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  • 1. Amaral, André F S
    et al.
    Newson, Roger B
    Abramson, Michael J
    Antó, Josep M
    Bono, Roberto
    Corsico, Angelo G
    de Marco, Roberto
    Demoly, Pascal
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gislason, Thorarinn
    Heinrich, Joachim
    Huerta, Ismael
    Janson, Christer
    Jõgi, Rain
    Kim, Jeong-Lim
    Maldonado, José
    Martinez-Moratalla Rovira, Jesús
    Neukirch, Catherine
    Nowak, Dennis
    Pin, Isabelle
    Probst-Hensch, Nicole
    Raherison-Semjen, Chantal
    Svanes, Cecilie
    Urrutia Landa, Isabel
    van Ree, Ronald
    Versteeg, Serge A
    Weyler, Joost
    Zock, Jan-Paul
    Burney, Peter G J
    Jarvis, Deborah L
    Changes in IgE sensitization and total IgE levels over 20 years of follow-up2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 137, no 6, p. 1788-1795Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect.

    OBJECTIVE: We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period.

    METHODS: Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse.

    RESULTS: Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (-4.6%; 95% CI, -7.0% to -2.1%). The prevalence of sensitization to house dust mite (-4.3%; 95% CI, -6.0% to -2.6%) and cat (-2.1%; 95% CI, -3.6% to -0.7%) decreased more than sensitization to grass (-0.6%; 95% CI, -2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts.

    CONCLUSION: Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years.

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  • 2.
    Badi, Yusef Eamon
    et al.
    National Heart and Lung Institute, the Imperial College London, London, United Kingdom; NIHR Imperial Biomedical Research Centre, London, United Kingdom; Data Science Institute, Imperial College London, London, United Kingdom.
    Pavel, Ana B.
    Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, NY, New York, United States; Department of Biomedical Engineering, The University of Mississippi, Miss, Oxford, United States.
    Pavlidis, Stelios
    Data Science Institute, Imperial College London, London, United Kingdom.
    Riley, John H.
    GSK Respiratory Therapeutic Area Unit, Stevenage, United Kingdom.
    Bates, Stewart
    GSK Respiratory Therapeutic Area Unit, Stevenage, United Kingdom.
    Kermani, Nazanin Zounemat
    Data Science Institute, Imperial College London, London, United Kingdom.
    Knowles, Richard
    Knowles Consulting, Stevenage, United Kingdom.
    Kolmert, Johan
    Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Wheelock, Craig E.
    Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Worsley, Sally
    GSK Value Evidence and Outcomes, Brentford, United Kingdom.
    Uddin, Mohib
    Respiratory Global Medicines Development, AstraZeneca, Gothenburg, Sweden.
    Alving, Kjell
    Department of Women's and Children's Health: Paediatric Research, Uppsala University, Uppsala, Sweden.
    Bakke, Per S.
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Caruso, Massimo
    Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
    Chanez, Pascal
    Aix-Marseille Universite, Assistance Publique des Hopitaux de Marseille, Clinic des Bronches, Allergies et Sommeil, Marseille, France.
    Fleming, Louise J.
    National Heart and Lung Institute, the Imperial College London, London, United Kingdom; NIHR Imperial Biomedical Research Centre, London, United Kingdom.
    Fowler, Stephen J.
    Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Manchester Academic Health Science Centre and NIHR Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
    Frey, Urs
    University Children's Hospital Basel, University of Basel, Basel, Switzerland.
    Howarth, Peter
    Clinical and Experimental Sciences and Human Development in Health, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, Newport, United Kingdom.
    Horváth, Ildikó
    Department of Public Health, Semmelweis University, Budapest, Hungary.
    Krug, Norbert
    Fraunhofer ITEM, Hannover, Germany.
    Maitland-van der Zee, Anke H.
    Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, The Netherlands, Amsterdam, Netherlands.
    Montuschi, Paolo
    Pharmacology, Catholic University of the Sacred Heart, Agostino Gemelli University Hospital Foundation, Rome, Italy.
    Roberts, Graham
    Clinical and Experimental Sciences and Human Development in Health, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, Newport, United Kingdom.
    Sanak, Marek
    Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
    Shaw, Dominick E.
    University of Nottingham, NIHR Biomedical Research Centre, Nottingham, United Kingdom.
    Singer, Florian
    Division of Respiratory Medicine, Department of Paediatrics, Inselspital, University of Bern, Bern, Switzerland.
    Sterk, Peter J.
    Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, The Netherlands, Amsterdam, Netherlands.
    Djukanovic, Ratko
    Clinical and Experimental Sciences and Human Development in Health, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, Newport, United Kingdom.
    Dahlen, Sven-Eric
    Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Guo, Yi-Ke
    Data Science Institute, Imperial College London, London, United Kingdom.
    Chung, Kian Fan
    National Heart and Lung Institute, the Imperial College London, London, United Kingdom; NIHR Imperial Biomedical Research Centre, London, United Kingdom.
    Guttman-Yassky, Emma
    Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, NY, New York, United States.
    Adcock, Ian M.
    National Heart and Lung Institute, the Imperial College London, London, United Kingdom; NIHR Imperial Biomedical Research Centre, London, United Kingdom.
    Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma2022In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 149, no 1, p. 89-101Article in journal (Refereed)
    Abstract [en]

    Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.

    Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.

    Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.

    Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P <.05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P <.05) and particularly in neutrophilic and mixed granulocytic sputum (P <.05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.

    Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.

  • 3. Berthold, Malin
    et al.
    Bjerg, Anders
    Winberg, Anna
    Mattsson, Lars
    Borres, Magnus
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Obstructive Lung Disease in Northern Sweden (OLIN) studies, Norrbotten county council, Luleå, Sweden.
    Association of Sensitization to Specific Pet Allergen Components with Asthma Symptoms in School Children2015In: 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]

    Animal sensitization is a known determinant of asthma in children. The objective was to study the association of asthma with sensitization to pet allergen components in schoolchildren. Methods: A random sample of 696 children (11-12 y) from a Swedish population-based cohort was analyzed for sensitization (≥0.1 kUA/L) to cat, dog and horse dander extracts using ImmunoCAP. Sensitized children were further analyzed for IgE antibodies to animal allergen components using ImmunoCAP ISAC112. An expanded ISAAC questionnaire was completed by the parents. Results: Of 259 animal-sensitized children (37%) the majority (75%) were sensitized to more than one species. Among the 11 % (n=77) with current asthma 69 % were sensitized to at least one animal extract, as compared to one third of children without current asthma (p<0.001). Current asthma and asthma symptoms upon contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. Already at moderate levels of IgE antibodies to Fel d 4 (1-15 ISU), at which level most children were sensitized also to Fel d 1, the prevalence of asthma symptoms upon contact with cats was significantly increased. Dog-sensitized children were commonly sensitized to several dog components, and the greatest risk for asthma was seen in children co-sensitized to Can f 5 and Can f 1/f 2. Conclusions: Among Northern Swedish schoolchildren furry animals were the main perennial sensitizers. Asthma symptoms were associated with sensitizations to multiple components within an animal species. In particular, cat Fel d 4 sensitization was strongly related to asthma symptoms.

  • 4.
    Bianchi, Matteo
    et al.
    Division of Immunology/Hematology/BMT, University Children’s Hospital, Zurich, Switzerland .
    Niemiec, Maria J.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Siler, Ulrich
    Division of Immunology/Hematology/BMT, University Children’s Hospital, Zurich, Switzerland .
    Urban, Constantin F.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Reichenbach, Janine
    Division of Immunology/Hematology/BMT, University Children’s Hospital, Zurich, Switzerland .
    Reply: redundant ability of phagocytes to kill Aspergillus species2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 3, p. 687-688Article in journal (Other academic)
  • 5. Bianchi, Matteo
    et al.
    Niemiec, Maria J
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Siler, Ulrich
    Urban, Constantin F.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Reichenbach, Janine
    Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 127, no 5, p. 1243-1252 e.7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Aspergillus spp infection is a potentially lethal disease in patients with neutropenia or impaired neutrophil function. We showed previously that Aspergillus hyphae, too large for neutrophil phagocytosis, are inhibited by reactive oxygen species-dependent neutrophil extracellular trap (NET) formation. This process is defective in chronic granulomatous disease (CGD) because of impaired phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function.

