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  • 1.
    Byström, IngMarie
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Health-Related Quality of Life in Children and Adolescents with Celiac Disease: From the Perspectives of Children and Parents2012In: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, Vol. 2012Article in journal (Refereed)
    Abstract [en]

    Aim. To examine how celiac children and adolescents on gluten-free diet valued their health-related quality of life, and if age and severity of the disease at onset affected the childrens self-valuation later in life. We also assessed the parents valuation of their childs quality of life. Methods. The DISABKIDS Chronic generic measure, short versions for both children and parents, was used on 160 families with celiac disease. A paediatric gastroenterologist classified manifestations of the disease at onset retrospectively. Results. Age or sex did not influence the outcome. Children diagnosed before the age of five scored higher than children diagnosed later. Children diagnosed more than eight years ago scored higher than more recently diagnosed children, and children who had the classical symptoms of the disease at onset scored higher than those who had atypical symptoms or were asymptomatic. The parents valuated their childrens quality of life as lower than the children did. Conclusion. Health-related quality of life in treated celiac children and adolescents was influenced by age at diagnosis, disease severity at onset, and years on gluten-free diet. The disagreement between child-parent valuations highlights the importance of letting the children themselves be heard about their perceived quality of life.

  • 2.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Coeliac Disease in Childhood: On the Intestinal Mucosa and the Use of Oats2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Coeliac disease (CD) is one of our most common chronic diseases in childhood. The disease causes an intense inflammation in the small intestinal mucosa after ingestion of gluten-containing cereals in genetically predisposed individuals. The mucosal lesion in CD is characterised by villous atrophy and crypt hyperplasia, and both the absorptive and the barrier functions of the enterocytes are disturbed. The treatment of CD is a life-long adherence to a gluten-free diet (GFD). The toxic fraction of wheat gluten is gliadin, and there are similar proteins in rye, barley and oats. In oats this protein is called avenin, and it is proposed to be less toxic than the others. The use of oats in CD has been debated, but it is now considered safe for the majority of both children and adults with CD.

    The aims of this thesis were to investigate the humoral and inflammatory reactions to oats in children with CD, and also to study the intestinal mucosa at different stages of the disease.

    In a retrospective study we found that children with CD had antibodies to oats avenin, and that the levels were significantly higher than in controls. The levels attenuated during GFD, and we also showed that there was no crossreactivity between antibodies to oats and gliadin.

    We then used our method for measuring antibodies to avenin in a randomised, double-blind trial of oats given to children with newly diagnosed CD. The children were given either a traditional GFD or a GFD supplemented with oats. There was a rapid decrease in antibody levels in both groups already after three months on diet, and at the end of the study period all but a few had normalised their levels. The same children were also studied using urinary nitric oxide (NO) products as markers for intestinal inflammation. Likewise, these values decreased significantly after three months. At the end of the study four children in the GFD-oats group and one in the standard GFD group still had extremely high concentrations of urinary NO metabolites. Taken together, these studies strengthen the clinical impression that oats can be tolerated by the majority of children with CD, but they also warrant a caution, since there seem to be children that do not tolerate oats in their diet.

    The structure and distribution of occludin and claudins 1-5, tight junction proteins known to play a crucial role in maintaining the barrier function, was studied in biopsy specimens from children at different stages of CD. There was an increased expression of occludin in untreated CD, which reflects the characteristics of crypt cell hyperplasia and altered barrier properties seen in active CD. The findings also indicate that gluten intake does not significantly influence the expression and distribution of claudins 1-5 in coeliac children.

    List of papers
    1. Antibodies to oat prolamines (avenins) in children with coeliac disease
    Open this publication in new window or tab >>Antibodies to oat prolamines (avenins) in children with coeliac disease
    Show others...
    2003 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 38, no 7, p. 742-746Article in journal (Refereed) Published
    Abstract [en]

    Background: The use of oats in a gluten-free diet for children with coeliac disease is presently under investigation. In this study we measured the content of antibodies to oat prolamines (avenin) in sera from coeliac children and reference children.

