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  • 1.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Duchén, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

    Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

    Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

    Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

    Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

  • 2.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lempinen, Esma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lindblad, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy2014In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, p. 387-393Article in journal (Refereed)
    Abstract [en]

    Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

    Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

    Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

    Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

  • 3.
    Ahlbeck, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Astmainhalator med återkopplingssystem gav bättre vård och sänkta kostnader [Asthma inhaler with feedback system provided better care and lower costs].2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 5, p. 160-160Article in journal (Other academic)
  • 4.
    Bergfors, Elisabet
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. University of Gothenburg, Sweden.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Valter, Lars
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Trollfors, Birger
    Sahlgrenska University Hospital-East, Gothenburg, Sweden .
    How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study2014In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 173, no 10, p. 1297-1307Article in journal (Refereed)
    Abstract [en]

    The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. Conclusion: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

  • 5.
    Bergfors, Elisabet
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Lundmark, Katarzyna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines2013In: BMJ Case Reports, ISSN 1757-790XArticle in journal (Refereed)
    Abstract [en]

    A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.

  • 6.
    Bernfort, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Chronic pain in a population 65 years and older: correlation with age of health care costs and quality of life2015Conference paper (Refereed)
  • 7.
    Bernfort, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Nyström Kronander, Ulla
    Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Allergenspecifik immunoterapi vid behandling av allergisk rinit: Behandlingseffekter, kostnader och kostnadseffektivitet2012Report (Other academic)
    Abstract [sv]

    Prevalensen av allergier har skattats till omkring 20 % i Sverige. Allergisk rinit är vanligast bland unga vuxna och prevalensen är högre i länder med hög levnadsstandard. På individnivå har miljön i tidig barndom stor betydelse för utveckling av allergier senare i livet. Symtomen förknippade med allergisk rinit ger upphov till nedsatt livskvalitet, vårdkostnader, och produktionsförluster till följd av sjukskrivningar.

    Tidigare fanns endast symtomlindrande behandlingar att tillgå, men på senare år har sjukdomsmodifierande behandlingar lanserats. Dessa består av allergenspecifika immunoterapier (ASIT) som bygger på en successivt ökad tillvänjning av allergenextrakt för att skapa immunitet. ASIT kan bestå av subkutan immunoterapi (SCIT) eller sublingual immunoterapi (SLIT). Det finns läkemedel av detta slag som ingår i den svenska läkemedelsförmånen, men med begränsningen att de får förskrivas endast när bästa möjliga symtomdämpande behandling inte ger ett tillfredsställande resultat. Syftet med denna rapport var att genom en litteraturgenomgång undersöka vilken evidens som finns för klinisk effekt, inverkan på kostnader, samt kostnadseffektivitet av ASIT jämfört med enbart symtomatisk behandling vid allergisk rinit. Litteraturgenomgången utgjorde sedan grund för en bedömning av behovet av att genomföra en svensk kostnadseffektstudie.

    Vad gäller klinisk effekt av ASIT jämfört med symtomatisk behandling hittades flera studier av såväl SCIT som SLIT. Studierna visade genomgående på signifikanta förbättringar jämfört med symtomatisk behandling med avseende på symtom, livskvalitet, och behov av symtomatisk medicinering. Även vårdkostnader andra än de för symtomatisk behandling är lägre med ASIT.

    Kostnadseffektiviteten av ASIT har analyserats i flera studier gällande europeiska förhållanden. I ett par av dessa studier har även svenska förhållanden studerats specifikt. Samtliga publicerade studier fann att kostnadseffektiviteten av ASIT var god, med kostnader per QALY under 200 000 kronor om bara direkta kostnader beaktas och betydligt lägre kostnader per QALY om även indirekta kostnader beaktas. Dessa resultat bekräftas i ett räkneexempel utifrån kända fakta som avslutar denna rapport.

    Sammantaget talar publicerade vetenskapliga studier enhälligt för att ASIT, jämfört med enbart symtomatisk behandling, är en kostnadseffektiv behandling. Det finns ingen anledning att tro att denna slutsats skulle förändras av att genomföra en kostnadseffektstudie under svenska förhållanden. Vid en sådan studie bör extra fokus ligga på att utreda effekter på livskvalitet (QALYs) och produktionsförluster.