    OBJECTIVE: To determine the antifungal agent and mechanism responsible for reconstitution of Aspergillus growth inhibition within NETs after complementation of NADPH oxidase function by gene therapy (GT) for CGD.

    METHODS: Antifungal activity of free and NET-released calprotectin was assessed by incubation of Aspergillus nidulans with purified calprotectin, induced NETs from human controls, and CGD neutrophils after GT in the presence or absence of Zn(2+) or alpha-S100A9 antibody, and with induced NETs from wild-type or S100A9(-/-) mouse neutrophils.

    RESULTS: We identified the host Zn(2+) chelator calprotectin as a neutrophil-associated antifungal agent expressed within NETs, reversibly preventing A nidulans growth at low concentrations, and leading to irreversible fungal starvation at higher concentrations. Specific antibody-blocking and Zn(2+) addition abolished calprotectin-mediated inhibition of A nidulans proliferation in vitro. The role of calprotectin in anti-Aspergillus defense was confirmed in calprotectin knockout mice.

    CONCLUSION: Reconstituted NET formation by GT for human CGD was associated with rapid cure of pre-existing therapy-refractory invasive pulmonary aspergillosis in vivo, underlining the role of functional NADPH oxidase in NET formation and calprotectin release for antifungal activity. These results demonstrate the critical role of calprotectin in human innate immune defense against Aspergillus infection.