    Methods: Crude avenin was prepared by extraction with ethanol and salt-solution and used as antigen in a three-step ELISA. Sera from 81 children, including 34 children with verified coeliac disease, were analysed for both IgA and IgG antibodies to avenin and gliadin. Sera were also incubated with gliadin before exposure to avenin, and vice versa, to assess a possible cross-reaction between the species. Keyhole limpet hemocyanin (KLH) was used as a negative control.

    Results: Children with coeliac disease on a normal diet had significantly higher levels of antibodies to avenin, both IgG and IgA, than reference children ( P < 0.001) and the levels correlated positively with gliadin antibodies, especially of IgA-type ( r = 0.798). Both anti-avenin and anti-gliadin antibodies were only absorbed by the corresponding protein.

    Conclusions: Children with coeliac disease have antibodies to oat proteins at significantly higher levels than reference children. The absorption test did not indicate a cross-reactivity between the prolamines of wheat and oats. The method will be employed for repeated sampling of anti-avenin antibodies during a prospective interventional study with a gluten-free diet supplemented with oats.

    Keywords
    Anti-avenin Antibodies, Coeliac Disease, Oats
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14131 (URN)10.1080/00365520310003156 (DOI)
    Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2009-08-18
    2. Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres
    Open this publication in new window or tab >>Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres
    Show others...
    2006 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 41, no 1, p. 42-47Article in journal (Refereed) Published
    Abstract [en]

    Objective. Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats.

    Material and methods. The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results.

    Results. There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples.

    Conclusions. Oats per se, do not seem to produce a humoral immune reaction in children with CD when given in an otherwise gluten-free diet, indicating that the reaction requires gluten challenge. Anti-avenin antibodies were equal in the two study groups, and these findings strengthen the clinical impression that oats can be tolerated by the majority of patients with CD.

    Keywords
    Anti-avenin antibodies; avenin; coeliac disease; oats
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14132 (URN)10.1080/00365520510023945 (DOI)
    Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2009-05-19
    3. Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease
    Open this publication in new window or tab >>Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease
    Show others...
    2006 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 41, no 11, p. 1272-1278Article in journal (Refereed) Published
    Abstract [en]

    Objective. Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats.

    Material and methods. The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months.

    Results. All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized.

    Conclusions. Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.

    Keywords
    coeliac disease; NO; oats; urinary nitrite/nitrate
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14133 (URN)10.1080/00365520600684563 (DOI)
    Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2009-05-19
    4. Increased expression of tight junction associated occludin but not of claudins in untreated coeliac disease in children
    Open this publication in new window or tab >>Increased expression of tight junction associated occludin but not of claudins in untreated coeliac disease in children
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14134 (URN)
    Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2010-01-13
  • 3.
    Hollén, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Laurin, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 41, no 11, p. 1272-1278Article in journal (Refereed)
    Abstract [en]

    Objective. Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats.

    Material and methods. The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months.

    Results. All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized.

    Conclusions. Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.

  • 4.
    Hollén, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Holmgren Peterson, Kajsa
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Grodzinsky, Ewa
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Laurin, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 41, no 1, p. 42-47Article in journal (Refereed)
    Abstract [en]

    Objective. Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats.

    Material and methods. The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results.

    Results. There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples.

    Conclusions. Oats per se, do not seem to produce a humoral immune reaction in children with CD when given in an otherwise gluten-free diet, indicating that the reaction requires gluten challenge. Anti-avenin antibodies were equal in the two study groups, and these findings strengthen the clinical impression that oats can be tolerated by the majority of patients with CD.

  • 5.
    Hollén, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Antibodies to oat prolamines (avenins) in children with coeliac disease2003In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 38, no 7, p. 742-746Article in journal (Refereed)
    Abstract [en]

    Background: The use of oats in a gluten-free diet for children with coeliac disease is presently under investigation. In this study we measured the content of antibodies to oat prolamines (avenin) in sera from coeliac children and reference children.