  • 8.
    Bousquet, J.
    et al.
    University Hospital Montpellier, France MACVIA LR, France ARIA, France European Academic Allergy and Clin Immunol, France European Innovat Partnership Act and Health Ageing, France European Innovat Partnership Act and Health Ageing, France University of Montpellier I, France .
    Addis, A.
    European Innovat Partnership Act and Health Ageing, France European Innovat Partnership Act and Health Ageing, Italy .
    Adcock, I.
    University of London Imperial Coll Science Technology and Med, England Royal Brompton and Harefield NIHR Biomed Research Unit, England .
    Agache, I.
    ARIA, France Romanian Alliance Chron Resp Disease, Romania Transylvania University, Romania .
    Agusti, A.
    University of Barcelona, Spain CIBER Enfermedades Resp, Spain .
    Alonso, A.
    Hospital Clin Barcelona, Spain .
    Annesi-Maesano, I.
    ARIA, France .
    M. Anto, J.
    University of Pompeu Fabra, Spain .
    Bachert, C.
    ARIA, France Ghent University Hospital, Belgium Ghent University Hospital, Belgium .
    E. Baena-Cagnani, C.
    ARIA, France Catholic University, Argentina .
    Bai, C.
    Chinese Medical Assoc, Peoples R China .
    Baigenzhin, A.
    EuroAsian Resp Soc, Kazakhstan .
    Barbara, C.
    European Innovat Partnership Act and Health Ageing, France Portuguese National Programme Resp Disease, Portugal .
    Barnes, P.J.
    University of London Imperial Coll Science Technology and Med, England Royal Brompton and Harefield NIHR Biomed Research Unit, England .
    Bateman, E.D.
    ARIA, France University of Cape Town, South Africa .
    Beck, L.
    Health Innovat Centre Southern Denmark, Denmark .
    Bedbrook, A.
    MACVIA LR, France ARIA, France .
    Bel, E.H.
    University of Amsterdam, Netherlands .
    Benezet, O.
    MACVIA LR, France .
    Bennoor, K.S.
    ARIA, France Bangladesh Lung Fdn, Bangladesh National Institute Disease Chest and Hospital, Bangladesh .
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Bernabeu-Wittel, M.
    European Innovat Partnership Act and Hlthy Ageing, Spain Andalusian Healthcare Serv, Spain .
    Bewick, M.
    NHS England, England .
    Bindslev-Jensen, C.
    ARIA, France Odense University Hospital, Denmark Odense University Hospital, Denmark .
    Blain, H.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France .
    Blasi, F.
    University of Milan, Italy .
    Bonini, M.
    ARIA, France University of Roma La Sapienza, Italy .
    Bonini, S.
    ARIA, France University of Naples 2, Italy Italian National Research Council, Italy .
    Boulet, L.P.
    ARIA, France University of Laval, Canada .
    Bourdin, A.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France INSERM, France .
    Bourret, R.
    University Hospital Montpellier, France MACVIA LR, France .
    Bousquet, P.J.
    ARIA, France .
    Brightling, C.E.
    Glenfield Hospital, England .
    Briggs, A.
    University of Glasgow, Scotland .
    Brozek, J.
    ARIA, France McMaster University, Canada McMaster University, Canada .
    Buh, R.
    Mainz University Hospital, Germany .
    Bush, A.
    ARIA, France University of London Imperial Coll Science Technology and Med, England University of London Imperial Coll Science Technology and Med, England .
    Caimmi, D.
    University Hospital Montpellier, France MACVIA LR, France .
    Calderon, M.
    University of Costa Rica, Costa Rica University of London Imperial Coll Science Technology and Med, England .
    Calverley, P.
    University of Liverpool, England Aintree University Hospital NHS Fdn Trust, England .
    Camargos, P.A.
    ARIA, France University of Federal Minas Gerais, Brazil .
    Camuzat, T.
    MACVIA LR, France .
    Canonica, G.W.
    ARIA, France University of Genoa, Italy .
    Carlsen, K.H.
    ARIA, France University of Oslo, Norway Oslo University Hospital, Norway .
    Casale, T.B.
    ARIA, France .
    Cazzola, M.
    University of Roma Tor Vergata, Italy .
    Cepeda Sarabia, A.M.
    ARIA, France University of Simon Bolivar, Colombia Soc Latinoamer Allergia Asma and Immunol, Italy .
    Cesario, A.
    IRCCS San Raffaele Pisana, Italy .
    Chen, Y.Z.
    Peking and Centre Asthma Research and Educ, Peoples R China .
    Chkhartishvili, E.
    Grigol Robakidze University, Rep of Georgia .
    Chavannes, N.
    ARIA, France Int Primary Care Resp Grp, Netherlands Leiden University, Netherlands .
    Chiron, R.
    University Hospital Montpellier, France MACVIA LR, France .
    Chuchalin, A.
    ARIA, France WHO, Russia Pulmonol Research Institute, Russia Russian Resp Soc, Russia .
    Chung, K.F.
    University of London Imperial Coll Science Technology and Med, England Royal Brompton and Harefield NIHR Biomed Research Unit, England .
    Cox, L.
    ARIA, France Nova SE University, FL USA .
    Crooks, G.
    NHS Scotland, Scotland .
    G. Crooks, M.
    Hull York Medical Sch, England .
    A. Cruz, A.
    ARIA, France WHO, Russia University of Federal Bahia, Brazil CNPq, Brazil .
    Custovic, A.
    ARIA, France European Academic Allergy and Clin Immunol, France University of Manchester, England .
    Dahl, R.
    ARIA, France Odense University Hospital, Denmark Odense University Hospital, Denmark .
    E. Dahlen, S.
    Karolinska Institute, Sweden .
    De Blay, F.
    ARIA, France Soc Francaise Allergol, France Strasbourg University, France .
    Dedeu, T.
    European Regional and Health Author, Belgium .
    Deleanu, D.
    ARIA, France University of Medical and Pharm Iuliu Hatieganu, Romania .
    Demoly, P.
    University Hospital Montpellier, France MACVIA LR, France ARIA, France European Academic Allergy and Clin Immunol, France European Innovat Partnership Act and Health Ageing, France University of Montpellier I, France .
    Devillier, P.
    ARIA, France University of Versailles St Quentin, France .
    Didier, A.
    Soc Pneumol Langue Francaise, France University of Toulouse, France .
    T. Dinh-Xuan, A.
    Paris Descartes University, France .
    Djukanovic, R.
    University of Southampton, England NIHR, England .
    Dokic, D.
    ARIA, France University of Ss Cyril and Methodius, Macedonia .
    Douagui, H.
    ARIA, France Centre Hospital University of Beni Messous, Algeria .
    Dubakiene, R.
    ARIA, France Lithuanian Soc Allergol and Clin Immunol, Lithuania Vilnius State University, Lithuania .
    Eglin, S.
    University of Liverpool, England .
    Elliot, F.
    NHS Scotland, Scotland .
    Emuzyte, R.
    ARIA, France Lithuanian Soc Allergol and Clin Immunol, Lithuania Vilnius State University, Lithuania .
    Fabbri, L.
    University of Modena and Reggio Emilia, Italy .
    Fink Wagner, A.
    Global Allergy and Asthma Patient Platform, Austria .
    Fletcher, M.
    WHO, Russia Educ Heatlh, England .
    Fokkens, W.J.
    ARIA, France University of Amsterdam, Netherlands European Rhinol Soc, Portugal .
    Fonseca, J.
    ARIA, France Portuguese National Programme Resp Disease, Portugal Porto Age Up Consortium, Portugal University of Porto, Portugal University of Porto, Portugal Institute and Hospital CUF Porto, Portugal .
    Franco, A.
    University of Nice Sophia Antipolis, France .
    Frith, P.
    Repatriat Gen Hospital, Australia .
    Furber, A.
    Wakefield Council, England .
    Gaga, M.
    Athens Chest Hospital, Greece Athens Chest Hospital, Greece .
    Garces, J.
    European Innovat Partnership Act and Health Ageing, Spain University of Valencia, Spain .
    Garcia-Aymerich, J.
    University of Pompeu Fabra, Spain .
    Gamkrelidze, A.
    ARIA, France National Centre Disease Control and Public Health Georgia, Rep of Georgia .
    Gonzales-Diaz, S.
    ARIA, France Soc Latinoamer Allergia Asma and Immunol, Italy .
    Gouzi, F.
    University Hospital Montpellier, France INSERM, France .
    A. Guzman, M.
    ARIA, France University of Chile, Chile .
    Haahtela, T.
    ARIA, France Helsinki University Hospital, Finland .
    Harrison, D.
    Public Health Blackburn Darwen, England .
    Hayot, M.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France .
    G. Heaney, L.
    Queens University of Belfast, North Ireland .
    Heinrich, J.
    MeDALL, Mechanisms of the Development of Allergy.
    Hellings, P. W.
    ARIA, France European Academic Allergy and Clin Immunol, France University Hospital Leuven, Belgium .
    Hooper, J.
    Public Health Kirklees, England .
    Humbert, M.
    Soc Pneumol Langue Francaise, France .
    Hyland, M.
    University of Plymouth, England .
    Iaccarino, G.
    University of Salerno, Italy IRCCS Multimed, Italy .
    Jakovenko, D.
    MACVIA LR, France .
    R. Jardim, J.
    University of Federal Sao Paulo, Brazil .
    Jeandel, C.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France .
    Jenkins, C.
    George Institute Global Heatlh, Australia University of Sydney, Australia .
    L. Johnston, S.
    ARIA, France University of London Imperial Coll Science Technology and Med, England .
    Jonquet, O.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France .
    Joos, G.
    Ghent University Hospital, Belgium .
    S. Jung, K.
    Hallym University, South Korea .
    Kalayci, O.
    ARIA, France European Academic Allergy and Clin Immunol, France Hacettepe University, Turkey .
    Karunanithi, S.
    Director of Public Health, Lancashire, UK.
    Keil, T.
    Charite, Germany University of Wurzburg, Germany .
    Khaltaev, N.
    ARIA, France WHO, Russia .
    Kolek, V.
    Czech Alliance Against Chron Resp Disease, Poland .
    L. Kowalski, M.
    Medical University of Lodz, Poland .
    Kull, I.
    Karolinska Institute, Sweden .
    Kuna, P.
    ARIA, France European Innovat Partnership Act and Health Ageing, France WHO, Russia Medical University of Lodz, Poland .
    Kvedariene, V.
    ARIA, France European Academic Allergy and Clin Immunol, France Lithuanian Soc Allergol and Clin Immunol, Lithuania Vilnius State University, Lithuania .
    T. Le, L.
    ARIA, France WHO, Russia University of Medical and Pharm, Vietnam .
    C. Lodrup Carlsen, K.
    ARIA, France University of Oslo, Norway Oslo University Hospital, Norway .
    Louis, R.
    University of Liege, Belgium .
    MacNee, W.
    University of Edinburgh, Scotland .
    Mair, A.
    Scottish Govt, Scotland .
    Majer, I.
    University of Bratislava, Slovakia .
    Manning, P.
    Bon Secours Hospital, Ireland .
    de Manuel Keenoy, E.
    European Innovat Partnership Act and Health Ageing, France Kronikgune, Spain .
    R. Masjedi, M.
    Shahid Beheshti University of Medical Science, Iran .
    Meten, E.
    ARIA, France Karolinska Institute, Sweden .
    Melo-Gomes, E.
    European Innovat Partnership Act and Health Ageing, France Portuguese National Programme Resp Disease, Portugal .
    Menzies-Gow, A.
    Royal Brompton Hospital, England .
    Mercier, G.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France .
    Mercier, J.
    University Hospital Montpellier, France MACVIA LR, France European Innovat Partnership Act and Health Ageing, France University of Montpellier I, France .
    P. Michel, J.
    Geneva School Med, Switzerland University Hospital Geneva, Switzerland .
    Miculinic, N.
    University Hospital Pulm Disease, Croatia .
    Mihaltan, F.
    ARIA, France Institute Pneumol Marius Nasta, Romania .
    Milenkovic, B.
    University of Belgrade, Serbia COPD Serbia, Serbia .
    Molimard, M.
    Bordeaux University, France .
    Mamas, I.
    Paris Descartes University, France Paris Municipal, France .
    Montilla-Santana, A.
    European Innovat Partnership Act and Hlthy Ageing, Spain .
    Morais-Almeida, M.
    Hospital CUF Descobertas, Portugal .
    Morgan, M.
    NHS England, England .
    NDiaye, M.
    Hop Polyclin Dakar IHS, Senegal .
    Nafti, S.
    ARIA, France Mustapha Hospital, Algeria .
    Nekam, K.
    ARIA, France Hospital Hospital Bros Buda, Hungary .
    Neou, A.
    Charite, Germany .
    Nicod, L.
    CHUV Lausanne, Switzerland .
    OHehir, R.
    ARIA, France Alfred Hospital, Australia Monash University, Australia .
    Ohta, K.
    ARIA, France Tokyo National Hospital, Japan Teikyo University, Japan .
    Paggiaro, P.
    University Hospital Pisa, Italy .
    Palkonen, S.
    ARIA, France .
    Palmer, S.
    University of York, England .
    Papadopoulos, N. G.
    ARIA, France European Academic Allergy and Clin Immunol, France University of Manchester, England University of Athens, Greece .
    Papi, A.
    University of Ferrara, Italy .
    Passalacqua, G.
    ARIA, France University of Genoa, Italy .
    Pavord, I.
    University of Oxford, England .
    Pigearias, B.
    SPLF, Espace francophone de Pneumologie.
    Plavec, D.
    University of JJ Strossmayer, Croatia .
    Postma, D. S.
    University of Groningen, Netherlands .
    Price, D.
    ARIA, France Int Primary Care Resp Grp, Netherlands University of Aberdeen, Scotland .
    Rabe, K. F.
    University of Kiel, Germany .
    Radier Pontal, F.
    MACVIA LR, France .
    Redon, J.
    European Innovat Partnership Act and Health Ageing, France University of Valencia, Spain .
    Rennard, S.
    University of Nebraska Medical Centre, NE USA .
    Roberts, J.
    Salford Royal NHS Fdn Trust, England .
    Robine, J. M.
    MACVIA LR, France INSERM, France .
    Roca, J.
    University of Barcelona, Spain CIBER Enfermedades Resp, Spain .
    Roche, N.
    University of Paris 05, France Soc Pneumol Langue Francaise, France .
    Rodenas, F.
    European Innovat Partnership Act and Health Ageing, Spain University of Valencia, Spain .
    Roggeri, A.
    Arcispedale S Maria Nuova Hospital, Italy .
    Rolland, C.
    Assoc Asthme and Allergies, France .
    Rosado-Pinto, J.
    ARIA, France European Innovat Partnership Act and Health Ageing, France Portuguese National Programme Resp Disease, Portugal WHO, Russia .
    Ryan, D.
    ARIA, France Int Primary Care Resp Grp, Netherlands Woodbrook Medical Centre, England University of Edinburgh, Scotland .
    Samolinski, B.
    European Innovat Partnership Act and Health Ageing, France Medical University of Lodz, Poland Medical University of Warsaw, Poland .
    Sanchez-Borges, M.
    Centre Medical Docente La Trinidad, Venezuela .
    Schunemann, H. J.
    McMaster University, Canada McMaster University, Canada .
    Sheikh, A.
    University of Edinburgh, Scotland Harvard University, MA 02115 USA .
    Shields, M.
    Queens University of Belfast, North Ireland Royal Belfast Hospital Sick Children, North Ireland .
    Siafakas, N.
    University Hospital Heraklion, Greece .
    Sibille, Y.
    Catholic University of Louvain, Belgium .
    Similowski, T.
    University of Paris 06, France INSERM, France Grp Hospital Pitie Salpetriere Charles Foix, France Fonds Dotat Rech Sante Resp Fdn Souffle, France .
    Small, I.
    National Advisory Group, Respiratory Managed Clinical Networks in Scotland.
    Sola-Morales, O.
    Health Institute Technology Transfer, Spain .
    Sooronbaev, T.
    ARIA, France WHO, Russia EuroAsian Resp Soc, Kyrgyzstan National Centre Cardiol and Internal Med, Kyrgyzstan .
    Stelmach, R.
    University of Sao Paulo, Brazil .
    Sterk, P. J.
    University of Amsterdam, Netherlands .
    Stiris, T.
    University of Oslo, Norway .
    Sud, P.
    Regional Medical Manager (North), NHS England, UK.
    Tellier, V.
    Observatoire wallon de la santé, Direction générale opérationnelle Pouvoirs locaux, action sociale et Santé, Service public de Wallonie, Belgium .
    To, T.
    WHO, Russia .
    Todo-Bom, A.
    Coimbra University Hospital, Portugal .
    Triggiani, M.
    University of Salerno, Italy .
    Valenta, R.
    ARIA, France Medical University of Vienna, Austria .
    Valero, A. L.
    University of Barcelona, Spain CIBER Enfermedades Resp, Spain .
    Valiulis, A.
    ARIA, France Lithuanian Soc Allergol and Clin Immunol, Lithuania Vilnius State University, Lithuania .
    Valovirta, E.
    University of Turku, Finland .
    Van Ganse, E.
    CHU Lyon, France CHU Lyon, France University of Lyon 1, France .
    Vandenplas, O.
    ARIA, France INSERM, France .
    Vasankari, T.
    FILHA, Finnish Lung Association.
    Vestbo, J.
    University of Manchester, England Odense University Hospital, Denmark .
    Vezzani, G.
    Arcispedale S Maria Nuova IRCCS, Italy .
    Viegi, G.
    CNR, Italy CNR, Italy Clin Physiol IFC, Italy .
    Visier, L.
    University Hospital Montpellier, France MACVIA LR, France University of Montpellier I, France .
    Vogelmeier, C.
    University of Marburg, Germany .
    Vontetsianos, T.
    Sotiria Hospital, Greece .
    Wagstaff, R.
    Cumbria County Council, PA USA .
    Wahn, U.
    Charite, Germany .
    Wallaert, B.
    Soc Francaise Allergol, France CHRU, France .
    Whalley, B.
    University of Plymouth, England .
    Wickman, M.
    ARIA, France Karolinska Institute, Sweden .
    M. Williams, D.
    University of N Carolina, NC USA .
    Wilson, N.
    North England EU Health Partnership, Belgium .
    Yawn, B. P.
    ARIA, France Olmsted Medical Centre, MN USA University of Minnesota, MN USA .
    Yiallouros, P.K.
    ARIA, France Cyprus University of Technology, Cyprus .
    Yorgancioglu, A.
    ARIA, France .
    Yusuf, O. M.
    WHO, Russia Allergy and Asthma Institute, Pakistan .
    Zar, H. J.
    University of Cape Town, South Africa .
    Zhong, N.
    Guangzhou Medical University, Peoples R China Guangzhou Medical University, Peoples R China .
    Zidarn, M.
    ARIA, France University of Clin Resp and Allerg Disease, Slovenia .
    Zuberbier, T.
    Charite, Germany .
    Integrated care pathways for airway diseases (AIRWAYS-ICPs)2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 2, p. 304-323Article in journal (Refereed)
    Abstract [en]

