. The study groups comprised 74 of all 86 (86%) VLBW and 64 of all 86 (74%) matched term children who were prospectively followed for 12 years. A questionnaire on asthmatic and allergic symptoms was completed and skin prick tests, spirometry and hypertonic saline provocation tests were performed at 12 years of age. Cytokine secretion was analysed in stimulated blood leukocyte cultures in 28 VLBW and 23 term children. A history of asthma was more frequent among the VLBW children, as compared with the term children at age 12 (22% vs. 9%, p = 0.046). Among the VLBW children, very preterm birth (gestational age: week 25 to 29) (RR 2.5, 95%CI 1.1–5.8), neonatal mechanical ventilation (RR 2.8, 95%CI 1.2–6.4) and neonatal oxygen supplementation (RR 4.3, 95%CI 1.3–14.0) were significantly associated with a history of asthma by the age of 12 years in univariate analyses. In multivariate logistic regression, neonatal oxygen supplementation ≥ 9 days was the only remaining significant risk factor for a history of asthma (adjusted OR 6.7, 95%CI 1.0–44). The VLBW children who required mechanical ventilation during the neonatal period were more likely to have bronchial hyperresponsiveness than those not requiring mechanical ventilation (60% vs. 28%, p = 0.050). The spirometric values were similar among the VLBW and the term children at 12 years. Very low birth weight was not significantly related to allergic rhinoconjunctivitis, eczema or positive skin prick tests. Furthermore, the levels of IL-4, IL-5 and IFN-γ in stimulated cell cultures were similar in the VLBW and the term children. A history of asthma by 12 years of age was twice as common among the VLBW as the term children, and neonatal oxygen supplementation seemed to be associated with the increased risk. Furthermore, mechanical ventilation during the neonatal period was associated with bronchial hyperresponsiveness at age 12. Very low birth weight per se was not, however, related to atopy.

  • 36.
    Mai, Xiaomei
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Gäddlin, Per-Olof
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Leijon, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Early rapid weight gain and current overweight in relation to asthma in adolescents born with very low birth weight2005Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, nr 5, s. 380-385Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Early catch-up growth and subsequent overweight are suggested to be associated with later cardiovascular diseases and later type II diabetes. However, the impact of early catch-up growth and childhood overweight on the development of asthma has been less studied, particularly in children born with very low birth weight (VLBW). A birth cohort of 74 VLBW children (birth weight ≤ 1500 g) was followed from birth and investigated on asthma at 12 yr of age. Early rapid weight gain was in one way defined as an increase of weight ≥1 standard deviation score (SDS) at 6 months of corrected postnatal age. Current overweight was defined by body mass index (BMI) exceeding 21.2 and 21.7 kg/m2, respectively, for boys and girls at 12 yr of age. Current asthma was diagnosed by a pediatrician, according to asthma ever in combination with a positive response to hypertonic saline bronchial provocation test and/or wheeze at physical examination at 12 yr old. Being overweight at 12 yr of age was associated with an increased risk for current asthma in the VLBW children [crude odds ratio (OR): 5.5, 95% confidence interval (CI): 1.3-22.2]. After adjustment for early weight gain and neonatal risk, the OR of overweight increased nearly three times (adjusted OR: 15.3, 95% CI: 2.5-90.6). Early rapid weight gain seemed to be inversely associated with current asthma (adjusted OR: 0.49 for an increase of weight equal to 1 SDS, 95% CI: 0.23-1.02, p = 0.06). In addition, early rapid weight gain was inversely associated with the magnitude of bronchial responsiveness at 12 yr (coefficient -1.15, p < 0.01). There was a strong and positive association between overweight and asthma at 12 yr of age in the VLBW children. This strong association had been reduced by early rapid weight gain, possibly via the reduction of bronchial responsiveness. © 2005 Blackwell Munksgaard.

