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  • 1. Bjerg, A.
    et al.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, R.
    Berthold, M.
    Borres, M.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Norrbotten City Council, OLIN Studies, Luleå, Sweden.
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Norrbotten City Council, OLIN Studies, Luleå, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Norrbotten City Council, OLIN Studies, Luleå, Sweden.
    Sensitization to animal allergen components in relation to asthma among young adults in Northern Sweden2019In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, p. 291-291Article in journal (Other academic)
  • 2.
    Bjerg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berthold, Malin
    Mattsson, Lars
    Borres, Magnus P
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.
    A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren2015In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, no 6, p. 557-563Article in journal (Refereed)
    Abstract [en]

    Background: Animal sensitization is a major determinant of asthma in children. Component-resolved studies of unselected pediatric populations are lacking. The aim was to describe sensitization to animal components and the association with asthma and rhinitis in animal-sensitized schoolchildren. Methods: A random sample of 696 children (11-12years) from a Swedish population-based cohort was tested for sensitization to cat, dog, and horse dander using ImmunoCAP. Sera from animal-sensitized children were further analyzed by microarray including three allergen components from cat, four from dog, and two from horse. The parents completed an expanded ISAAC questionnaire. Results: Of 259 animal-sensitized children (0.1 kU(A)/l), 51% were sensitized to all three, 23% to two, and 25% to one species. Current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. This association was seen already at moderate-level sensitization (1-15 ISU) to Fel d 4, at which level most children were sensitized to Fel d 1, as well. In dog-sensitized children, the majority was sensitized to more than one dog component, and co-sensitization to Can f 5 and Can f 1/f 2 conferred the greatest risk for asthma. Sensitization to the highly cross-reactive serum albumins was uncommon and not associated with asthma. Conclusions: Among schoolchildren in northern Sweden, where mite allergy is uncommon, furry animals were the primary perennial sensitizers. Asthma was associated with higher levels of component sensitization, and sensitization to more than one component from the same animal conferred the greatest risk.

  • 3.
    Nordstrom, Lisbet
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nylander, Annica
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Jonsell, A.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Validation of new recipes for double-blind placebo-controlled food challenges in children2012In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 67, no Suppl. 1, p. 371-371Article in journal (Other academic)
  • 4.
    Persson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordström, Lisbeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vitamin D deficiency at the Arctic Circle a study in food-allergic adolescents and controls2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 6, p. 644-649Article in journal (Refereed)
    Abstract [en]

    Aim At the extremes of latitude, UVB intensity is insufficient for adequate vitamin D synthesis in winter. Fatty fish, vitamin D enriched milk, margarine and eggs are main dietary sources of vitamin D. Their elimination may increase the risk of vitamin D deficiency. The aim was to assess vitamin D status in food-allergic adolescents eliminating milk, egg and/or fish compared with adolescents on normal diets. Methods In winter, vitamin D intake was assessed by a food frequency questionnaire in 20 food-allergic adolescents and 42 controls in the population-based Obstructive Lung Disease In Northern Sweden (OLIN) cohort studies. Vitamin D supplementation was queried. Serum 25-hydroxyvitamin D [S-25(OH)D] and S-parathormone (S-PTH) levels were determined. Results Mean (SD) dietary vitamin D intake was 7.9 (3.6) g/day in allergic adolescents and 7.8 (3.4) in controls (p>0.05). Mean (SD) S-25(OH)D levels in supplement consumers were 44 (18) nmol/L compared with 35 (10) in non-consumers (p=0.03). S-25(OH)D and S-PTH levels were similar in food-allergic adolescents and controls (p>0.05). Eighty-two percentage had deficient S-25(OH)D levels <50nmol/L, and none reached levels >75nmol/L. Conclusion Vitamin D deficiency was as common in food-allergic adolescents as in controls although the vitamin D intake met national recommendations. Large-scale studies on the prevalence of vitamin D deficiency in this region are needed.