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYS-ICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

  • 9.
    Boyle, R J
    et al.
    Imperial College London.
    Pedroletti, C
    Karolinska Institutet, Stockholm.
    Wickman, M
    Karolinska Institutet, Stockholm.
    Bjermer, L
    Lund University Hospital.
    Valovirta, E
    Terveystalo Allergy Clinic, Turku, Finland.
    Dahl, R
    Aarhus University Hospital, Denmark .
    Von Berg, A
    Marien-Hospital, Wesel, Germany .
    Zetterström, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Warner, J O
    Imperial College London.
    Nocturnal temperature controller laminar airflow for treating atopic asthma: a randomised controlled trial2012In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 67, no 3, p. 215-221Article in journal (Refereed)
    Abstract [en]

       Objective To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. <br> <br>Design Randomised, double-blind, placebo-controlled, parallel-group trial. <br> <br>Setting Nineteen European asthma clinics. <br> <br>Participants 312 patients aged 7-70 with inadequately controlled persistent atopic asthma. <br> <br>Main outcome measure Proportion of patients with an increase of &gt;= 0.5 points in asthma quality of life score after 1 year of treatment. <br> <br>Results TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).(3) In patients aged &gt;= 12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of -7.1 ppb (-13.6 to -0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. <br> <br>Conclusion Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma.

  • 10.
    Brodtkorb, Thor-Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Zetterström, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Tinghög, Gustav
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Cost-effectiveness of clean air administered to the breathing zone in allergic asthma2010In: CLINICAL RESPIRATORY JOURNAL, ISSN 1752-6981, Vol. 4, no 2, p. 104-110Article in journal (Refereed)
    Abstract [en]

    Introduction: Airsonett Airshower (AA) is a novel non-pharmaceutical treatment for patients with perennial allergic asthma that uses a laminar airflow directed to the breathing zone of patients during sleep. It has been shown that AA treatment in addition to optimized standard therapy significantly increases asthma-related quality of life among adolescent asthmatics. However, the cost-effectiveness of AA treatment has not yet been assessed. As reimbursement decisions are increasingly guided by results from the cost-effectiveness analysis, such information is valuable for health-care policy-makers. Objective: The objective of this study was to estimate the cost-effectiveness of adding AA treatment with allergen-free air during night sleep to optimized standard therapy for adolescents with perennial allergic asthma compared with placebo. Materials and Methods: A probabilistic Markov model was developed to estimate costs and health outcomes over a 5-year period. Costs and effects are presented from a Swedish health-care perspective (QALYs). The main outcome of interest was cost per QALY gained. Results: The Airshower strategy resulted in a mean gain of 0.25 QALYs per patient, thus yielding a cost per QALY gained of under 35 000 as long as the cost of Airshower is below 8200. Conclusions: Adding AA treatment to optimized standard therapy for adolescents with perennial allergic asthma compared with placebo is generating additional QALYs at a reasonable cost. However, further studies taking more detailed resource use and events such as exacerbations into account would be needed to fully evaluate the cost-effectiveness of AA treatment. Please cite this paper as: Brodtkorb T-H, Zetterstrom O and Tinghog G. Cost-effectiveness of clean air administered to the breathing zone in allergic asthma.

  • 11.
    Bruhn, Sören
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fang, Yu
    Guiyang Medical Coll, Peoples R China University of Gothenburg, Sweden .
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Konstantinell, Aelita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Kronke, Andrea
    Cenix BioScience GmbH, Germany .
    Sonnichsen, Birte
    Cenix BioScience GmbH, Germany .
    Bresnick, Anne
    Albert Einstein Coll Med, NY 10461 USA .
    Dulyaninova, Natalya
    Albert Einstein Coll Med, NY 10461 USA .
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhao, Yelin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Klingelhofer, Jorg
    University of Copenhagen, Denmark .
    Ambartsumian, Noona
    University of Copenhagen, Denmark .
    Beck, Mette K.
    Technical University of Denmark, Denmark .
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bona, Elsa
    Boras Hospital, Sweden .
    Xiang, Zou
    University of Gothenburg, Sweden .
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy2014In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 6, no 218Article in journal (Refereed)
    Abstract [en]

    The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identified a T helper 2 (T(H)2) cell module by small interfering RNA-mediated knockdown of 25 putative IL13-regulating transcription factors followed by expression profiling. The module contained candidate genes whose diagnostic potential was supported by clinical studies. Functional studies of human TH2 cells as well as mouse models of allergy showed that deletion of one of the genes, S100A4, resulted in decreased signs of allergy including TH2 cell activation, humoral immunity, and infiltration of effector cells. Specifically, dendritic cells required S100A4 for activating T cells. Treatment with an anti-S100A4 antibody resulted in decreased signs of allergy in the mouse model as well as in allergen-challenged T cells from allergic patients. This strategy, which may be generally applicable to complex diseases, identified and validated an important diagnostic and therapeutic candidate gene in allergy.

  • 12.
    Edström, Måns
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Huddinge University Hospital.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines2014Manuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND Regulatory T cells (Treg) are critical for immune regulation and homeostasis. In multiple sclerosis (MS), the function of these cells has been shown to be impaired, although the underlying mechanism has yet to be shown. In the current study, we aimed to characterize and assess the phenotypical, functional and transcriptional characteristics of memory and naïve Treg in MS patients and controls.

    MATERIAL AND METHODS 27 patients with relapsing-remitting disease were included, along with 29 healthy controls. Flow cytometry was used for detailed phenotyping of Treg subpopulations CD4+CD45RA+/- and CD4dimCD25++ and their expression of FOXP3, CD39 and HELIOS. CFSE (proliferation marker) and CD69 (activation marker) were used to investigate the functional capacity of Treg. A microarray was employed for genome-wide transcriptional characterization of isolated Treg.

    RESULTS CD4+CD45RA–CD25++ activated Treg displayed a higher expression of FOXP3 and CD39 than resting CD4+CD45RA+CD25+ Treg, while no significant phenotypical differences were observed in Treg subpopulations between patients and controls. However, a lower anti-proliferative capacity was observed in activated Treg of MS patients compared with those of controls (p<0.05), while suppression of activation was similar to controls. Gene set enrichment analysis (GSEA) of microarray data revealed enrichment for the GO gene set ‘chemokine receptor binding’ in MS Treg.

    CONCLUSION Although numerical phenotypical assessment of resting and activated Tregs did not reveal any significant difference between patients and controls, functional co-culturing experiments showed an impaired function in activated Treg of MS patients. Furthermore, GSEA revealed immune-related gene sets overexpressed in Treg of MS patients, possibly containing clues to the functional impairment. In particular over-activity in chemokine signalling in Treg would be of interest for further investigation.

  • 13.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    James, A. Rani
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Liljenstrom, R.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Muraro, A.
    Padua University Hospital, Italy .
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    The Allergic Airway Inflammation Repository - a user-friendly, curated resource of mRNA expression levels in studies of allergic airways2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 8, p. 1115-1117Article in journal (Refereed)
    Abstract [en]

    Public microarray databases allow analysis of expression levels of candidate genes in different contexts. However, finding relevant microarray data is complicated by the large number of available studies. We have compiled a user-friendly, open-access database of mRNA microarray experiments relevant to allergic airway inflammation, the Allergic Airway Inflammation Repository (AAIR, http://aair.cimed.ike.liu.se/). The aim is to allow allergy researchers to determine the expression profile of their genes of interest in multiple clinical data sets and several experimental systems quickly and intuitively. AAIR also provides quick links to other relevant information such as experimental protocols, related literature and raw data files.

  • 14.
    Genuneit, J.
    et al.
    Ulm University, Germany.
    Cantelmo, J. L.
    National Heart and Lung Institute, Imperial College London, UK .
    Weinmayr, G.
    Ulm University, Germany.
    Wong, G. W. K.
    Prince of Wales Hospital, Chinese University of Hong Kong, China.
    Cooper, P. J.
    Centro de Investigaciónes FEPIS, Quinindé, Ecuador.
    Riikjärv, M.-A.
    Tallinn Children's Hospital, Tallinn, Estonia.
    Gotua, M.
    Center of Allergy and Immunology, Tbilisi, Georgia.
    Kabesch, M.
    Hannover Medical School, Germany.
    von Mutius, E.
    Ludwig-Maximilians University, Munich, Germany.
    Forastiere, F.
    Local Health Authority Rome, Italy.
    Crane, J.
    Wellington School of Medicine and Health Sciences, New Zealand .
    Nystad, W.
    Norwegian Institute of Public Health, Oslo, Norway.
    El-Sharif, N.
    AL-Quds University, Jerusalem, Palestine.
    Batlles-Garrido, J.
    Torrecárdenas Hospital, Almería, Spain.
    García-Marcos, L.
    Arrixaca University Children's Hospital and CIBER of Epidemiology and Public Health (CIBERESP), Murcia, Spain.
    García-Hernández, G.
    12 de Octubre Children's Hospital, Madrid, Spain.
    Morales-Suarez-Varela, M.
    University of Valencia, Valencia, Spain.
    Nilsson, Lennart J.
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Bråbäck, L
    Sundsvall Hospital, Sweden,.
    Saraçlar, Y
    Hacettepe University, Ankara, Turkey.
    Weiland, S. K.
    Ulm University, Germany.
    Cookson, W. O. C.
    National Heart and Lung Institute, Imperial College London, UK .
    Strachan, D.
    St George's, University of London, UK.
    Moffatt, M. F.
    National Heart and Lung Institute, Imperial College London, UK .
    A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 22009In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 39, no 12, p. 1875-1888Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.

    METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis.

    RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies.

    CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

  • 15.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Edström, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Tojo, James
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Kockum, Ingrid
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Olsson, Tomas
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Serra-Musach, Jordi
    IDIBELL, Spain .
    Bonifaci, Nuria
    IDIBELL, Spain .
    Angel Pujana, Miguel
    IDIBELL, Spain .
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment2014In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 17Article in journal (Refereed)
    Abstract [en]

    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

  • 16.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barabasi, Albert-Laszlo
    Northeastern University, MA 02115 USA.
    Baranzini, Sergio
    University of Calif San Francisco, CA 94143 USA.
    Brunak, Soeren
    Technical University of Denmark, Denmark; University of Copenhagen, Denmark.
    Fan Chung, Kian
    University of London Imperial Coll Science Technology and Med, England.
    Federoff, Howard J.
    Georgetown University, DC 20057 USA.
    Gavin, Anne-Claude
    European Molecular Biol Lab, Germany.
    Meehan, Richard R.
    University of Edinburgh, Scotland.
    Picotti, Paola
    University of Zurich, Switzerland.
    Angel Pujana, Miguel
    Bellvitge Biomed Research Institute IDIBELL, Spain.
    Rajewsky, Nikolaus
    Max Delbruck Centre Molecular Med, Germany.
    Smith, Kenneth G. C.
    University of Cambridge, England; University of Cambridge, England.
    Sterk, Peter J.
    University of Amsterdam, Netherlands.
    Villoslada, Pablo
    Hospital Clin Barcelona, Spain; Hospital Clin Barcelona, Spain.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Modules, networks and systems medicine for understanding disease and aiding diagnosis2014In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 82Article, review/survey (Refereed)
    Abstract [en]

    Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.

  • 17.
    Hallander, H
    et al.
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Gustafsson, L
    Swedish Institute for Communicable Disease Control, Stockholm.
    Is adolescent perutssis vaccination prefrable to natural booster infections?2011In: Expert Review of Clinical Pharmacology, ISSN 1751-2433, Vol. 4, no 6, p. 705-711Article, review/survey (Refereed)
    Abstract [en]

    Pertussis is still poorly controlled in both adolescents and adults. As a result, an adolescent pertussis booster vaccine dose has already been implemented or decided on in many countries. The reasons for this have been twofold: a worrying increase of infections in the target group of adolescents and a wish to prevent serious pertussis disease among young yet unvaccinated, and partly vaccinated, infants. Currently, it is still too early to evaluate the effect of the late booster on the circulation of Bordetella pertussis owing to the lack of relevant follow-up data. A universal adolescent booster vaccination will reduce the incidence of pertussis in the target group but the duration of immunity is uncertain. It is an open question as to what extent boosters should be offered to older age groups or if natural infections would be preferable. On the one hand, circulating B. pertussis may be hazardous to the youngest unvaccinated infants. On the other hand, subclinical natural boosters might be beneficial to population immunity. As the duration of immunity is shorter after vaccination than after natural infections, an unwanted consequence of adolescent boosters might shift the infection peak to older child-bearing adults. It is therefore recommended that recurrent serosurveys are used to follow the influence of vaccination on the antigenic pressure, as well as the duration of protective immunity. For this purpose, standardization of symptoms and laboratory criteria used for notification, as well as the methodology for seroepidemiology, must be established. Adverse reactions after adolescent vaccination and outbreaks owing to new B. pertussis variants must also be carefully monitored. In this article, we have used Swedish surveillance data and the results from Swedish seroepidemiology to illustrate these problem areas.

  • 18.
    Hallander, Hans O.
    et al.
    Swedish Institute for Infectious Disease Control (SMI), Solna, Sweden.
    Ljungman, Margretha
    Swedish Institute for Infectious Disease Control (SMI), Solna, Sweden.
    Jahnmatz, Maja
    Swedish Institute for Infectious Disease Control (SMI), Solna, Sweden.
    Storsaeter, Jann
    Norwegian institute of Public Health, Oslo, Norway.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Gustafsson, Lennart
    Swedish Institute for Infectious Disease Control (SMI), Solna, Sweden.
    Should fimbriae be included in pertussis vaccines? Studies on ELISA IgG anti-Fim2/3 antibodies after vaccination and infection2009In: APMIS: Acta pathologica, microbiologica et immunologica Scandinavica. Supplementum, ISSN 0903-465X, E-ISSN 1600-5503, Vol. 117, no 9, p. 660-671Article in journal (Refereed)
    Abstract [en]

    The anti-Fim response and long-term persistence after vaccination and infection may be of importance in understanding population immunity. Longitudinal serum samples (n = 1330) from 542 non-infected children related to a Swedish vaccine trial showed that the post vaccination (DTPa5) antibody decay curve for pertussis ELISA IgG anti-fimbriae2/3 (anti-Fim2/3) was bi-phasic. A slower one followed an initial rapid decay approximately 5-6 months after the third dose at 12 months of age. After 71 months, however, 60% still had concentrations above > or =5 EU/ml, a level that had been shown to correlate with decreased risk of disease. Booster responses after re-vaccination with DTPa5 at 4, 5 and 6 years of age were strong and appeared within 1 week after vaccination, indicating immune memory. Ninety-six young children with verified pertussis infection, for whom we had serum samples both before, during and after the infection, showed a high response if they had been primed with fimbriae (either DTPa5 or DTPwc). In contrast, 76% of infected children not primed with fimbriae (a DTPa2 or DT group) only had concentrations below the minimum level of detection in all samples taken during and after the infection. In two Swedish seroepidemiological surveys, one from 1997 just after reintroduction of universal childhood vaccination against pertussis and one from 2007, the proportion of children 2-3 years with anti-Fim2/3 concentrations <5 EU/ml was similar and above 90%. This reflects that the two- or three-component pertussis vaccines (DTPa2 and DTPa3) that were introduced in Sweden in 1996 do not induce anti-Fim2/3 antibodies. In previous studies it was shown in multivariate analyses that levels of IgG anti-Fim2/3 > or =5 EU/ml reduced short-term risk of pertussis in small children. As the antibody response to Fim2/3 after infection is poor in children who have not been primed earlier in life, inclusion of immunogenic Fim2/3 in future pertussis vaccines should be considered.

  • 19.
    Jahnmatz, Maja
    et al.
    Public Health Agency Sweden, Sweden; Karolinska Institute, Sweden.
    Ljungman, Margaretha
    Public Health Agency Sweden, Sweden.
    Netterlid, Eva
    Public Health Agency Sweden, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Public Health Agency Sweden, Sweden.
    Thorstensson, Rigmor
    Public Health Agency Sweden, Sweden.
    Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 9, p. 1301-1308Article in journal (Refereed)
    Abstract [en]

    In order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n = 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria-tetanus-5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus-low-dose diphtheria-5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin- and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents.

  • 20.
    Kilpi, Terhi M
    et al.
    National Public Health Institute, Finland.
    Arne Silfverdal, Sven
    University of Örebro.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Syrjanen, Ritva
    San Matteo Hospital.
    Desole, Maria
    AUSL 1, Italy.
    Triban, Chiara
    GlaxoSmithKline.
    Storsaeter, Jann
    GlaxoSmithKline.
    Soila, Maaria
    GlaxoSmithKline.
    Jacquet, Jeanne-Marie
    GlaxoSmithKline.
    Immunogenicity and reactogenicity of two diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccines administered at 3, 5 and 11-12 months of age2009In: HUMAN VACCINES, ISSN 1554-8619, Vol. 5, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    The use of combination vaccines in the routine childhood program reduces distress to the recipients and is likely to improve uptake rates and timeliness of vaccination but requires careful evaluation and surveillance. The aim of this study was to evaluate the immunogenicity and reactogenicity of two commercial diphtheria-tetanus-acellular pertussis-hepatitis b-inactivated polio virus-Haemophilus influenzae type b (DTaP-HBV-IPV/Hib) combination vaccines when administered to infants at 3, 5 and 11-12 months of age. A total of 494 infants were randomized to receive three doses of either Infanrix hexa T (GlaxoSmithKline Biologicals; N = 246) or Hexavac (TM) (Sanofi Pasteur MSD; N = 248) in 10 centers in Italy, Finland and Sweden. After the third dose, antibodies to diphtheria, tetanus, polio and Hib were at the protective level in nearly all infants in both groups whereas the proportion of subjects who had achieved the protective concentration of = 10 mIU/ml to hepatitis B surface antigen was 99.1% (95% CI 96.7-99.9) in the Infanrix hexa T group as compared to 94.4% (95% CI 90.4-97.1) in the Hexavac T group. Antibody titers to all three polio antigens were highest in Italy and lowest in Finland. Clinically relevant general reactions (such as fever of >39.5 degrees C) were mostly reported in less than 5% of the vaccinees. Three doses of DTaP-HBV-IPV/Hib combination vaccines produced sufficient immune responses in nearly all vaccinees.

  • 21.
    Kivling, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Faresjö, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    How and when to pick up the best signals from markers associated with T-regulatory cells?2009In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 345, no 1-2, p. 29-39Article in journal (Refereed)
    Abstract [en]

    Regulatory T (Treg) cells are important tools with the purpose to control and regulate the immune system. These cells use FOXP3, TGF-beta, CTLA-4 and sCTLA-4 to regulate other T-cells. Since cryopreservation of peripheral blood mononuclear cells (PBMC) is a convenient way to handle samples, we investigated whether these cells will change their mRNA expression of Treg associated markers, as well as secretion of TGF-beta1, after cryopreservation. Additionally, we aimed to investigate the mRNA expression after two different time intervals of in vitro antigen stimulation. PBMC from healthy adults were stimulated either fresh (48/96 h) or after cryopreservation (48 h), with PHA, tetanus toxoid, beta-lactoglobulin, ovalbumin or in culture medium exclusively (spontaneous). The mRNA expression of FOXP3, TGF-beta, CTLA-4 and sCTLA-4 were studied with multiplex real-time RT-PCR and TGF-beta1 with ELISA. Cryopreserved PBMC were appropriate for detection of the Treg associated markers FOXP3, TGF-beta, CTLA-4 and sCTLA-4 expressed spontaneously. Also antigen-induced mRNA expression of CTLA-4, sCTLA-4 and TGF-beta and secreted TGF-beta1, with the exception of FOXP3, preserved a stable transcription activity after cryopreservation. Further, a stimulation period of 48 h in general revealed the highest mRNA expression of the markers studied. In conclusion, cryopreserved cells are in general suitable for studying Treg associated markers.

