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  • 1.
    Abrahamsson, T. R.
    et al.
    Dept Clin & Expt Med, Div Pediat, Linköping Univ, Linköping, Sweden.
    Jakobsson, H. E.
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Andersson, A. F.
    Sch Biotechnol, Div Gene Technol, Sci Life Lab, Royal Inst Technol (KTH ), Stockholm, Sweden.
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Engstrand, L.
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden; Div Gene Technol, Sci Life Lab, KTH Royal Inst Technol, Sch Biotechnol, Stockholm, Sweden.
    Jenmalm, M. C.
    Dept Clin & Expt Med, Div Pediat, Linköping Univ, Linköping, Sweden; Dept Clin & Expt Med, Div Clin Immunol, Unit Autoimmun & Immune Regulat, Linköping Univ, Linköping, Sweden.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 2. Abrahamsson, T. R.
    et al.
    Jakobsson, H. E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, B.
    Engstrand, Lars
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, M. C.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 3.
    Abrahamsson, Thomas
    et al.
    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.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

    OBJECTIVE:

    To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.

    METHODS:

    The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).

    RESULTS:

    Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.

    CONCLUSION AND CLINICAL RELEVANCE:

    Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 4.
    Abrahamsson, Thomas
    et al.
    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.
    Sandberg, Martina
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Forsberg, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 12, p. 1729-1739Article in journal (Refereed)
    Abstract [en]

    Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo. less thanbrgreater than less thanbrgreater thanObjective To relate circulating Th1- and Th2-associated chemokines in infancy to allergic disease, sensitization and probiotic supplementation. less thanbrgreater than less thanbrgreater thanMethods Circulating levels of Th1-associated CXC-chemokine ligand (CXCL) 9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17 and CCL22 were assessed with Luminex and CCL18 with enzyme-linked immunosorbent assay at birth (n = 109), 6 (n = 104), 12 (n = 116) and 24 months (n = 123) in 161 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding the development of allergic disease and sensitization until 2 years of age. less thanbrgreater than less thanbrgreater thanResults The Th2-associated chemokines CCL17 and CCL22 were the highest at birth and then decreased, whereas CCL18 and the Th1-associated chemokines increased with age. High Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated levels of the Th2-associated CCL22 and reduced levels of the Th1-associated CXCL11 already at birth. The Th2-associated CCL17 was also elevated at birth in infants developing recurrent wheeze. A high Th2/Th1 ratio (CCL22/CXCL10) at birth associated with both sensitization and eczema development. The presence of L. reuteri in stool in the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months of age. High Th1-associated chemokine levels were associated with day-care. less thanbrgreater than less thanbrgreater thanConclusion and Clinical Relevance Allergic disease and sensitization in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels already from birth. Circulating chemokines are useful for investigating the Th1/Th2 imbalance in allergic disease in vivo. Elucidation of the role of chemokines in allergic diseases may lead to future treatments.

  • 5. Ahlroth Pind, C.
    et al.
    Gunnbjörnsdottír, M.
    Bjerg, A.
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundbäck, B.
    Malinovschi, A.
    Middelveld, R.
    Nilsson Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Norbäck, D.
    Janson, C.
    Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: a cross-sectional study2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1383-1389Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An association between dampness at home and respiratory conditions has been convincingly demonstrated in children. Fewer studies have been performed in adults, and data are lacking for chronic rhinosinusitis (CRS). With a prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of life, as well as economy.

    OBJECTIVE: Our aim was to study CRS and other respiratory conditions in relation to dampness at home in a representative sample of adults.

    METHODS: The Swedish GA(2) LEN questionnaire was answered by 26 577 adults (16-75 years) and included questions on respiratory symptoms, smoking, education and environmental exposure. CRS was defined according to the EP(3) OS criteria. Dampness was defined as reporting water damage, floor dampness or visible moulds in the home during the last 12 months. The dampness score was ranked from 0 to 3, counting the number of signs of dampness reported.

    RESULTS: Dampness at home was reported by 11.3% and was independently related to respiratory conditions after adjustment for demographic and socio-economic factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR 1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other respiratory conditions was further elevated in subjects reporting multiple signs of dampness.

    CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an independent association between dampness at home and CRS in adults. The high burden of this and the other respiratory conditions studied is a strong argument in favour of countering indoor dampness by improving building standards.

  • 6.
    Ahlroth Pind, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Gunnbjörnsdottír, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. National University Hospital of Iceland, Reykjavik, Iceland.
    Bjerg, A
    Karolinska Inst, Stockholm, Sweden.
    Järvholm, B
    Umeå Univ, Umeå, Sweden.
    Lundbäck, B
    Univ Gothenburg, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, R
    Karolinska Inst, Stockholm, Sweden.
    Nilsson Sommar, J
    Umeå Univ, Umeå, Sweden.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: A cross-sectional study2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1383-1389Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An association between dampness at home and respiratory conditions has been convincingly demonstrated in children. Fewer studies have been performed in adults, and data are lacking for chronic rhinosinusitis (CRS). With a prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of life, as well as economy.

    OBJECTIVE: Our aim was to study CRS and other respiratory conditions in relation to dampness at home in a representative sample of adults.

    METHODS: The Swedish GA2 LEN questionnaire was answered by 26 577 adults (16-75 years) and included questions on respiratory symptoms, smoking, education and environmental exposure. CRS was defined according to the EP3 OS criteria. Dampness was defined as reporting water damage, floor dampness or visible moulds in the home during the last 12 months. The dampness score was ranked from 0 to 3, counting the number of signs of dampness reported.

    RESULTS: Dampness at home was reported by 11.3% and was independently related to respiratory conditions after adjustment for demographic and socio-economic factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR 1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other respiratory conditions was further elevated in subjects reporting multiple signs of dampness.

    CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an independent association between dampness at home and CRS in adults. The high burden of this and the other respiratory conditions studied is a strong argument in favour of countering indoor dampness by improving building standards.

  • 7. Alcocer, M. J. C.
    et al.
    Murtagh, G. J.
    Mirotti, L.
    Brans, A.
    Harnett, W.
    Rundqvist, Louise
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    The allergenicity of 2S plant albumins2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 12, p. 1827-1827Article in journal (Refereed)
  • 8.
    Almqvist, C
    et al.
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Egmar, Ann-Charlotte
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Hedlin, G
    Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm.
    Lundqvist, M
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Nordvall, S L
    Institute of Woman and Child Health, Uppsala University, Uppsala.
    Pershagen, G
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm.
    Svartengren, M
    Department of Public Health Sciences, Karolinska Institutet, Stockholm.
    van Hage-Hamsten, M
    Department of Medicine, Unit of Clinical Immunology and Allergy, Karolinska Institutet and Hospital, Stockholm.
    Wickman, M
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Direct and indirect exposure to pets: - risk of sensitization and asthma at 4 years in a birth cohort2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 9, p. 1190-1197Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results.

    OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study.

    METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders.

    RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38).

    CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.

  • 9. Al-Shamkhi, N.
    et al.
    Alving, K.
    Dahlen, S. E.
    Hedlin, G.
    Middelveld, R.
    Bjerg, A.
    Ekerljung, L.
    Olin, A. C.
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Janson, C.
    Malinovschi, A.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma: results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and male gender, as well as individual characteristics, as IgE sensitisation and smoking, affect levels of FeNO in population-based studies. However their effect on FeNO in subjects with asthma has been scarcely studied.

    OBJECTIVE: To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics.

    MATERIAL AND METHODS: FeNO was measured in 557 subjects with asthma from the Swedish GA2LEN study. Allergic sensitisation was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood, hormonal status (for women) were questionnaire-assessed.