  • 37.
    Mai, Xiaomei
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Kjellman, Max
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Hypertonic saline challenge tests in the diagnosis of bronchial hyperresponsiveness and asthma in children2002Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 13, nr 5, s. 361-367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hypertonic saline challenge test is the recommended method to assess bronchial hyperresponsiveness in the International Study of Asthma and Allergies in Childhood (ISAAC). The sensitivity of this procedure to assess asthma symptoms, however, has been reported to vary among study centers. The purpose of our study was to evaluate the value of this provocation test in an epidemiological survey in children, and to relate the degree of bronchial hyperresponsiveness to the severity of asthma symptoms. All 11–13-year-old children from 16 randomly selected schools in Linköping, Sweden received a questionnaire regarding respiratory symptoms and allergic disease. Skin prick tests with eight inhalant allergens were performed. In addition, all children with wheeze over the past 12 months (current wheeze) and a random sample of children without current wheeze were invited to perform hypertonic saline provocation tests. A complete data set was available for 170 children, including 50 with and 120 without current wheeze. Bronchial hyperresponsiveness (BHR) was defined as at least 15% decline in FEV1. The degree of BHR was represented by the response/dose ratio, i.e. the fall in FEV1 divided by total dose of inhaled saline. The severity of asthma symptoms was classified by the number of wheezing episodes over the past 12 months. ‘Asthma ever’ was defined by a combination of symptoms in the questionnaires. Children with ‘asthma ever’ and current wheeze were considered as having current asthma. Current atopic asthma was defined as current asthma with at least one positive skin prick test. The sensitivity of the procedure to detect ‘asthma ever’, current asthma and current atopic asthma was 62, 61 and 83%, and the specificity 83, 81 and 60%, respectively. The positive challenge rate was 52, 34, 13 and 7% among current wheezers, previous wheezers, non-wheezers with a history of allergy and healthy children. The degree of bronchial hyperresponsiveness increased with the number of wheezing episodes. Thus, the median and range of the response/dose ratio were 4.8%/ml (2.1–14.8), 2.6%/ml (0.7–8.6) and 1.3%/ml (0.8–2.7), respectively, for children with ≥ 4 episodes, 1–3 episodes and no wheezing episodes over the past 12 months (p<0.001). In conclusion, hypertonic saline provocation test is useful as a tool to detect asthma in epidemiological studies in children. The degree of bronchial hyperresponsiveness, as represented by the response/dose ratio, reflects the severity of asthma symptoms.

  • 38.
    Marschan, E
    et al.
    University of Helsinki .
    Honkanen, J
    University of Helsinki .
    Kukkonen, K
    University of Helsinki .
    Kuitunen, M
    University of Helsinki .
    Savilahti, E
    University of Helsinki .
    Vaarala, Outi
    University of Helsinki .
    Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with igE sensitization2008Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 19, nr 2, s. 132-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Risk of allergic diseases has been linked to abnormal patterns of fetal immune development, suggesting that priming of the immune system may occur in utero. The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells (CBMC) shows association with allergic diseases and IgE sensitization at 2 yr of age, and to study the effect of maternal probiotic supplementation on CBMC immune responses. CBMC were isolated from 98 neonates in a randomized double-blinded intervention study. CBMC were stimulated with beta-lactoglobulin, and phytohemaglutinin (PHA). Secretion of interferon-gamma (IFN-γ), interleukin-5 (IL-5), and IL-13 was measured by an ELISA; IL-2, IL-4, and IL-10 by a cytokine bead assay. T-cell polarization-associated IL-4 receptor and IL-12R expressions, and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR. The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age, and with the maternal probiotic or placebo supplementation. PHA-stimulated GATA-3 expression and IL-2 secretion in CBMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized, non-allergic children (p = 0.03 and 0.026). PHA-induced expression of GATA-3 correlated with IL-5 (p = 0.003, r = 0.300) and IL-13 (p = 0.007, r = 0.278) secretion of CBMC, and IL-5 secretion of β-lactoglobulin-stimulated CBMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized, non-allergic children (p = 0.013). Probiotic bacteria had no effect on CBMC immune responses. In CBMC-enhanced induction of GATA-3, which activates several Th2 cytokines genes, was a risk factor for IgE sensitization. The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens.