  • 22.
    Koch, Andrea
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Clinical Aspects of Inflammation in Non-small Cell Lung Cancer2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lung cancer is the most common cause of cancer death worldwide, with about 1.2 million deaths every year. In Sweden, about 3500 new cases are diagnosed every year. The majority of patients presents with advanced non-small cell lung cancer (NSCLC) and is treated with palliative intent. Standard treatment in these patients in performance status 0-2 is combination chemotherapy. Radiotherapy may be added for palliative purposes. Median survival time with such treatment is 6-10 months. New treatment strategies are urgently needed. There is growing evidence for a link between cancer and inflammation and consequently, inflammation may be a possible target for the treatment of lung cancer.

    The aim of this thesis was to study clinical aspects of inflammation in non-small cell lung cancer. A central issue was to adapt the projects as close to clinical routine as possible.

    In a retrospective study of 289 patients (paper I), we investigated the prognostic value of Creactive protein (CRP), a nonspecific marker of systemic inflammation, and smoking in patients with advanced NSCLC treated with palliative first-line chemotherapy. We found that patients with elevated CRP values (≥10 mg/ml) and current smokers at onset of treatment had inferior survival compared to patients with normal CRP values and patients who were not smoking. CRP and smoking status were independent prognostic factors and provided additional information to established prognostic factors such as stage of disease and performance status.

    The expression of COX-2, an important enzyme involved in inflammation, was prospectively analysed in 53 patients with cytologically diagnosed lung cancer (paper II). The study showed that the analysis of COX-2 expression in cytological material is technically easy to perform with routine diagnostic methods and results in good quality slides. There was great variation in the proportion of COX-2 positive cells between the patients as well as in the intensity of staining between individual cells in many single cases.

    The major project (paper III) of this thesis was the CYCLUS study, an academic, randomised, double-blind, phase III trial. The scientific question was if addition of the COX-2 inhibitor celecoxib to first-line palliative chemotherapy would prolong survival in patients with advanced NSCLC. 316 patients were included at 13 centres in Sweden. There was no survival difference between the treatment arms. Celecoxib appeared to have more favourable effect on survival in women than in men, but the differences were not significant. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.

    List of papers
    1. Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy.
    Open this publication in new window or tab >>Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy.
    2009 (English)In: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, ISSN 1556-1380, Vol. 4, no 3, p. 326-32Article in journal (Refereed) Published
    Abstract [en]

    HYPOTHESIS: The objective of the study was to analyze if C-reactive protein (CRP) and smoking status provide prognostic information in patients with advanced non-small cell lung cancer (NSCLC) receiving palliative first-line chemotherapy. METHODS: Retrospective, single-institutional study, comprising all patients with NSCLC stage IIIB/IV and World Health Organization performance status (PS) 0-2 who started palliative first-line chemotherapy between January 1, 2002, and January 31, 2007. Patient records were reviewed. Cox's proportional hazards model was used to identify prognostic factors. RESULTS: Two hundred eight-nine consecutive patients were evaluable. Sixty-eight percent had stage IV disease and 67% had PS 0 or 1. Median survival was 7.4 months. At onset of chemotherapy, 206 patients (71%) had elevated CRP values (> or = 10 mg/liter). One-hundred-forty-four patients (50%) were current smokers. On univariate analysis, patients with elevated CRP levels had inferior survival (hazard ratio [HR] = 1.67, 95% confidence interval [CI], 1.28-2.19, p < 0.001). Smoking at onset of treatment was associated with shorter survival (HR 1.56, 95% CI, 1.22-1.98, p < 0.001). Ever smokers had shorter survival than never smokers (HR 1.80, 95% CI, 1.25-2.59, p = 0.001). On multivariate analysis, with stage, PS, albumin, and gender as covariates, both smoking at start of chemotherapy and CRP elevation were independent negative prognostic factors for survival. CONCLUSIONS: CRP and smoking status are independent prognostic factors for survival in patients with advanced NSCLC receiving palliative first-line chemotherapy and provide additional information to established prognostic factors such as stage of disease and performance status.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18964 (URN)10.1097/JTO.0b013e31819578c8 (DOI)19155996 (PubMedID)
    Available from: 2009-06-06 Created: 2009-06-06 Last updated: 2014-04-08
    2. Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry
    Open this publication in new window or tab >>Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry
    2011 (English)In: Diagnostic Cytopathology, ISSN 8755-1039, E-ISSN 1097-0339, Vol. 39, no 3, p. 188-193Article in journal (Refereed) Published
    Abstract [en]

    Cyclooxygenase-2 (COX-2) expression may be a prognostic factor in lung cancer. In previous studies, COX-2 expression has almost exclusively been evaluated with immunohistochemical methods performed on histology sections of tissue biopsies. However, in clinical practice, lung cancer is often diagnosed with cytological techniques only. We present methodology and results from analysis of COX-2 expression with immunochemistry on cytological material in 53 patients with lung cancer. Preparation and staining with the method established at our laboratory were easy to perform and resulted in good quality slides. The percentage COX-2-stained cells and the intensity of staining varied widely between and within the different cases. The proportion of positively stained tumor cells was as follows: <1% in 20 patients, 1-10% in 7 patients, 11-50% in 17 patients, and more than 50% in 9 patients. In 17 cases, groups of cells with different intensity of COX-2 staining were found in the same slide. In conclusion, immunocytochemical analysis of COX-2 expression is technically easy to perform with routine diagnostic procedures. There is a great variation in the proportion of COX-2-positive cells among patients and in the intensity of staining among individual cells in many single cases. Diagn. Cytopathol.2011;39:188-193. © 2010 Wiley-Liss, Inc.

    Place, publisher, year, edition, pages
    John Wiley and Sons, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66083 (URN)10.1002/dc.21366 (DOI)000288035400006 ()21319320 (PubMedID)
    Available from: 2011-03-04 Created: 2011-03-02 Last updated: 2017-12-11Bibliographically approved
    3. Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group
    Open this publication in new window or tab >>Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group
    Show others...
    2011 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 10, p. 1546-1555Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Increased expression of cyclooxygenase-2 (COX-2) is common in non-small cell lung cancer (NSCLC) and has been associated with poor prognosis. Experimental and clinical phase II trials have indicated that the addition of the COX-2 inhibitor celecoxib to palliative chemotherapy might increase survival time in patients with advanced NSCLC.

    METHODS: We performed a double-blind, placebo-controlled multicentre phase III trial at 13 centres in Sweden. Three hundred and nineteen patients with advanced NSCLC stage IIIB-IV and performance status 0-2 were randomised to receive celecoxib 400mg b.i.d. or placebo in addition to palliative chemotherapy. The primary objective was to compare overall survival. Other end-points were quality of life, progression-free survival, toxicity, cardiovascular events and biological markers. The trial is registered with ClinicalTrials.gov, No. NCT00300729.

    FINDINGS: Three hundred and sixteen patients were included in the analysis, 158 in each treatment group. Median survival time was 8.5months. There was no survival difference between the treatment arms. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.

    INTERPRETATION: This study failed to demonstrate a survival benefit of the addition of celecoxib to palliative chemotherapy.

    Place, publisher, year, edition, pages
    Elsevier, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-68748 (URN)10.1016/j.ejca.2011.03.035 (DOI)000292946200015 ()21565487 (PubMedID)
    Available from: 2011-06-01 Created: 2011-06-01 Last updated: 2017-12-11Bibliographically approved
  • 23.
    Koch, Andrea
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Bergman, Bengt
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Holmberg, Erik
    Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden.
    Sederholm, Christer
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine UHL.
    Ek, Lars
    Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund, Sweden.
    Kosieradzki, Jaroslaw
    Department of Respiratory Medicine and Allergology, Skåne University Hospital, Malmö, Sweden.
    Lamberg, Kristina
    Department of Pulmonary Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Thaning, Lars
    Department of Pulmonary Medicine, University Hospital, Örebro, Sweden.
    Ydreborg, Sven-Olof
    Department of Medicine, County Hospital Ryhov, 551 85 Jönköping, Sweden.
    Sörenson, Sverre
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine UHL.
    Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 10, p. 1546-1555Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increased expression of cyclooxygenase-2 (COX-2) is common in non-small cell lung cancer (NSCLC) and has been associated with poor prognosis. Experimental and clinical phase II trials have indicated that the addition of the COX-2 inhibitor celecoxib to palliative chemotherapy might increase survival time in patients with advanced NSCLC.

    METHODS: We performed a double-blind, placebo-controlled multicentre phase III trial at 13 centres in Sweden. Three hundred and nineteen patients with advanced NSCLC stage IIIB-IV and performance status 0-2 were randomised to receive celecoxib 400mg b.i.d. or placebo in addition to palliative chemotherapy. The primary objective was to compare overall survival. Other end-points were quality of life, progression-free survival, toxicity, cardiovascular events and biological markers. The trial is registered with ClinicalTrials.gov, No. NCT00300729.

    FINDINGS: Three hundred and sixteen patients were included in the analysis, 158 in each treatment group. Median survival time was 8.5months. There was no survival difference between the treatment arms. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.

    INTERPRETATION: This study failed to demonstrate a survival benefit of the addition of celecoxib to palliative chemotherapy.

  • 24.
    Koch, Andrea
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Gustafsson, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Sörenson, Sverre
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine UHL.
    Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry2011In: Diagnostic Cytopathology, ISSN 8755-1039, E-ISSN 1097-0339, Vol. 39, no 3, p. 188-193Article in journal (Refereed)
    Abstract [en]

    Cyclooxygenase-2 (COX-2) expression may be a prognostic factor in lung cancer. In previous studies, COX-2 expression has almost exclusively been evaluated with immunohistochemical methods performed on histology sections of tissue biopsies. However, in clinical practice, lung cancer is often diagnosed with cytological techniques only. We present methodology and results from analysis of COX-2 expression with immunochemistry on cytological material in 53 patients with lung cancer. Preparation and staining with the method established at our laboratory were easy to perform and resulted in good quality slides. The percentage COX-2-stained cells and the intensity of staining varied widely between and within the different cases. The proportion of positively stained tumor cells was as follows: <1% in 20 patients, 1-10% in 7 patients, 11-50% in 17 patients, and more than 50% in 9 patients. In 17 cases, groups of cells with different intensity of COX-2 staining were found in the same slide. In conclusion, immunocytochemical analysis of COX-2 expression is technically easy to perform with routine diagnostic procedures. There is a great variation in the proportion of COX-2-positive cells among patients and in the intensity of staining among individual cells in many single cases. Diagn. Cytopathol.2011;39:188-193. © 2010 Wiley-Liss, Inc.