    RESULTS: Male gender (p<0.001), greater height (p<0.001) and sensitisation to both perennial allergens and pollen (p<0.001) related to higher FeNO levels. Current smoking (p<0.001) and having both parents smoking during childhood, vs having neither (p<0.001) or only one parent smoking (p=0.002), related to lower FeNO. Women with menarche between 9-11 years of age had lower FeNO than those with menarche between 12-14 years of age (p = 0.03) or 15-17 years of age (p=0.003).

    CONCLUSIONS AND CLINICAL RELEVANCE: Interpreting FeNO levels in clinical practice is complex and constitutional determinants, as well as smoking and IgE sensitization, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

  • 10.
    Al-Shamkhi, Nasrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Dahlen, S. E.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Hedlin, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Middelveld, R.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Bjerg, A.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Ekerljung, L.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Olin, A. C.
    Univ Gothenburg, Sect Occupat & Environm Med, Dept Publ Hlth & Community Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Sommar, J.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Forsberg, B.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

    Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2)LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

  • 11.
    Amin, Kawa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Rinne, Juhani
    Haahtela, Tari
    Simola, Markku
    Peterson, Christer G. B.
    Roomans, Godfried M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Malmeberg, Henrik
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sevéus, Lahja
    Inflammatory cell and epithelial characteristics of perennial allergic and nonallergic rhinitis with a symptom history of 1 to 3 years' duration2001In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 107, no 2, p. 249-257Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Perennial rhinitis is an inflammatory condition of the mucosal lining of the nose that may be caused by allergic and nonallergic mechanisms.

    OBJECTIVE: We sought to characterize the cellular pattern and structural changes in the nasal mucous membrane of patients with perennial rhinitis and compare them with those of control subjects.

    METHODS: Biopsy specimens were obtained from 27 patients with perennial allergic rhinitis (PAR), from 12 patients with perennial nonallergic rhinitis (PNAR) with eosinophils present in the nasal smear, and from 6 control subjects without rhinitis. In 10 of 27 patients with PAR who were also allergic to pollen, biopsy specimens were taken within the respective season (PARseason). In the other 17 patients, the biopsy was taken outside the pollen season (PARoutside season). Inflammatory cells were identified by using mAbs to their unique granular proteins.

    RESULTS: The characteristic feature of perennial rhinitis was the accumulation of activated (degranulated) mast cells and eosinophils in the nasal mucosa. The tissue eosinophil/neutrophil ratio was higher, and the loss of epithelial integrity was greater in all patient groups compared with the control subjects. The extent of epithelial damage was significantly larger in patients in the PARseason group compared with that in the PARoutside season and PNAR groups, which did not significantly differ from each other in this respect. The number of eosinophils and mast cells was higher in the PNAR group compared with the PAR groups. In all patient groups, the number of eosinophils correlated with the loss of epithelial integrity. The number of mast cells did not correlate with the extent of epithelial damage nor did the number of neutrophils, except in patients in the PARseason group.

    CONCLUSION: The accumulation of eosinophils and mast cells, as well as loss of epithelial integrity, was characteristic for perennial rhinitis. Loss of epithelial integrity in the nasal mucosa may be a consequence of the activity of accumulated eosinophils.

  • 12. Annus, T
    et al.
    Björkstén, B
    Mai, X M
    Nilsson, L
    Riikjärv, M A
    Sandin, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bråbäck, L
    Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren.2001In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, no 12, p. 1846-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors.

    OBJECTIVE: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries.

    METHODS: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Linköping (n = 911) and Ostersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol.

    RESULTS: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in Ostersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Linköping and 58% in Ostersund) bronchial hyper-responsiveness (BHR) (48% in Linköping and Ostersund) and anti-asthmatic treatment (63% in Linköping and 81% in Ostersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (Ostersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children.

    CONCLUSIONS: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

  • 13. Annus, T
    et al.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Mai, Xiaomei
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Riikjärv, MA
    Sandin, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Bråbäck, L
    Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren2001In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, no 12, p. 1846-1853Article in journal (Refereed)
    Abstract [en]

    Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

  • 14.
    Backman, Helena
    et al.
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university, Umeå, Sweden.
    Jansson, Sven-Arne
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university, Umeå, Sweden.
    Stridsman, Caroline
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Eriksson, Berne
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden, 4 Dept of Internal Medicine, Cen tral County Hospital of Halland, Halmstad, Sweden.
    Hedman, Linnea
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university, Umeå, Sweden.
    Eklund, Britt-Marie
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university, Umeå, Sweden.
    Sandström, Thomas
    Dept of Public Health and Clinical Medicine, Division of Medicine, Umeå university, Umeå, Sweden.
    Lindberg, Anne
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university, Umeå, Sweden.
    Lundbäck, Bo
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university, Umeå, Sweden Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Dept of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, the OLIN unit, Umeå university.
    Severe asthma: A population study perspective2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 819-828Article in journal (Refereed)
    Abstract [en]

    BackgroundSevere asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.

    ObjectiveTo describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.

    MethodsN=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.

    ResultsThe prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.

    Conclusions and clinical relevanceSevere asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.

  • 15.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stridsman, Caroline
    Eriksson, Berne
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eklund, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Severe asthma: A population study perspective2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 819-828Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.

    OBJECTIVE: To describe characteristics and estimate the prevalence of severe asthma in a large adult population-based asthma cohort followed for 10-28 years.

    METHODS: N=1006 subjects with asthma participated in a follow-up during 2012-14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well-known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.

    RESULTS: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.

    CONCLUSIONS AND CLINICAL RELEVANCE: Severe asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the general population.

  • 16.
    Backman, Helena
    et al.
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, The OLIN Unit, Umeå University.
    Räisänen, Petri
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Hedman, Linnea
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Stridsman, Caroline
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Andersson, Martin
    Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN Unit, Umeå University.
    Lindberg, Anne
    Department of Public Health and Clinical Medicine, Division of Medicine/the OLIN unit, Umeå University.
    Lundbäck, Bo
    Krefting Research Centre, Institute of Medicine, University of Gothenburg.
    Rönmark, Eva
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016: results from three population surveys2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1426-1435Article in journal (Refereed)
    Abstract [en]

    Background

    During the latter half of the 20th century, the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends among adults after 2010, especially regarding studies separating allergic asthma from non-allergic asthma, is lacking.

    Objective

    The aim was to estimate prevalence trends of current asthma among adults, both allergic and non-allergic, from 1996 to 2016.

    Methods

    Three cross-sectional samples from the same area of Sweden, 20-69 years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis (ARC) was used as a marker for allergic sensitization to define allergic asthma.

    Results

    The prevalence of current asthma increased from 8.4% (95% CI: 7.8-9.0) in 1996 to 9.9% (95% CI: 9.2-10.6) in 2006 and 10.9% (95% CI: 10.1-11.7) in 2016 (P<.001). Allergic asthma increased from 5.0% (95% CI: 4.5-5.5) in 1996 to 6.0% (95% CI: 5.4-6.6) in 2006 and further to 7.3% (95% CI: 6.6-8.0) in 2016 (P<.001), while the prevalence of non-allergic asthma remained stable around 3.4%-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use and ARC also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016.

    Conclusions and Clinical Relevance

    The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.