  • 5. Strinnholm, A.
    et al.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, L.
    Ronmark, E.
    Prevalence and symptom expression of food hypersensitivity among schoolchildren2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no Supplement: 99, p. 270-270Article in journal (Refereed)
  • 6.
    Strinnholm, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Nursing.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Health Sciences, Division of Nursing, Luleå University of Technology.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Health Related Quality of Life among schoolchildren aged 12-13 years in relation to food hypersensitivity phenotypes: a population-based study2017In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 7, article id 20Article in journal (Other academic)
    Abstract [en]

    Background:

    While Health Related Quality of Life has been investigated among children with IgE-mediated food allergy, less is known about quality of life among children with other types of hypersensitivity to food. The aim of this study was to investigate Health Related Quality of Life (HRQL) in children with and without food hypersensitivity. Further, we compared HRQL between children with different phenotypes of food hypersensitivity.  

    Methods:

    In a large population-based cohort of schoolchildren in Northern Sweden, the parents of 2,612 (96% of invited) completed a questionnaire. All 125 (5%) children who reported complete elimination of milk, egg, fish or wheat due to food hypersensitivity were invited to a clinical examination and 94 children participated. Of these, 75 children also completed a generic (KIDSCREEN -52) and a disease-specific HRQL questionnaire (FAQLQ-TF). Thereafter, these children were categorised into the different phenotypes: current food allergy, outgrown food allergy, and lactose intolerance. Additionally, 209 children with unrestricted diets answered the generic questionnaire.

    Results:

    The median score of all KIDSCREEN -52 domains were above the population norm of 50 both in children with and without food hypersensitivity. No significant differences in distribution in generic or disease-specific HRQL were found between children with or without food hypersensitivity. There were no significant differences in HRQL between children with different phenotypes of food hypersensitivity. However, children with current food allergy tended to have the lowest HRQL. Further, poor HRQL defined as ≥75th percentile for the disease specific score was significantly more common in the current food allergy phenotype in the domain Emotional impact and the total FAQLQ, compared to the other phenotypes.

    Conclusions:  

    In this population-based study, 12-13 year old children reported good HRQL regardless of having food hypersensitivity or not. However, the children with the current phenotype reported lower HRQL than the other phenotypes. 

  • 7.
    Strinnholm, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Nursing.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Lule Univ Technol, Dept Hlth Sci, Div Nursing, Lulea, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Unit, Umeå University, Umeå, Sweden..
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Reintroduction failure is common among adolescents after double-blind placebo-controlled food challenges2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 2, p. 282-287Article in journal (Refereed)
    Abstract [en]

    AIM: There has been a lack of research on adolescents' who undergo double-blind placebo-controlled food challenges. The aim of this study was to investigate food allergic adolescents' experiences and consequences of double-blind placebo-controlled food challenges.

    METHODS: This qualitative, descriptive interview study included 17 adolescents aged 14-15 years with total elimination of cows' milk, hens' eggs or cod due to food allergies. The participants, who were initially identified from a large population-based cohort study, were interviewed 18 months after completing their challenges.

    RESULTS: The double-blind placebo-controlled food challenge proved to be a complex experience for the adolescents, involving fear of potential reactions and the hope that the food could be reintroduced. Experiences during the challenge were described in three themes: facing fears in a secure environment, being hesitant but curious about unknown tastes and waiting for unknown food reactions. Experiences after the challenge were desribed in two themes: gaining control and freedom and continuing old habits. A negative challenge was not consistently associated with the reintroduction of the challenged food.

    CONCLUSION: This study highlighted the importance of considering the adolescents' expectations and experiences of the challenge and the reintroduction process to ensure desirable changes in their dietary habits. Follow ups should be performed regardless of the outcome of challenges.

  • 8.
    Strinnholm, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    To face fear: a qualitative study of adolescents' experiences of double-blind, placebo-controlled food challenges2015In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 70, p. 386-386Article in journal (Other academic)
    Abstract [en]

    Background: Double-blind, placebo-controlled food challenges are the gold standard for diagnosing the clinical relevance of a suspected food allergy. Hitherto there are no descriptions on how adolescents' experience this procedure. The aim of this study was to describe adolescents' experiences of double-blind, placebo-controlled food challenges and to what extent the provoked food was reintroduced following the challenge. Method: Seventeen adolescents were interviewed after participating in double-blind, placebo-controlled food challenges. The interview data was analyzed using qualitative content analysis.Results: Experiences during the challenge were: challenging fears in a secure environment, being curious but also hesitant to unknown tastes and waiting for unknown food reactions. Experiences after the challenge were: gaining control and freedom or to stay in old habits. Out of 20 challenges the outcome was negative in 11 cases and positive in 9. Five adolescents with a negative outcome and 4 with mild reactions reintroduced the provoked food. Conclusions: During the challenge the adolescents received knowledge about whether and how they reacted to the provoked food. Reintroduction of the food was not always consistent with the challenge outcome. Independent of the outcome of the challenge and the choices made based on the challenge result, all the adolescents strived for what they felt was a normal life. This study provides a better understanding of young people's experience of double-blind, placebo-controlled food challenge and their motivations to introduce -or not- the previously eliminated food. The result indicate that follow ups are important since the adolescents need support in their striving to manage new food-related situations after the challenge, independent of the outcome.