  • 39.
    Muraro, A.
    et al.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI Past President, Lerum, Sweden.
    Halken, S.
    Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
    Host, A.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Niggemann, B.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Marien-Hospital, Abt. für Kinderheilkunde, Wesel, Germany.
    Carlsen, K.-H.
    Voksentoppen Natl. Centre of Asthma, Lung Diseases in Children, Oslo, Norway.
    Duschen, K.
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Eigenmann, P.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, Vic., Australia.
    Jones, C.
    Child Health, Southampton General Hospital, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Dept. of Dermatology and Venerology, Univ. Hospital (Sophia) Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hosp. Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Vandenplas, Y.
    A.Z.-Kinderen, Free University of Brussels, Brussels, Belgium.
    Wahn, U.
    A.Z.-Kinderen, Free University of Brussels, Brussels, Belgium.
    Warner, J.A.
    Child Health, Southampton General Hospital, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, Southampton, United Kingdom.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children. Part II: Evaluation of methods in allergy prevention studies and sensitization markers. Definitions and diagnostic criteria of allergic diseases2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, nr 3, s. 196-205Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    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. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. In this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies.

  • 40.
    Muraro, A.
    et al.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI, Lerum, Sweden.
    Halken, S.
    Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
    Host, A.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Niggemann, B.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St. Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Marien-Hospital, Abt. für Kinderheilkunde, Wesel, Germany.
    Carlsen, K.-H.
    Voksentoppen Natl. Ctr. of Asthma, Oslo, Norway.
    Duschen, K.
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Eigenmann, P.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, Vic., Australia.
    Jones, C.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Dept. of Dermatology and Venerology, Univ. Hospital (Sophia) Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hosp. Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Vandenplas, Y.
    A.Z.-Kinderen, Free University of Brussels, Brussels, Belgium.
    Wahn, U.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Warner, J.A.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, nr 4, s. 291-307Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    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 on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.

  • 41.
    Murarol, A.
    et al.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI, Lerum, Sweden.
    Halken, S.
    Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
    Host, A.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Niggemann, B.
    Dept. of Pneumology and Immunology, Univ. Children's Hospital Charite, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Marien-Hospital, Abt. für Kinderheilkunde, Wesel, Germany.
    Kon, Carlsen K.-H.
    Kon Carlsen, K.-H., Voksentoppen Natl. Centre of Asthma, Oslo, Norway.
    Duschen, K.
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Eigenmann, P.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, Vic., Australia.
    Jones, C.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Dept. of Dermatology and Venerology, Univ. Hospital (Sophia) Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hosp. Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Vandenplas, Y.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Wahn, U.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Warner, J.A.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children: Part I2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, nr 2, s. 103-111Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    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.

  • 42.
    Nilsson, Lennart
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    Brockow, Knut
    Technical University Munich, Munich, Germany.
    Alm, Johan
    Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    Cardona, Victoria
    Hospital Universitari Vall d'Hebron, Barcelona, Spain.
    Caubet, Jean-Christoph
    University of Geneva, Genève, Switzerland.
    Gomes, Eva
    CHP, Porto, Portugal.
    Jenmalm, Maria Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Lau, Susanne
    Charité Universitätsmedizin, Berlin, Germany.
    Netterlid, Eva
    Lund University, Malmö, The Public Health Agency of Sweden, Stockholm, Sweden.The University of Edinburgh, Edinburgh, UK.
    Schwarze, Jürgen
    The University of Edinburgh, Edinburgh, UK.
    Sheikh, Aziz
    The University of Edinburgh, Edinburgh, UK..
    Storsaeter, Jann
    Norwegian Institute of Public Health, Oslo, Norway.
    Skevaki, Chrysanthi
    Philipps University Marburg, University Hospital Giessen and Marburg GmbH, Marburg, Germany.
    Terreehorst, Ingrid
    Department of ENT, AMC, Amsterdam, the Netherlands.
    Zanoni, Giovanna
    Immunology Unit, University Hospital, Verona, Italy.
    Vaccination and allergy: EAACI position paper, practical aspects2017Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Immunization is highly effective in preventing infectious diseases and therefore an indispensable public health measure. Allergic patients deserve access to the same publicly recommended immunizations as nonallergic patients unless risks associated with vaccination outweigh the gains. Whereas the number of reported possible allergic reactions to vaccines is high, confirmed vaccine-triggered allergic reactions are rare. Anaphylaxis following vaccination is rare, affecting less than 1/100,000, but can occur in any patient. Some patient groups, notably those with a previous allergic reaction to a vaccine or its components, are at heightened risk of allergic reaction and require special precautions. Allergic reactions, however, may occur in patients without known risk factors and cannot be predicted by currently available tools. Unwarranted fear and uncertainty can result in incomplete vaccination coverage for children and adults with or without allergy. In addition to concerns about an allergic reaction to the vaccine itself, there is fear that routine childhood immunization may promote the development of allergic sensitization and disease. Thus, although there is no evidence that routine childhood immunization increases the risk of allergy development, such risks need to be discussed. This article is protected by copyright. All rights reserved.

