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  • 51.
    Fagerås Böttcher, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Hmani-Aifa, Mounira
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Lindström Lundberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria Christina
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Mai, Xiao-Mei
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    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.
    Aniansson Zdolsek, Helena
    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.
    Björkstén, Bengt
    Centre for Allergy Research and Institute of Environmental Medicine, Karolinska Institute, Stockholm;.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children2004In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 114, no 3, p. 561-567Article in journal (Refereed)
    Abstract [en]

    Background

    Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases.

    Objective

    The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children.

    Methods

    The TLR4 (Asp299Gly) and CD14/−159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-γ responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden).

    Results

    Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis.

    Conclusion

    A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.

  • 52.
    Forsberg, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Bengtsson, Mathias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Eringfält, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Mjösberg, Jenny
    Department of Medicine, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Letter: GATA binding protein 3(+) group 2 innate lymphoid cells are present in cord blood and in higher proportions in male than in female neonates.2014In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 134, no 1, p. 228-230Article in journal (Refereed)
  • 53. Gaber, Flora
    et al.
    James, Anna
    Delin, Ingrid
    Wetterholm, Anders
    Sampson, Anthony P
    Dahlén, Barbro
    Dahlén, Sven-Erik
    Kumlin, Maria
    Sophiahemmet University.
    Assessment of in vivo 5-lipoxygenase activity by analysis of leukotriene B4 in saliva: effects of treatment with zileuton2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, p. 1267-8Article in journal (Other academic)
  • 54. Gendrin, Claire
    et al.
    Shubin, Nicholas J
    Boldenow, Erica
    Merillat, Sean
    Clauson, Morgan
    Power, Danial
    Doran, Kelly S
    Abrink, Magnus
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Department of Anatomy, Physiology and Biochemistry, the Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Rajagopal, Lakshmi
    Piliponsky, Adrian M
    Mast cell chymase decreases the severity of group B Streptococcus infections2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 142, no 1, p. 120-129Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Group B Streptococcus (GBS) or Streptococcus agalactiae are β-hemolytic gram-positive bacteria that colonize the lower genital tracts of women and are frequently associated with infections during pregnancy. Innate immune defenses are critical for controlling GBS dissemination and systemic infection. Mast cells are resident sentinel cells that come into contact with pathogens early during colonization and infection.

    OBJECTIVE: We aimed to investigate the contribution of chymase to systemic GBS infection and rates of preterm birth.

    METHODS: Pharmacologic and genetic approaches using mice deficient in mast cell protease (MCPT) 4, the mouse functional homologue of human chymase, were used.

    RESULTS: Our studies show that mast cells release a protease with chymotrypsin-like cleavage specificity in response to GBS. Additionally, increased GBS systemic infection and preterm births were observed in MCPT4-deficient mice versus MCPT4-sufficient mice. Furthermore, we observed that proteolytic cleavage of the host extracellular matrix protein fibronectin by peritoneal cell-derived mast cell lysates diminished GBS adherence. Consistent with this observation, the increase in GBS dissemination and preterm births observed in MCPT4-deficient mice was abolished when GBS was deficient in expression of the fibronectin-binding protein SfbA.

    CONCLUSIONS: Taken together, our results suggest that the protective effect of MCPT4 against GBS dissemination and preterm labor can be attributed in part to MCPT4-mediated proteolysis of fibronectin. Our studies reveal a novel role of mast cells in defense against bacterial infections.

  • 55.
    Guerrerio, Pamela A.
    et al.
    NIAID, LAD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Rasooly, Marjohn
    NIAID, LAD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Gu, Wenjuan
    Leidos Biomed Res Inc, bClin Res Directorate, Clin Monitoring Res Program, NCI Campus, Frederick, MD USA.
    Levin, Samara
    NIAID, LAD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Jhamnani, Rekha
    NIAID, LAD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Milner, Joshua D.
    NIAID, LAD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Stone, Kelly D.
    NIAID, NIH, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Guerrerio, Anthony L.
    Johns Hopkins Univ, Baltimore, MD USA.
    Jones, Joseph
    Phadia US Inc, dImmuno Diagnost Branch, Thermo Fisher Sci, Portage, MI USA.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research. ThermoFisher Sci, Uppsala, Sweden.
    Brittain, Erica
    NIH, Biostat Res Branch, DCR, Bldg 10, Bethesda, MD 20892 USA.
    IgE Testing Can Predict Food Allergy Status in Patients with Moderate-Severe Atopic Dermatitis2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 2, p. AB130-AB130, article id 392Article in journal (Other academic)
  • 56. Gyllfors, Pär
    et al.
    Dahlén, Sven-Erik
    Kumlin, Maria
    Sophiahemmet University.
    Larsson, Kjell
    Dahlén, Barbro
    Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate2006In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 118, no 1, p. 78-83Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved. OBJECTIVE: We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma. METHODS: In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis. RESULTS: Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations. CONCLUSION: These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids. CLINICAL IMPLICATIONS: The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.

  • 57. Gómez Real, Francisco
    et al.
    Svanes, Cecilie
    Omenaas, Ernst Reidar
    Antó, Josep Maria
    Plana, Estel
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Jarvis, Deborah
    Zemp, Elisabeth
    Wjst, Matthias
    Leynaert, B
    Sunyer, Jordi
    Menstrual irregularity and asthma and lung function2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 120, no 3, p. 557-564Article in journal (Refereed)
    Abstract [en]

    Background: Oligomenorrhea was associated with more asthma (Respiratory Health in Northern Europe study), but a possible association with lung function has not been investigated previously. Objective: To investigate whether oligomenorrhea was related to lung function and asthma, and whether body mass index and physical activity modified associations. Methods: Women age 28 to 44 years (n = 1631) participating in the European Community Respiratory Health Survey were included. Women who were taking exogenous sex hormones, were pregnant, or had recently given birth were excluded. Results: Long or irregular menstrual cycles were reported by 313 women (19%). Oligomenorrhea was significantly associated with more asthma symptoms (odds ratio [OR], 1.76; 95% CI, 1.29-2.40), allergic asthma (OR, 2.46; 95% CI, 1.43-4.23), and lower forced vital capacity (FVC; adjusted difference, 63 mL; 95% CI, -124 to -1). When excluding women using asthma medication, very lean women, or women exercising daily, these associations remained significant. Effects of oligomenorrhea were additive to those of body mass index (BMI) on asthma and FVC. Asthma symptoms increased significantly with BMI. FVC and FEV1 increased with BMI until 25 kg/m2 and thereafter decreased with increasing BMI. Excluding women exercising daily, asthma symptoms increased significantly with decreasing physical activity (OR, 1.09; 95% CI, 1.001-1.19) per category of physical activity) independently of oligomenorrhea. Among women exercising daily, oligomenorrhea predicted very high risk for asthma symptoms (OR, 12.6; 95% CI, 3.7-43). Conclusion: Women with oligomenorrhea have reduced lung function and more asthma, particularly allergic asthma, independent of BMI and physical activity. Airways pathology may have not only a hormonal but also a metabolic component. Clinical implications: Women with oligomenorrhea should be investigated with regard to asthma and lung function. Underlying metabolic disturbance should be considered in asthma.

  • 58. Hartmann, Karin
    et al.
    Escribano, Luis
    Grattan, Clive
    Brockow, Knut
    Carter, Melody C
    Alvarez-Twose, Ivan
    Matito, Almudena
    Broesby-Olsen, Sigurd
    Siebenhaar, Frank
    Lange, Magdalena
    Niedoszytko, Marek
    Castells, Mariana
    Oude Elberink, Joanna N G
    Bonadonna, Patrizia
    Zanotti, Roberta
    Hornick, Jason L
    Torrelo, Antonio
    Grabbe, Jürgen
    Rabenhorst, Anja
    Nedoszytko, Boguslaw
    Butterfield, Joseph H
    Gotlib, Jason
    Reiter, Andreas
    Radia, Deepti
    Hermine, Olivier
    Sotlar, Karl
    George, Tracy I
    Kristensen, Thomas K
    Kluin-Nelemans, Hanneke C
    Yavuz, Selim
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sperr, Wolfgang R
    Schwartz, Lawrence B
    Triggiani, Massimo
    Maurer, Marcus
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Horny, Hans-Peter
    Arock, Michel
    Orfao, Alberto
    Metcalfe, Dean D
    Akin, Cem
    Valent, Peter
    Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825Article in journal (Refereed)
    Abstract [en]

    Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.