    Methods: Crude avenin was prepared by extraction with ethanol and salt-solution and used as antigen in a three-step ELISA. Sera from 81 children, including 34 children with verified coeliac disease, were analysed for both IgA and IgG antibodies to avenin and gliadin. Sera were also incubated with gliadin before exposure to avenin, and vice versa, to assess a possible cross-reaction between the species. Keyhole limpet hemocyanin (KLH) was used as a negative control.

    Results: Children with coeliac disease on a normal diet had significantly higher levels of antibodies to avenin, both IgG and IgA, than reference children ( P < 0.001) and the levels correlated positively with gliadin antibodies, especially of IgA-type ( r = 0.798). Both anti-avenin and anti-gliadin antibodies were only absorbed by the corresponding protein.

    Conclusions: Children with coeliac disease have antibodies to oat proteins at significantly higher levels than reference children. The absorption test did not indicate a cross-reactivity between the prolamines of wheat and oats. The method will be employed for repeated sampling of anti-avenin antibodies during a prospective interventional study with a gluten-free diet supplemented with oats.

  • 6.
    Sjöberg, Veronika
    et al.
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Pietz, Grzegorz
    ology, Immunology, Umeå University, Umeå, Sweden.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Sundström, Mia
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Holmgren Peterson, Kajsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sandström, Olof
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Hernell, Olle
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Hammarström, Sten
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Hammarström, Marie-Louise
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease.2014In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 5, no e58Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.

    METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.

    RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).

    CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.

  • 7.
    Tapsas, Dimitrios
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 11, p. 1311-1317Article in journal (Refereed)
    Abstract [en]

    Objective. Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Materials and Methods. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Results. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 mu M. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, less than 1400 mu M, while 29.8% demonstrated high levels, that is, greater than 1400 mu M. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. Conclusion. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

  • 8.
    Tapsas, Dimitrios
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Hammersjö, Jan-Åke
    Västervik Hospital, Sweden.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Swedish children with celiac disease comply well with a gluten-free diet, and most include oats without reporting any adverse effects: a long-term follow-up study2014In: Nutrition Research, ISSN 0271-5317, E-ISSN 1879-0739, Vol. 34, no 5, p. 436-441Article in journal (Refereed)
    Abstract [en]

    The only known treatment for celiac disease is a gluten-free diet (GFD), which initially meant abstention from wheat, rye, barley, and oats. Recently, oats free from contamination with wheat have been accepted in the GFD. Yet, reports indicate that all celiac disease patients may not tolerate oats. We hypothesized that celiac children comply well with a GFD and that most have included oats in their diet. A food questionnaire was used to check our patients; 316 questionnaires were returned. Mean time on the GFD was 6.9 years, and 96.8% of the children reported that they were trying to keep a strict GFD. However, accidental transgressions occurred in 263 children (83.2%). In 2 of 3 cases, mistakes took place when the patients were not at home. Symptoms after incidental gluten intake were experienced by 162(61.6%) patients, mostly (87.5%) from the gastrointestinal tract. Small amounts of gluten (less than4 g) caused symptoms in 38% of the cases, and 68% reported symptoms during the first 3 hours after gluten consumption. Oats were included in the diet of 89.4% of the children for a mean of 3.4 years. Most (81.9%) ate purified oats, and 45.3% consumed oats less than once a week. Among those who did not consume oats, only 5.9% refrained because of symptoms. General compliance with the GFD was good. Only the duration of the GFD appeared to influence adherence to the diet. Most patients did not report adverse effects after long-term consumption of oats.

  • 9.
    Tapsas, Dimitrios
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    The clinical presentation of celiac disease in 1030 Swedish children: changing features over the past 41 years: a long-term follow-up study2016In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 1, p. 16-22Article in journal (Refereed)
    Abstract [en]

    Background- Aims

    The features of pediatric celiac disease have changed in recent decades. We hypothesized that the age at diagnosis continued to increase, whereas the severity of symptoms should decrease.