  • 43.
    Norrman, Gunilla
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fälth-Magnusson, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Adverse reactions to skin prick tests in children: prevalence and possible risk factors2009Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 20, nr 3, s. 273-278Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Skin prick test (SPT) is usually considered to be a safe procedure, but recently there have been occasional case reports of generalized allergic reactions. This study was performed to delineate the prevalence of, and evaluate possible risk factors for, adverse reactions to SPT in a prospective study. Altogether 5,908 patients aged ≤18 yr from 11 different pediatric settings were included. The adverse reactions were classified into two groups: (1) Generalized allergic reactions (GAR), (2) Vasovagal reactions (VVR). Adverse reactions were observed in 14 out of 5,908 children examined with SPT. Seven of the adverse reactions were GARs and required medication, yielding a 0.12% risk for GAR. Seven of 14 were VVRs, giving the same risk, 0.12%. Identified risk factors for GAR were low age (<1 yr) (RR 6.28) and active eczema (RR 16.98). For VVR, the risk factors were female sex (RR 7.32) and multiple skin pricks performed on a single patient (p < 0.05). We conclude that GARs do occur, albeit rarely, so the need for proper emergency handling should always be acknowledged. The risk factors suggested may help to identify patients who need extra attention.

  • 44.
    Paajanen, Laura
    et al.
    Foundation for Nutrition Research, Finland .
    Vaarala, Outi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Karttunen, Riitta
    Dept of Pediatrics and Medical Microbiology, Oulu Finland .
    Tuure, Tuula
    Valio Ltd, Finland.
    Korpela, Riitta
    Valio Ltd, Finland .
    Kokkonen, Jorma
    Dept of Pediatrics and Medical Microbiology, Oulu, Finland .
    Increased IFN-γ secretion from duodenal biopsy samples in delayed-type cow's milk allergy2005Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, nr 5, s. 439-444Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A delayed and local gastrointestinal hypersensitivity to cow's milk (CM) protein is difficult to diagnose and there are limited data on this disorder. The aim of this study was to investigate local intestinal cytokine secretion in the upper small intestine in children with delayed-type cow's milk allergy (CMA). Duodenal biopsy samples from 31 children with delayed CMA, 14 with celiac disease (CD), and 14 healthy controls were studied for the spontaneous release of IFN-γ, TNF-α, IL-2, IL-4, IL-5, and IL-10, measured by cytometric bead array, and of TGF-β and IL-6 measured by ELISA. The children with delayed CMA secreted more IFN-γ than the controls (p = 0.006) and the children with CD (p = 0.006). The children with CD secreted more IL-6 compared to the controls (p = 0.008) and the children with delayed CMA (p = 0.002). The children with delayed CMA who had continuously been exposed to CM secreted less TGF-β than the children with delayed CMA who avoided CM (p = 0.050), and showed a tendency towards lower secretion compared to the controls (p = 0.078). Secretions of TNF-α, IL-2, IL-4, IL-5, and IL-10 were low in general, however, the children with delayed CMA who did not avoid CM secreted more IL-4 and IL-10 than the controls (p = 0.016, 0.059). In conclusion, the children with delayed CMA showed up-regulation of IFN-γ. Interestingly, TGF-β secretion was up-regulated in those children with delayed CMA who avoided CM suggesting recovery of regulation mechanisms. © 2005 Blackwell Munksgaard.