  • 59. Heinrich, Joachim
    et al.
    Bedada, Getahun Bero
    Zock, Jan-Paul
    Chinn, Susan
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Olivieri, Mario
    Svanes, Cecilie
    Ponzio, Michela
    Verlato, Giuseppe
    Villani, Simona
    Jarvis, Deborah
    Luczynska, Christina
    Cat allergen level: its determinants and relationship to specific IgE to cat across European centers2006In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 118, no 3, p. 674-681Article in journal (Refereed)
    Abstract [en]

    Background: Cat allergen level in settled house dust and its determinants in Europe are unknown.

    Objective: The aim of this study is to quantify the level of cat allergens in mattress dust, to study its determinants, and to analyze the relationship with cat specific IgE on community level across European centers.

    Methods: Trained field workers collected dust from approximately 3000 mattresses during home visits in 22 European Community Respiratory Health Survey II centers. Sieved dust extracts were assayed for cat allergen using a mAb ELISA assay.

    Results: The overall geometric mean cat allergen was 0.94 mu g/g, ranging from 0.12 mu g/g in Huelva, Spain, to 3.76 mu g/g in Antwerp, Belgium. Current cat owners' homes showed substantially higher levels than past cat owners' and never cat owners' homes (geometric mean and 95% CI, 61.4 mu g/g [48.4-77.9] vs 1.37 mu g/g [0.97-1.9] vs 0.29 mu g/g [0.27-0.31]x). Community prevalence of cat ownership was moderately correlated with cat allergen levels in noncat owners (r(s) = 0.50), but not for past or current cat owners. The multilevel model identified community prevalence of cat keeping as the only statistically significant determinant of mattress cat allergen levels for noncat owners. However, averaged cat allergen levels per center were not related to community prevalence of detectable specific IgE to cat.

    Conclusion: Not having a cat in the home is associated with substantially lower Fel d 1 concentration, but does not protect against high Fel d 1 exposure in communities where cat ownership is common.

    Clinical implications: People (including patients with cat allergy) who do not own cats may be exposed to high levels of cat allergen in their home, particularly if they live in communities with high levels of cat ownership.

  • 60.
    Hellberg, Sandra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Forsberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Winqvist, Ola
    Karolinska Inst, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Maintained thymic output of conventional and regulatory T cells during human pregnancy2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 2, p. 771-775.e7Article in journal (Other academic)
    Abstract [en]

    n/a

  • 61.
    Henmyr, Viktor
    et al.
    Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Forskningsmiljön Biomedicin.
    Vandeplas, Griet
    University Hospital Ghent.
    Halldén, Christer
    Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Forskningsmiljön Biomedicin.
    Säll, Torbjörn
    Lund University.
    Olze, Heidi
    Charité Berlin.
    Bachert, Claus
    Karolinska Institutet.
    Cardell, Lars Olaf
    Karolinska Institutet.
    Replication study of genetic variants associated with chronic rhinosinusitis and nasal polyposis2014In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 133, no 1, p. 273-275Article in journal (Refereed)
  • 62.
    Hohlfeld, Jens M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schmiedl, Andreas
    Erpenbeck, Veit J.
    Venge, Per
    Krug, Norbert
    Eosinophil cationic protein alters pulmonary surfactant structure and function in asthma2004In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 113, no 3, p. 496-502Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Impaired surfactant function has been demonstrated in patients with asthma. Inhibitory proteins originating from plasma or inflammatory mediators are good candidates to contribute to this dysfunction. Eosinophils are potent effector cells in asthma, which, on activation, release inflammatory mediators, especially reactive granula proteins such as eosinophil cationic protein (ECP).

    OBJECTIVE: Because the potential role of ECP in the inhibition of surfactant function is not known, we tested the hypothesis of whether ECP levels in bronchoalveolar lavage fluid (BALF) of patients with asthma after segmental allergen provocation correlate to surfactant dysfunction. Furthermore, we tested the effect of purified ECP on surfactant function and structure in vitro.

    METHODS: Surfactant isolated from BALF of asthmatic patients was assessed for biophysical function with the Pulsating Bubble Surfactometer and the Capillary Surfactometer and correlated to ECP levels. Purified ECP and plasma proteins at various concentrations were incubated with natural surfactant. Surfactant function was studied with the Capillary Surfactometer, and surfactant structure was determined by electron microscopy.

    RESULTS: ECP is elevated in BALF from patients with asthma after allergen challenge compared with baseline. ECP levels after allergen challenge correlate well to surfactant dysfunction. In vitro, ECP induces a concentration-dependent inhibition of surfactant function that can be inhibited by antibodies against ECP. ECP is more potent compared with albumin or fibrinogen. Finally, ECP induces severe ultrastructural changes to surfactant vesicles that are more pronounced than changes induced by either fibrinogen or albumin.

    CONCLUSIONS: ECP contributes to surfactant dysfunction in asthma, which in turn could lead to airway obstruction.

  • 63.
    Håkansson, L
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stålenheim, G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Migratory responses of eosinophil and neutrophil granulocytes from patients with asthma1990In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 85, no 4, p. 743-750Article in journal (Refereed)
    Abstract [en]

    In the present study the migratory function of eosinophil and neutrophil granulocytes from patients with asthma were investigated. Fifty-seven patients with asthmatic disease of varying severity were included. Eosinophil and neutrophil chemotactic responses to 5% pooled normal human serum (NHS), 5% allergen-challenge serum, 2.5% zymosan-activated serum, N-formyl-methionyl-leucyl-phenylalanine (10 nmol/L), chemokinetic responses to albumin (2 gm/L) and 5% NHS, and the eosinophil and neutrophil chemotactic and chemokinetic activities of serum were investigated. Eosinophils from patients with asthma demonstrated significantly (p less than 0.02) increased chemotactic responses to allergen-challenge serum, zymosan-activated serum, and N-formyl-methionyl-leucyl-phenylalanine, compared with eosinophils from references. The chemokinetic responses to albumin and NHS were increased (p less than 0.01) by eosinophils from the patients who had blood eosinophilia (greater than 400 X 10(6)/L). Sera from the patients with asthma demonstrated raised eosinophil chemotactic activity (p less than 0.001) and raised eosinophil and neutrophil chemokinetic activity (p less than 0.001). The eosinophil chemokinetic activity of serum was correlated to the relative peak expiratory flow rate of the patients (r = -0.43; p less than 0.02). The increased migratory responses were specific for the eosinophils, since the migratory responses of their neutrophils were not altered compared with that of the references. These results suggest that the eosinophils from the patients with asthma had been exposed to a priming mechanism in vivo.

  • 64.
    Håkansson, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Heinrich, Christina
    Rak, Sabina
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Priming of eosinophil adhesion in patients with birch pollen allergy during pollen season: effect of immunotherapy1997In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 99, no 4, p. 551-562Article in journal (Refereed)
    Abstract [en]

    The adhesion of eosinophil granulocytes to E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was investigated before and during birch pollen season in 24 patients allergic to birch pollen who had rhinoconjunctivitis and, in half of the cases, asthma during season. Half of the patients were undergoing specific immunotherapy for birch pollen allergy. Increased adhesion to VCAM-1 and ICAM-1 (p < 0.05) during season as compared with before season was demonstrated by eosinophils of patients in the control group and by eosinophils of the patients without asthma treated with immunotherapy, but not by eosinophils from the immunotherapy-treated patients with asthma. Eosinophils from the control group of patients demonstrated increased cell surface expression of CD18 and CD49d (p < 0.05 and p < 0.01, respectively) during season as compared with before season, and eosinophils from the immunotherapy-treated patients showed increased cell surface expression of CD49d (p < 0.01) during season. Simultaneous measurement of neutrophil adhesion revealed increased adhesion to E-selectin and ICAM-1 (p < 0.01) during season compared with before season in the immunotherapy-treated group of patients. Neutrophils from the control subjects without asthma showed increased adhesion to E-selectin (p < 0.05) during season. In conclusion, eosinophils from patients allergic to birch pollen demonstrated priming of the adhesion to VCAM-1 to ICAM-1 during birch pollen season. Immunotherapy treatment prevented the priming of eosinophil adhesion during pollen season in the patients allergic to birch pollen who had asthma, but not in those without asthma. In contrast, neutrophils from the immunotherapy-treated patients, both with and without asthma, demonstrated priming of the adhesion to E-selectin and ICAM-1 during season. The latter results indicate that immunotherapy, in case of the patients allergic to birch pollen with asthma induced a shift from the production of primarily eosinophil priming agents to primarily neutrophil priming agents, which may be caused by a shift from Th2 to Th1 lymphocytes.