  • 9.
    Strinnholm, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Food hypersensitivity is common in Swedish schoolchildren, especially oral reactions to fruit and gastrointestinal reactions to milk2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 12, p. 1290-1296Article in journal (Refereed)
    Abstract [en]

    AIM: This study examined the prevalence, symptom expression and risk factors for food hypersensitivity among Swedish schoolchildren.

    METHODS: Parents of 2585 (96% of invited) children aged 7-8 years completed a questionnaire regarding food hypersensitivity and allergic diseases. A random sample of 1700 children (90% of invited) also participated in skin prick testing with ten airborne allergens.

    RESULTS: The overall prevalence of reported food hypersensitivity to milk, egg, fish, wheat, soya, fruits and, or, nuts was 21%, with symptoms caused by milk (9%) being the most common. The most frequently reported symptoms were oral symptoms (47.4%), mainly caused by fruit, and gastrointestinal symptoms (45.7%), mainly caused by milk. Factors associated with any food hypersensitivity were female sex, allergic heredity and a positive skin prick test. Eczema was consistently associated with symptoms caused by milk, egg, fish, wheat, soya, fruits and nuts. Rhinitis was associated to the same foods, except milk.

    CONCLUSION: Reported food hypersensitivity was common among Swedish schoolchildren. The most frequent symptom expressions were oral symptoms triggered by fruits and gastrointestinal symptoms triggered by milk. The high prevalence of reported symptoms should be validated by clinical examinations to provide a diagnosis.

  • 10. Thunqvist, Per
    et al.
    Tufvesson, Ellen
    Bjermer, Leif
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Melén, Erik
    Norman, Mikael
    Hallberg, Jenny
    Lung function after extremely preterm birth: A population-based cohort study (EXPRESS)2018In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 53, no 1, p. 64-72Article in journal (Refereed)
    Abstract [en]

    Background and objectives: Follow-up studies of children and young adults born very-to-moderately preterm show persistent and significant lung function deficits. The aim of the study was to determine lung function and airway mechanics in school-aged children born in 2004 to 2007 and extremely preterm (after 22-26 weeks of gestation).

    Methods: In a population-based cohort of children born extremely preterm and controls born at term (n=350), follow-up at 61/2-years-of-age was performed using spirometry and impulse oscillometry. Associations to gestational age, smallness for gestational age (SGA), and bronchopulmonary dysplasia (BPD) were assessed.

    Results: Children born extremely preterm had lower forced vital capacity (FVC, z-score: -0.7, 95%CI: -1.0;-0.4), forced expiratory volume (FEV1, z-score: -1.1, 95%CI: -1.4; -0.8), higher frequency-dependence of resistance (R5-20, 0.09, 95%CI: 0.05; 0.12 kPaL(-1)s(-1)) and larger area under the reactance curve (AX, 0.78, 95%CI: 0.49; 1.07kPaL(-1)) than controls. In children born at 22-24 weeks of gestation, 24% had FVC and 44% had FEV1 below the lower limit of normal. SGA and severe BPD only marginally contributed to pulmonary outcomes. Asthma-like disease was reported in 40% of extremely preterm children and 15% of controls.

    Conclusion: Many children born extremely preterm have altered airway mechanics and significant obstructive reduction in lung function. This warrants consideration for treatment and continued follow-up.

  • 11.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Epidemiology of food hypersensitivity in schoolchildren: Validation with double-blind placebo-controlled food challenges and biomarkers2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: This thesis focuses on the incidence and remission of reported food hypersensitivity in schoolchildren followed from 8 to 12 -years of age and the prevalence of hypersensitivity to milk, egg, cod and wheat among 12-year olds investigated by reported data, clinical investigation and double-blind placebo-controlled food challenges and biomarkers.