  • 45.
    Roel, Eduardo
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Allmänmedicin.
    Olsen-Faresjö, Åshild
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Allmänmedicin.
    Zetterström, Olle
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Allergicentrum. Östergötlands Läns Landsting, Medicincentrum, Allergicentrum US.
    Faresjö, Tomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Allmänmedicin.
    Perinatal, Socila, and Environmental Factors and the Risk for Childhood Asthma in a 10-Year Follow-Up2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 17, nr 2, s. 146-150Artikel i tidskrift (Refereegranskat)
  • 46.
    Rytkonen, J.
    et al.
    Rytkönen, J., Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland, Department of Pathology, University of Oulu, Oulu, Finland, Laboratory of Biotechnology, University of Oulu, Sotkamo, Finland.
    Karttunen, T.J.
    Department of Pathology, University of Oulu, Oulu, Finland.
    Karttunen, R.
    Department of Medical Microbiology, University of Oulu, Oulu, Finland.
    Valkonen, K.H.
    Laboratory of Biotechnology, University of Oulu, Sotkamo, Finland.
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Kokkonen, J.
    Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland, Department of Pediatrics, University Hospital, Oulu, Finland.
    BCG vaccine modulates intestinal and systemic response to ß-lactoglobulin2004Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, nr 5, s. 408-414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ß-Lactoglobulin (BLG) is a clinically important antigen in cow's milk and one of the major allergens causing cow's milk allergy. Bacillus Calmette-Guérin (BCG) vaccination has been suggested to modify immune response possibly decreasing the risk of allergy to some antigens in both human and experimental animals. In the present study, we have analyzed whether the early BCG vaccination has any effect on the markers of systemic and gastrointestinal (GI) sensitization to BLG. We immunized two groups of Hooded-Lister rat puppets with intraperitoneal injections of native BLG at 43 and 62 days with pertussis vaccine as adjuvant, one group receiving additionally BCG. The animals were then fed native and denatured milk products twice weekly from 73 to 131 days of age, when they were killed. Control group was not vaccinated and received normal rat forage. Total immunoglobulin E (IgE) levels and BLG-specific IgG1 and IgG2a concentrations were determined in serum samples. Spontaneous interleukin (IL)-4 and interferon (IFN)-? production from duodenal specimens were measured, and the inflammatory cells were quantitated in specimens from different sections of the GI tract. Administration of BCG simultaneously with BLG resulted in reduced IgE concentration in serum, while the specific IgG1 and IgG2a antibody responses and the spontaneous secretion of IL-4 and IFN-? were not affected. Furthermore, BCG-induced eosinophilic infiltration and increase of intraepithelial lymphocytes (IEL) in the GI mucosa, and a trend toward increased number of lamina propria mononuclear inflammatory cells in the colon (BCG compared with BLG, p = 0.09, BCG compared with controls, p = 0.02). Controls showed increment of IgG1 response in comparison with the BLG group (p = 0.04) and increase of mucosal eosinophilic infiltration. The BCG modified the response to BLG both at the systemic level as shown by decrease of total IgE and at GI mucosa where increase of eosinophilic infiltration and increased number of IEL were seen. Increment of IgG1 level and eosinophils in the controls might be related with the lack of modulatory effect of pertussis vaccination. A shift of response toward the lower GI tract after BCG immunization as shown by a trend for increase of mononuclear inflammatory cells in colon lamina propria mimics disease development in some cases of clinical food allergy, and emphasizes the need for evaluation of the changes in the whole GI tract in food allergy models.