  • 65.
    Ingelsson, Erik
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Yin, Li
    Bäck, Magnus
    Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 3, p. 702-707.e2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The leukotriene pathway has been associated with an increased cardiovascular risk. However, the effects of the antileukotriene treatment used in asthmatic patients on cardiovascular outcomes have remained largely unexplored.

    OBJECTIVE: We sought to examine a potential protective role of the leukotriene receptor antagonist montelukast on future risk of incident and recurrent myocardial infarction and ischemic stroke.

    METHODS: A nationwide population-based cohort of approximately 7 million persons integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational, and Emigration Registers was followed from July 1, 2005, to December 31, 2008. Analyses were performed in the whole population after exclusion of subjects with a prior cardiovascular diagnosis (incident events; sample size, n = 6,910,923 for myocardial infarction and n = 6,932,578 for stroke) and in subjects with a prior diagnosis (recurrent events; n = 153,937 and n = 132,291 for stroke and myocardial infarction, respectively).

    RESULTS: Cox proportional hazard ratios (HRs) did not reveal an association of montelukast use with incident events. In contrast to these findings, montelukast use was associated with a lower risk for recurrent stroke (HR, 0.62; 95% CI, 0.38-0.99) accounting for age, sex, education level, and yearly income. Adjusting the latter finding also for respiratory and cardiovascular medications and diagnoses revealed similar point estimates (HR, 0.62; 95% CI, 0.39-1.0). Post hoc analyses revealed a significant association of montelukast use with a lower risk for recurrent myocardial infarction in male subjects (HR, 0.65; 95% CI, 0.43-0.99).

    CONCLUSION: These data provide a first indication for a potential role of the antiasthma drug montelukast for secondary prevention of cardiovascular disease.

  • 66. Ito, Komei
    et al.
    Sjölander, Sigrid
    Sato, Sakura
    Movérare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Tanaka, Akira
    Soderstrom, Lars
    Borres, Magnus
    Poorafshar, Maryam
    Ebisawa, Motohiro
    IgE to Gly m 5 and Gly m 6 is associated with severe allergic reactions to soybean in Japanese children2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 3, p. 673-675Article in journal (Refereed)
  • 67. James, Hayley R
    et al.
    Perzanowski, Matthew S.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bjerg, Anders
    Schuyler, Alexander J
    Workman, Lisa J
    Lundback, Bo
    Platts-Mills, Thomas A E
    IgE Antibodies to Mammalian Allergens Are a Major Risk Factor for Prevalence, Severity, and Persistence of Asthma in Northern Sweden2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 2, p. AB22-AB22Article in journal (Other academic)
    Abstract [en]

    IgE to mammalian allergens can contribute significantly to asthma risk. Studying the details of the relationship between animal sensitization and asthma is simpler in an environment where mite, fungal, and cockroach allergens make little or no contribution to asthma risk. Methods: Quantitative assays for IgE to eight allergens were carried out on 963 sera from 19-year-olds in a population-based cohort in northern Sweden, and associations with questionnaire data from ages 7, 12, and 19 on asthma symptoms, diagnosis, and treatment were tested. Results: Overall, 79 (53%) of the students with a physician diagnosis of asthma were positive to one or more of the mammalian allergens (cat, dog, or horse danders) tested. Of the allergens assessed, only mammalian allergens, birch, and timothy grass pollen showed a significant relationship with asthma diagnosis. Multivariate analysis showed that high titer (>17.5 IU/ml) IgE to any mammalian allergen had the strongest relationship with asthma at age 19 (odds ratio 5.1 [3.0-8.6]). Furthermore, IgE to mammalian allergens gave an odds ratio of 8.5 [4.9-15] for asthma that started before age 12 and was still present at age 19. Sensitization to Fel d 1 and Fel d 4 was strongly associated with asthma and significantly reduced in cat owners. Conclusions: Sensitization to cat and dog related allergens, and specifically to the components Fel d 1 and Fel d 4, is a major risk factor for the persistence and severity of asthma in an area where these are the only significant perennial allergens.

  • 68.
    Janson, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Asbjornsdottir, Hulda
    Birgisdottir, Alda
    Sigurjonsdottir, R B
    Gunnbjörnsdottir, María
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gislason, D
    Olafsson, Isleifur
    Cook, E
    Jögi, Rain
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gislason, Thorarinn
    Thjodleifsson, Bjarni
    The effect of infectious burden on the prevalence of atopy and respiratory allergies in Iceland, Estonia, and Sweden2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 120, no 3, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiologic reports on the effect of microbe exposure on the development of atopy and allergic asthma are inconsistent. Objectives: The study investigates the association between serologic markers of infections and occurrence of atopy, allergic asthma, and rhinitis among adults in Iceland, Sweden, and Estonia. Methods: Individuals (n = 1249; mean age, 42 years) from Iceland, Sweden, and Estonia underwent a structured interview and blood sampling. Specific IgE was measured against 4 allergens, and IgG antibodies were measured against Helicobacter pylori, Toxoplasmosis gondii, hepatitis A virus, herpes simplex virus 1, Chlamydia pneumoniae, EBV, and cytomegalovirus. Results: Nonatopic subjects more often had positive serology for Helicobacter pylori, herpes simplex virus 1, Chlamydia pneumoniae, and cytomegalovirus. Having a low number (≤3) of IgG antibodies against the various infectious agents was an independent risk factor for atopy (odds ratio [OR], 1.43; 95% CI, 1.06-1.93), allergic asthma (OR, 1.82; 95% CI, 1.12-2.98), and allergic rhinitis (OR, 1.69; 95% CI, 1.21-2.37). The proportion of atopy that can be explained by a lower number (≤3) of infections was 6.7% in Iceland, 9.2% in Estonia, and 16.4% in Sweden, and 6.7%, 48.2%, and 33.4% for allergic asthma, respectively. Conclusion: Our data are consistent with cumulative protective effect of infections against atopy and respiratory allergies irrespective of route of infection. Clinical implications: The study indicates what microbes or combination of microbes play a role in the complex interplay between hygiene and allergy and may contribute toward the understanding of the allergy epidemic.Background: Epidemiologic reports on the effect of microbe exposure on the development of atopy and allergic asthma are inconsistent. Objectives: The study investigates the association between serologic markers of infections and occurrence of atopy, allergic asthma, and rhinitis among adults in Iceland, Sweden, and Estonia. Methods: Individuals (n = 1249; mean age, 42 years) from Iceland, Sweden, and Estonia underwent a structured interview and blood sampling. Specific IgE was measured against 4 allergens, and IgG antibodies were measured against Helicobacter pylori, Toxoplasmosis gondii, hepatitis A virus, herpes simplex virus 1, Chlamydia pneumoniae, EBV, and cytomegalovirus. Results: Nonatopic subjects more often had positive serology for Helicobacter pylori, herpes simplex virus 1, Chlamydia pneumoniae, and cytomegalovirus. Having a low number (≤3) of IgG antibodies against the various infectious agents was an independent risk factor for atopy (odds ratio [OR], 1.43; 95% CI, 1.06-1.93), allergic asthma (OR, 1.82; 95% CI, 1.12-2.98), and allergic rhinitis (OR, 1.69; 95% CI, 1.21-2.37). The proportion of atopy that can be explained by a lower number (≤3) of infections was 6.7% in Iceland, 9.2% in Estonia, and 16.4% in Sweden, and 6.7%, 48.2%, and 33.4% for allergic asthma, respectively. Conclusion: Our data are consistent with cumulative protective effect of infections against atopy and respiratory allergies irrespective of route of infection. Clinical implications: The study indicates what microbes or combination of microbes play a role in the complex interplay between hygiene and allergy and may contribute toward the understanding of the allergy epidemic.