    Methods: The studies are mainly based on a population based cohort recruited in 2006 from three municipalities in Northern Sweden. All children in first and second grade, aged 7-8 years, were invited to a parental questionnaire study and 2585 (96% of invited) participated. The children in two of the municipalities were also invited to a skin prick test with airborne allergens. At age 11-12 years, there was a follow-up of the cohort using the same methods, with the addition of a child interview and assessment of body mass index (BMI).

    At the follow-up, children who reported milk hypersensitivity were invited to structured interviews and children reporting complete elimination of milk, egg, cod or wheat due to perceived hypersensitivity were invited to a clinical examination and blood sampling. According to test results, the children were categorized into different food hypersensitivity phenotypes according to preset criteria. Children categorized as current food allergy were then invited to further evaluation with a double-blind placebo-controlled food-challenge using newly developed recipes. Before their use, the recipes were successfully validated regarding detectable sensorial differences between the active and placebo substances in a separate cohort of healthy schoolchildren (n=275).

    Before and after the challenge series blood samples were collected for analyses of cytokine mRNA expression in peripheral blood mononuclear cells including hallmark cytokines for the humoral allergy-promoting T helper (Th) 2 response, cellular cytotoxicity-promoting Th1 response, inflammatory-, and T regulatory responses. Fecal inflammatory biomarkers were also analyzed before and after the challenge series.

    Results: Reported food hypersensitivity increased from 21% at age 7-8 years to 26% at 11-12 years. There was a high incidence (15%) as well as a high remission (33%) of reported food hypersensitivity. Risk factors associated with incidence and remission were different for milk hypersensitivity and hypersensitivity to foods other than milk. The agreement between reported symptoms to milk, egg, cod, wheat, soy and peanut and sensitization to the culprit food was poor. At 11 to 12-years of age the prevalence of reported allergy to milk, egg, cod or wheat was 4.8% while the allergy prevalence according to clinical evaluation was 1.4%. This figure was further halved when evaluated with double-blind placebo-controlled food challenges.

    The majority of children with reported allergy to milk, egg, cod and wheat were categorized as other food hypersensitivity phenotypes, the most common being probable lactose intolerance (40%) and outgrown food allergy (19%). Even though reported milk hypersensitivity among the 11-12 year olds was 14.5%, only 3% were categorized as current milk allergy. Current and outgrown milk allergy was associated with other atopic disorders and a lower BMI (OR 0.8, 95% CI 0.80-0.98). Before the challenge series, the mRNA expression of the cytokines IL-13 and IL-10 were higher among children with a positive compared to a negative challenge outcome.

    Conclusion: Reported food hypersensitivity was common among school children in Northern Sweden and increased from 7-8 years to 11-12 years of age, and both the incidence and remission of reported hypersensitivity was high. There was an 8-fold difference in the prevalence of allergy to milk, egg, cod or wheat when reported data was assessed by clinical examinations and double-blind placebo-controlled food challenges. Allergy to milk, egg, cod and wheat was an uncommon cause of complete avoidance of these foods due to perceived hypersensitivity. Some of the analyzed biomarkers might serve as prognostic markers for symptomatic, IgE-mediated food allergy but need further validation.

  • 12.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bjerg, A.
    Berthold, M.
    Lindback, J.
    Mattsson, L.
    Borres, M.
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Furry animal sensitisation to allergen components and asthma diagnosis in a child cohort from northern Sweden2012In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 67, no Suppl. 1, p. 539-539Article in journal (Other academic)
  • 13.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundell, Catarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Arencibia, Ignacio
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Mincheva Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series2016In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 88, p. 259-266Article in journal (Refereed)
    Abstract [en]