  • 6. Bousquet, Jean
    et al.
    Hellings, Peter W.
    Agache, Ioana
    Amat, Flore
    Annesi-Maesano, Isabella
    Ansotegui, Ignacio J.
    Anto, Josep M.
    Bachert, Claus
    Bateman, Eric D.
    Bedbrook, Anna
    Bennoor, Kazi
    Bewick, Mickael
    Bindslev-Jensen, Carsten
    Bosnic-Anticevich, Sinthia
    Bosse, Isabelle
    Brozek, Jan
    Brussino, Luisa
    Canonica, Giorgio W.
    Cardona, Victoria
    Casale, Thomas
    Sarabia, Alfonso M. Cepeda
    Chavannes, Niels H.
    Cecchi, Lorenzo
    de Sousa, Jaime Correia
    Costa, Elisio
    Cruz, Alvaro A.
    Czarlewski, Wienczyslawa
    De Carlo, Giuseppe
    De Feo, Giulia
    Demoly, Pascal
    Devillier, Philippe
    Dykewicz, Mark S.
    El-Gamal, Yehia
    Eller, Esben E.
    Fonseca, Joao A.
    Fontaine, Jean-Francois
    Fokkens, Wytske J.
    Guzman, Maria-Antonieta
    Haahtela, Tari
    Illario, Maddalena
    Ivancevich, Juan-Carlos
    Just, Jocelyne
    Kaidashev, Igor
    Khaitov, Musa
    Kalayci, Omer
    Keil, Thomas
    Klimek, Ludger
    Kowalski, Marek L.
    Kuna, Piotr
    Kvedariene, Violeta
    Larenas-Linnemann, Desiree
    Laune, Daniel
    Le, Lan T. T.
    Carlsen, Karin Lodrup
    Lourenco, Olga
    Mahboub, Bassam
    Mair, Alpana
    Menditto, Enrica
    Milenkovic, Branislava
    Morais-Almeida, Mario
    Mosges, Ralph
    Mullol, Joaquim
    Murray, Ruth
    Naclerio, Robert
    Namazova-Baranova, Leyla
    Novellino, Ettore
    O'Hehir, Robyn E.
    Ohta, Ken
    Okamoto, Yoshitaka
    Okubo, Kimi
    Onorato, Gabrielle L.
    Palkonen, Susanna
    Panzner, Petr
    Papadopoulos, Nikos G.
    Park, Hae-Sim
    Paulino, Ema
    Pawankar, Ruby
    Pfaar, Oliver
    Plavec, Davor
    Popov, Ted A.
    Potter, Paul
    Prokopakis, Emmanuel P.
    Rottem, Menachem
    Ryan, Dermot
    Salimaki, Johanna
    Samolinski, Boleslaw
    Sanchez-Borges, Mario
    Schunemann, Holger J.
    Sheikh, Aziz
    Sisul, Juan-Carlos
    Rajabian-Soderlund, Rojin
    Sooronbaev, Talant
    Stellato, Cristiana
    To, Teresa
    Todo-Bom, Ana-Maria
    Tomazic, Peter-Valentin
    Toppila-Salmi, Sanna
    Valero, Antonio
    Valiulis, Arunas
    Valovirta, Erkka
    Ventura, Maria-Teresa
    Wagenmann, Martin
    Wang, De Yun
    Wallace, Dana
    Waserman, Susan
    Wickman, Magnus
    Yorgancioglu, Arzu
    Zhang, Luo
    Zhong, Nanshan
    Zidarn, Mihaela
    Zuberbier, Torsten
    Bousquet, J.
    Hellings, P. W.
    Aberer, W.
    Agache, I.
    Akdis, C. A.
    Akdis, M.
    Alberti, M. R.
    Almeida, R.
    Amat, F.
    Angles, R.
    Annesi-Maesano, I.
    Ansotegui, I. J.
    Anto, J. M.
    Arnavielle, S.
    Asayag, E.
    Asarnoj, A.
    Arshad, H.
    Avolio, F.
    Bacci, E.
    Bachert, C.
    Baiardini, I.
    Barbara, C.
    Barbagallo, M.
    Baroni, I.
    Barreto, B. A.
    Basagana, X.
    Bateman, E. D.
    Bedolla-Barajas, M.
    Bedbrook, A.
    Bewick, M.
    Beghe, B.
    Bel, E. H.
    Bergmann, K. C.
    Bennoor, K. S.
    Benson, M.
    Bertorello, L.
    Biaoszewski, A. Z.
    Bieber, T.
    Bialek, S.
    Bindslev-Jensen, C.
    Bjermer, L.
    Blain, H.
    Blasi, F.
    Blua, A.
    Marciniak, M. Bochenska
    Bogus-Buczynska, I.
    Boner, A. L.
    Bonini, M.
    Bonini, S.
    Bosnic-Anticevich, C. S.
    Bosse, I.
    Bouchard, J.
    Boulet, L. P.
    Bourret, R.
    Bousquet, P. J.
    Braido, F.
    Briedis, V.
    Brightling, C. E.
    Brozek, J.
    Bucca, C.
    Buhl, R.
    Buonaiuto, R.
    Panaitescu, C.
    Cabanas, M. T. Burguete
    Burte, E.
    Bush, A.
    Caballero-Fonseca, F.
    Caillot, D.
    Caimmi, D.
    Calderon, M. A.
    Camargos, P. A. M.
    Camuzat, T.
    Canfora, G.
    Canonica, G. W.
    Cardona, V.
    Carlsen, K. H.
    Carreiro-Martins, P.
    Carriazo, A. M.
    Carr, W.
    Cartier, C.
    Casale, T.
    Castellano, G.
    Cecchi, L.
    Sarabia, A. M. Cepeda
    Chavannes, N. H.
    Chen, Y.
    Chiron, R.
    Chivato, T.
    Chkhartishvili, E.
    Chuchalin, A. G.
    Chung, K. F.
    Ciaravolo, M. M.
    Ciceran, A.
    Cingi, C.
    Ciprandi, G.
    Coehlo, A. C. Carvalho
    Colas, L.
    Colgan, E.
    Coll, J.
    Conforti, D.
    de Sousa, J. Correia
    Cortes-Grimaldo, R. M.
    Corti, F.
    Costa, E.
    Costa-Dominguez, C.
    Courbis, A. L.
    Cox, L.
    Crescenzo, M.
    Cruz, A. A.
    Custovic, A.
    Czarlewski, W.
    Dahlen, S. E.
    Dario, C.
    da Silva, J.
    Dauvilliers, Y.
    Darsow, U.
    De Blay, F.
    De Carlo, G.
    Dedeu, T.
    Emerson, M. de Fatima
    De Feo, G.
    De Vries, G.
    De Martino, B.
    Rubini, N. de Paula Motta
    Deleanu, D.
    Demoly, P.
    Denburg, J. A.
    Devillier, P.
    Ercolano, S. Di Capua
    Di Carluccio, N.
    Didier, A.
    Dokic, D.
    Dominguez-Silva, M. G.
    Douagui, H.
    Dray, G.
    Dubakiene, R.
    Durham, S. R.
    Du Toit, G.
    Dykewicz, M. S.
    El-Gamal, Y.
    Eklund, Patrik
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Eller, E.
    Emuzyte, R.
    Farrell, J.
    Farsi, A.
    de Mello, J. Ferreira, Jr.
    Ferrero, J.
    Fink-Wagner, A.
    Fiocchi, A.
    Fokkens, W. J.
    Fonseca, J. A.
    Fontaine, J. F.
    Forti, S.
    Fuentes-Perez, J. M.
    Galvez-Romero, J. L.
    Gamkrelidze, A.
    Garcia-Aymerich, J.
    Garcia-Cobas, C. Y.
    Garcia-Cruz, M. H.
    Gemicioglu, B.
    Genova, S.
    Christoff, G.
    Gereda, J. E.
    van Wijk, R. Gerth
    Gomez, R. M.
    Gomez-Vera, J.
    Diaz, S. Gonzalez
    Gotua, M.
    Grisle, I.
    Guidacci, M.
    Guldemond, N. A.
    Gutter, Z.
    Guzman, M. A.
    Haahtela, T.
    Hajjam, J.
    Hernandez, L.
    Hourihane, J. O 'B.
    Huerta-Villalobos, Y. R.
    Humbert, M.
    Iaccarino, G.
    Illario, M.
    Ivancevich, J. C.
    Jares, E. J.
    Jassem, E.
    Johnston, S. L.
    Joos, G.
    Jung, K. S.
    Jutel, M.
    Kaidashev, I.
    Kalayci, O.
    Kalyoncu, A. F.
    Karjalainen, J.
    Kardas, P.
    Keil, T.
    Keith, P. K.
    Khaitov, M.
    Khaltaev, N.
    Kleine-Tebbe, J.
    Klimek, L.
    Kowalski, M. L.
    Kuitunen, M.
    Kull, I.
    Kuna, P.
    Kupczyk, M.
    Kvedariene, V.
    Krzych-Fata, E.
    Lacwik, P.
    Larenas-Linnemann, D.
    Laune, D.
    Lauri, D.
    Lavrut, J.
    Le, L. T. T.
    Lessa, M.
    Levato, G.
    Li, J.
    Lieberman, P.
    Lipiec, A.
    Lipworth, B.
    Carlsen, K. C. Lodrup
    Louis, R.
    Lourenco, O.
    Luna-Pech, J. A.
    Maciej, K.
    Magnan, A.
    Mahboub, B.
    Maier, D.
    Mair, A.
    Majer, I.
    Malva, J.
    Mandajieva, E.
    Manning, P.
    Keenoy, E. De Manuel
    Marshall, G. D.
    Masjedi, M. R.
    Maspero, J. F.
    Mathieu-Dupas, E.
    Campos, J. J. Matta
    Matos, A. L.
    Maurer, M.
    Mavale-Manuel, S.
    Mayora, O.
    Medina-Avalos, M. A.
    Melen, E.
    Melo-Gomes, E.
    Meltzer, E. O.
    Menditto, E.
    Mercier, J.
    Miculinic, N.
    Mihaltan, F.
    Milenkovic, B.
    Moda, G.
    Mogica-Martinez, M. D.
    Mohammad, Y.
    Momas, I.
    Montefort, S.
    Monti, R.
    Bogado, D. Mora
    Morais-Almeida, M.
    Morato-Castro, F. F.
    Mosges, R.
    Mota-Pinto, A.
    Santo, P. Moura
    Mullol, J.
    Munter, L.
    Muraro, A.
    Murray, R.
    Naclerio, R.
    Nadif, R.
    Nalin, M.
    Napoli, L.
    Namazova-Baranova, L.
    Neffen, H.
    Niedeberger, V.
    Nekam, K.
    Neou, A.
    Nieto, A.
    Nogueira-Silva, L.
    Nogues, M.
    Novellino, E.
    Nyembue, T. D.
    O'Hehir, R. E.
    Odzhakova, C.
    Ohta, K.
    Okamoto, Y.
    Okubo, K.
    Onorato, G. L.
    Cisneros, M. Ortega
    Ouedraogo, S.
    Pali-Scholl, I.
    Palkonen, S.
    Panzner, P.
    Papadopoulos, N. G.
    Park, H. S.
    Papi, A.
    Passalacqua, G.
    Paulino, E.
    Pawankar, R.
    Pedersen, S.
    Pepin, J. L.
    Pereira, A. M.
    Persico, M.
    Pfaar, O.
    Phillips, J.
    Picard, R.
    Pigearias, B.
    Pin, I.
    Pitsios, C.
    Plavec, D.
    Pohl, W.
    Popov, T. A.
    Portejoie, F.
    Potter, P.
    Pozzi, A. C.
    Price, D.
    Prokopakis, E. P.
    Puy, R.
    Pugin, B.
    Ross, R. E. Pulido
    Przemecka, M.
    Rabe, K. F.
    Raciborski, F.
    Rajabian-Soderlund, R.
    Reitsma, S.
    Ribeirinho, I.
    Rimmer, J.
    Rivero-Yeverino, D.
    Rizzo, J. A.
    Rizzo, M. C.
    Robalo-Cordeiro, C.
    Rodenas, F.
    Rodo, X.
    Gonzalez, M. Rodriguez
    Rodriguez-Manas, L.
    Rolland, C.
    Valle, S. Rodrigues
    Rodriguez, M. Roman
    Romano, A.
    Rodriguez-Zagal, E.
    Rolla, G.
    Roller-Wirnsberger, R. E.
    Romano, M.
    Rosado-Pinto, J.
    Rosario, N.
    Rottem, M.
    Ryan, D.
    Sagara, H.
    Salimaki, J.
    Samolinski, B.
    Sanchez-Borges, M.
    Sastre-Dominguez, J.
    Scadding, G. K.
    Schunemann, H. J.
    Scichilone, N.
    Schmid-Grendelmeier, P.
    Serpa, F. S.
    Shamai, S.
    Sheikh, A.
    Sierra, M.
    Simons, F. E. R.
    Siroux, V.
    Sisul, J. C.
    Skrindo, I.
    Sole, D.
    Somekh, D.
    Sondermann, M.
    Sooronbaev, T.
    Sova, M.
    Sorensen, M.
    Sorlini, M.
    Spranger, O.
    Stellato, C.
    Stelmach, R.
    Stukas, R.
    Sunyer, J.
    Strozek, J.
    Szylling, A.
    Tebyrica, J. N.
    Thibaudon, M.
    To, T.
    Todo-Bom, A.
    Tomazic, P. V.
    Toppila-Salmi, S.
    Trama, U.
    Triggiani, M.
    Ulrik, C. Suppli
    Urrutia-Pereira, M.
    Valenta, R.
    Valero, A.
    Valiulis, A.
    Valovirta, E.
    van Eerd, M.
    van Ganse, E.
    van Hague, M.
    Vandenplas, O.
    Ventura, M. T.
    Vezzani, G.
    Vasankari, T.
    Vatrella, A.
    Verissimo, M. T.
    Viart, F.
    Viegi, M.
    Vicheva, D.
    Vontetsianos, T.
    Wagenmann, M.
    Walker, S.
    Wallace, D.
    Wang, D. Y.
    Waserman, S.
    Werfel, T.
    Westman, M.
    Wickman, M.
    Williams, D. M.
    Williams, S.
    Wilson, N.
    Wright, J.
    Wroczynski, P.
    Yakovliev, P.
    Yawn, B. P.
    Yiallouros, P. K.
    Yorgancioglu, A.
    Yusuf, O. M.
    Zar, H. J.
    Zhang, L.
    Zhong, N.
    Zernotti, M. E.
    Zidarn, M.
    Zuberbier, T.
    Zubrinich, C.
    Zurkuhlen, A.
    Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 3, p. 864-879Article in journal (Refereed)
    Abstract [en]

    Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

  • 7.
    Brandsma, Joost
    et al.
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Schofield, James P.R.
    National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom; Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom.
    Yang, Xian
    Data Science Institute, Imperial College, London, United Kingdom.
    Strazzeri, Fabio
    Mathematical Sciences, University of Southampton, Southampton, United Kingdom.
    Barber, Clair
    National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Goss, Victoria M.
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Koster, Grielof
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Bakke, Per S.
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Caruso, Massimo
    Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
    Chanez, Pascal
    Department of Respiratory Diseases, Aix-Marseille University, Marseille, France.
    Dahlén, Sven-Erik
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Fowler, Stephen J.
    Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, United Kingdom; Manchester Academic Health Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
    Horváth, Ildikó
    Department of Pulmonology, Semmelweis University, Budapest, Hungary.
    Krug, Norbert
    Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
    Montuschi, Paolo
    Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy; National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Sanak, Marek
    Department of Medicine, Jagiellonian University, Krakow, Poland.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Shaw, Dominick E.
    National Institute for Health Research Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom.
    Chung, Kian Fan
    National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Singer, Florian
    Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Paediatrics and Adolescent Medicine, Division of Paediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria.
    Fleming, Louise J.
    National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Adcock, Ian M.
    National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Pandis, Ioannis
    Data Science Institute, Imperial College, London, United Kingdom.
    Bansal, Aruna T.
    Acclarogen Ltd, St John's Innovation Centre, Cambridge, United Kingdom.
    Corfield, Julie
    Areteva Ltd, Nottingham, United Kingdom.
    Sousa, Ana R.
    Respiratory Therapy Unit, GlaxoSmithKline, London, United Kingdom.
    Sterk, Peter J.
    Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
    Sánchez-García, Rubén J.
    Mathematical Sciences, University of Southampton, Southampton, United Kingdom.
    Skipp, Paul J.
    Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom.
    Postle, Anthony D.
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
    Djukanović, Ratko
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Stratification of asthma by lipidomic profiling of induced sputum supernatant2023In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 152, no 1, p. 117-125Article in journal (Refereed)
    Abstract [en]

    Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.

    Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.

    Methods: Induced sputum supernatant was collected from 211 adults with asthma and 41 healthy individuals enrolled onto the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study. Sputum lipidomes were characterized by semiquantitative shotgun mass spectrometry and clustered using topologic data analysis to identify lipid phenotypes.

    Results: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of 9 molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthma patients and healthy controls, but also within the asthma patient population. Matching clinical, pathobiologic, proteomic, and transcriptomic data helped inform the underlying disease processes. Sputum lipid phenotypes with higher levels of nonendogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts.

    Conclusion: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthma patients resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.

  • 8. Brinkman, Paul
    et al.
    Wagener, Ariane H.
    Hekking, Pieter-Paul
    Bansal, Aruna T.
    Maitland-van der Zee, Anke-Hilse
    Wang, Yuanyue
    Weda, Hans
    Knobel, Hugo H.
    Vink, Teunis J.
    Rattray, Nicholas J.
    D'Amico, Arnaldo
    Pennazza, Giorgio
    Santonico, Marco
    Lefaudeux, Diane
    De Meulder, Bertrand
    Auffray, Charles
    Bakke, Per S.
    Caruso, Massimo
    Chanez, Pascal
    Chung, Kian F.
    Corfield, Julie
    Dahlen, Sven-Erik
    Djukanovic, Ratko
    Geiser, Thomas
    Horvath, Ildiko
    Krug, Nobert
    Musial, Jacek
    Sun, Kai
    Riley, John H.
    Shaw, Dominic E.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sousa, Ana R.
    Montuschi, Paolo
    Fowler, Stephen J.
    Sterk, Peter J.
    Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 5, p. 1811-1820.e7Article in journal (Refereed)
    Abstract [en]

    Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes.

    Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to withinpatient clinical and inflammatory changes.

    Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability.

    Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNosedriven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045).

    Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.

  • 9.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Olsson, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Grandmaternal smoking during pregnancy and asthma in grandchildren2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, no 2, article id 624Article in journal (Refereed)
  • 10. Burte, Emilie
    et al.
    Leynaert, Bénédicte
    Marcon, Alessandro
    Bousquet, Jean
    Benmerad, Meriem
    Bono, Roberto
    Carsin, Anne-Elie
    de Hoogh, Kees
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Gormand, Frederic
    Heinrich, Joachim
    Just, Jocelyne
    Nieuwenhuijsen, Mark
    Pin, Isabelle
    Stempfelet, Morgane
    Sunyer, Jordi
    Villani, Simona
    Künzli, Nino
    Siroux, Valérie
    Jarvis, Deborah
    Nadif, Rachel
    Jacquemin, Bénédicte
    Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts2020In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 145, no 3, p. 834-842.e6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults.

    OBJECTIVE: We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis.

    METHODS: Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO2, PM10, PM2.5, and PMcoarse (calculated by subtracting PM2.5 from PM10) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants' residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used.

    RESULTS: A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM10 was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 μg/m3 increase in PM10: for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM2.5. Higher exposure to NO2 was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO2. CONCLUSIONS: People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association.

  • 11. Commins, Scott P.
    et al.
    James, Hayley R.
    Kelly, Libby A.
    Pochan, Shawna L.
    Workman, Lisa J.
    Perzanowski, Matthew S.
    Kocan, Katherine M.
    Fahy, John V.
    Nganga, Lucy W.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Cooper, Philip J.
    Platts-Mills, Thomas A. E.
    The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 127, no 5, p. 1286-1293.e6Article in journal (Refereed)
    Abstract [en]

    Background: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur.

    Methods: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP.

    Results: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (chi(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001).

    Conclusion: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.

  • 12. 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.

  • 13. 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, Section of 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.

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  • 14. Johannessen, Ane
    et al.
    Lønnebotn, Marianne
    Calciano, Lucia
    Benediktsdóttir, Bryndis
    Bertelsen, Randi Jacobsen
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Dharmage, Shyamali
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gislason, Thorarinn
    Holm, Mathias
    Janson, Christer
    Jarvis, Deborah
    Jogi, Rain
    Kim, Jeong-Lim
    Kirkeleit, Jorunn
    Lodge, Caroline
    Malinovschi, Andrei
    Martinez-Moratalla, Jesus
    Nilsen, Roy Miodini
    Pereira-Vega, Antonio
    Real, Francisco Gómez
    Schlünssen, Vivi
    Accordini, Simone
    Svanes, Cecilie
    Being overweight in childhood, puberty, or early adulthood: Changing asthma risk in the next generation?2020In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 145, no 3, p. 791-799Article in journal (Refereed)
    Abstract [en]

    Background: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation.

    Objective: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring.

    Methods: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status.

    Results: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found.

    Conclusion: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health.

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  • 15. 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.

  • 16. 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)
  • 17. 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.

  • 18. 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.

  • 19.
    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)
  • 20. 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)
  • 21. 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.

  • 22. Nagatake, Takahiro
    et al.
    Shiogama, Yumiko
    Inoue, Asuka
    Kikuta, Junichi
    Honda, Tetsuya
    Tiwari, Prabha
    Kishi, Takayuki
    Yanagisawa, Atsushi
    Isobe, Yosuke
    Matsumoto, Naomi
    Shimojou, Michiko
    Morimoto, Sakiko
    Suzuki, Hidehiko
    Hirata, So-ichiro
    Steneberg, Pär
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Edlund, Helena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Aoki, Junken
    Arita, Makoto
    Kiyono, Hiroshi
    Yasutomi, Yasuhiro
    Ishii, Masaru
    Kabashima, Kenji
    Kunisawa, Jun
    The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques2018In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 142, no 2, p. 470-482.e12Article in journal (Refereed)
    Abstract [en]

    Background: Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated. Objective: We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE. Methods: Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-alpha shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment. Results: We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40. Conclusion: 17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases.