  • 69. Jarvis, Deborah
    et al.
    Zock, Jan-Paul
    Heinrich, Joachim
    Svanes, Cecilie
    Verlato, Giuseppe
    Olivieri, Mario
    Villani, Simona
    Ponzio, Michela
    Leynaert, Benedicte
    Sunyer, Jordi
    Dahlman-Höglund, Anna
    Chinn, Susan
    Luczynska, Christina
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Burney, Peter
    Cat and dust mite allergen levels, specific IgG and IgG4, and respiratory symptoms in adults2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 3, p. 697-704Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to allergen may induce a modified TH2 response characterized by high IgG4 levels, absence of IgE sensitization, and a decreased risk of allergic respiratory symptoms. Objective: To assess the association of IgG4 level with allergic respiratory symptoms in a community-based sample of adults. Methods: Information on exposure to cats, respiratory symptoms, and mattress allergen levels was obtained from 2780 adults. Levels of cat and house dust mite (HDM) specific IgE, IgG, and IgG4 were measured. The association of exposure to allergen with IgG4 and of IgG4 with symptoms was assessed. Results: Geometric mean (GM) cat specific IgG and IgG4 was higher in subjects who had a cat that was allowed in the bedroom than in subjects without a cat (adjusted ratio of GM IgG4, 1.41; 95% CI, 1.25-1.57). Levels of HDM specific IgG and IgG4 were similar in subjects with undetectable and high (>20.22 μg/g) mattress Der 1 levels (adjusted ratio of GM IgG4, 1.02; 95% CI, 0.89-1.17). There was no evidence that high cat or HDM specific IgG4 levels were associated with less IgE sensitization or with fewer symptoms. Conclusion: In this community-based sample of adults, high IgG4 levels to cat or HDM were not associated with a lower risk of allergic respiratory symptoms. Clinical implications: In adults, high cat allergen exposure does not protect against respiratory symptoms.

  • 70.
    Jenmalm, Maria
    et al.
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Exposure to cow's milk during the first 3 months of life is associated with increased levels of IgG subclass antibodies to beta-lactoglobulin to 8 years1998In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 102, p. 671-678Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Exposure to allergens early in life influences the development of allergen-specific immune responses. In animal models, the development of tolerance to proteins delivered to the gastrointestinal and the respiratory mucosa is influenced by age and genetic background. Late introduction of cow's milk in infants is associated with slower increase and lower peak IgG antibody responses to milk during early childhood, but the long-term effects have not been investigated, nor is the relation to atopic disease later in life clear.

    OBJECTIVE:

    The purpose of this study was to investigate the development of IgG subclass antibodies to beta-lactoglobulin in relation to early exposure to cow's milk, atopic heredity, and the development of atopic disease.

    METHODS:

    IgG subclass antibodies to beta-lactoglobulin were analyzed by ELISA at birth, at 6 and 18 months, and at 8 years in 96 children followed prospectively.

    RESULTS:

    The levels of IgG subclass antibodies to beta-lactoglobulin peaked in early childhood and then declined up to 8 years of age. Exposure to cow's milk during the first 3 months of life was associated with high IgG subclass antibody levels to beta-lactoglobulin up to 8 years, particularly in children with maternal atopy. Children with atopic symptoms and sensitivity to allergens often had high levels of IgG4 antibodies to beta-lactoglobulin at 8 years of age, even if they were not exposed to cow's milk during the first 3 months of life. Furthermore, atopic dermatitis was associated with high levels of IgG subclass antibodies to beta-lactoglobulin in early childhood.

    CONCLUSIONS:

    IgG subclass antibody levels to milk peak during early infancy, with particularly high levels in children with atopic dermatitis, and decline thereafter. Exposure to cow's milk during early infancy has long-lasting effects on the humoral antigen-specific responses, indicating less effective tolerance-inducing mechanisms in the intestinal mucosa during the first months of life.

  • 71.
    Jenmalm, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Macaubas, C
    Fac Hlth Sci, Div Paediat, Linkoping, Sweden TVW Telethon Inst Child Hlth Res, Perth, WA, Australia.
    Holt, P
    Holt, B
    Smallacombe, T
    Fac Hlth Sci, Div Paediat, Linkoping, Sweden TVW Telethon Inst Child Hlth Res, Perth, WA, Australia.
    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.
    Allergen induced cytokine responses at birth in relation to development of atopic disease and sensitisation2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, no 1, p. 329-Conference paper (Other academic)
  • 72. Jevnikar, Zala
    et al.
    Ostling, Jorgen
    Calven, Jenny
    Thorn, Kristofer
    Israelsson, Elisabeth
    Oberg, Lisa
    Singhania, Akul
    Lau, Laurie C. K.
    Wilson, Susan J.
    Ward, Jonathan A.
    Chauhan, Anoop
    Sousa, Ana R.
    De Meulder, Bertrand
    Loza, Matthew J.
    Baribaud, Frederic
    Sterk, Peter J.
    Chung, Kian Fan
    Sun, Kai
    Guo, Yike
    Adcock, Ian M.
    Payne, Debbie
    Dahlen, Barbro
    Chanez, Pascal
    Shaw, Dominick E.
    Krug, Norbert
    Hohlfeld, Jens M.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Djukanovic, Ratko
    James, Anna
    Hinks, Timothy S. C.
    Howarth, Peter H.
    Vaarala, Outi
    van Geest, Marleen
    Olsson, Henric
    Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 2, p. 577-590Article in journal (Refereed)
    Abstract [en]

    Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear.

    Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients.

    Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens.

    Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta.

    Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.

  • 73. Konradsen, Jon R
    et al.
    Fujisawa, Takao
    van Hage, Marianne
    Hedlin, Gunilla
    Hilger, Christiane
    Kleine-Tebbe, Jörg
    Matsui, Elizabeth C
    Roberts, Graham
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Platts-Mills, Tom
    Allergy to furry animals: new insights, diagnostic approaches, and challenges2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 3, p. 616-625Article in journal (Refereed)
    Abstract [en]

    The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.

  • 74.
    Konradsen, Jon R.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Nordlund, Bjorn
    Karolinska Inst, Bromma, Sweden..
    Ohrmalm, Lars
    Karolinska Inst, Stockholm, Sweden..
    Broliden, Kristina
    Karolinska Inst, Stockholm, Sweden..
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Hedlin, Gunilla
    Karolinska Inst, Stockholm, Sweden..
    Microbiological findings in children with severe asthma2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 141, no 2, p. AB99-AB99Article in journal (Other academic)
  • 75. Konradsen, Jon R.
    et al.
    van Hage, Marianne
    Hedlin, Gunilla
    Hilger, Christiane
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Platts-Mills, Tom
    The risk of sensitization to furry animals in patients already sensitized to cat/dog: An in vitro evaluation using molecular-based allergy diagnostics Reply2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 6, p. 1666-1667Article in journal (Refereed)
  • 76.
    Konya, Viktoria
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Czarnewski, Paulo
    Sci Life Lab, Sweden.
    Forkel, Marianne
    Karolinska Inst, Sweden.
    Rao, Anna
    Karolinska Inst, Sweden.
    Kokkinou, Efthymia
    Karolinska Inst, Sweden.
    Villablanca, Eduardo J.
    Sci Life Lab, Sweden.
    Almer, Sven
    Karolinska Univ Hosp, Sweden.
    Lindforss, Ulrik
    Karolinska Univ Hosp, Sweden.
    Friberg, Danielle
    Karolinska Univ Hosp, Sweden.
    Hoeoeg, Charlotte
    Karolinska Univ Hosp, Sweden.
    Bergman, Peter
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 141, no 1, p. 279-292Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident group 3 innate lymphoid cells (ILC3s) play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy. Objective: We set out to define the role of 1 alpha,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3s to IL-23 plus Il-1 beta stimulation. Methods: Transcriptomes of sorted tonsillar ILC3s were assessed by using microarray analysis. ILC3 cytokine production, proliferation, and differentiation were determined by means of flow cytometry, ELISA, and multiplex immunoassay. Intestinal cell suspensions and ILC3s sorted from gut biopsy specimens of patients with IBD were also analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection. Results: ILC3s stimulated with IL-23 plus IL-1 beta upregulated the vitamin D receptor and responded to 1,25D with downregulation of the IL-23 receptor pathway. Consequently, 1,25D suppressed IL-22, IL-17F, and GM-CSF production from tonsillar and gut ILC3s. In parallel, 1,25D upregulated genes linked to the IL-1 beta signaling pathway, as well as the IL-1 beta-inducible cytokines IL-6, IL-8, and macrophage inflammatory protein IL/1 beta. The 1,25D-triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation, or phenotype. Finally, we confirmed low 25D plasma levels in patients with IBD with active inflammation. Conclusion: In light of the beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.