  • 17.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Räisänen, Petri
    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. Department of Health Sciences, Luleå University, Luleå, Sweden.
    Stridsman, Caroline
    Department of Health Sciences, Luleå University, Luleå, Sweden.
    Andersson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundbäck, Bo
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016: results from three population surveys2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1426-1435Article in journal (Refereed)
    Abstract [en]

    Background: During the latter half of the 20th century, the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends among adults after 2010, especially regarding studies separating allergic asthma from non-allergic asthma, is lacking.

    Objective: The aim was to estimate prevalence trends of current asthma among adults, both allergic and non-allergic, from 1996 to 2016.

    Methods: Three cross-sectional samples from the same area of Sweden, 20-69 years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis (ARC) was used as a marker for allergic sensitization to define allergic asthma.

    Results: The prevalence of current asthma increased from 8.4% (95% CI: 7.8-9.0) in 1996 to 9.9% (95% CI: 9.2-10.6) in 2006 and 10.9% (95% CI: 10.1-11.7) in 2016 (P<.001). Allergic asthma increased from 5.0% (95% CI: 4.5-5.5) in 1996 to 6.0% (95% CI: 5.4-6.6) in 2006 and further to 7.3% (95% CI: 6.6-8.0) in 2016 (P<.001), while the prevalence of non-allergic asthma remained stable around 3.4%-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use and ARC also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016.

    Conclusions and clinical relevance: The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.

  • 18.
    Bakolis, Ioannis
    et al.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Biostat & Hlth Informat, London, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, Hlth Serv & Populat Res Dept, Ctr Implementat Sci, London, England.
    Hooper, Richard
    Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Ctr Primary Care & Publ Hlth, London, England.
    Bachert, Claus
    Univ Ghent, Upper Airway Res Lab, Ghent, Belgium.
    Lange, Bibi
    Odense Univ Hosp, Dept Otorhinolaryngol, Odense, Denmark.
    Haahtela, Tari
    Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland.
    Keil, Thomas
    Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Lodz, Germany;Wurzburg Univ, Inst Clin Epidemiol & Biometry, Wurzburg, Germany.
    Hofmaier, Stephanie
    Charite Univ Med Berlin, Dept Paediat Pneumol & Immunol, Berlin, Germany.
    Fokkens, Wytske
    Acad Med Ctr, Otorhinolaryngol Dept, Amsterdam, Netherlands.
    Rymarczyk, Barbara
    Med Univ Silesia, Clin Dept Internal Dis Allergol & Clin Immunol, Katowice, Poland.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Burney, Peter G. J.
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Med, London, England.
    Garcia-Larsen, Vanessa
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Med, London, England;Johns Hopkins Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
    Dietary patterns and respiratory health in adults from nine European countries-Evidence from the GA2LEN study2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 11, p. 1474-1482Article in journal (Refereed)
    Abstract [en]

    Background: Dietary patterns defined using principal component analysis (PCA) offer an alternative to the analysis of individual foods and nutrients and have been linked with asthma and allergic disease. However, results have not been reproducible in different settings.

    Objective: To identify dietary patterns common to different European countries and examine their associations with asthma and allergic symptoms. Methods: In sixteen study centers in nine European countries, 3206 individuals aged 15-77 years completed a common, internationally validated, food frequency questionnaire and a respiratory symptoms questionnaire. The outcomes of interest were current asthma, asthma symptoms score (derived based on responses to 5 asthma symptom-related questions), atopy (positive skin prick test). Spirometry was used to estimate forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), the FEV1/FVC, spirometric restriction (FVC below the lower limit of normal (<LLN)) and FEV1/FVC < LLN. A novel meta-analytic approach was used to identify dietary patterns using PCA and to examine associations with asthma and allergic symptoms.

    Results: Two dietary patterns emerged, generally correlating with the same foods in different countries: one associated with intake of animal proteins and carbohydrates; the other with fruit and vegetables. There was evidence that the former pattern was associated with a higher asthma score (RR 1.63, 95% CI: 1.33-2.01), current asthma (RR 2.03, 95% CI: 1.52-2.71), wheeze (RR 1.84, 95% CI: 1.30-2.60), atopic status (RR 1.68, 95% CI: 1.16-2.44) and with decreased lung function, including an FVC <LLN (RR 4.57, 95% CI: 2.27-9.21).

    Conclusions and Clinical Relevance: Our findings suggest an increase in sensitisation to common allergens, an increase in asthma symptoms, and a reduction in lung function in those eating a diet rich in animal proteins and carbohydrates. We found little evidence of an association between these outcomes and eating a diet rich in fruits and vegetables.

  • 19.
    Bendtsen, Preben
    et al.
    University of Southern Denmark.
    Gronbeck, M
    University of Southern Denmark.
    Kjaer, SK
    Danish Cancer Society.
    Munk, C
    Danish Cancer Society.
    Linneberg, A
    Glostrup University Hospital.
    Tolstrup, JS
    University of Southern Denmark.
    Alcohol consumption and the risk of self-reported perennial and seasonal allergic rhinitis in young adult women in a population-based cohort study2008In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 38, no 7, p. 1179-1185Article in journal (Refereed)
    Abstract [en]

    Background Alcohol consumption has been suggested to be associated with the development of allergic rhinitis (AR), but there is limited data on the topic.

    Objectives The objective of this study was to investigate the association between alcohol consumption and the risk of developing AR among young women.

    Methods Five thousand eight hundred and seventy Danish women aged 20–29 years participated in a prospective cohort study, and were free of seasonal and perennial AR at baseline (1991–1993). Alcohol consumption was assessed by a food frequency questionnaire. The main outcome measures were self-reported information on seasonal and perennial AR debuting during a mean follow-up period of 7.8 years.

    Results During follow-up, 831 women developed seasonal AR and 523 women developed perennial AR, corresponding to 14% and 9%. Alcohol consumption was positively associated with the risk of developing perennial AR. The adjusted odds ratio (OR) for perennial AR was 1.78 (95% CI, 1.13–2.80) among women drinking more than 14 drinks/week compared with women drinking <1 drink/week. There was no association between alcohol consumption and seasonal AR. Having one or two parents with asthma was, after adjustment, significantly associated with the risk of developing seasonal (OR, 2.01; 95% CI, 1.65–2.45) and perennial AR (OR, 2.28; 95% CI, 1.70–2.74). Smoking was not associated with an increased risk of developing AR.

    Conclusion In this population of young adult women, alcohol consumption was associated with an increased risk of developing perennial AR.

  • 20.
    Benson, Mikael
    et al.
    Malmö General Hospital, Sweden.
    Adner, M
    Malmö General Hospital, Sweden.
    Cardell, L O
    Malmö General Hospital, Sweden.
    Cytokines and cytokine receptors in allergic rhinitis: how do they relate to the Th2 hypothesis in allergy?2001In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, no 3, p. 361-367Article in journal (Refereed)
  • 21.
    Benson, Mikael
    et al.
    Malmö University Hospital, Sweden and Queen Silvia Children’s Hospital, Gothenburg, Sweden.
    Jansson, L.
    Astra Zeneca R&D Lund, Sweden.
    Adner, M.
    Malmö University Hospital, Sweden.
    Luts, A.
    Astra Zeneca R&D Lund, Sweden.
    Uddman, R.
    Malmö University Hospital, Sweden.
    Cardell, L.O.
    Malmö University Hospital, Sweden.
    Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis2005In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 35, no 4, p. 473-478Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample.

    OBJECTIVE:

    To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls.

    METHODS:

    Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants.

    RESULTS:

    Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05).

    CONCLUSION:

    IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.