  • 23. Palmer, Debra J.
    et al.
    Metcalfe, Jessica
    Makrides, Maria
    Gold, Michael S.
    Quinn, Patrick
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Loh, Richard
    Prescott, Susan L.
    Early regular egg exposure in infants with eczema: a randomized controlled trial2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 132, no 2, p. 387-392Article in journal (Refereed)
    Abstract [en]

    Background: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. Objective: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. Methods: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. Results: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had eggspecific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P 5.11). Egg-specific IgG4 levels were significantly (P <.001) greater in the egg group at both 8 and 12 months. Conclusion: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.

  • 24. Perzanowski, Matthew S
    et al.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    James, Hayley R
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Schuyler, Alexander J
    Bjerg, Anders
    Lundback, Bo
    Platts-Mills, Thomas A E
    Relevance of specific IgE antibody titer to the prevalence, severity, and persistence of asthma among 19-year-olds in northern Sweden2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 138, no 6, p. 1582-1590Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although sensitization to indoor allergens is strongly associated with asthma, there are questions as to how this relates to asthma symptoms.

    OBJECTIVE: We sought to study the relevance of IgE antibodies to cat and dog allergens in an area in which (1) the climate discourages cockroach, fungal, and mite growth and (2) dander allergens are known to be present in schools and houses without animals.

    METHODS: IgE to 8 allergens was tested in 963 sera from a population-based study on 19-year-olds, and associations with asthma symptoms, diagnosis, and treatment were examined. In positive sera IgE to specific cat and dog allergens was also assayed.

    RESULTS: IgE specific for animal dander had the highest prevalence and strongest relationship to asthma diagnosis. Furthermore, asthma severity, as judged by the frequency of symptoms and use of treatment, was directly associated with the titer of IgE antibodies to animal dander. Among the 103 subjects who had current asthma at age 19 years, 50 had asthma before age 12 years. Among those 50, the odds ratios for asthma related to any IgE antibodies to animal dander or high-titer IgE antibodies (≥17.5 IU/mL) were 9.2 (95% CI, 4.9-17) and 13 (95% CI, 6.9-25), respectively. In multivariable analysis IgE antibodies to Fel d 1 and Can f 5 were each associated with current asthma.

    CONCLUSION: High-titer IgE antibodies to cat and dog allergens were strongly associated with the diagnosis, severity, and persistence of asthma; however, a large proportion of patients with current asthma did not live in a house with a cat or dog.

  • 25. Platts-Mills, Thomas A. E.
    et al.
    Schuyler, Alexander J.
    Workman, Lisa J.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Avila, Lydiana
    Heymann, Peter W.
    Specific IgE and IgG Antibodies to Human Rhinovirus 16 Capsid Protein VP1 Among Asthmatic and Non-Asthmatic Children from Costa Rica: Comparison with Virginia and Northern Sweden2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 137, no 2, p. AB174-AB174Article in journal (Other academic)
  • 26. Schofield, James P. R.
    et al.
    Burg, Dominic
    Nicholas, Ben
    Strazzeri, Fabio
    Brandsma, Joost
    Staykova, Doroteya
    Folisi, Caterina
    Bansal, Aruna T.
    Xian, Yang
    Guo, Yike
    Rowe, Anthony
    Corfield, Julie
    Wilson, Susan
    Ward, Jonathan
    Lutter, Rene
    Shaw, Dominick E.
    Bakke, Per S.
    Caruso, Massimo
    Dahlen, Sven-Erik
    Fowler, Stephen J.
    Horvath, Ildiko
    Howarth, Peter
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sun, Kai
    Pandis, Ioannis
    Riley, John
    Auffray, Charles
    De Meulder, Bertrand
    Lefaudeux, Diane
    Sousa, Ana R.
    Adcock, Ian M.
    Chung, Kian Fan
    Sterk, Peter J.
    Skipp, Paul J.
    Djukanovic, Ratko
    Ahmed, H.
    Allen, D.
    Badorrek, P.
    Ballereau, S.
    Baribaud, F.
    Batuwitage, M. K.
    Bedding, A.
    Behndig, A. F.
    Berglind, A.
    Berton, A.
    Bigler, J.
    Boedigheimer, M. J.
    Bonnelykke, K.
    Brinkman, P.
    Bush, A.
    Campagna, D.
    Casaulta, C.
    Chaiboonchoe, A.
    Davison, T.
    De Meulder, B.
    Delin, I.
    Dennison, P.
    Dodson, P.
    El Hadjam, L.
    Erzen, D.
    Faulenbach, C.
    Fichtner, K.
    Fitch, N.
    Formaggio, E.
    Gahlemann, M.
    Galffy, G.
    Garissi, D.
    Garret, T.
    Gent, J.
    Guillmant-Farry, E.
    Henriksson, E.
    Hoda, U.
    Hohlfeld, J. M.
    Hu, X.
    James, A.
    Johnson, K.
    Jullian, N.
    Kerry, G.
    Klueglich, M.
    Knowles, R.
    Konradsen, J. R.
    Kretsos, K.
    Krueger, L.
    Lantz, A. -S
    Larminie, C.
    Latzin, P.
    Lefaudeux, D.
    Lemonnier, N.
    Lowe, L. A.
    Lutter, R.
    Manta, A.
    Mazein, A.
    McEvoy, L.
    Menzies-Gow, A.
    Mores, N.
    Murray, C. S.
    Nething, K.
    Nihlen, U.
    Niven, R.
    Nordlund, B.
    Nsubuga, S.
    Pellet, J.
    Pison, C.
    Pratico, G.
    Puig Valls, M.
    Riemann, K.
    Rocha, J. P.
    Rossios, C.
    Santini, G.
    Saqi, M.
    Scott, S.
    Sehgal, N.
    Selby, A.
    Soderman, P.
    Sogbesan, A.
    Spycher, F.
    Stephan, S.
    Stokholm, J.
    Sunther, M.
    Szentkereszty, M.
    Tamasi, L.
    Tariq, K.
    Valente, S.
    van Aalderen, W. M.
    van Drunen, C. M.
    Van Eyll, J.
    Vyas, A.
    Yu, W.
    Zetterquist, W.
    Zolkipli, Z.
    Zwinderman, A. H.
    Adriaens, Nora
    Aliprantis, Antonios
    Alving, Kjell
    Bakke, Per
    Balgoma, David
    Barber, Clair
    Baribaud, Frederic
    Bates, Stewart
    Bautmans, An
    Beleta, Jorge
    Bochenek, Grazyna
    Braun, Armin
    Carayannopoulos, Leon
    Rocha, Joao Pedro Carvalho da Purificacao
    Chaleckis, Romanas
    D'Amico, Arnaldo
    De Alba, Jorge
    De Lepeleire, Inge
    Dekker, Tamara
    Dijkhuis, Annemiek
    Draper, Aleksandra
    Edwards, Jessica
    Emma, Rosalia
    Ericsson, Magnus
    Flood, Breda
    Gallart, Hector
    Gomez, Cristina
    Gove, Kerry
    Gozzard, Neil
    Haughney, John
    Hewitt, Lorraine
    Hohlfeld, Jens
    Holweg, Cecile
    Hu, Richard
    Hu, Sile
    Kamphuis, Juliette
    Kennington, Erika J.
    Kerry, Dyson
    Knobel, Hugo
    Kolmert, Johan
    Kots, Maxim
    Kuo, Scott
    Kupczyk, Maciej
    Lambrecht, Bart
    Lone-Latif, Saeeda
    Loza, Matthew J.
    Marouzet, Lisa
    Martin, Jane
    Masefield, Sarah
    Mathon, Caroline
    Meah, Sally
    Meiser, Andrea
    Metcalf, Leanne
    Mikus, Maria
    Miralpeix, Montse
    Monk, Philip
    Naz, Shama
    Nilsson, Peter
    Ostling, Jorgen
    Pacino, Antonio
    Palkonen, Susanna
    Pavlidis, Stelios
    Pennazza, Giorgio
    Petren, Anne
    Pink, Sandy
    Postle, Anthony
    Powell, Pippa
    Rahman-Amin, Malayka
    Rao, Navin
    Ravanetti, Lara
    Ray, Emma
    Reinke, Stacey
    Reynolds, Leanne
    Robberechts, Martine
    Roberts, Amanda
    Russell, Kirsty
    Rutgers, Michael
    Santoninco, Marco
    Schoelch, Corinna
    Sjodin, Marcus
    Smids, Barbara
    Smith, Caroline
    Smith, Jessica
    Smith, Katherine M.
    Thorngren, John-Olof
    Thornton, Bob
    Thorsen, Jonathan
    van de Pol, Marianne
    van Geest, Marleen
    Versnel, Jenny
    Vink, Anton
    Wald, Frans
    Walker, Samantha
    Weiszhart, Zsoka
    Wetzel, Kristiane
    Wheelock, Craig E.
    Wiegman, Coen
    Williams, Sian
    Wilson, Susan J.
    Woodcock, Ashley
    Yang, Xian
    Yeyasingham, Elizabeth
    Prins, Jan-Bas
    Gahlemann, Martina
    Visintin, Luigi
    Evans, Hazel
    Puhl, Martine
    Buzermaniene, Lina
    Hudson, Val
    Bond, Laura
    de Boer, Pim
    Widdershoven, Guy
    Sigmund, Ralf
    Supple, David
    Hamerlijnck, Dominique
    Negus, Jenny
    Kamphuis, Julitte
    Sergison, Lehanne
    Onstein, Susanne
    MacNee, William
    Bernardini, Renato
    Bont, Louis
    Wecksell, Per-Ake
    Stratification of asthma phenotypes by airway proteomic signatures2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, no 1, p. 70-82Article in journal (Refereed)
    Abstract [en]

    Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms.

    Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification.

    Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms.

    Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysisidentified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms.

    Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.

  • 27. Schuyler, Alexander J
    et al.
    James, Hayley R
    Rispens, Theo
    Workman, Lisa J
    Perzanowski, Matthew S
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Commins, Scott P
    Platts-Mills, Thomas A E
    Quantitative Binding Assay for Measuring Specific IgG Antibodies to Alpha-Gal Using the Neoglycoprotein Gal-alpha-1,3-Gal-beta-1,4-Glcnac-Human Serum Albumin2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 2, p. AB188-AB188Article in journal (Other academic)
    Abstract [en]

    Tick bites are known to induce IgE production to alpha-gal. Elevated alpha-gal IgG1 compared to natural alpha-gal IgG2 production has been reported in alpha-gal IgE+ subjects. We here report further investigation of the relationship between alpha-gal IgG and both reactions to red meat and exposure to ticks. Methods: IgG from serum was absorbed onto recombinant Protein G-Sepharose and incubated with radiolabeled allergen. The radioactivity of bound allergen was measured using a gamma counter. A control curve was generated in parallel to assign unitage. Additional testing of serum immunoglobulins was performed via ImmunoCAP and nephelometry. Results: Alpha-gal IgG was measured in a Northern Sweden cohort and in subjects presenting to allergy clinics in Virginia with delayed reactions to red meat. Alpha-gal IgG was significantly higher in alpha-gal IgE+ subjects versus alpha-gal IgE- subjects, and longitudinal serology in several alpha-gal IgE+ subjects demonstrates parallel alpha-gal IgE and IgG response trends. Among the alpha-gal IgE+ subjects, alpha-gal IgG was higher in those with alpha-gal IgE:total IgE ratios >25%, but was not related to reported severity to red meat. Compared to the alpha-gal IgE- subjects in Virginia, alpha-gal IgG was lower in the group from Northern Sweden, where alpha-gal IgE-mediated hypersensitivity is absent and ticks are rare. Conclusions: Alpha-gal IgG is strongly related to alpha-gal IgE and is significantly lower in prevalence and titer in subjects without tick exposure. The absence of a relationship between alpha-gal IgG and severity of reactions to red meat suggests that the alpha-gal syndrome may not be a suitable candidate for conventional immunotherapy.

  • 28. Sjölander, Sigrid
    et al.
    Bjerg, Anders
    Ekerljung, Linda
    Bengtsson-Gref, Otti
    Borres, Magnus
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lötvall, Jan
    Lundbäck, Bo
    IgE to Furry Animal Allergen Components Was Associated with Asthma in a Population-Based Study of Adults2015In: 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]

    Atopic sensitization increases the risk of asthma. Our aim was to investigate patterns of sensitization to allergens and allergen components in relation to asthma among adults in a Swedish population-based sample. Methods: A questionnaire targeting asthma was sent to 30 000 randomly selected adults (16-75 y) in west Sweden. Of the 18 087 responders, a randomly selected sample of 2000 subjects and in addition all 1536 subjects reporting asthma were invited to clinical examinations. Sera were received from 906 subjects with asthma and from 1000 without reported asthma (controls) and were tested for three IgE panels of inhalant and food allergens. Samples with a level of IgE >0.35 kUA/l were further analyzed for IgE against each individual allergen and nine allergen components related to furry animals. Results: The risk of being sensitized to any of the 21 tested allergens was significantly higher in the asthma group. The risk was highest for individuals sensitized to furry animals (risk ratios 4,5-7,9). The level of IgE to animal allergens was also significantly higher in the asthma group. Co-sensitization to more than one cat and/or dog allergen component conferred a greater risk for asthma. Simultaneous sensitization to the cat allergens Fel d 1 and Fel d 4 was associated with asthma. Conclusions: In this large population-based study subjects with asthma were commonly co-sensitized to more than one animal allergen component, especially to Fel d 1 and Fel d 4. Component-resolved analysis has the potential to increase precision when assessing asthma in adults.

  • 29. Stray-Pedersen, Asbjorg
    et al.
    Sorte, Hanne Sormo
    Samarakoon, Pubudu
    Gambin, Tomasz
    Chinn, Ivan K.
    Akdemir, Zeynep H. Coban
    Erichsen, Hans Christian
    Forbes, Lisa R.
    Gu, Shen
    Yuan, Bo
    Jhangiani, Shalini N.
    Muzny, Donna M.
    Rodningen, Olaug Kristin
    Sheng, Ying
    Nicholas, Sarah K.
    Noroski, Lenora M.
    Seeborg, Filiz O.
    Davis, Carla M.
    Canter, Debra L.
    Mace, Emily M.
    Vece, Timothy J.
    Allen, Carl E.
    Abhyankar, Harshal A.
    Boone, Philip M.
    Beck, Christine R.
    Wiszniewski, Wojciech
    Fevang, Borre
    Aukrust, Pal
    Tjonnfjord, Geir E.
    Gedde-Dahl, Tobias
    Hjorth-Hansen, Henrik
    Dybedal, Ingunn
    Nordoy, Ingvild
    Jorgensen, Silje F.
    Abrahamsen, Tore G.
    Overland, Torstein
    Bechensteen, Anne Grete
    Skogen, Vegard
    Osnes, Liv T. N.
    Kulseth, Mari Ann
    Prescott, Trine E.
    Rustad, Cecilie F.
    Heimdal, Ketil R.
    Belmont, John W.
    Rider, Nicholas L.
    Chinen, Javier
    Cao, Tram N.
    Smith, Eric A.
    Soledad Caldirola, Maria
    Bezrodnik, Liliana
    Lugo Reyes, Saul Oswaldo
    Espinosa Rosales, Francisco J.
    Guerrero-Cursaru, Nina Denisse
    Pedroza, Luis Alberto
    Poli, Cecilia M.
    Franco, Jose L.
    Trujillo Vargas, Claudia M.
    Aldave Becerra, Juan Carlos
    Wright, Nicola
    Issekutz, Thomas B.
    Issekutz, Andrew C.
    Abbott, Jordan
    Caldwell, Jason W.
    Bayer, Diana K.
    Chan, Alice Y.
    Aiuti, Alessandro
    Cancrini, Caterina
    Holmberg, Eva
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Burstedt, Magnus
    Karaca, Ender
    Yesil, Gozde
    Artac, Hasibe
    Bayram, Yavuz
    Atik, Mehmed Musa
    Eldomery, Mohammad K.
    Ehlayel, Mohammad S.
    Jolles, Stephen
    Flato, Berit
    Bertuch, Alison A.
    Hanson, I. Celine
    Zhang, Victor W.
    Wong, Lee-Jun
    Hu, Jianhong
    Walkiewicz, Magdalena
    Yang, Yaping
    Eng, Christine M.
    Boerwinkle, Eric
    Gibbs, Richard A.
    Shearer, William T.
    Lyle, Robert
    Orange, Jordan S.
    Lupski, James R.
    Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 1, p. 232-245Article in journal (Refereed)
    Abstract [en]

    Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

  • 30. Tjalvin, Gro
    et al.
    Svanes, Øistein
    Igland, Jannicke
    Bertelsen, Randi Jacobsen
    Benediktsdóttir, Bryndís
    Dharmage, Shyamali
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Holm, Mathias
    Janson, Christer
    Jõgi, Nils Oskar
    Johannessen, Ane
    Malinovschi, Andrei
    Pape, Kathrine
    Real, Francisco Gomez
    Sigsgaard, Torben
    Torén, Kjell
    Vindenes, Hilde Kristin
    Zock, Jan-Paul
    Schlünssen, Vivi
    Svanes, Cecilie
    Maternal preconception occupational exposure to cleaning products and disinfectants and offspring asthma2022In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 149, no 1, p. 422-431.eArticle in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emerging research suggests health effects in offspring after parental chemical exposures before conception. Many future mothers are exposed to potent chemicals at work, but potential offspring health effects are hardly investigated.

    OBJECTIVE: We sought to investigate childhood asthma in relation to mother's occupational exposure to cleaning products and disinfectants before conception.

    METHODS: The multicenter Respiratory Health In Northern Europe/Respiratory Health In Northern Europe, Spain and Australia generation study investigated asthma and wheeze starting at age less than 10 years in 3318 mother-offspring pairs. From an asthma-specific Job-Exposure Matrix and mothers' occupational history, we defined maternal occupational exposure to indoor cleaning agents (cleaning products/detergents and disinfectants) starting before conception, in the 2-year period around conception and pregnancy, or after birth. Never-employed mothers were excluded. Exposed groups include cleaners, health care workers, cooks, and so forth. Associations were analyzed using mixed-effects logistic regression and ordinary logistic regression with clustered robust SEs and adjustment for maternal education.

    RESULTS: Maternal occupational exposure to indoor cleaning starting preconception and continuing (n = 610) was associated with offspring's childhood asthma: odds ratio 1.56 (95% CI, 1.05-2.31), childhood asthma with nasal allergies: 1.77 (1.13-2.77), and childhood wheeze and/or asthma: 1.71 (95% CI, 1.19-2.44). Exposure starting around conception and pregnancy (n = 77) was associated with increased childhood wheeze and/or asthma: 2.25 (95% CI, 1.03-4.91). Exposure starting after birth was not associated with asthma outcomes (1.13 [95% CI, 0.71-1.80], 1.15 [95% CI, 0.67-1.97], 1.08 [95% CI, 0.69-1.67]).

    CONCLUSIONS: Mother's occupational exposure to indoor cleaning agents starting before conception, or around conception and pregnancy, was associated with more childhood asthma and wheeze in offspring. Considering potential implications for vast numbers of women in childbearing age using cleaning agents, and their children, further research is imperative.

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  • 31. Triebner, Kai
    et al.
    Johannessen, Ane
    Puggini, Luca
    Benediktsdottir, Bryndis
    Bertelsen, Randi J.
    Bifulco, Ersilia
    Dharmage, Shyamali C.
    Dratva, Julia
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gislason, Thorarinn
    Holm, Mathias
    Jarvis, Deborah
    Leynaert, Benedicte
    Lindberg, Eva
    Malinovschi, Andrei
    Macsali, Ferenc
    Norbäck, Dan
    Omenaas, Ernst R.
    Rodriguez, Francisco J.
    Saure, Eirunn
    Schlunssen, Vivi
    Sigsgaard, Torben
    Skorge, Trude D.
    Wieslander, Gunilla
    Zemp, Elisabeth
    Svanes, Cecilie
    Hustad, Steinar
    Real, Francisco Gomez
    Menopause as a predictor of new-onset asthma: A longitudinal Northern European population study2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 137, no 1, p. 50-+Article in journal (Refereed)
    Abstract [en]

    Background: There is limited and conflicting evidence on the effect of menopause on asthma. Objectives: We sought to study whether the incidence of asthma and respiratory symptoms differ by menopausal status in a longitudinal population-based study with an average follow-up of 12 years. Methods: The Respiratory Health in Northern Europe study provided questionnaire data pertaining to respiratory and reproductive health at baseline (1999-2001) and follow-up (2010-2012). The study cohort included women aged 45 to 65 years at follow-up, without asthma at baseline, and not using exogenous hormones (n = 2322). Menopausal status was defined as nonmenopausal, transitional, early postmenopausal, and late postmenopausal. Associations with asthma (defined by the use of asthma medication, having asthma attacks, or both) and respiratory symptoms scores were analyzed by using logistic (asthma) and negative binomial (respiratory symptoms) regressions, adjusting for age, body mass index, physical activity, smoking, education, and study center. Results: The odds of new-onset asthma were increased in women who were transitional (odds ratio, 2.40; 95% CI, 1.09-5.30), early postmenopausal (odds ratio, 2.11; 95% CI, 1.06-4.20), and late postmenopausal (odds ratio, 3.44; 95% CI, 1.31-9.05) at follow-up compared with nonmenopausal women. The risk of respiratory symptoms increased in early postmenopausal (coefficient, 0.40; 95% CI, 0.06-0.75) and late postmenopausal (coefficient, 0.69; 95% CI, 0.15-1.23) women. These findings were consistent irrespective of smoking status and across study centers. Conclusions: New-onset asthma and respiratory symptoms increased in women becoming postmenopausal in a longitudinal population-based study. Clinicians should be aware that respiratory health might deteriorate in women during reproductive aging.

  • 32.
    Warm, Katja
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease in Northern Sweden Studies, Norrbotten County Council, Luleå, Sweden.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, Bo
    Obstructive Lung Disease in Northern Sweden Studies, Norrbotten County Council, Luleå, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Low incidence and high remission of allergic sensitization among adults2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 1, p. 136-142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prospective studies on the incidence and remission of allergic sensitization among adults are rare.

    OBJECTIVE: We sought to assess the incidence, remission, risk factors, and prevalence of allergic sensitization in relation to aging over a 10-year period.

    METHODS: In 1994, a sample of 664 adults (68% of invited) participated in clinical examinations, including a structured interview and skin prick tests (SPTs). The sample was randomly selected from a large questionnaire survey in Northern Sweden. In 2004, 555 subjects (93% of invited) were re-examined by using the same methods as in 1994. IgE levels were also measured in 2004.

    RESULTS: In 1994, the prevalence of any positive SPT response was significantly related to age, with the highest prevalence (55%) in subjects aged 20 to 29 years and the lowest prevalence (26%) in subjects aged 50 to 60 years. A similar age-related prevalence was found in 2004, and sensitization to pollen and pets was most common in both years. The results of the SPTs were verified by means of specific IgE measurement. The incidence of any positive SPT response was low. Only 9 subjects had any positive SPT response (ie, a cumulative incidence of 5% over 10 years). Remission was greater (ie, 32% over 10 years). The main risk factors for allergic sensitization were young age and a family history of allergy. Having had furred animals at home during childhood was negatively related to specific IgE levels.

    CONCLUSION: The low incidence and high remission in adulthood explain the decreasing prevalence of allergic sensitization by age. Thus the low prevalence of allergic sensitization among the elderly found in cross-sectional studies is an effect of normal aging and not primarily a birth cohort effect.

  • 33.
    Warm, Katja
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lötvall, Jan
    Lundbäck, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Allergic sensitization is age-dependently associated with rhinitis, but less so with asthma2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 136, no 6, p. 1559-U201Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiologic data describing the association between allergic sensitization and asthma and allergic rhinitis in adults are scarce.