    Methods

    In the present study, filed data about 1030 pediatric patients diagnosed with celiac disease between 1973 and 2013 were analysed. Available information covered 99.8% of the small bowel biopsies, and included information on sex, age, and clinical symptoms.

    Results

    The age at diagnosis increased significantly, from a mean of 2.2 years during the first 10 years to 8.2 years the current years. The proportion of children with severe symptoms declined from 92.8% to 78%, as did the proportion of biopsies characterized by severe pathology. In recent years, the monosymptomatic form of celiac disease has been more common, and the number of patients detected at screening has increased. The frequency of patients with gastrointestinal symptoms, extra-intestinal symptoms, and failure to thrive and/or short stature at presentation decreased.

    Conclusions

    The mean age of newly diagnosed patients increased the last 15 years. Currently celiac disease shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, and adolescents from extra-intestinal manifestations.

  • 10.
    Tapsas, Dimitrios
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Unusually High Incidence of Paediatric Coeliac Disease in Sweden during the Period 1973 – 2013: a long-term follow-up study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12Article in journal (Refereed)
    Abstract [en]

    Objective

    The prevalence of coeliac disease in Sweden during the “epidemic period” (1984−1996) was one of the highest in the world. The aim of this study was to assess the coeliac disease incidence in our region over the 41-year period, and how diagnostic activity and diagnostic accuracy were affected by the introduction of antibody testing. We also looked into how patients with mild enteropathy were evaluated.

    Methods

    In the county of Östergötland in Sweden, 2790 paediatric patients were investigated for suspected coeliac disease between 1973 and 2013. Notes were scrutinised for data on sex, age, histopathological reports and final diagnosis. For comparative purposes this period was divided into three sub-periods (1973−1983, 1984−1996 and 1997−2013) named pre-epidemic, epidemic and post-epidemic.

    Results

    Coeliac disease diagnosis was received by 1,030 patients. The peak incidence rate, 301 cases/100,000 in 1994 for the age group 0−1.9 years is the highest figure ever reported. The other age groups, 2−4.9, 5−14.9, and 15−17.9 years, also had high incidence rates. After the 1984−1996 “epidemic period” the incidence decreased for the youngest group but continued to increase for the other groups. The cumulative incidence at 18 years-of-age for children born 1994 reached 14 cases/1000 births, the highest figure hitherto reported. Diagnostic activity differed significantly between the three sub-periods (p<0.001) increasing gradually from 1984 and reaching a peak value of 0.87 in 2012. Cases of mild enteropathy were more frequently regarded as non-coeliac disease cases, decreasing significantly in the “postepidemic” period (p<0.001).

    Conclusions

    The incidence rate and cumulative incidence of coeliac disease among children were possibly the highest ever reported. Changes in diagnostic activity and accuracy could not be attributed to the introduction of new antibody tests, possibly because of other changes e.g. variations in the symptoms at presentation and improved knowledge of the disease among parents and health professionals.

  • 11.
    Tjellstrom, B.
    et al.
    Karolinska Institute, Sweden Norrkoping Hospital, Sweden .
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Norin, E.
    Karolinska Institute, Sweden .
    Midtvedt, T.
    Karolinska Institute, Sweden .
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    The effects of oats on the function of gut microflora in children with coeliac disease2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 39, no 10, p. 1156-1160Article in journal (Refereed)
    Abstract [en]

    Background Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. Aim To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1year with a GFD with or without oats. Methods This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1year on a GFD. Faecal SCFAs were analysed. Results The GFD-std group had a significantly lower total faecal SCFA concentration at 12months compared with 0months (Pless than0.05). In contrast, total SCFA in the GFD-oats group remained high after 1year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (Pless than0.05), n-butyric acid (Pless than0.05) and total SCFA concentration (Pless than0.01) after 1-year diet treatment compared to the GFD-std group. Conclusions Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.

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