  • 22.
    Benson, Mikael
    et al.
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Olsson, M
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Rudemo, M
    Chalmers University of Technology, Gothenburg, Sweden.
    Wennergren, G
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Cardell, L O
    Malmö University Hospital, Sweden.
    Pros and cons of microarray technology in allergy research2004In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 7, p. 1001-1006Article in journal (Refereed)
  • 23.
    Benson, Mikael
    et al.
    Malmö University Hospital, Sweden.
    Svensson, P A
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, B
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Jernås, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Reinholdt, J
    Aarhus University Hospital, Denmark.
    Cardell, L O
    Malmö University Hospital, Sweden.
    Carlsson, L
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    DNA microarrays to study gene expression in allergic airways2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 2, p. 301-308Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample.

    OBJECTIVE: To study gene expression in nasal mucosal biopsies from patients with allergic rhinitis using DNA micro-arrays.

    METHODS: Nasal biopsies were obtained from 14 patients with symptomatic birch pollen-induced allergic rhinitis and five healthy controls. RNA was extracted from the biopsies and pooled into one patient pool and one control pool. These were analysed in duplicate with DNA micro-arrays containing more than 12 000 known genes.

    RESULTS: Approximately half of the genes were expressed in the patient and control samples. Guided by the current literature we chose 32 genes of possible relevance to allergic airway inflammation and investigated their relative expression. Among these, transcripts encoding immunoglobulins and their receptors were most abundant. The expression of cytokines and growth factors was low, whereas their corresponding receptors and cell surface markers displayed higher expression levels. IgA had the highest expression of all 12 626 genes. RT-PCR showed that IgA1 was the predominant subclass. This was confirmed by the protein level in nasal fluids. Allergen-specific IgA was significantly higher in patients than in controls and correlated significantly with eosinophil granulae proteins.

    CONCLUSION: DNA micro-array analysis can be used to identify genes of possible relevance to allergic airway inflammation. In this study, the expression profile in the nasal mucosa was quantitatively dominated by immunoglobulins, particularly IgA. Protein analyses in nasal fluids indicated a role for allergen-specific IgA in eosinophil degranulation.

  • 24.
    Bertelsen, R. J.
    et al.
    Univ Bergen, Dept Clin Sci, POB 7804, N-5020 Bergen, Norway.;Haukeland Hosp, Dept Occupat Med, Bergen, Norway..
    Rava, M.
    INSERM U1168, VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, Villejuif, France.;Univ Versailles St Quentin En Yvelines, UMR S 1168, Montigny Le Bretonneux, France.;Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain..
    Carsin, A. E.
    Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain.;Univ Pompeu Fabra, Barcelona, Spain.;CIBERESP, Barcelona, Spain..
    Accordini, S.
    Univ Verona, Unit Epidemiol & Med Stat, Dept Diagnost & Publ Hlth, Verona, Italy..
    Benediktsdottir, B.
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Dratva, J.
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland..
    Franklin, K. A.
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Heinrich, J.
    Helmholtz Zentrum Munchen, Inst Epidemiol 1, German Res Ctr Environm Hlth, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany..
    Holm, M.
    Sahlgrens Univ Hosp, Dept Occupat & Environm Med, Gothenburg, Sweden..
    Janson, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Johannessen, A.
    Univ Bergen, Ctr Int Hlth, Dept Global Publ Hlth & Primary Care, Bergen, Norway.;Haukeland Hosp, Clin Res Ctr, Bergen, Norway..
    Jarvis, D. L.
    Imperial Coll, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London, England..
    Jogi, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Tartu Univ Hosp, Lung Clin, Tartu, Estonia..
    Leynaert, B.
    INSERM, UMR 1152, Pathophysiol & Epidemiol Resp Dis, Epidemiol Team, Paris, France.;Univ Paris Diderot Paris 7, UMR 1152, Paris, France..
    Norback, D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Omenaas, E. R.
    Univ Bergen, Dept Clin Sci, POB 7804, N-5020 Bergen, Norway.;Haukeland Hosp, Clin Res Ctr, Bergen, Norway..
    Raherison, C.
    Bordeaux Univ, INSERM U897, Bordeaux, France..
    Sanchez-Ramos, J. L.
    Univ Huelva, Dept Nursing, Huelva, Spain..
    Schlunssen, V.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.;Natl Res Ctr Working Environm, Copenhagen, Denmark..
    Sigsgaard, T.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark..
    Dharmage, S. C.
    Univ Melbourne, Melbourne Sch Populat Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic, Australia..
    Svanes, C.
    Haukeland Hosp, Dept Occupat Med, Bergen, Norway.;Univ Bergen, Ctr Int Hlth, Dept Global Publ Hlth & Primary Care, Bergen, Norway..
    Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 5, p. 627-638Article in journal (Refereed)
    Abstract [en]

    Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

  • 25. Bertelsen, R. J.
    et al.
    Rava, M.
    Carsin, A. E.
    Accordini, S.
    Benediktsdottir, B.
    Dratva, J.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Heinrich, J.
    Holm, M.
    Janson, C.
    Johannessen, A.
    Jarvis, D. L.
    Jogi, R.
    Leynaert, B.
    Norback, D.
    Omenaas, E. R.
    Raherison, C.
    Sanchez-Ramos, J. L.
    Schlunssen, V.
    Sigsgaard, T.
    Dharmage, S. C.
    Svanes, C.
    Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 5, p. 627-638Article in journal (Refereed)
    Abstract [en]

    Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans.

    Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever.

    Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions.

    Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth.

    Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

  • 26.
    Bjerg, A.
    et al.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Ekerljung, L.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Eriksson, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Naslund, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Sjölander, S.
    ThermoFisher Sci, ImmunoDiagnost, Uppsala, Sweden..
    Rönmark, E.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;OLIN Unit, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Dahl, Å.
    Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Holmberg, K.
    Sahlgrens Univ Hosp, Dept Otorhinolaryngol, Gothenburg, Sweden..
    Wennergren, G.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;Gothenburg Univ, Dept Pediat, Gothenburg, Sweden..
    Torén, K.
    Gothenburg Univ, Sahlgrenska Acad, Dept Publ Hlth & Community Med, Gothenburg, Sweden..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Lötvall, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Lundbäck, B.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 10, p. 1328-1336Article in journal (Refereed)
    Abstract [en]

    Background To date, most studies of the 'allergy epidemic' have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults. Objective To study allergic sensitization, its risk factors and time trends in prevalence. Methods Within West Sweden Asthma Study (WSAS), a population-based sample of 788 adults (17-60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009-2012. Specific IgE was analysed in 750 of the participants. Those aged 20-46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20-46 year from the same area (n = 591) in 1991-1992. Results Among those aged 20-46 years, the prevalence of positive SPT to pollen increased, timothy from 17.1% to 29.0% (P < 0.001) and birch from 15.6% to 23.7% (P = 0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60 years, any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98), respectively. Conclusion Pollen sensitization has increased in Swedish adults since the early 1990s, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.

  • 27. Bjerg, Anders
    et al.
    Ekerljung, Linda
    Eriksson, Jonas
    Näslund, Jonas
    Sjölander, Sigrid
    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, Gothenburg University, Göteborg.
    Dahl, Åslög
    Holmberg, Kenneth
    Wennergren, Göran
    Torén, Kjell
    Borres, Magnus P
    Lötvall, Jan
    Lundbäck, Bo
    Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 10, p. 1328-1336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To date, most studies of the "allergy epidemic" have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults.

    OBJECTIVE: To study allergic sensitization, its risk factors, and time trends in prevalence.