  • 25.
    Lindskog, Sven
    et al.
    DentoSyst Scandinavia AB.
    Blomlof, Johan
    DentoSyst Scandinavia AB.
    Persson, Inger
    DentoSyst Scandinavia AB.
    Niklason, Anders
    Med Competence Resources.
    Hedin, Anders
    Perioscience, Eskilstuna.
    Ericsson, Leif
    Vastervik Hospital.
    Ericsson, Mats
    Roslagstandlakarna.
    Jarncrantz, Bo
    FTV Kringlan.
    Palo, Ulf
    FTV Sodertalje Centre.
    Tellefsen, Georg
    Danakliniken.
    Zetterström, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Blomlof, Leif
    DentoSyst Scandinavia AB.
    Validation of an Algorithm for Chronic Periodontitis Risk Assessment and Prognostication: Risk Predictors, Explanatory Values, Measures of Quality, and Clinical Use2010In: JOURNAL OF PERIODONTOLOGY, ISSN 0022-3492, Vol. 81, no 4, p. 584-593Article in journal (Refereed)
    Abstract [en]

    Background: The American Academy of Periodontology has recently stated that, "[risk assessment will become] increasingly important in periodontal treatment planning and should be part of every comprehensive dental and periodontal evaluation." (J Periodontol 2006;77:1608). Unaided risk assessment and prognostication show significant variability because chronic periodontitis is a multifactorial disease. This report summarizes the clinical validation of an algorithm for chronic periodontitis risk assessment and prognostication. The algorithm is a Web-based analytic tool that integrates some 20 risk predictors and calculates scores indicating levels of risk for chronic periodontitis for the dentition (Level I) and, if an elevated risk is found, prognosticates disease progression tooth by tooth (Level II). Methods: An independent clinical validation sample was generated in an open, prospective clinical trial and analyzed in a predetermined validation plan. Results: The analyses identified two threshold scores above which significant progression of periodontitis was found. Based on these scores, sufficiently high explanatory values with significant and increasing parameter estimates for increasing risk were established in Level I, justifying detailed analysis tooth by tooth in Level II. Subsequent prognostication of chronic periodontitis in Level II was found to be accompanied by clinically relevant measures of quality in relation to rates of disease progression. Three score intervals representing increasing levels of periodontitis progression were identified corresponding to increasing levels of significant annual marginal bone loss. Conclusions: The predictors included in the algorithm reflect a relevant selection for periodontitis risk assessment. Risk assessment and prognostication with the algorithm provides the clinician with a validated, reliable, consistent, and objective tool supporting treatment planning.

  • 26.
    Lindskog, Sven
    et al.
    DentoSyst Scandinavia AB, Stockholm.
    Blomlof, Johan
    DentoSyst Scandinavia AB, Stockholm.
    Persson, Inger
    DentoSyst Scandinavia AB, Stockholm.
    Niklason, Anders
    Medical Competence Resources, Bandhagen.
    Hedin, Anders
    Private practice, Perioscience, Eskilstuna.
    Ericsson, Leif
    Västervik Hospital.
    Ericsson, Mats
    Private practice, Roslagstandläkarna, Norrtälje.
    Järncrantz, Bo
    Folktandvården Kringlan, Södertälje.
    Palo, Ulf
    Folktandvården Södertälje Centrum.
    Tellefsen, Georg
    Danakliniken, Danderyd.
    Zetterström, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Blomlof, Leif
    DentoSyst Scandinavia AB, Stockholm.
    Validation of an Algorithm for Chronic Periodontitis Risk Assessment and Prognostication: Analysis of an Inflammatory Reactivity Test and Selected Risk Predictors2010In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 81, no 6, p. 837-847Article in journal (Refereed)
    Abstract [en]

    Background: Patients with severe forms of chronic periodontitis present with varying degrees of decreased inflammatory reactivity. A previously reported algorithm for chronic periodontitis risk assessment and prognostication is based on the analysis of some 20 risk predictors. One of these predictors is a skin provocation test that assesses the individual patient's reactivity to a lipid A challenge. The aim of this report was to analyze results from validation data for the algorithm with respect to the contribution of results of the skin provocation test as a risk predictor for the progression of chronic periodontitis and to compare these results with the contribution from other predictors, namely smoking, angular bony destruction, furcation involvement, abutment teeth, and endodontic pathology.

    Methods: Data from a previously reported clinical validation sample were used for the analysis, including the calculation of quality measures and explanatory values using different types of regression analysis and non-parametric testing.

    Results: Smoking, endodontic pathology, abutment teeth, angular bony destruction, and furcation involvement presented with individual explanatory values for periodontitis progression between 4% and 13% and highly significant parameter estimates. Explanatory values for the results of the skin provocation test ranged between 2.6% and 5.1% depending on the disease severity group, with a positive predictive value of 82% for the identification of high-risk patients.

    Conclusion: The skin provocation test provided a clinically significant contribution to the quality of analysis with the periodontitis risk and prognostication algorithm, in particular in the selection of high-risk patients for in-depth individual tooth analysis.

  • 27.
    Nestor, Colm
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bruhn, Sören
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Jornsten, Rebecka
    University of Gothenburg, Sweden .
    Langston, Michael A.
    University of Tennessee, TN USA .
    Rogers, Gary
    University of Tennessee, TN USA .
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4(+) T-Cell Population Structure2014In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 1, p. e1004059-Article in journal (Refereed)
    Abstract [en]

    Altered DNA methylation patterns in CD4(+) T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR) is an optimal disease model for the study of DNA methylation because of its welldefined phenotype and etiology. We generated genome-wide DNA methylation (N-patients = 8, N-controls = 8) and gene expression (N-patients = 9, N-controls = 10) profiles of CD4(+) T-cells from SAR patients and healthy controls using Illuminas HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (N-patients = 12, N-controls = 12), but not by gene expression (N-patients = 21, N-controls = 21) was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (N-patients = 35) and controls (N-controls = 12), which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4(+) T cells.

  • 28.
    Nestor, Colm E
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Dadfa, Elham
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sublingual immunotherapy alters expression of IL-4 and its soluble and membrane-bound receptors2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 11, p. 1564-1566Article in journal (Refereed)
    Abstract [en]

    Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T-helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL-4, and its soluble and membrane-bound receptor in SAR patients before and after SIT. Using allergen-challenge assays, we found that SIT treatment decreased IL-4 cytokine levels, as previously reported. We also observed a significant decrease in the IL-4 membrane-bound receptor (mIL4R) at both the level of mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL-4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.

  • 29.
    Nestor, Colm E
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting. MRC Human Genetics Unit, IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK.
    Reddington, James P
    MRC Human Genetics Unit, IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Meehan, Richard R
    MRC Human Genetics Unit, IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK.
    Investigating 5-hydroxymethylcytosine (5hmC): the state of the art2014In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1094, p. 243-58Article in journal (Refereed)
    Abstract [en]

    The discovery of 5-hydroxymethylcytosine (5hmC) as an abundant base in mammalian genomes has excited the field of epigenetics, and stimulated an intense period of research activity aimed at decoding its biological significance. However, initial research efforts were hampered by a lack of assays capable of specifically detecting 5hmC. Consequently, the last 3 years have seen the development of a plethora of new techniques designed to detect both global levels and locus-specific profiles of 5hmC in mammalian genomes. This research effort has culminated in the recent publication of two complementary techniques for quantitative, base-resolution mapping of 5hmC in mammalian genomes, the first true mammalian hydroxymethylomes. Here, we review the techniques currently available to researchers studying 5hmC, discuss their advantages and disadvantages, and explore the technical hurdles which remain to be overcome.

  • 30.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Carlsson, Rose-Marie
    Smittskyddsinstitutet, Solna.
    Hallander, Hans Olof
    Konsult.
    Ljungman, Margaretha
    Smittskyddsinstitutet, Solna.
    Hallberg, Mårten
    Centrallasarettet, Västerås.
    Storsaeter, Jann
    GlaxoSmithKline, Solna.
    Bra immunsvar av vaccination mot difteri, stelkramp och kikhosta i årskurs 4: Lokala reaktioner mycket vanliga – och förväntade2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 38, p. 2357-2361Article in journal (Refereed)
    Abstract [sv]

    Acellulärt kikhostevaccin, difterivaccin och stelkrampsvaccin gav bra serologiska svar vid påfyllnadsvaccination vid 10 års ålder. Även skolbarn som aldrig fått kikhostevaccin svarade med antikroppar mot kikhosta efter endast en dos acellulärt kikhostevaccin.

    Lokala biverkningar som ont i armen, rodnad/svullnad och klåda var mycket vanliga, och dessa lokalreaktioner höll i sig vanligtvis 3–4 dagar.

    Större lokala reaktioner om minst fem centimeters rodnad eller svullnad drabbade mellan vart tredje till vart sjätte barn.

    Dessa reaktioner är ofarliga, men det är viktigt att korrekt informera skolelever och föräldrar om vilka vanliga reaktioner som kan förväntas vid påfyllnadsvaccination mot difteri, stelkramp och kikhosta i denna ålder.

  • 31.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Lepp, Tiia
    Swedish Institute Communicable Disease Control.
    von Segebaden, Kerstin
    Swedish Institute Communicable Disease Control.
    Hallander, Hans
    Swedish Institute Communicable Disease Control.
    Gustafsson, Lennart
    Swedish Institute Communicable Disease Control.
    Pertussis vaccination in infancy lowers the incidence of pertussis disease and the rate of hospitalisation after one and two doses: Analyses of 10 years of pertussis surveillance2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 21, p. 3239-3247Article in journal (Refereed)
    Abstract [en]

    Objectives: Shortly after pertussis vaccination was reintroduced in Sweden in 1996, an intensified pertussis disease surveillance programme was set up. In this study, we report on in-depth analyses of age-dose-number-specific incidences and the rate of pertussis hospitalisation for children with no, 1 or 2 doses of an acellular pertussis vaccine before pertussis disease. Vaccine coverage, the timeliness of childhood vaccination and the effect of later than scheduled pertussis vaccination(s) are also examined. less thanbrgreater than less thanbrgreater thanStudy design: Children with notified laboratory-confirmed (culture or PCR) pertussis disease were evaluated among the surveillance population of about 1 million infants, born between 1996 and 2007 and followed for pertussis disease from October 1997 to December 2007, for nearly 6 million person-years. Birth and vaccination dates of the diseased children are known from the surveillance programme. To estimate denominators of the age-dose-number-specific pertussis incidences, we used birth and vaccination dates from a vaccine trial with more than 72,000 infants combined with national pertussis vaccine coverage data for children in the surveillance population. less thanbrgreater than less thanbrgreater thanResults: For infants from 3 to andlt;5 months of age, the incidence of pertussis disease with at least 14 days of cough decreased from 264/100,000 for unvaccinated infants to 155/100,000 for infants with one dose of a pertussis vaccine prior to onset of the disease. In the age range 5 to andlt;12 months, the age-dose specific incidences were 526, 95, and 24/100,000 for infants with no, 1 and 2 doses, respectively. The rate of hospitalisation for infants with 1 dose of a pertussis vaccine prior to onset of the disease was significantly lower than for unvaccinated infants of the same age. less thanbrgreater than less thanbrgreater thanFor many infants, there is a delay in administration of the vaccine doses according to the regular 3-5-12 month schedule (which has been the case for many years). Hypothetically, if all infants had been vaccinated exactly on schedule, we would expect about 28% fewer pertussis cases with at least 14 days of cough and 38% fewer hospitalisations due to pertussis, of cases possible to influence by vaccinations on schedule. less thanbrgreater than less thanbrgreater thanConclusion: Pertussis vaccination had a significant effect among infants already after the first dose. This is particularly important for premature infants and infants with severe respiratory and cardiac diseases. A moderate decrease in the incidence of pertussis disease in infants and rate of hospitalisation could be expected if primary vaccinations were carried out closer to the scheduled time than is currently the practice in Sweden.