  • 47. Rytkonen, J
    et al.
    Karttunen, TJ
    Karttunen, R
    Valkonen, KH
    Jenmalm, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Alatossava, T
    Björkstén, B
    Kokkonen, J
    Effect of heat denaturation on beta-lactoglobulin-induced gastrointestinal sensitization in rats: denatured betaLG induces a more intensive local immunologic response than native betaLG2002Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 13, nr 4, s. 269-277Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Beta-lactoglobulin (▀LG) is one of the first foreign antigens encountered by a newborn child, and it is the major allergen causing cow's milk allergy. Heat denaturation causes changes to the protein structure, but the significance of heat-induced changes for immunogenicity or allergenicity is not known. To clarify how heat denaturation affects allergenicity and immunogenicity, we immunized Hooded-Lister rat pups with intra-peritoneal injections of native or heat-denatured ▀LG at days 43 and 62 after birth. The animals were then fed native and denatured milk products twice weekly from 73 to 101 days of age with a feeding tube, after which they were allowed cheese and milk ad libitum, until they were killed on day 131. Total immunoglobulin (Ig)E and ▀LG-specific IgG1 and IgG2a levels were determined from serum samples. Spontaneous interleukin-4 (IL-4) and interferon-? (IFN-?) production was measured from duodenal specimens, and specimens of gastrointestinal mucosae were studied for the presence of inflammatory cells. The rats immunized with native ▀LG had higher levels of total serum IgE than the unimmunized controls or the rats immunized with heat-denatured ▀LG, while heat-denatured ▀LG induced a significantly more intensive mononuclear inflammatory cell and eosinophil infiltration in the gastroduodenal mucosa. The ▀LG -specific IgG antibody and IL-4 and IFN-? responses were similar in the two groups of immunized animals. Hence, denaturation modifies the immunogenic and allergenic properties of ▀LG. Heat-denatured ▀LG induces a more intensive local reaction in the gastrointestinal mucosa, while there is some evidence for enhanced systemic allergic sensitization by native ▀LG. ⌐ 2002 Blackwell Munksgaard.

  • 48.
    Sandin, Anna
    et al.
    Umea University.
    Bjorksten, Bengt
    Karolinska Institute.
    Fagerås Böttcher, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Englund, Erling
    County Council Vasternorrland.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Braback, Lennart
    Umea University.
    High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants2011Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 22, nr 5, s. 477-481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n = 67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late-onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p = 0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p = 0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p = 0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late-onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.

  • 49.
    Sjögren, YM
    et al.
    Dept of Immunology Wennergren Inst, Stockholm.
    Duchén, Karel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Lindh, F
    Isosep AB Tullinge, Sweden.
    Björkstén, Bengt
    Inst of Environmental Medicine KI, Stockholm.
    Sverremark-Ekström, E
    Dept of Immunology Wennergren Inst, Stockholm.
    Neutral oligosaccharides in colostrum in relation to maternal allergy and allergy development in children up to 18 months of age2007Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 18, nr 1, s. 20-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several recent studies have demonstrated a relationship between the composition of the gut microbiota in infancy and subsequent development of allergic disease. Human milk is the major food in infancy and may thus profoundly influence the composition of the gut flora. Oligosaccharides in breast milk survive the passage through the stomach and are utilized by the gut microbiota. As the relationship between breast feeding and childhood allergy is controversial we hypothesized that the composition of oligosaccharides in breast milk might explain the controversy. Nine of the most abundant neutral oligosaccharides in human milk were analysed in colostrum samples from allergic and non-allergic women and related to subsequent development of allergy in their children. The carbohydrate fraction of the colostrum was separated by gel permeation chromatography and neutral oligosaccharides, tri- to hexasaccharides were collected. Neutral oligosaccharides were analysed with high-performance liquid chromatography. There was a large variation in the concentration of neutral oligosaccharides in colostrum, which could not be explained by the allergic status of the women. Allergic children consumed higher amounts of neutral oligosaccharides in total, although not significantly (p = 0.12). When different oligosaccharides were analysed separately, there was no significant difference in consumption between the infants who developed atopic allergy later (n = 9) and infants who did not (n = 11). Thus, the amount of neutral oligosaccharides in colostrum does not directly correlate with maternal allergy, nor with allergy development in children up to 18 months of age. © 2007 The Authors.

  • 50.
    Tittanden, M
    et al.
    Dept of Viral Diseases and Immunology Helsinki, Finland.
    Paronen, Johanna
    Dept of Viral Diseases and Immunology Helsinki, Finland.
    Savilahti, Erkki
    Hospital for Children And Adolescents Helsinki, Finland.
    Virtanen, Suvi
    Dept of Epidemilogy and Health Promotion National Public Health Inst, Finland.
    Ilonen, Jorma
    Dept of Clinical Microbiology University of Kuopio, Finland.
    Knip, Mikael
    Hospital for Children and Adolescents University of Helsinki, Finland.
    Åkerblom, Hans
    Hospital for chldren and Adolescents University of Helsinki, Finland.
    Vaarala, Outi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Dietary insulin as an immunogen and tolerogen2006Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 17, nr 7, s. 538-543Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030), this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance. © 2006 The Authors.

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