    METHODS: Within West Sweden Asthma Study (WSAS) a population-based sample of 788 adults (17-60y) underwent skin prick tests (SPT) for 11 aeroallergens 2009-2012. Specific IgE was analyzed in 750 of the participants. Those aged 20-46y (n=379) were compared with the European Community Respiratory Health Survey sample aged 20-46y from the same area (n=591) in 1991-1992.

    RESULTS: Among those aged 20-46y the prevalence of positive SPT to pollen increased; timothy from 17.1% to 29.0% (p<0.001) and birch from 15.6% to 23.7% (p=0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60y any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98) respectively.

    CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990's, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.

  • 28.
    Bjerg, Anders
    et al.
    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.
    Perzanowski, Matthew
    Wennergren, Göran
    Lundbäck, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Decreased importance of environmental risk factors for childhood asthma from 1996 to 20062015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 1, p. 146-153Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The large increase in asthma prevalence continues in several, but not all areas. Despite the individual risk factors that have been identified, the reasons for the observed trends in prevalence are largely unknown.

    OBJECTIVE: This study sought to characterize what trends in risk factors accompanied trends in asthma prevalence.

    METHODS: Two population-based cohorts of 7-8-year-old children from the same Swedish study areas examined by expanded ISAAC questionnaires were compared 10 years apart. In 1996 3,430 (97% participation) and in 2006 2,585 (96% participation) questionnaires were completed. A subset was skin-prick tested: in 1996, 2,148 (88% participation) and in 2006, 1,700 (90% participation) children. The adjusted population attributable fraction (aPAF) was calculated using the prevalence and multivariate odds ratio of each risk factor.

    RESULTS: The prevalence of current asthma and wheeze were similar in 1996 and 2006. Allergic sensitisation however increased from 21% to 30%. The prevalence of parental asthma increased from 17% to 24% while respiratory infections and maternal smoking decreased (60% to 29% and 32% to 16%, respectively). The aPAFs of non-environmental risk factors for current asthma increased 1996-2006: Allergic sensitization from 35% to 41%, parental asthma from 27% to 45% and male sex from 20% to 25%. Conversely, the aPAFs of environmental risk factors decreased: Respiratory infections from 36% to 32% and damp home and maternal smoking from 14% and 19% respectively to near zero in 2006.

    CONCLUSIONS AND CLINICAL RELEVANCE: From 1996 to 2006 the non-environmental risk factors parental asthma, allergic sensitisation and male sex had an increasing or constant importance for current asthma in 7-8-year-old children. The importance of the environmental exposures damp home, respiratory infections and maternal smoking decreased. This counter-balancing in risk factors may explain the level prevalence of current asthma.

  • 29.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Unmet needs in the treatment of asthmatic children and adolescents.2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30Article in journal (Refereed)
  • 30.
    Björkstén, B
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Naaber, P
    Sepp, E
    Mikelsaar, M
    The intestinal microflora in allergic Estonian and Swedish 2-year-old children. 1999In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, p. 342-346Article in journal (Refereed)
  • 31.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Holgate, Stephen
    Kelly, Frank
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan
    Frew, Anthony
    Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 6, p. 777-782Article in journal (Refereed)
    Abstract [en]

    Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group.

    Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility.

    Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78.

    Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects.

    Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.

  • 32.
    Braback, Lennart
    et al.
    Sundsvall Hospital.
    Vogt, Hartmut
    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.
    Hjern, A.
    National Board for Health and Welfare, Stockholm.
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

    Background Studies of asthma in migrant populations illustrate the effects of environmental changes. Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent. Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6-25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma. Results International adoptees and children born in Sweden by foreign-born parents had three-to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71-0.85] for those adopted at 1-2 years, 0.51 (0.42-0.61) at 3-4 years and 0.35 (0.27-0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0-4 years, at 5-9 years, at 10-14 years and at 15 years or more were 0.73 (0.63-0.86), 0.56 (CI 0.46-0.68) and 0.35 (CI 0.28-0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators. Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.

  • 33.
    Brandstrom, J.
    et al.
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, S-11883 Stockholm, Sweden..
    Nopp, A.
    Karolinska Inst, Dept Med, Clin Immunol & Allergy Unit, Stockholm, Sweden.;Karolinska Hosp, S-10401 Stockholm, Sweden..
    Johansson, S. G. O.
    Karolinska Inst, Dept Med, Clin Immunol & Allergy Unit, Stockholm, Sweden.;Karolinska Hosp, S-10401 Stockholm, Sweden..
    Lilja, G.
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, S-11883 Stockholm, Sweden..
    Sundqvist, A. -C
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Uppsala, Sweden..
    Nilsson, C.
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, S-11883 Stockholm, Sweden..
    Basophil allergen threshold sensitivity and component-resolved diagnostics improve hazelnut allergy diagnosis2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 9, p. 1412-1418Article in journal (Refereed)
    Abstract [en]

    BackgroundIgE sensitization to hazelnut is common, especially in birch endemic areas. However, its clinical significance often needs to be confirmed by a food challenge. ObjectiveTo evaluate the clinical significance of IgE antibodies to hazelnut components and basophil allergen threshold sensitivity (CD-sens) to hazelnut, in relation to double-blind placebo-controlled food challenge (DBPCFC) in children with a suspected hazelnut allergy. MethodsForty children underwent a DBPCFC. CD-sens to hazelnut as well as IgE antibodies to hazelnut and its components Cor a 1, Cor a 8, Cor a 9 and Cor a 14 were analysed. Serum tryptase was measured before, during and after DBPCFC. ResultsEight children had a positive DBPCFC, and all of them had a high CD-sens value to hazelnut. Of the 32 children that passed the DBPCFC, 31 were very low or negative in CD-sens. A positive DBPCFC corresponded with significantly higher CD-sens values (median 8.9, range 3.3-281) compared to children negative in challenge (median 0.05, range 0-34.7, P<0.0001). Children positive in challenge also had higher levels of IgE-ab to Cor a 9 and Cor a 14 (P<0.01 and P<0.001, respectively) compared with those with a negative challenge. In relation to the results from DBPCFC, the sensitivity of CD-sens and IgE-ab to Cor a 14 was excellent (100%) and the specificity was very high (>97% and >94%, respectively). Five of the eight patients positive at challenge showed an increase in tryptase >20% compared to tryptase baseline levels. Conclusions and Clinical RelevanceCD-sens and component-resolved diagnostics to hazelnut, used separately or in combination, may improve the diagnostic accuracy and safety and reduce overdiagnosis of hazelnut allergy.

  • 34. Brandstrom, J.
    et al.
    Vetander, M.
    Lilja, G.
    Johansson, S. G. O.
    Sundqvist, A. -C
    Kalm, Frida
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. Karolinska Univ Hosp, Sweden.
    Nilsson, C.
    Nopp, A.
    Individually dosed omalizumab: an effective treatment for severe peanut allergy2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 4, p. 540-550Article in journal (Refereed)
    Abstract [en]

    Background Treatment with omalizumab has shown a positive effect on food allergies, but no dosages are established. Basophil allergen threshold sensitivity (CD-sens) can be used to objectively measure omalizumab treatment efficacy and correlates with the outcome of double-blind placebo-controlled food challenge to peanut. Objective To evaluate whether individualized omalizumab treatment monitored by CD-sens could be an effective intervention for suppression of allergic reactions to peanut. Methods Severely peanut allergic adolescents (n = 23) were treated with omalizumab for 8 weeks, and CD-sens was analysed before and after. Based on whether CD-sens was suppressed after 8 weeks, the patients either were subject to a peanut challenge or received eight more weeks with increased dose of omalizumab, followed by peanut challenge or another 8-week cycle of omalizumab. IgE and IgE-antibodies to peanut and its components were analysed before treatment. Results After individualized omalizumab treatment (8-24 weeks), all patients continued with an open peanut challenge with no (n = 18) or mild (n = 5) objective allergic symptoms. Patients (n = 15) needing an elevated omalizumab dose (ED) to suppress CD-sens had significantly higher CD-sens values at baseline 1.49 (0.44-20.5) compared to those (n = 8) who managed with normal dose (ND) 0.32 (0.24-5.5) (P < 0.01). Median ratios for Ara h 2 IgE-ab/IgE were significantly higher in the ED group (17%) compared to the ND group (11%). Conclusions and Clinical Relevance Individually dosed omalizumab, monitored by CD-sens, is an effective and safe treatment for severe peanut allergy. The ratio of IgE-ab to storage protein Ara h 2/IgE as well as CD-sens to peanut may predict the need of a higher omalizumab dose.