    Background: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. Objective: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included. Methods: Twelve-year-old children from a population-based cohort reporting complete avoidance of milk, egg, cod or wheat due to perceived hypersensitivity were clinically examined and those with suspected food allergy were evaluated with a 3-session double-blind placebo-controlled food challenge (n = 18). Seven healthy controls participated in a double-blind challenge with egg. Before and after the challenge series, the cytokine mRNA expression was quantified for 13 cytokines discriminating between humoral Th2-, cytotoxic Thl-, regulatory Th3/Tr1- and inflammatory responses. Fecal calprotectin and eosinophil-derived neurotoxin (EDN) were also analyzed in children with suspected food allergy before and after the challenge series. Results: Pre challenge, children with suspected food allergy had higher IL-13 and TNF-alpha expression and lower IFN-gamma and IL-15 expression compared to healthy controls (all p < 0.05). Children with challenge proven food allergy had increased IL13 and IL-10 expression compared to the levels seen in negative challenges (p < 0.05). Post challenge, IL-1 beta and IL-6 mRNA levels were elevated in the food allergic children compared to controls (p < 0.05). Fecal calprotectin and EDN levels were higher in challenge-proven food allergy compared to a negative challenge although not statistically significantly. Conclusion & clinical relevance: Increased baseline mRNA levels of the Th2-related cytokine IL-13 and the regulatory cytokine IL-10 predicted a positive food challenge outcome. These cytokines in combination with fecal calprotectin and EDN might serve as future prognostic markers for symptomatic, IgEmediated food allergy but need further validation in a larger patient cohort.

  • 14.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordström, Lisbeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nylander, Annica
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Jonsäll, Anette
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    New validated recipes for double-blind placebo-controlled low-dose food challenges2013In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 3, p. 282-287Article in journal (Refereed)
    Abstract [en]

    Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acidbased product, with or without added food allergens. The test panels consisted of 275 school children, aged 810 and 1415yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p>0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice.

  • 15.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Perzanowski, Matthew S.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    High incidence and remission of reported food hypersensitivity in Swedish children followed from 8 to 12 years of age: a population based cohort study2014In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 4, article id 32Article in journal (Refereed)
    Abstract [en]

    Background: Few population-based cohort studies have examined reported food hypersensitivity longitudinally. We investigated prevalence, incidence and remission of perceived food hypersensitivity among schoolchildren from 8 to 12 years of age, and risk factors associated with incidence and remission. Methods: A population-based cohort including all 7-8 year-old children in three Swedish towns was recruited in 2006. A total of 2,585 (96% of invited) children participated in a parental questionnaire. The children in two of the towns, n = 1,700 (90% of invited) also participated in skin-prick-testing with airborne allergens. The cohort was followed using the same methods at 11-12 years of age. At study follow up, specific IgE to foods was analyzed in a randomized subset of children (n = 652). Results: The prevalence of perceived food hypersensitivity increased from 21% at 8 years to 26% at 12 years of age. During this four-year-period, the cumulative incidence of food hypersensitivity was high (15%), as was remission (33%). This pattern was particularly evident for hypersensitivity to cow's milk, while the incidence of hypersensitivity to other foods was lower. Female sex, allergic heredity, current rhinitis and allergic sensitization were associated with the incidence of food hypersensitivity and allergic sensitization was negatively associated with remission. Risk-factor-patterns for both incidence and remission were different for hypersensitivity to milk compared with hypersensitivity to other foods. Generally, the agreement between reported food hypersensitivity and IgE-sensitization to the implicated food was poor. Conclusions: In this longitudinal, population-based cohort-study perceived food hypersensitivity was common among children between ages 8 and 12, often transient and not well correlated with food-specific IgE. While these findings suggest an overestimated prevalence of food hypersensitivity, the public-health-significance remains high as they reflect the perceived reality to which the children adapt their life and food intakes.

  • 16.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Perzanowski, M.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    High incidence and remission of reported food hypersensitivity in Swedish children followed from 8 to 12 years of age2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no Supplement: 99, p. 151-151Article in journal (Refereed)
  • 17.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordström, Lisbet
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Assessment of Allergy to Milk, Egg, Cod, and Wheat in Swedish Schoolchildren: A Population Based Cohort Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0131804Article in journal (Refereed)
    Abstract [en]