  • 32.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Von Segebaden, Kerstin
    Blennow, Margareta
    Linde, Annika
    Uhnoo, Ingrid
    [Whooping cough is a risk to infants. The disease is circulating among adolescents and adults].2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 37, p. 1599-1602Article in journal (Refereed)
  • 33.
    Nyström Kronander, Ulla
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Urtikaria – utredning och behandling2010In: Allergi i Praxis, ISSN 0806-5462Article in journal (Other academic)
  • 34.
    Nyström Kronander, Ulla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Äggallergi och vaccin mot nya influensan. Handlingsplan finns i Östergötland2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 48, p. 3230-Article in journal (Refereed)
    Abstract [sv]

    Det har diskuterats om barn och vuxna med äggallergi ska erhålla vaccin mot den nya influen­san. Det finns nämligen spårmängder av äggprotein i vaccinet.

    Risken för allergisk reaktion är dock mycket liten, eftersom mängderna är i storleksordningen några nanogram.

    Vi har i Östergötland påbörjat en handlingsplan för vaccination av barn och vuxna med äggallergi.

  • 35.
    Pedroletti, C
    et al.
    Karolinska University Hospital.
    Millinger, Eva
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Allergy Centre UHL.
    Dahlen, B
    Karolinska University Hospital.
    Soderman, P
    Karolinska University Hospital.
    Zetterström, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Allergy Centre UHL.
    Clinical effects of purified air administered to the breathing zone in allergic asthma: A double-blind randomized cross-over trial2009In: RESPIRATORY MEDICINE, ISSN 0954-6111, Vol. 103, no 9, p. 1313-1319Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to inhaled allergens is a pathogenetic factor in allergic asthma. However, most studies that previously looked at air cleaning devices have shown little or no effect on patients with perennial allergic asthma. Aims and objectives: We examined a novel treatment using temperature regulated laminar airflow with a very low particle concentration directed to the breathing zone of teenagers and young adults with mild to moderate allergic asthma during night steep. We hypothesised that the decreased allergen exposure during the night would have an effect on bronchial inflammation and quality of life. Method: Twenty-two patients (mean 18.8 years) were randomized to start with active or placebo treatment for 10 weeks. At( patients received both active and placebo treatment with unfiltered air, with a 2-week wash-out period in between treatments. Maintenance treatment with inhaled corticosteroids was unaltered during the trial period. Health related quality of life (miniAQLQ) was the primary effectiveness measure. Exhaled nitric oxide (FeNO) and spirometry were also investigated. Results: Active treatment resulted in an improved miniAQLQ compared to placebo (mean score 0.54, p andlt; 0.05, n = 20). An effect on bronchial, inflammation was also detected with significantly tower FeNO values during the active treatment period (mean -6.95 ppb, p andlt; 0.05, n = 22). Both effects were evident after 5 weeks. The change in lung function was not statistically significant. Conclusion: Clean air, administered directly to the breathing zone during steep, can have a positive effect on bronchial. inflammation and quality of life in patients with perennial allergic asthma.

  • 36.
    Peolsson, Anneli
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Landén Ludvigsson, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Overmeer, Thomas
    Malardalen University, Sweden .
    Dedering, Asa
    Karolinska University Hospital, Sweden .
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Johansson, Gun
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Kammerlind, Ann-Sofi
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Peterson, Gunnel
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Effects of neck-specific exercise with or without a behavioural approach in addition to prescribed physical activity for individuals with chronic whiplash-associated disorders: a prospective randomised study2013In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 14, no 311Article in journal (Refereed)
    Abstract [en]

    Background: Up to 50% of chronic whiplash associated disorders (WAD) patients experience considerable pain and disability and remain on sick-leave. No evidence supports the use of physiotherapy treatment of chronic WAD, although exercise is recommended. Previous randomised controlled studies did not evaluate the value of adding a behavioural therapy intervention to neck-specific exercises, nor did they compare these treatments to prescription of general physical activity. Few exercise studies focus on patients with chronic WAD, and few have looked at patients ability to return to work and the cost-effectiveness of treatments. Thus, there is a great need to develop successful evidence-based rehabilitation models. The study aim is to investigate whether neck-specific exercise with or without a behavioural approach (facilitated by a single caregiver per patient) improves functioning compared to prescription of general physical activity for individuals with chronic WAD. less thanbrgreater than less thanbrgreater thanMethods/Design: The study is a prospective, randomised, controlled, multi-centre study with a 2-year follow-up that includes 216 patients with chronic WAD (andgt;6 months and andlt;3 years). The patients (aged 18 to 63) must be classified as WAD grade 2 or 3. Eligibility will be determined with a questionnaire, telephone interview and clinical examination. The participants will be randomised into one of three treatments: (A) neck-specific exercise followed by prescription of physical activity; (B) neck-specific exercise with a behavioural approach followed by prescription of physical activity; or (C) prescription of physical activity alone without neck-specific exercises. Treatments will be performed for 3 months. We will examine physical and psychological function, pain intensity, health care consumption, the ability to resume work and economic health benefits. An independent, blinded investigator will perform the measurements at baseline and 3, 6, 12 and 24 months after inclusion. The main study outcome will be improvement in neck-specific disability as measured with the Neck Disability Index. All treatments will be recorded in treatment diaries and medical records. less thanbrgreater than less thanbrgreater thanDiscussion: The study findings will help improve the treatment of patients with chronic WAD.

  • 37.
    Peolsson, Anneli
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Wibault, Johanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Dedering, Åsa
    Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Kammerlind, Ann-Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Futurum, County Council Jönköping, Sweden .
    Persson, Liselott
    Lunds University, Sweden.
    Löfgren, Håkan
    Ryhov Hospital, Jönköping, Sweden .
    Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial2014In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 15, no 34Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness.

    METHODS/DESIGN:

    This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated.

    DISCUSSION:

    We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease.

  • 38.
    Roel, Eduardo
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Zetterström, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Trell, Erik
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Why are some children with early onset of asthma getting better over the years? - Diagnostic failure or salutogenetic factors2009In: International Journal of Medical Sciences, ISSN 1449-1907, E-ISSN 1449-1907, Vol. 6, no 6, p. 348-357Article in journal (Refereed)
    Abstract [en]

    Among children earlier having been identified with a hospital or primary care diagnosis of asthma at least once between 0-7 years of age, almost 40 % of their parents reported in the ISAAC-questionnaire as never having had asthma (NA). These are further analysed and compared with the persisting asthma cases (A) in this study. All these childrens medical records were scrutinized concerning their asthma diagnose retrospectively. The aim of this study was to analyse possible factors related to the outcome in an Asthma diagnosis reassessment by parental questionnaire at the age of ten of the children earlier having been identified with a hospital or primary health care diagnosis of asthma at least once between 0-7 years of age in a total birth-year cohort in a defined Swedish geographical area. A multiple logistic analysis revealed four significant and independent factors associated to the improvement/non-report of asthma at the age of ten. These factors were; not having any past experiences of allergic symptoms (pless than0.0001), only having one or two visits at the hospital for asthma diagnosis in the 0-7 interval (p=0.001), not living in a flat but a villa at the age of ten (p=0.029) and no previous perception of mist or mould damage in the house (p=0.052). In the early postnatal stage, obstructive and bronchospastic symptoms typical of asthma may be unspecific, and those cases not continuing to persisting disease tend to have identifiable salutogenetic factors of constitutional rather than environmental nature, namely, an overall reduced allergic predisposition.

  • 39.
    Sandberg, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Frykman, Anne
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Cord blood cytokines and chemokines and development of allergic disease2009In: PEDIATRIC ALLERGY AND IMMUNOLOGY, ISSN 0905-6157, Vol. 20, no 6, p. 519-527Article in journal (Refereed)
    Abstract [en]

    Exposure to ubiquitous allergens early in life, even before birth, may influence the incidence of allergic diseases later in life. During pregnancy, the fetomaternal interface is surrounded by high levels of T-helper (Th)2-like cytokines, possibly favouring the development of Th2-like immune responses in the offspring. The aim of this study was to evaluate the relation between cord blood (CB) IgE antibodies, Th1- and Th2-like cytokines and chemokines, maternal allergy and development of allergic disease during the first 2 yr of life in the offspring. The CB cytokine and chemokine levels from children of 20 allergic and 36 non-allergic women were determined by a multiplexed Luminex assay and ELISA. Total CB and maternal IgE antibody concentrations were quantified using ImmunoCAP technology. The maternal IgE levels during and after pregnancy correlated with CB IgE and Th2-associated macrophage-derived chemokine [MDC (CCL22)] levels. Development of allergic disease and sensitization was associated with increased CB IgE and MDC (CCL22) levels, as well as high ratios of MDC (CCL22) to Th1-associated interferon-gamma inducible protein 10 [IP-10 (CXCL10)] and interferon-gamma inducible T-cell alpha-chemoattractant [I-TAC (CXCL11) (n = 7 allergic vs. n = 25 non-allergic)]. The correlations between maternal IgE and CB IgE and MDC (CCL22) levels possibly indicate that the maternal immunity can affect the Th1/Th2 profile in the neonate. Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of CB IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11).