  • 77.
    Käck, Ulrika
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, S1,Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    Asarnoj, Anna
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Inst, Dept Med, Solna Immunol & Allergy Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Grönlund, Hans
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research. Thermo Fisher Sci, Uppsala, Sweden.
    van Hage, Marianne
    Karolinska Inst, Dept Med, Solna Immunol & Allergy Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Lilja, Gunnar
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, S1,Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    Konradsen, Jon R.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Inst, Dept Med, Solna Immunol & Allergy Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Molecular allergy diagnostics refine characterization of children sensitized to dog dander2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 142, no 4, p. 1113-+Article in journal (Refereed)
    Abstract [en]

    Background: Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. Objectives: We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). Methods: Sixty children (age, 10-18 years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kU(A)/L or greater was considered positive. Results: There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P = .01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), in particular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). Conclusion: Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.

  • 78.
    Käck, Ulrika
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Asarnoj, Anna
    Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Grönlund, Hans
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research. ThermoFisher Sci, Uppsala, Sweden.
    van Hage, Marianne
    Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Lilja, Gunnar
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Konradsen, Jon R.
    Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Reply to: Can f 5 as a suitable marker of dog allergy: Assess male dog exposure before banning it2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 4, p. 1658-1659Article in journal (Refereed)
  • 79. Laitinen, Lauri A.
    et al.
    Laitinen, Annika
    Altraja, Alan
    Virtanen, Ismo
    Kämpe, Mary
    Simonsson, Bo G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Sven-Erik
    Håkansson, Lena
    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.
    Sillastu, Heinart
    Bronchial biopsy findings in intermittent or "early" asthma1996In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 98, no 5 Pt 2, p. S3-6, discussion S33-40Article in journal (Refereed)
    Abstract [en]

    Bronchial biopsy specimens from subjects with intermittent or "early" asthma were compared with specimens taken from healthy subjects. Patients with early asthma included those with seasonal asthma and occupational asthma. There was a small but statistically significant increase in the thickness of the subepithelial extracellular matrix protein tenascin in subjects with seasonal and occupational asthma compared with control subjects. Collagen types IV and VII were increased only in patients with occupational asthma. Eosinophils were the only inflammatory cells that were significantly increased in subjects with seasonal asthma compared with control subjects. These data show that inflammation is present in the airways of patients with early asthma, and the increase in tenascin expression in the basement membrane zone suggests that structural changes are also initiated at an early stage of the disease.

  • 80. Lawrence, Monica G
    et al.
    Payne, Spencer
    Workman, Lisa J
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Routes, John M
    Cunningham-Rundles, Charlotte
    Platts-Mills, Thomas A E
    Borish, Larry
    Undetectable Serum IgE Is a Sensitive and Specific Marker of Common Variable Immunodeficiency (CVID)2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 2, p. AB275-AB275Article in journal (Other academic)
    Abstract [en]

    Common variable immunodeficiency (CVID) is characterized by antibody deficiency and recurrent infections as well as autoimmunity, lymphoproliferation, and hematologic malignancy. The current diagnostic criteria for CVID include reduction in serum immunoglobulin (Ig)G and either IgA or IgM and failure of antibody production. Serum IgE level is not currently considered in establishing the diagnosis of CVID. Methods: A cohort of 123 subjects from the University of Virginia Health Systems, Medical College of Wisconsin and Mount Sinai School of Medicine were diagnosed with CVID by an experienced immunologist on the basis of currently accepted diagnostic criteria, including clinical history, serum IgG, IgA and IgM, and antibody response to vaccinations. Serum IgE was measured in all of these subjects using the Phadia ImmunoCap system. Serum IgE was also measured in an unbiased control cohort of 963 healthy 17-18 year olds from northern Sweden. Results: The prevalence of undetectable (<2 IU/ml) total serum IgE in our cohort of 123 subjects with CVID was 84.6% and the prevalence of IgE <10 IU/ml was 97.6%. In comparison, IgE <2 IU/ml was found in only 3.8% of controls, in agreement with other published population estimates. Conclusions: The finding of an undetectable (<2 IU/ml) serum IgE has both a high sensitivity of 84.6% and a high specificity of 96.2% for the diagnosis of CVID. Based on this observation, measurement of serum IgE should be included as a part of the routine laboratory work-up for CVID, and an undetectable serum IgE included as a component of the diagnostic criteria.

  • 81. Lefaudeux, Diane
    et al.
    De Meulder, Bertrand
    Loza, Matthew J
    Peffer, Nancy
    Rowe, Anthony
    Baribaud, Frédéric
    Bansal, Aruna T
    Lutter, Rene
    Sousa, Ana R
    Corfield, Julie
    Pandis, Ioannis
    Bakke, Per S
    Caruso, Massimo
    Chanez, Pascal
    Dahlén, Sven-Erik
    Fleming, Louise J
    Fowler, Stephen J
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shaw, Dominic E
    Singer, Florian
    Sterk, Peter J
    Roberts, Graham
    Adcock, Ian M
    Djukanovic, Ratko
    Auffray, Charles
    Chung, Kian Fan
    U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 6, p. 1797-1807Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided.

    OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum.

    METHODS: Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data.

    RESULTS: Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels.

    CONCLUSION: Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

  • 82. Levänen, Bettina
    et al.
    Bhakta, Nirav R
    Torregrosa Paredes, Patricia
    Barbeau, Rebecca
    Hiltbrunner, Stefanie
    Pollack, Joshua L
    Sköld, C Magnus
    Svartengren, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Grunewald, Johan
    Gabrielsson, Susanne
    Eklund, Anders
    Larsson, Britt-Marie
    Woodruff, Prescott G
    Erle, David J
    Wheelock, Åsa M
    Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients.2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 3, p. 894-903Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge.

    OBJECTIVE: To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure.

    METHODS: Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling.

    RESULTS: The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q(2) = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles.

    CONCLUSION: These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.

  • 83. Lindvik, Helene
    et al.
    Mowinckel, Petter
    Navaratnam, Jesintha
    Carlsen, Karin Cecilie Lodrup
    Borres, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kvenshagen, Bente
    Carlsen, Kai Hakon
    Does Peanut Allergen Conjunctival Provocation Test Reflect Specific IgE Levels To Peanut?2014In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 133, no 2, p. AB110-AB110Article in journal (Other academic)
  • 84. Liu, X
    et al.
    Nickel, R
    Beyer, K
    Wahn, U
    Ehrilick, E
    Freidhoff, R
    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.
    Beaty, TH
    Huang, S-K
    An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German Multicenter Atopy Study (MAS-90)2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 106, no 1 I, p. 167-170Article in journal (Refereed)
    Abstract [en]

    Background: Allergic diseases are one of the major causes of morbidity in the developed countries today, and the prevalence of these diseases is increasing steadily. Study of total serum IgE level is important in understanding the genetics of allergic diseases because IgE levels are considered to be a crucial pathogenic component. IL-13 plays an important role in the induction of IgE synthesis and in the pathogenesis of allergic diseases. Objective: We sought to examine potential variation at the IL13 gene and estimate its effect on elevated IgE level and atopic dermatitis (AD). Methods: We conducted mutational analyses of the IL13 gene by using single-stranded conformation polymorphism and DNA sequencing. Case control studies for high-IgE phenotype and AD were performed by using subjects from the German MAS-90 cohort. Results: A novel IL13 coding region variant at 4257 bp (G to A, fourth exon) was identified. Case control studies of a German sample from the MAS-90 cohort showed significant associations between the presence of the A allele and two atopic phenotypes: high IgE (odds ratio, 2.38, 95% confidence interval, 1.35-4.21, P = .0026) and AD (odds ratio, 1.77, 95% confidence interval, 1.06-2.96, P = .03). Conclusion: This IL13 coding region variant may be involved in the pathogenesis of AD and high total serum IgE level in a study population of white subjects.