    OBJECTIVE: To determine the prevalence and impact of specific sensitization to airborne allergens on asthma and allergic rhinitis among adults in relation to age.

    METHODS: A random population sample (age 21-86 years) was examined with structured interview and analysis of specific IgE to 9 common airborne allergens. Of those invited, 692 (68%) subjects participated in blood sampling. IgE level of 0.35 U/mL or more to the specific allergen was defined as a positive test result.

    RESULTS: Allergic sensitization decreased with increasing age, both in the population sample and among subjects with asthma and allergic rhinitis. In a multivariate model, sensitization to animal was significantly positively associated with asthma (odds ratio [OR], 4.80; 95% CI, 2.68-8.60), whereas sensitization to both animal (OR, 3.90; 95% CI, 2.31-6.58) and pollen (OR, 4.25; 95% CI, 2.55-7.06) was significantly associated with allergic rhinitis. The association between allergic sensitization and rhinitis was consistently strongest among the youngest age group, whereas this pattern was not found for asthma. The prevalence of allergic sensitization among patients with asthma decreased by increasing age of asthma onset, 86% with asthma onset at age 6 y or less, 56% at age 7 to 19 years, and 26% with asthma onset at age 20 years or more.

    CONCLUSIONS: Sensitization to animal was associated with asthma across all age groups; allergic rhinitis was associated with sensitization to both pollen and animal and consistently stronger among younger than among older adults. Early onset of asthma was associated with allergic sensitization among adults with asthma.

  • 34.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Renz, Harald
    Jenmalm, Maria C
    Kozyrskyj, Anita L
    Allen, Katrina J
    Vuillermin, Peter
    Prescott, Susan L
    The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 1, p. 3-14Article in journal (Refereed)
    Abstract [en]

    Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.

  • 35.
    Wilson, Jeffrey M.
    et al.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Keshavarz, Behnam
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    James, Hayley R.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Retterer, Maya K.C.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Schuyler, Alexander J.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Knoedler, Alice
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Workman, Lisa J.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Ng'ang'a, Lucy
    United States International University, Nairobi, Kenya.
    Chico, Martha E.
    Fundación Ecuatoriana Para Investigación para Salud, Quinindé, Ecuador.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Heymann, Peter W.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Perzanowski, Matthew S.
    Mailman School of Public Health, Columbia University, NY, New York, United States.
    Platts-Mills, Thomas A.E.
    Division of Allergy & Clinical Immunology, University of Virginia, Va, Charlottesville, United States.
    Cooper, Philip J.
    Fundación Ecuatoriana Para Investigación para Salud, Quinindé, Ecuador; Institute of Infection and Immunity, St George's University of London, London, United Kingdom; Escuela de Medicina, Universidad Internacional del Ecuador, Quito, Ecuador.
    α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG42021In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 147, no 4, p. 1393-1401.e7Article in journal (Refereed)
    Abstract [en]

    Background: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated. Objective: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya. Methods: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children. Results: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States. Conclusions: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.

  • 36. Wilson, Jeffrey M.
    et al.
    Keshavarz, Behnam
    Retterer, Maya
    Workman, Lisa J.
    Schuyler, Alexander J.
    McGowan, Emily C.
    Lane, Charles
    Kandeel, Alaaddin
    Purser, Jane
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    LaRussa, Joseph
    Commins, Scott P.
    Merritt, Tina
    Platts-Mills, Thomas A. E.
    A dynamic relationship between two regional causes of IgE-mediated anaphylaxis: alpha-Gal syndrome and imported fire ant2021In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 147, no 2, p. 643-652.e7Article in journal (Refereed)
    Abstract [en]

    Background: A syndrome of mammalian meat allergy relating to IgE specific for galactose-alpha-1,3-galactose (alpha-Gal) was first reported 10 years ago in the southeastern United States and has been related to bites of the lone star tick (Amblyomma americanum).

    Objective: Here we investigated the epidemiology of the "alpha-Gal syndrome'' in the United States and sought additional evidence for the connection to tick bites.

    Methods: A survey of allergists was conducted by using a snowball approach. A second tier of the survey included questions about anaphylaxis to imported fire ants (IFAs). History of tick bites and tick-related febrile illness were assessed as part of a case-control study in Virginia. Antibody assays were conducted on sera from subjects reporting allergic reactions to mammalian meat or IFA.

    Results: In North America the alpha-Gal syndrome is recognized across the Southeast, Midwest, and Atlantic Coast, with many providers in this area managing more than 100 patients each. The distribution of cases generally conformed to the reported range of A americanum, although within this range there was an inverse relationship between alpha-Gal cases and cases of IFA anaphylaxis that were closely related to the territory of IFA. The connection between tick bites and alpha-Gal sensitization was further supported by patients' responses to a questionnaire and the results of serologic tests.

    Conclusions: The alpha-Gal syndrome is commonly acquired in adulthood as a consequence of tick bites and has a regional distribution that largely conforms to the territory of the lone star tick. The epidemiology of the syndrome is expected to be dynamic and shifting north because of climate change and ecologic competition from IFA.

  • 37. Wopereis, Harm
    et al.
    Van Ampting, Marleen
    Candy, David C. A.
    Peroni, Diego
    Vandenplas, Yvan
    Fox, Adam
    Nijhuis, Manon M. Oude
    Harthoorn, Lucien
    Michaelis, Louise J.
    Knol, Jan
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gut Microbiota Composition of Non-IgE Mediated Cow's Milk Allergic Infants before and after Dietary Management with a Synbiotics-Supplemented Amino Acid-Based Formula2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 2, p. AB53-AB53Article in journal (Refereed)
  • 38.
    Österlund, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bodén, Stina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Revised Swedish infant feeding guidelines are associated with earlier introduction of allergenic foods2023In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825Article in journal (Refereed)
    Abstract [en]

    Background: Randomized controlled trials have demonstrated that early introduction of allergenic foods, such as peanut and egg, can reduce food allergy in high-risk children. Many international guidelines recommend introduction of allergenic foods in the first year of life, and accordingly, the Swedish National Food agency released updated guidelines in June 2019.

    Objective: Our aim was to examine whether the age at introduction and consumption frequency of allergenic foods have changed since release of the revised national guidelines on the introduction of solid foods in Sweden.

    Methods: Children born between June 2016 and December 2018 (n = 1925) were compared with children born between June 2019 and April 2021 (n = 1761) by using data from the NorthPop Birth Cohort study. Data on food introduction, eczema, and food allergy were prospectively collected until age 18 months by using web-based questionnaires. IgE sensitization was assessed at 18 age months.

    Results: The proportion of participants who had been introduced to egg, legume, soy products, peanut, almond, and cashew nut during the first year of life increased after implementation of the revised national guidelines. The most significant changes were seen for legume (from 55.2% to 69.8% [adjusted odds ratio = 1.90 (95% CI = 1.62-2.24)] and peanut (from 29.2% to 43.2% adjusted odds ratio = 1.87 (95% CI = 1.55-2.24)]); consumption frequency had also increased. No differences in the prevalence of eczema, food allergy, or sensitization to the foods of interest were found.

    Conclusion: Since release of the revised guidelines, infants in the general population are introduced to and consume a variety of allergenic foods earlier and more frequently; however, early manifestations of allergic disease have remained unchanged.

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  • 39. Östling, Jörgen
    et al.
    van Geest, Marleen
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    Jevnikar, Zala
    Wilson, Susan
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    Bakke, Per S.
    Caruso, Massimo
    Dahlen, Sven-Erik
    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, Section of Medicine.
    Sun, Kai
    Pandis, Ioannis
    Auffray, Charles
    Sousa, Ana R.
    Guo, Yike
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    Chung, Kian Fan
    Bigler, Jeanette
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    Sousa, A. R.
    Sterk, P. J.
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    IL-17-high asthma with features of a psoriasis immunophenotype2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, no 5, p. 1198-1213Article in journal (Refereed)
    Abstract [en]

    Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.

    Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.

    Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.

    Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1BIL6IL8, and β-defensin.

    Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

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