  • 40.
    Schoenrock, Andrew
    et al.
    Carleton University, Ottawa, Canada.
    Samanfar, Bahram
    Carleton University, Ottawa, Canada.
    Pitre, Sylvain
    Carleton University, Ottawa, Canada.
    Hooshyar, Mohsen
    Carleton University, Ottawa, Canada.
    Jin, Ke
    University of Toronto, Toronto, Canada.
    Phillips, Charles A
    University of Tennessee, Knoxville, Tennessee, USA.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Gothenburg University, Gothenburg, Sweden.
    Phanse, Sadhna
    University of Toronto, Toronto, Canada.
    Omidi, Katayoun
    University of Toronto, Toronto, Canada.
    Gui, Yuan
    University of Toronto, Toronto, Canada.
    Alamgir, Md
    University of Toronto, Toronto, Canada.
    Wong, Alex
    University of Toronto, Toronto, Canada.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Gothenburg University, Gothenburg, Sweden.
    Babu, Mohan
    University of Regina, Regina, Saskatchewan, Canada.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Gothenburg University, Gothenburg, Sweden.
    Langston, Michael A
    Carleton University, Ottawa, Canada.
    Green, James R
    Carleton University, Ottawa, Canada.
    Dehne, Frank
    Carleton University, Ottawa, Canada.
    Golshani, Ashkan
    Carleton University, Ottawa, Canada.
    Efficient prediction of human protein-protein interactions at a global scale2014In: BMC bioinformatics, ISSN 1471-2105, Vol. 15, no 1, p. 383-Article in journal (Refereed)
    Abstract [en]

    BackgroundOur knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods.ResultsOn the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments.ConclusionsThe speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.

  • 41.
    Silfverdal, Sven-Arne
    et al.
    Umea University.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Blennow, Margareta
    Stockholm S General Hospital.
    Carlsson, Rose-Marie
    Swedish Armed Forces.
    Hanson, Lars A
    Gothenburg University.
    Lindberg, Anders
    County Council Halland.
    Lindquist, Lars
    Karolinska University Hospital.
    Magnusson, Margaretha
    Uppsala Akademic Hospital.
    Norlund, Anders
    Karolinska Institute.
    Nyren, Olof
    Karolinska Institute.
    Olcen, Per
    Orebro University Hospital.
    Olin, Patrick
    Swedish Institute Infectious Disease.
    Sawe, Juliette
    Swedish Council Technology Assessment Health Care.
    Soderstrom, Ann
    Department Communicable Disease Control, Gothenburg.
    Trollfors, Birger
    Sahlgrenska University Hospital .
    Ortqvist, Ake
    Karolinska Institute.
    Vaccination of children - summary and conclusions from a systematic reviewThe full review can be found in Acta Paediatrica 2010; 99: s4612010In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 9, p. 1287-1289Article in journal (Other academic)
  • 42.
    Ställberg, B.
    et al.
    Trosa Health Care Centre, Trosa, Sweden, Dept. of Public Health/Caring Sci., University of Uppsala, Uppsala, Sweden.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Olsson, P.
    Sjöbo Health Care Centre, Sjöbo, Sweden.
    Gottberg, L.
    Dept. Respiratory Medicine/Allergy, University Hospital of Huddinge, Huddinge, Sweden.
    Rönmark, E.
    The OLIN Studies, Sunderby Central Hosp. of Norrbotten, Luleå, Sweden, Dept. Respiratory Medicine/Allergy, University of Umeå, Umeå, Sweden, Lung and Allergy Research, National Institute of Environ. Med., Karolinska Institute, Stockholm, Sweden.
    Lundbäck, B.
    The OLIN Studies, Sunderby Central Hosp. of Norrbotten, Luleå, Sweden, Lung and Allergy Research, National Institute of Environ. Med., Karolinska Institute, Stockholm, Sweden.
    Living with asthma in Sweden - The ALMA study2003In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 97, no 7, p. 835-843Article in journal (Refereed)
    Abstract [en]

    Background: Recently performed studies have found a number of limitations in the daily lives of asthmatics, and a large disparity between the perception of the sufferers and what health care professionals believe matters to asthmatics. Aim: What matters to Swedish asthma patients, what medicines do they use, and are they compliant with given prescriptions? A further aim was to compare perceptions about asthma and asthma management in asthmatics and among Swedish general practitioners (GP). Design: A structured telephone interview of a representative sample of Swedish asthmatics, and a mailed questionnaire survey among GPs from different parts of Sweden. Methods: Screening by telephone of a random sample of 10,350 subjects aged 18-45. Of those, 240 were subsequently selected for a detailed structured telephone interview about their asthma. A mailed structured questionnaire containing similar questions to those asked of the asthmatics was sent to 600 GPs, and 139 returned completed answers. Results: 16% of the asthmatics reported (asthma) symptoms occurring every day during the previous month. Nocturnal symptoms at least twice per week were reported by 19%. Both these were reported by considerably higher proportions of the asthmatics than the GPs had expected. A large majority classified their disease as mild or very mild, although great majority reported frequent symptoms. Activities or situations which caused symptoms of asthma often or "now and then" were physical exertion, 67%, bad weather, 59%, contact with animals/pets, 58%, and visits to cafés or restaurants, 36%, and several asthmatics avoided these activities due to their asthma. Conclusion: A great majority of asthmatics report a large number of symptoms and limitations in their daily living in proportions which were roughly expected by the GPs. © 2003 Elsevier Science Ltd. All rights reserved.

  • 43.
    Sörenson, Sverre
    et al.
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Lindgren, Andrea
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Lindskog, Magnus
    Uppsala University, Sweden .
    Bergman, Bengt
    Sahlgrens University Hospital, Sweden .
    Sederholm, Christer
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Ek, Lars
    Skåne University Hospital, Sweden .
    Lamberg, Kristina
    University of Uppsala Hospital, Sweden .
    Clinchy, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy2013In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 1, p. 115-120Article in journal (Refereed)
    Abstract [en]

    Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.

  • 44.
    Vogt, Hartmut
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Bråbäck, Lennart
    Occupational & Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Kling, Anna-Maria
    Department of Analysis and Prevention, Swedish Institute for Cummunicable Disease Control (SMI), Stockholm, Solna, Sweden.
    Grünewald, Maria
    Department of Analysis and Prevention, Swedish Institute for Cummunicable Disease Control (SMI), Stockholm, Solna, Sweden.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Pertussis Immunization in Infancy and Adolescent Asthma Medication2014In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 134, no 4, p. 721-728Article in journal (Refereed)
    Abstract [en]

    Context: Lack of infections might contribute to increased risk of asthma among children according to the ‘hygiene hypothesis’. Childhood immunization may play a causal role in the development of asthma.

    Objective: To determine whether pertussis immunization in infancy is associated with asthma medication in adolescence.

    Design, Settings and Participants: After 14 years of no general pertussis vaccination, almost 80,000 children were immunized for pertussis during a 12-month period in a vaccination trial. They were compared with almost 100,000 non-vaccinated children born during a 6-month period before and after the vaccination trial in a Swedish national cohort study. Information concerning dispensed prescribed asthma medication for each individual in the cohort during 2008–2010 was obtained from the National Prescription database. Multivariable regression models were used to calculate the effect size of vaccination on dispensed asthma medication (Odds ratios and 95% confidence intervals), both in an intent-to-treat model as well as per protocol. The large study size also enabled us to detect very small effects.

    Main Outcome Measure: Dispensed prescribed asthma medication at the age of 15 years occurring after pertussis immunization in infancy.

    Results: No statistically significant effect of vaccination was found, regardless of vaccination schedule or vaccine type. The prevalence rates of any dispensed anti-inflammatory medication or any asthma medication at 15 years of age were 4.6% and 7.0%, respectively. The crude odds ratios (OR) for any asthma medication and anti-inflammatory treatment in pertussis-vaccinated children after intent-to-treat analysis were 0.97 (95% CI 0.93 – 1.00) and 0.94 (0.90 – 0.98),respectively. Corresponding adjusted ORs were 0.99 (0.95 – 1.03) and 0.97 (0.92 – 1.01),respectively. Similar ORs were found after per-protocol analysis.

    Conclusion: Pertussis immunization in infancy does not increase the risk of asthma medication in adolescents. Our study presents evidence that pertussis immunization in early childhood can be considered safe with respect to long-term development of asthma.

  • 45.
    Vogt, Hartmut
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Bråbäck, Lennart
    Occupational & Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Zetterström, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Zara, Katalin
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences.
    Asthma heredity, cord blood IgE and asthma-related symptoms and medication in adulthood: a long-term follow-up in a Swedish birth cohort2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e66777.-Article in journal (Refereed)
    Abstract [en]

    Cord blood IgE has previously been studied as a possible predictor of asthma and allergic diseases. Results from different studies have been contradictory, and most have focused on high-risk infants and early infancy. Few studies have followed their study population into adulthood. This study assessed whether cord blood IgE levels and a family history of asthma were associated with, and could predict, asthma medication and allergy-related respiratory symptoms in adults.

    A follow-up was carried out in a Swedish birth cohort comprising 1701 consecutively born children. In all, 1661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1227 responded to a postal questionnaire. Cord blood IgE and family history of asthma were correlated with reported respiratory symptoms and dispensed asthma medication at 32–34 years.

    Elevated cord blood IgE was associated with a two- to threefold increased risk of pollen-induced respiratory symptoms and dispensed anti-inflammatory asthma medication. Similarly, a family history of asthma was associated with an increased risk of pollen-induced respiratory symptoms and anti-inflammatory medication. However, only 8% of the individuals with elevated cord blood IgE or a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication at follow-up.

    Elevated cord blood IgE and a positive family history of asthma were associated with reported respiratory symptoms and dispensed asthma medication in adulthood, but their predictive power was poor in this long-time follow-up.

  • 46.
    Wang, Kai
    et al.
    University of Tennessee, Knoxville, USA.
    Phillips, Charles A
    University of Tennessee, Knoxville, USA.
    Rogers, Gary L
    National Institute for Computational Sciences, Oak Ridge, Tennessee, USA.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Langston, Michael A
    University of Tennessee, Knoxville, USA.
    Differential Shannon entropy and differential coefficient of variation: alternatives and augmentations to differential expression in the search for disease-related genes2014In: International journal of computational biology and drug design, ISSN 1756-0756, Vol. 7, no 2-3, p. 183-94Article in journal (Refereed)
    Abstract [en]

    Differential expression has been a standard tool for analysing case-control transcriptomic data since the advent of microarray technology. It has proved invaluable in characterising the molecular mechanisms of disease. Nevertheless, the expression profile of a gene across samples can be perturbed in ways that leave the expression level unaltered, while a biological effect is nonetheless present. This paper describes and analyses differential Shannon entropy and differential coefficient of variation, two alternate techniques for identifying genes of interest. Ontological analysis across 16 human disease datasets demonstrates that these alternatives are effective at identifying disease-related genes not found by mere differential expression alone. Because the two alternate techniques are based on somewhat different mathematical formulations, they tend to produce somewhat different gene lists. Moreover, each may pinpoint genes completely overlooked by the other. Thus, measures of entropy and variation can be used to replace or better yet augment standard differential expression computations.

  • 47.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Chung, Kian Fan
    Experimental Studies, National Heart and Lung Institute, Imperial College London, London, UK / NIHR Respiratory Biomedical Research Unit at the Royal Brompton NHS Foundation Trust and Imperial College London, London, UK; Royal Brompton NHS Fdn Trust, NIHR Resp Biomed Res Unit, London, England.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Targeted omics and systems medicine: personalising care2014In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 2, no 10, p. 785-787Article in journal (Other academic)
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