  • 85.
    Lowe, Adrian
    et al.
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University.
    Bråbäck, Lennart
    Ekeus, Cecilia
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Forsberg, Bertil
    Maternal obesity during pregnancy as a risk for early-life asthma2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 5, p. 1107-1109Article in journal (Refereed)
  • 86.
    Lowe, Adrian
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ekeus, Cecilia
    Hjern, Anders
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Maternal obesity during pregnancy as a risk for early-life asthma2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 5, p. 1107-1109Article in journal (Refereed)
  • 87. Lowe, Adrian J
    et al.
    Williamson, Elizabeth
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lodge, Caroline J
    Dharmage, Shyamali C
    The mediating effect of microbial colonization on the effect of cesarean section delivery2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 2, p. 584-585Article in journal (Refereed)
  • 88. Macsali, Ferenc
    et al.
    Real, Francisco Gómez
    Omenaas, Ernst Reidar
    Bjorge, Line
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Franklin, Karl
    Svanes, Cecilie
    Oral contraception, body mass index, and asthma: a cross-sectional Nordic-Baltic population survey2009In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 123, no 2, p. 391-397Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emerging evidence suggests that sex steroid hormones may influence airways obstruction, and that metabolic status may modify potential effects. OBJECTIVE: This study investigated the association between use of oral contraceptive pills (OCPs) and asthma in a Nordic-Baltic population-based study, while taking into account possible interplay with body mass index (BMI). METHODS: Postal questionnaires were sent to subjects in Denmark, Estonia, Iceland, Norway, and Sweden from 1999 to 2001 (response rate in women, 77%). Pregnant women, women using hormone replacement therapy, and women >45 years were excluded. Analyses included 5791 women 25 to 44 years old, of whom 961 (17%) used OCP. Logistic regression analyses included adjustment for smoking, irregular menstruation, BMI, age, type of dwelling, and center. RESULTS: Oral contraceptive pills were associated with increased risk for asthma (odds ratio, 1.42; 95% CI, 1.09-1.86), asthma with hay fever (1.48; 1.08-2.03), wheeze with shortness of breath (1.27; 1.02-1.60), hay fever (1.25; 1.06-1.48), and >/=3 asthma symptoms (1.29; 1.05-1.58). The findings were consistent between centers. The associations were present only among normal weight women (BMI 20-25 kg/m(2), asthma: 1.45; 1.02-2.05) and overweight women (BMI >25kg/m(2): 1.91; 1.20-3.02), but not among lean women (BMI <20 kg/m(2): 0.41; 0.12-1.40). Interaction between BMI and OCP in association with asthma was significant (P(interaction) < .05). CONCLUSIONS: Women using oral contraceptive pills had more asthma. This was found only in normal weight and overweight women, indicating interplay between sex hormones and metabolic status in effect on the airways. The findings originate from a cross-sectional postal survey and should be interpreted with caution; it is recommended that asthma symptoms are included in clinical trials of oral contraception.

  • 89. Macsali, Ferenc
    et al.
    Real, Francisco Gómez
    Omenaas, Ernst Reidar
    Bjorge, Line
    Janson, Christer
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Svanes, Cecilie
    Oral contraception, body mass index, and asthma: a cross-sectional Nordic-Baltic population survey2009In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 123, no 2, p. 391-397Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emerging evidence suggests that sex steroid hormones may influence airways obstruction, and that metabolic status may modify potential effects.

    OBJECTIVE: This study investigated the association between use of oral contraceptive pills (OCPs) and asthma in a Nordic-Baltic population-based study, while taking into account possible interplay with body mass index (BMI).

    METHODS: Postal questionnaires were sent to subjects in Denmark, Estonia, Iceland, Norway, and Sweden from 1999 to 2001 (response rate in women, 77%). Pregnant women, women using hormone replacement therapy, and women >45 years were excluded. Analyses included 5791 women 25 to 44 years old, of whom 961 (17%) used OCP. Logistic regression analyses included adjustment for smoking, irregular menstruation, BMI, age, type of dwelling, and center.

    RESULTS: Oral contraceptive pills were associated with increased risk for asthma (odds ratio, 1.42; 95% CI, 1.09-1.86), asthma with hay fever (1.48; 1.08-2.03), wheeze with shortness of breath (1.27; 1.02-1.60), hay fever (1.25; 1.06-1.48), and >/=3 asthma symptoms (1.29; 1.05-1.58). The findings were consistent between centers. The associations were present only among normal weight women (BMI 20-25 kg/m(2), asthma: 1.45; 1.02-2.05) and overweight women (BMI >25kg/m(2): 1.91; 1.20-3.02), but not among lean women (BMI <20 kg/m(2): 0.41; 0.12-1.40). Interaction between BMI and OCP in association with asthma was significant (P(interaction) < .05).

    CONCLUSIONS: Women using oral contraceptive pills had more asthma. This was found only in normal weight and overweight women, indicating interplay between sex hormones and metabolic status in effect on the airways. The findings originate from a cross-sectional postal survey and should be interpreted with caution; it is recommended that asthma symptoms are included in clinical trials of oral contraception.

  • 90.
    Magnusson, Jessica
    et al.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Ekstrom, Sandra
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Kull, Inger
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;South Gen Hosp, Sachs Childrens Hosp, Dept Pediat, Stockholm, Sweden;Karolinska Inst, Dept Educ & Clin Sci, Stockholm, Sweden.
    Håkansson, Niclas
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Nilsson, Sara
    Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Wickman, Magnus
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;South Gen Hosp, Sachs Childrens Hosp, Dept Pediat, Stockholm, Sweden.
    Melen, Erik
    Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Inst Environm Med, Stockholm, Sweden;South Gen Hosp, Sachs Childrens Hosp, Dept Pediat, Stockholm, Sweden.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Bergström, Anna
    Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Polyunsaturated fatty acids in plasma at 8 years and subsequent allergic disease2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 142, no 2, p. 510-516Article in journal (Refereed)
    Abstract [en]

    Background: Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate the risk of allergic disease. However, evidence from previous studies is inconclusive, and limited longitudinal data exist using circulating biomarkers of PUFA intake and metabolism. Objective: We aimed to investigate associations between n-3 and n-6 PUFAs at age 8 years and asthma, rhinitis, and aeroallergen sensitization at age 16 years. Methods: Proportions of n-3 PUFAs (very long-chain n-3 [VLC n-3; sum of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid] anda-linolenic acid) and n-6PUFAs (linoleic acid and arachidonic acid [AA]) in blood samples at age 8 years weremeasured for 940 children fromthe prospective Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology). Allergic disease phenotypes were defined by using questionnaires and IgE measures at the ages of 8 and 16 years. Logistic regression was used to examine potential associations. Results: A higher proportion of total VLC n-3 PUFAs in plasma at age 8 years was associated with a reduced risk of prevalent asthma, rhinitis, and aeroallergen sensitization at age 16 years and with incidence of asthma between 8 and 16 years (adjusted odds ratio, 0.67; 95% CI, 0.47-0.94). AA was associated with a reduced risk of asthma, aeroallergen sensitization, and allergic rhinitis. The findings were most evident for allergic phenotypes of asthma and rhinitis. Additionally, AA was associated with an increased probability of asthma and rhinitis remission between 8 and 16 years of age. Conclusion: Higher proportions of certain VLC n-3 and very long-chain n-6 PUFAs in plasma phospholipids at age 8 years were associated with a reduced risk of allergic disease at age 16 years.

  • 91.
    Malinovschi, Andrei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Fonseca, Joao A.
    Jacinto, Tiago
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 132, no 4, p. 821-+Article in journal (Refereed)
    Abstract [en]

    Background: Fraction of exhaled nitric oxide (FENO) and blood eosinophil count (B-Eos) values, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known about the relation of these markers to reportedwheeze and asthma events in a random population sample. Objectives: We sought to determine the individual and independent values of B-Eos and FENO in relation to wheeze, asthma diagnosis, and asthma events in a cross-sectional study. Methods: FENO and B-Eos values were measured in 12,408 subjects aged 6 to 80 years from the National Health and Nutrition Examination Survey 2007-2008 and 2009-2010. Current wheeze and asthma diagnosis, as well as asthma attacks and asthma-related emergency department (ED) visits within the last 12 months, were assessed by means of questionnaires. Results: Intermediate or high FENO values and intermediate or high B-Eos values were independently associated with having asthma, wheeze, and asthma attacks. However, only intermediate and high B-Eos values were independently associated with asthma-related ED visits. High FENO (>= 50 ppb) and B-Eos (>= 500 cells/ mm(3)) values rendered an adjusted odds ratio of 4.5 of having wheeze, 5.1 of having asthma, 5.4 for asthma attacks, and 2.9 for asthma-related ED visits compared with normal FENO (< 25 ppb) and B-Eos (< 300 cells/ mm(3)) values. Conclusions: Exhaled nitric oxide and B-Eos values offered independent information in relation to the prevalence of wheeze, asthma diagnosis, and asthma events in this random population sample. The clinical importance of these findings in asthmatic patients with regard to phenotyping and individualized treatment, considering both local and systemic eosinophilic inflammation, needs to be determined.