    Objectives Knowledge about the prevalence of allergies to foods in childhood and adolescence is incomplete. The purpose of this study was to investigate the prevalence of allergies to milk, egg, cod, and wheat using reported data, clinical examinations, and double-blind placebo-controlled food challenges, and to describe the phenotypes of reported food hypersensitivity in a cohort of Swedish schoolchildren. Methods In a population-based cohort of 12-year-old children, the parents of 2612 (96% of invited) completed a questionnaire. Specific IgE antibodies to foods were analyzed in a random sample (n=695). Children reporting complete avoidance of milk, egg, cod, or wheat due to perceived hypersensitivity and without physician-diagnosed celiac disease were invited to undergo clinical examination that included specific IgE testing, a celiac screening test, and categorization into phenotypes of food hypersensitivity according to preset criteria. Children with possible food allergy were further evaluated with double-blind challenges. Results In this cohort, the prevalence of reported food allergy to milk, egg, cod, or wheat was 4.8%. Food allergy was diagnosed in 1.4% of the children after clinical evaluation and in 0.6% following double-blind placebo-controlled food challenge. After clinical examination, children who completely avoided one or more essential foods due to perceived food hypersensitivity were categorized with the following phenotypes: allergy (29%), outgrown allergy (19%), lactose intolerance (40%), and unclear (12%). Conclusions There was a high discrepancy in the prevalence of allergy to milk, egg, cod and wheat as assessed by reported data, clinical evaluation, and double-blind food challenges. Food hypersensitivity phenotyping according to preset criteria was helpful for identifying children with food allergy.

  • 18.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nordström, Lisbet
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Assessment of allergy to cow's milk, hen's egg, cod, and wheat in a population-based cohort of Swedish schoolchildren2015In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 70, p. 266-267Article in journal (Other academic)
  • 19.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordström, Lisbeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Milk allergy is a minor cause of milk avoidance due to perceived hypersensitivity among schoolchildren in Northern Sweden2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 2, p. 206-214Article in journal (Refereed)
    Abstract [en]

    AIM: We investigated phenotypes of milk hypersensitivity among schoolchildren aged 11-12 in Northern Sweden.

    METHODS: In a population-based cohort, 1,824 (98%) children aged 11-12 participated in a questionnaire survey, skin prick testing, interviews on food hypersensitivity and assessment of body mass index (BMI). Of the 265 children reporting milk hypersensitivity, milk avoidance and no celiac disease, 236 (89%) participated in a structured interview and blood samples for analyses of milk-specific Immunoglobulin E. The children were then categorised into milk hypersensitivity phenotypes according to preset criteria.

    RESULTS: In all, 14.5% reported milk hypersensitivity. Of these, 3% were categorised as current milk allergy, 23% as outgrown milk allergy, 40% as probable lactose intolerance and 11% were non-definable. Furthermore, 23% had discontinued their elimination diet. Milk allergy was associated with other atopic disorders and lower BMI, with an odds Ratio of 0.82 and 95% confidence interval of 0.80-0.98. Only 2% had previously undergone an oral challenge.

    CONCLUSION: The most common symptom phenotypes among Swedish children aged 11-12 with self-reported milk hypersensitivity and milk avoidance, were lactose intolerance and outgrown milk allergy while current milk allergy was uncommon. Children with milk allergy had a lower BMI and most lacked a challenge proven diagnosis. 

  • 20.
    Österlund, J.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, C. E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    A 10-year review found increasing incidence trends of emergency egg allergy reactions and food-induced anaphylaxis in children2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 2, p. 314-320Article, review/survey (Refereed)
    Abstract [en]

    Aim: International reports have suggested that food allergies and food‐induced anaphylaxis have increased in children. We investigated the incidence of emergency food reactions over a 10‐year period.

    Methods: This study retrospectively reviewed the medical records of children presenting to Umeå University hospital, Sweden, with an emergency food reaction from January 1, 2006 to December 31, 2015. Cases were identified using discharge codes for allergies and anaphylaxis. Anaphylaxis cases were included if they fulfilled the international criteria.

    Results: We found emergency food allergy reactions in 519 children (58% boys) from 2006–2015 at a median age of 1.3 years. One‐third were hospitalised (32%) including 71/99 cases of anaphylaxis. Milk and eggs were the most commonly identified triggers. Emergency reactions to eggs increased during the study period with a Spearman rank correlation coefficient of 0.770 (p < 0.01) and the figures for anaphylaxis were 0.745 (p = 0.013). The incidence of food‐induced anaphylaxis increased and was 30 per 100 000 person‐years for the study period.

    Conclusion: Most of the emergency reactions, treated by secondary care paediatricians and emergency physicians, were to milk and eggs. Allergic reactions to eggs increased from 2006 to 2015, as did food‐related anaphylaxis.

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