  • 35.
    Brew, Bronwyn K.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Gong, Tong
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; Sweden Pediatric Allergy and Pulmonology Unit,t Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    The familial aggregation of atopic diseases and depression or anxiety in children2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 6, p. 703-711Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Children with asthma and atopic diseases have an increased risk of depression or anxiety. Each of these diseases have strong genetic and environmental components, therefore it seems likely that there is a shared liability rather than causative risk.

    OBJECTIVE: To investigate the existence and nature of familial aggregation for the comorbidity of atopic diseases and depression or anxiety.

    METHODS: Participants came from the Childhood and Adolescent Twin Study in Sweden (CATSS), n= 14197. Current and ever asthma, eczema, hayfever and food-allergy were reported by parents. Internalizing disorders were identified using validated questionnaires. Familial co-aggregation analysis compared monozygotic MZ twins and same-sex dizygotic DZ twins for atopic disease in one twin with internalizing disorder in the other to test for genetic liability. Several familial liability candidates were also tested including parental education, recent maternal psychological stress, childhood family trauma and parental country of birth.

    RESULTS: Familial co-aggregation analysis found that if one twin had at least one current atopic disease the partner twin was at risk of having an internalizing disorder regardless of their own atopic status (Adjusted OR 1.22 (95% CI 1.08, 1.37). Similar results were found for each atopic disease ever and current. MZ associations were not higher than DZ associations suggesting that the liability is not genetic in nature. Including other familial candidates to the models made little difference to effect estimates.

    CONCLUSIONS AND CLINICAL RELEVANCE: Atopic diseases and depression or anxiety tend to occur together in families, therefore when treating for one disease the physician should consider comorbidity in both the individual and the individual's siblings. We did not find evidence to support a genetic explanation for comorbidity and further exploration is needed to disentangle the environmental and epigenetic reasons for familial aggregation.

  • 36.
    Brew, Bronwyn K.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Soderberg, Joakim
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lundholm, Cecilia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Afshar, Soren
    Karolinska Univ Hosp, Dept Med, Div Resp Med, Stockholm, Sweden.
    Holmberg, Kirsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social medicine/CHAP.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Pediat Allergy & Pulmonol Unit, Stockholm, Sweden.
    Academic achievement of adolescents with asthma or atopic disease2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 892-899Article in journal (Refereed)
    Abstract [en]

    Background

    Over a fifth of children and adolescents suffer with asthma or atopic disease. It is unclear whether asthma impacts academic performance in children and adolescents, and little is known about the association of eczema, food allergy or hayfever and academic performance.

    Objective

    To examine whether asthma, eczema, food allergy or hayfever impacts on adolescent academic performance and to assess the role of unmeasured confounding.

    Methods

    This study used the Childhood and Adolescent Twin Study of Sweden cohort born 1992‐1998. At age 9‐12 years, parents reported on their child's ever or current asthma, eczema, food allergy and hayfever status (n = 10 963). At age 15, linked national patient and medication register information was used to create current and ever asthma definitions including severe and uncontrolled asthma for the same children. Academic outcomes in Grade 9 (age 15‐16 years) included: eligibility for high school (Grades 10‐12), and total mark of the best 16 subject units, retrieved from the Grade 9 academic register. Whole cohort analyses adjusted for known covariates were performed, and co‐twin control analyses to assess unmeasured confounders.

    Results

    There were no associations found for asthma or food allergy at 9‐12 years and academic outcomes in adolescence. In addition, at age 15, there were no statistically significant associations with current, ever, severe or uncontrolled asthma and academic outcomes. Eczema and hayfever at age 9‐12 years were found to be positively associated with academic outcomes; however, co‐twin control analyses did not support these findings, suggesting the main analyses may be subject to unmeasured confounding.

    Conclusion and clinical relevance

    Having asthma or an atopic disease during childhood or adolescence does not negatively impact on academic performance. This information can be used by clinicians when talking with children and parents about the implications of living with asthma or atopic disease.

  • 37.
    Brough, H. A.
    et al.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Guys & St Thomass NHS Fdn Trust, Childrens Allergy Serv, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Kull, I.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden;Soder Sjukhuset, Sachs Childrens Hosp, Stockholm, Sweden.
    Richards, K.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Hallner, E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Söderhäll, C.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Douiri, A.
    Kings Coll London, Div Hlth & Social Care Res, London, England.
    Penagos, M.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Melen, E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Soder Sjukhuset, Sachs Childrens Hosp, Stockholm, Sweden.
    Bergström, A.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.
    Turcanu, V.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Wickman, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Lack, G.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Guys & St Thomass NHS Fdn Trust, Childrens Allergy Serv, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Environmental peanut exposure increases the risk of peanut sensitization in high-risk children2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 5, p. 586-593Article in journal (Refereed)
    Abstract [en]

    Background: High household peanut consumption is associated with the development of peanut allergy, especially when peanut allergic cases are compared against atopic controls; thus, environmental peanut exposure (EPE) may be a risk factor for peanut sensitization and allergy. In this study, we explored the relationship between EPE and school-age peanut sensitization in a population-based cohort.

    Methods: Maternal bed dust was collected postnatally, and EPE was quantified using a polyclonal peanut ELISA. Peanut sensitization was assessed by specific IgE to peanut extract and sIgE to peanut protein component allergens Ara h 1, 2 or 3 >= 0.35kU/L (primary peanut sensitization). Initial nested case-control analysis was performed comparing peanut-sensitized cases against high-risk controls (matched for parental atopy) (n = 411) using a conditional regression analysis. This was followed by whole cohort analysis (n = 1878) comparing EPE against peanut sIgE sensitization at ages 4 and 8 years using generalized estimating equations and against primary peanut sensitization at age 8 years using a logistic regression model. Finally, a subgroup analysis was performed comparing the impact of EPE in peanut-sensitized vs egg-sensitized, peanut-tolerant individuals using logistic regression analysis. Levels of EPE were compared between groups using the Mann-Whitney U test.

    Results: In the nested case-control analysis, a higher level of EPE around birth was associated with peanut-specific IgE sensitization at age 4 years (OR=1.41, 95% CI:1.05-1.90) and primary peanut sensitization at age 8 years (OR=2.11, 95% CI:1.38-3.22) compared against high-risk controls. When the whole BAMSE cohort was assessed, EPE was no longer associated with peanut sensitization; however, on subgroup analysis, EPE was associated with primary peanut sensitization when compared against egg-sensitized peanut-tolerant controls with an adjusted odds ratio of 1.44 per unit EPE (95% CI:1.06-1.94). There was no significant interaction between EPE and FLG loss-of-function mutations, egg sensitization at age 4 years, infantile eczema or parental atopy on peanut sensitization.