  • 92.
    Malinovschi, Andrei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 138, no 5, p. 1301-1308Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have previously described that fraction of exhaled nitric oxide (Feno) levels and blood eosinophil counts offer additive information in relation to asthma and asthma exacerbations when analyzing data from a large population study.

    OBJECTIVE: We sought to investigate increased Feno levels and blood eosinophil counts in relation to lung function, bronchial hyperresponsiveness (BHR), and asthma control in a cohort of young asthmatic patients.

    METHODS: Measurements of Feno levels and blood eosinophil counts were available in 406 subjects (208 women) aged 10 to 35 years. Asthma control was assessed through the Asthma Control Test. Moderate-to-severe BHR was defined as a cumulative dose of methacholine of less than 0.3 mg causing an FEV1 decrease of 20%.

    RESULTS: Subjects with simultaneously increased Feno levels (≥20-25 ppb) and blood eosinophil counts (≥0.3 × 10(9)/L) had a higher prevalence of uncontrolled asthma (Asthma Control Test score, <20) than subjects with singly increased blood eosinophil counts (40.5% vs 21.1%, P = .01). This difference remained significant (P = .006), and a significant difference was also found between subjects with both increased Feno levels and blood eosinophil counts and subjects with normal Feno levels and blood eosinophil counts (P = .02) after adjusting for confounders. Having increased Feno levels and blood eosinophil counts related to a higher prevalence of moderate-to-severe BHR than having normal Feno levels and blood eosinophil counts or singly increased Feno levels or blood eosinophil counts (85.7% vs 35.8% or 63.3% or 60%, P < .05 all comparisons).

    CONCLUSION: We have shown that simultaneously increased local (Feno) and systemic (blood eosinophil) markers of type 2 inflammation related to a higher likelihood of BHR and uncontrolled asthma in a large cohort of young asthmatic patients.

  • 93. Marcon, Alessandro
    et al.
    Cerveri, Isa
    Wjst, Matthias
    Anto, Josep
    Heinrich, Joachim
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Jarvis, Deborah
    Leynaert, Benedicte
    Probst-Hensch, Nicole
    Svanes, Cecilie
    Toren, Kjell
    Burney, Peter
    de Marco, Roberto
    Can an airway challenge test predict respiratory diseases?: A population-based international study2014In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 133, no 1, p. 104-+Article in journal (Refereed)
    Abstract [en]

    Background: Evidence on the longitudinal association of airway responsiveness with respiratory diseases is scarce. The best indicator of responsiveness is still undetermined. Objective: We investigated the association of airway responsiveness with the incidence of asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis. Methods: We studied 3851 subjects who underwent spirometry and methacholine challenge tests both at baseline (1991-1993), when they were 20 to 44 years old, and at follow-up (1999-2002) in the European Community Respiratory Health Survey. Airway responsiveness was defined based on the methacholine dose-response slope on both occasions. Incidence rate ratios for the association of airway responsiveness with disease occurrence were computed by using Poisson regression. Results: With respect to reference (slope of the fourth quintile or greater), subjects with the greatest degree of airway responsiveness (slope less than the first quintile) showed the greatest risk of developing asthma, COPD, and allergic rhinitis (incidence rate ratios of 10.82, 5.53, and 4.84, respectively; all P < .01). A low slope predicted disease occurrence, even in subjects who did not reach a 20% decrease in FEV1 at the cumulative dose of 1 mg of methacholine (PD20 > 1 mg). A decrease in slope over time was an independent predictor of disease risk. Conclusion: Airway responsiveness predicted new-onset asthma, COPD, and allergic rhinitis. Our study supports the use of a continuous noncensored indicator of airway responsiveness, such as the slope of the methacholine dose-response curve, in clinical practice and research because it showed clear advantages over PD20.

  • 94. Marcon, Alessandro
    et al.
    Corsico, Angelo
    Cazzoletti, Lucia
    Bugiani, Massimiliano
    Accordini, Simone
    Almar, Enrique
    Cerveri, Isa
    Gislason, David
    Gulsvik, Amund
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Jarvis, Deborah
    Martínez-Moratalla, Jesús
    Pin, Isabelle
    de Marco, Roberto
    Body mass index, weight gain, and other determinants of lung function decline in adult asthma2009In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 123, no 5, p. 1069-1074Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about factors associated with lung function decline in asthma. OBJECTIVE: To identify the determinants of FEV(1) decline in adults with asthma with and without airflow obstruction at baseline. METHODS: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV(1) decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV(1)/forced vital capacity < 0.70) at baseline. RESULTS: In the group of individuals without airflow obstruction (n = 544), a faster FEV(1) decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV(1) decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV(1) decline, whereas weight gain was not associated with decline. CONCLUSIONS: The detrimental effect of weight gain on FEV(1) decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma.

  • 95.
    Maric, Jovana
    et al.
    Med Univ Graz, Austria; Karolinska Inst, Sweden.
    Ravindran, Avinash
    Karolinska Inst, Sweden.
    Mazzurana, Luca
    Karolinska Inst, Sweden.
    Bjorklund, Asa K.
    Uppsala Univ, Sweden.
    Van Acker, Aline
    Karolinska Inst, Sweden.
    Rao, Anna
    Karolinska Inst, Sweden.
    Friberg, Danielle
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Dahlen, Sven-Erik
    Karolinska Inst, Sweden.
    Heinemann, Akos
    Med Univ Graz, Austria.
    Konya, Viktoria
    Med Univ Graz, Austria; Karolinska Inst, Sweden.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Prostaglandin E-2 suppresses human group 2 innate lymphoid cell function2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 141, no 5, p. 1761-+Article in journal (Refereed)
    Abstract [en]

    Background: Group 2 innate lymphoid cells (ILC2s) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. Prostaglandin (PG) E-2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. Objective: We set out to investigate how PGE(2) regulates human ILC2 function. Methods: The effects of PGE(2) on human ILC2 proliferation and intracellular cytokine and transcription factor expression were assessed by means of flow cytometry. Cytokine production was measured by using ELISA, and real-time quantitative PCR was performed to detect PGE(2) receptor expression. Results: PGE(2) inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5 and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore, PGE(2) downregulated the expression of IL-2 receptor alpha (CD25). In line with this observation, PGE(2) decreased ILC2 proliferation. These effects were mediated by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors, which were specifically expressed on ILC2s. Conclusion: Our findings reveal that PGE(2) limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as a promising therapeutic approach in treating allergic diseases by suppressing ILC2 function.

  • 96.
    Maric, Jovana
    et al.
    Med Univ Graz, Inst Expt & Clin Pharmacol, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Ravindran, Avinash
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Stockholm, Sweden.
    Mazzurana, Luca
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Björklund, Åsa K.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Van Acker, Aline
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Rao, Anna
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Friberg, Danielle
    Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden;Karolinska Inst, CLINTEC, Stockholm, Sweden.
    Dahlen, Sven-Erik
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res, Stockholm, Sweden.
    Heinemann, Akos
    Med Univ Graz, Inst Expt & Clin Pharmacol, Graz, Austria.
    Konya, Viktoria
    Med Univ Graz, Inst Expt & Clin Pharmacol, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Mjösberg, Jenny
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Prostaglandin E-2 suppresses human group 2 innate lymphoid cell function2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 141, no 5, p. 1761-1773.e6Article in journal (Refereed)
    Abstract [en]

    Background: Group 2 innate lymphoid cells (ILC2s) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. Prostaglandin (PG) E-2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation.

    Objective: We set out to investigate how PGE(2) regulates human ILC2 function.

    Methods: The effects of PGE(2) on human ILC2 proliferation and intracellular cytokine and transcription factor expression were assessed by means of flow cytometry. Cytokine production was measured by using ELISA, and real-time quantitative PCR was performed to detect PGE(2) receptor expression.

    Results: PGE(2) inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5 and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore, PGE(2) downregulated the expression of IL-2 receptor alpha (CD25). In line with this observation, PGE(2) decreased ILC2 proliferation. These effects were mediated by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors, which were specifically expressed on ILC2s.

    Conclusion: Our findings reveal that PGE(2) limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as a promising therapeutic approach in treating allergic diseases by suppressing ILC2 function.