    Conclusions: Higher levels of environmental exposure to peanut in the first few months of life appear to increase the probability of developing school-age peanut sensitization in atopic children (based on egg sensitization and parental atopy).

  • 38. Brussino, L.
    et al.
    Badiu, I.
    Sciascia, S.
    Bugiani, M.
    Heffler, E.
    Guida, G.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bucca, C.
    Rolla, G.
    Oxidative stress and airway inflammation after allergen challenge evaluated by exhaled breath condensate analysis2010In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 40, no 11, p. 1642-1647Article in journal (Refereed)
    Abstract [en]

    Background Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane. Objective The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE(2)) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen. Results At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14-53.61) vs. 21.56 pg/mL (19.92, 23.35), P < 0.001], cys-LTs increased [27.37 pg/mL (24.09-31.10) vs. 13.28 pg/mL (11.32, 15.57), P < 0.001] and PGE(2) decreased [18.69 pg/mL (12.26, 28.50) vs. 39.95 pg/mL (34.37, 46.43), P < 0.001]. The trend of increasing 8-isoprostane after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R2=0.85, P < 0.001) whereas the trend of decreasing PGE(2) after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R2=0.52, P=0.001). Conclusions and Clinical Relevance The increase in EBC 8-isoprostane observed after allergen challenge indicates that allergen exposure increases airway oxidative stress in allergic asthma. The strict correlation between cys-LTs and 8-isoprostane underlines the relationship between allergic inflammation and oxidative stress. A shift of arachidonic acid metabolism towards lipoxygenase pathway is induced by the allergen challenge. Airway oxidative stress occurs after allergen challenge even in patients with mild intermittent allergic asthma.

  • 39. Bråbäck, L.
    et al.
    Vogt, H.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

    Background Studies of asthma in migrant populations illustrate the effects of environmental changes.

    Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent.

    Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6–25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma.

    Results International adoptees and children born in Sweden by foreign-born parents had three- to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71–0.85] for those adopted at 1–2 years, 0.51 (0.42–0.61) at 3–4 years and 0.35 (0.27–0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0–4 years, at 5–9 years, at 10–14 years and at 15 years or more were 0.73 (0.63–0.86), 0.56 (CI 0.46–0.68) and 0.35 (CI 0.28–0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators.

    Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.

  • 40.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Vogt, H.
    Hjern, A.
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

    Background Studies of asthma in migrant populations illustrate the effects of environmental changes. Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent. Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6-25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma. Results International adoptees and children born in Sweden by foreign-born parents had three-to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71-0.85] for those adopted at 1-2 years, 0.51 (0.42-0.61) at 3-4 years and 0.35 (0.27-0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0-4 years, at 5-9 years, at 10-14 years and at 15 years or more were 0.73 (0.63-0.86), 0.56 (CI 0.46-0.68) and 0.35 (CI 0.28-0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators. Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.

  • 41.
    Byström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Garcia, R. C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Håkansson, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karawajczyk, Malgorzata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Soukka, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eosinophil cationic protein is stored in, but not produced by, peripheral blood neutrophils2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 7, p. 1082-1091Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Eosinophil cationic protein (ECP) is an eosinophil-derived protein, which has been shown to be present in circulating neutrophils.

    OBJECTIVE: To establish whether ECP is produced or internalized by peripheral blood neutrophils.

    METHODS: This was done using microscopy, flow cytometry, fractionation of cells and RT-PCR techniques.

    RESULTS: No ECP mRNA was detected after extensive cell purification to eliminate all traces of contaminating eosinophils. Examination of immunostained neutrophils by light, confocal, electron microscopy together with cell fraction experiments, established that ECP is present intracellularly and is mostly associated to cell granules. Uptake studies by flow cytometry and by using both cold and radiolabelled ECP showed that it is internalized by neutrophils and stored in some proportion in their primary granules. Upon stimulation with serum-treated Sephadex particles, the internalized ECP was partially released from cells.

    CONCLUSION: ECP is not produced but can be internalized by circulating neutrophils, which take it from the environment and partially store it in their primary granules.

  • 42.
    Byström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Garcia, Rodolfo
    Håkansson, Lena
    Karawajczyk, Malgorzata
    Moberg, Lena
    Soukka, Juri
    Venge, Per
    Eosinophil Cationic Protein is stored in, but not produced by, peripheral blood neutrophils2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 7, p. 1082-1091Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Eosinophil cationic protein (ECP) is an eosinophil-derived protein, which has been shown to be present in circulating neutrophils.

    OBJECTIVE: To establish whether ECP is produced or internalized by peripheral blood neutrophils.

    METHODS: This was done using microscopy, flow cytometry, fractionation of cells and RT-PCR techniques.

    RESULTS: No ECP mRNA was detected after extensive cell purification to eliminate all traces of contaminating eosinophils. Examination of immunostained neutrophils by light, confocal, electron microscopy together with cell fraction experiments, established that ECP is present intracellularly and is mostly associated to cell granules. Uptake studies by flow cytometry and by using both cold and radiolabelled ECP showed that it is internalized by neutrophils and stored in some proportion in their primary granules. Upon stimulation with serum-treated Sephadex particles, the internalized ECP was partially released from cells.

    CONCLUSION: ECP is not produced but can be internalized by circulating neutrophils, which take it from the environment and partially store it in their primary granules.

  • 43.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Häggström, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Björksten, Bengt
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Total and allergen-specific immunoglobulin a levels in saliva in relation to the development of allergy in infants up to 2 years of age2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 9, p. 1293-1298Article in journal (Refereed)
    Abstract [en]

    Background: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. Objective: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. Methods: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and ▀-lactoglobulin specific IgA levels were analysed with ELISA. Results: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to ▀-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. Conclusion: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.

  • 44.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Breastfeeding and the development of atopic disease during childhood2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 2, p. 159-161Article in journal (Refereed)
  • 45.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Nordin, EK
    Linkoping Univ, Fac Hlth Sci, Dept Hlth & Environm, Div Paediat, Linkoping, Sweden Karolinska Inst, Div Microbial Ecol, Dept Cellular & Microbial Biol, Stockholm, Sweden Ostersund Cty Hosp, Dept Paediat, Ostersund, Sweden.
    Sandin, A
    Midtvedt, T
    Linkoping Univ, Fac Hlth Sci, Dept Hlth & Environm, Div Paediat, Linkoping, Sweden Karolinska Inst, Div Microbial Ecol, Dept Cellular & Microbial Biol, Stockholm, Sweden Ostersund Cty Hosp, Dept Paediat, Ostersund, Sweden.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Microflora-associated characteristics in faeces from allergic and nonallergic infants2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, no 11, p. 1590-1596Article in journal (Refereed)
    Abstract [en]

    Background The prevalence of allergic diseases has increased particularly over the past 30-40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation. Objective The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11-18), through analysing microflora-associated biochemical markers in faeces. Methods Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically. Results The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups. Conclusion The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora. that may disturb the development of a normal Th1-/Th2-balance in allergic children.

  • 46.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Norin, EK
    Sandin, A
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Microflora associated characteristics in faeces from allergic and non-allergic infants.2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, p. 1591-1597Article in journal (Refereed)
  • 47.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Djerf, P.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Häggström, P.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ferrándiz, R.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björksten, B.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Circulating cat allergen and immune complexes in cat- allergic children1998In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 10, p. 1258-1263Article in journal (Refereed)
    Abstract [en]

    Background

    The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

    Objective

    To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

    Methods

    Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

    Results

    Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

    Conclusion

    Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

  • 48.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood2004In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, p. 591-596Article in journal (Refereed)
    Abstract [en]

    Background We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero.