  • 97.
    Maric, Jovana
    et al.
    Med Univ Graz, Otto Loewi Res Ctr, Pharmacol Sect, Graz, Austria;BioTechMed, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Ravindran, Avinash
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Solna, Sweden;Karolinska Univ Hosp, Clin Immunol & Transfus Med, Stockholm, Sweden.
    Mazzurana, Luca
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Van Acker, Aline
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Rao, Anna
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Kokkinou, Efthymia
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Ekoff, Maria
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Solna, Sweden;Karolinska Univ Hosp, Clin Immunol & Transfus Med, Stockholm, Sweden.
    Thomas, Dominique
    Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany.
    Fauland, Alexander
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden.
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Karolinska Inst, Dept Med, Immunol & Allergy Unit, Solna, Sweden;Karolinska Univ Hosp, Clin Immunol & Transfus Med, Stockholm, Sweden.
    Wheelock, Craig E.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden.
    Dahlen, Sven-Erik
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res, Stockholm, Sweden.
    Ferreiros, Nerea
    Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany.
    Geisslinger, Gerd
    Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany;Fraunhofer Inst Mol Biol & Appl Ecol IME, Project Grp Translat Med & Pharmacol TMP, Frankfurt, Germany.
    Friberg, Danielle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Karolinska Inst, Dept Clin Sci Intervent & Technol, CLINTEC, Stockholm, Sweden.
    Heinemann, Akos
    Med Univ Graz, Otto Loewi Res Ctr, Pharmacol Sect, Graz, Austria;BioTechMed, Graz, Austria.
    Konya, Viktoria
    Med Univ Graz, Otto Loewi Res Ctr, Pharmacol Sect, Graz, Austria;BioTechMed, Graz, Austria;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
    Mjosberg, Jenny
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Cytokine-induced endogenous production of prostaglandin D-2 is essential for human group 2 innate lymphoid cell activation2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 6, p. 2202-2214.e5Article in journal (Refereed)
    Abstract [en]

    Objective: We set out to examine PG production in human ILC2s and the implications of such endogenous production on ILC2 function. Methods: The effects of the COX-1/2 inhibitor flurbiprofen, the hematopoietic prostaglandin D2 synthase (HPGDS) inhibitor KMN698, and the CRTH2 antagonist CAY10471 on human ILC2s were determined by assessing receptor and transcription factor expression, cytokine production, and gene expression with flow cytometry, ELISA, and quantitative RT-PCR, respectively. Concentrations of lipid mediators were measured by using liquid chromatography-tandem mass spectrometry and ELISA. Results: We show that ILC2s constitutively express HPGDS and upregulate COX-2 upon IL-2, IL-25, and IL-33 plus thymic stromal lymphopoietin stimulation. Consequently, PGD2 and its metabolites can be detected in ILC2 supernatants. We reveal that endogenously produced PGD2 is essential in cytokine-induced ILC2 activation because blocking of the COX-1/2 or HPGDS enzymes or the CRTH2 receptor abolishes ILC2 responses. Conclusion: PGD2 produced by ILC2s is, in a paracrine/autocrine manner, essential in cytokine-induced ILC2 activation. Hence we provide the detailed mechanism behind how CRTH2 antagonists represent promising therapeutic tools for allergic diseases by controlling ILC2 function.

  • 98.
    Maric, Jovana
    et al.
    Med Univ Graz, Austria; BioTechMed, Austria; Karolinska Inst, Sweden.
    Ravindran, Avinash
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Mazzurana, Luca
    Karolinska Inst, Sweden.
    Van Acker, Aline
    Karolinska Inst, Sweden.
    Rao, Anna
    Karolinska Inst, Sweden.
    Kokkinou, Efthymia
    Karolinska Inst, Sweden.
    Ekoff, Maria
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Thomas, Dominique
    Goethe Univ Frankfurt, Germany.
    Fauland, Alexander
    Karolinska Inst, Sweden.
    Nilsson, Gunnar
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Uppsala Univ, Sweden.
    Wheelock, Craig E.
    Karolinska Inst, Sweden.
    Dahlen, Sven-Erik
    Karolinska Inst, Sweden.
    Ferreiros, Nerea
    Goethe Univ Frankfurt, Germany.
    Geisslinger, Gerd
    Goethe Univ Frankfurt, Germany; Fraunhofer Inst Mol Biol and Appl Ecol IME, Germany.
    Friberg, Danielle
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Heinemann, Akos
    Med Univ Graz, Austria; BioTechMed, Austria.
    Konya, Viktoria
    Med Univ Graz, Austria; BioTechMed, Austria; Karolinska Inst, Sweden.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Cytokine-induced endogenous production of prostaglandin D-2 is essential for human group 2 innate lymphoid cell activation2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 6, p. 2202-+Article in journal (Refereed)
    Abstract [en]

    Objective: We set out to examine PG production in human ILC2s and the implications of such endogenous production on ILC2 function. Methods: The effects of the COX-1/2 inhibitor flurbiprofen, the hematopoietic prostaglandin D2 synthase (HPGDS) inhibitor KMN698, and the CRTH2 antagonist CAY10471 on human ILC2s were determined by assessing receptor and transcription factor expression, cytokine production, and gene expression with flow cytometry, ELISA, and quantitative RT-PCR, respectively. Concentrations of lipid mediators were measured by using liquid chromatography-tandem mass spectrometry and ELISA. Results: We show that ILC2s constitutively express HPGDS and upregulate COX-2 upon IL-2, IL-25, and IL-33 plus thymic stromal lymphopoietin stimulation. Consequently, PGD2 and its metabolites can be detected in ILC2 supernatants. We reveal that endogenously produced PGD2 is essential in cytokine-induced ILC2 activation because blocking of the COX-1/2 or HPGDS enzymes or the CRTH2 receptor abolishes ILC2 responses. Conclusion: PGD2 produced by ILC2s is, in a paracrine/autocrine manner, essential in cytokine-induced ILC2 activation. Hence we provide the detailed mechanism behind how CRTH2 antagonists represent promising therapeutic tools for allergic diseases by controlling ILC2 function.

  • 99.
    Mascialino, Barbara
    et al.
    Thermo Fisher Sci, Uppsala, Sweden.
    Yang, Brian
    Thermo Fisher Sci, Portage, MI USA.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research. Thermo Fisher Sci, Uppsala, Sweden.
    Screening With Serology Testing Children With Asthma Could Contribute To Substantial Cost Savings To US Payors: A Population-Based Simulation Study2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 2, p. AB222-AB222, article id 675Article in journal (Other academic)
  • 100. Matheson, Melanie Claire
    et al.
    Dharmage, Shyamali Chandrika
    Abramson, Michael John
    Walters, Eugene Haydn
    Sunyer, Jordi
    de Marco, Roberto
    Leynaert, Benedicte
    Heinrich, Joachim
    Jarvis, Deborah
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Raherison, Chantal
    Wjst, Matthias
    Svanes, Cecilie
    Early-life risk factors and incidence of rhinitis: Results from the European Community Respiratory Health Study - an international population-based cohort study2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 4, p. 816-823.e5Article in journal (Refereed)
    Abstract [en]

    Background: Rhinitis is an increasingly common condition with a heavy health care burden, but relatively little is known about its risk factors.

    Objective: To examine the association between early-life factors and the development of rhinitis in the European Community Respiratory Health Study (ECRHS).

    Methods: In 1992-1994, community-based samples of 20-44-year-old people were recruited from 48 centers in 22 countries. On average, 8.9 years later, 28 centers reinvestigated their samples. Onset of rhinitis was reported by 8486 participants in interviewer-led questionnaires. Cox regression was used to assess independent predictors of rhinitis at ages <= 5, 6-10, 11-20, and >= 21 years.

    Results: The crude lifelong incidence of rhinitis was 7.00/1000/year (men) and 7.95/1000/year (women) (P = .002). Women developed less rhinitis in later childhood (hazard ratios [HR], 0.63; 95% CI, 0.47-0.85) and more rhinitis in adulthood (HR, 1.36; 95% CI, 1.11-1.66) than did men. In atopic subjects, siblings were associated with lower risk of rhinitis throughout life (pooled HR, 0.94; 95% CI, 0.91-0.98 per 1 sibling). Early contact with children in the family or day care was associated with less incidence of rhinitis, predominantly before age 5 years (HR, 0.84; 95% CI, 0.72-0.99). Early childhood pets or growing up on a farm was associated with less incidence of rhinitis in adolescence (HR, 0.50; 95% CI, 0.37-0.68). Combining these factors showed evidence of a dose-response relationship (trend P = .0001).

    Conclusions: Gender is a strong risk factor for rhinitis, with age patterns varying according to atopic status. Protective effects of early contact with children and animals were suggested for incident rhinitis, with risk patterns varying by age window and atopic status.

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