    Objective To relate the presence of Fel d 1–IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen.

    Methods CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1–IgG IC.

    Results The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-γ by CBMC was not influenced by maternal atopy, but IFN-γ was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC.

    Conclusion Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-γ seems to be related with the presence of IC in cord blood.

  • 49.
    Cederbrant, Karin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Marcusson-Ståhl, M.
    AstraZeneca R & D Södertälje, Safety Assessment, Department of Molecular Toxicology and Immunotoxicology, Södertälje, Sweden.
    Hultman, Per
    Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, no 10, p. 1450-1459Article in journal (Refereed)
    Abstract [en]

    Background

    Antigen-specific cell lines or clones are often used as models of drug-specific allergy. However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems.

    Objective

    Using bacampicillin-allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy. The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed.

    Methods

    A total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included. Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls. All subjects were LTT tested. Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR-Vβ repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures.

    Results

    LTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms. 69% of the patients with type I allergies were patch test-positive. Results from LTT and skin test correlated in 87% of the cases. The combined sensitivity of LTT and skin tests was 92%. The specificity of LTT was 90% in healthy controls. Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients. The TCR-Vβ profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vβ2, Vβ3, Vβ5.1 and/or Vβ14. An increased expression of IFNγ was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients. IL-5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls. This Th2 environment could also be verified by CD23 and CD134 expression.

    Conclusion

    LTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects. When the two tests are combined, the sensitivity increases. The patch test is useful not only for detection of type IV but also for the identification of type I allergies. When using primary PBMC cultures, IFNγ is the most suitable cytokine to discriminate between type I and type IV allergy. IL-5 can possibly be used as a general marker for bacampicillin induced allergy. Thus, primary cell cultures may be considered as an alternative to T-cell lines or clones for the study of drug induced allergy.

  • 50.
    Courbis, Anne-Lise
    et al.
    Univ Montpellier, IMT Mines Ales, LGI2P, Ales, France.
    Murray, Ruth Brigid
    Medscript NZ Ltd, Dept Allerg Dis, Kapiti Coast, New Zealand.
    Arnavielhe, Sylvie
    Kyomed, Montpellier, France.
    Caimmi, Davide
    Montpellier Univ Hosp, Dept Resp Dis, Montpellier, France.
    Bedbrook, Anna
    Contre Malad Chron Vleillissement Actif France Eu, Montpellier, France.
    Van Eerd, Michiel
    Peercode BV, Geldermalsen, Netherlands.
    De Vries, Govert
    Peercode BV, Geldermalsen, Netherlands.
    Dray, Gerard
    Univ Montpellier, IMT Mines Ales, LGI2P, Ales, France.
    Agache, Ioana
    Transylvania Univ Brasov, Brasov, Romania.
    Morais-Almeida, Mario
    CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal.
    Bachert, Claus
    Ghent Univ Hosp, Upper Airways Res Lab, ENT Dept, Ghent, Belgium.
    Bergmann, Karl Christian
    Charite Univ Med Berlin, Dept Dermatol & Allergy, Allergy Ctr Charite, Berlin, Germany.
    Bosnic-Anticevich, Sinthia
    Univ Sydney, Woolcock Inst Med Res, Glebe, NSW, Australia;Sydney Local Hlth Dist, Glebe, NSW, Australia.
    Brozek, Jan
    McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
    Bucca, Caterina
    Univ Pneumol Unit AOU Molinette, Hosp City Hlth & Sci Torino, Turin, Italy.
    Camargos, Paulo
    Univ Fed Minas Gerais, Med Sch, Dept Pediat, Belo Horizonte, MG, Brazil.
    Canonica, Giorgio Walter
    Humanitas Univ & Res Hosp, Personalized Med Asthma & Allergy Clin, Milan, Italy.
    Carr, Warner
    Allergy & Asthma Associates Southern Calif, Mission Viejo, CA USA.
    Casale, Thomas
    Univ S Florida, Morsani Coll Med, Div Allergy & Immunol, Tampa, FL USA.
    Fonseca, Joao A.
    Univ Porto, Fac Med, CINTESIS, Porto, Portugal;LDA, MEDIDA, Porto, Portugal.
    Haahtela, Tari
    Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland.
    Kalayci, Omer
    Hacettepe Univ, Sch Med, Dept Pediat Allergy, Ankara, Turkey.
    Klimek, Ludger
    Ctr Rhinol & Allergol, Wiesbaden, Germany.
    Kuna, Piotr
    Med Univ Lodz, Barlicki Univ Hosp, Lodz, Poland.
    Kvedariene, Violeta
    Vilnius Univ, Inst Biomed Sci, Clin Infect Chest Dis Dermatol & Allergol, Dept Pathol,Fac Med, Vilnius, Lithuania.
    Larenas Linnemann, Desiree
    Hosp Med Sur, Clin Alergia Asma & Pediat, Mexico City, DF, Mexico.
    Lieberman, Phil
    Univ Tennessee, Coll Med, Dept Internal Med & Pediat, Div Allergy & Immunol, Germantown, TN USA.
    Mullol, Joaquim
    Univ Barcelona, Hosp Clin Clin & Expt Resp Immunoallergy, ENT Dept, IDIBAPS,CIBERES, Barcelona, Spain.
    Ohehir, Robyn
    Monash Univ, Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia;Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia.
    Papadopoulos, Nikolaos
    Univ Manchester, Div Infect Immun & Resp Med, Manchester, Lancs, England;Univ Athens, Pediat Clin 2, Allergy Dept, Athens, Greece.
    Price, David
    Observat & Pragmat Res Inst, Singapore, Singapore.
    Ryan, Dermot
    Univ Edinburgh, Med Sch, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Samolinski, Boleslaw
    Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland.
    Simons, F. Estelle
    Univ Manitoba, Fac Med, Dept Immunol, Dept Pediat & Child Hlth, Winnipeg, MB, Canada.
    Tomazic, Peter
    Med Univ Graz, Dept ENT, Graz, Austria.
    Triggiani, Massimo
    Univ Salerno, Div Allergy & Clin Immunol, Salerno, Italy.
    Valiulis, Arunas
    Vilnius Univ, Inst Clin Med Dis, Clin Childrens Dis, Dept Publ Hlth,Inst Hlth Sci,Fac Med, Vilnius, Lithuania.
    Valovirta, Erkka
    Univ Turku, Dept Lung Dis & Clin Allergol, Turku, Finland;Terveystalo, Allergy Clin, Turku, Finland.
    Wagenmann, Martin
    Univ Klinikum Dusseldorf, HNO Klin, Dept Otorhinolaryngol, Dusseldorf, Germany.
    Wickman, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Yorgancioglu, Arzu
    Celal Bayar Univ, Fac Med, Dept Pulmonol, Manisa, Turkey.
    Bousquet, Jean
    Contre Malad Chron Vleillissement Actif France Eu, Montpellier, France;VIMA Ageing & Chron Dis Epidemiol & Publ Hlth App, INSERM, U 1168, Villejuif, France;Univ Versailles St Quentin en Yvelines, UMRS 1168, Montigny Le Bretonneux, France;CHU Montpellier, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France.
    Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 12, p. 1640-1653Article in journal (Refereed)
    Abstract [en]

    Background: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management.

    Objective: To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion.

    Methods: The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios; (b) expert consensus on treatment recommendations; (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios; (d) digitization of these algorithms to form the e-CDSS; and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing.

    Results: Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations.

    Conclusion: The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32].

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