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  • 1.
    Ahlroth Pind, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Gunnbjörnsdottír, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. National University Hospital of Iceland, Reykjavik, Iceland.
    Bjerg, A
    Karolinska Inst, Stockholm, Sweden.
    Järvholm, B
    Umeå Univ, Umeå, Sweden.
    Lundbäck, B
    Univ Gothenburg, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, R
    Karolinska Inst, Stockholm, Sweden.
    Nilsson Sommar, J
    Umeå Univ, Umeå, Sweden.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: A cross-sectional study2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1383-1389Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

  • 4.
    Bakolis, Ioannis
    et al.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Biostat & Hlth Informat, London, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, Hlth Serv & Populat Res Dept, Ctr Implementat Sci, London, England.
    Hooper, Richard
    Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Ctr Primary Care & Publ Hlth, London, England.
    Bachert, Claus
    Univ Ghent, Upper Airway Res Lab, Ghent, Belgium.
    Lange, Bibi
    Odense Univ Hosp, Dept Otorhinolaryngol, Odense, Denmark.
    Haahtela, Tari
    Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland.
    Keil, Thomas
    Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Lodz, Germany;Wurzburg Univ, Inst Clin Epidemiol & Biometry, Wurzburg, Germany.
    Hofmaier, Stephanie
    Charite Univ Med Berlin, Dept Paediat Pneumol & Immunol, Berlin, Germany.
    Fokkens, Wytske
    Acad Med Ctr, Otorhinolaryngol Dept, Amsterdam, Netherlands.
    Rymarczyk, Barbara
    Med Univ Silesia, Clin Dept Internal Dis Allergol & Clin Immunol, Katowice, Poland.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Burney, Peter G. J.
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Med, London, England.
    Garcia-Larsen, Vanessa
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Med, London, England;Johns Hopkins Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
    Dietary patterns and respiratory health in adults from nine European countries-Evidence from the GA2LEN study2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 11, p. 1474-1482Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

  • 6.
    Bjerg, A.
    et al.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Ekerljung, L.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Eriksson, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Naslund, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Sjölander, S.
    ThermoFisher Sci, ImmunoDiagnost, Uppsala, Sweden..
    Rönmark, E.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;OLIN Unit, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Dahl, Å.
    Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Holmberg, K.
    Sahlgrens Univ Hosp, Dept Otorhinolaryngol, Gothenburg, Sweden..
    Wennergren, G.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;Gothenburg Univ, Dept Pediat, Gothenburg, Sweden..
    Torén, K.
    Gothenburg Univ, Sahlgrenska Acad, Dept Publ Hlth & Community Med, Gothenburg, Sweden..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Lötvall, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Lundbäck, B.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 10, p. 1328-1336Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Brandstrom, J.
    et al.
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, S-11883 Stockholm, Sweden..
    Nopp, A.
    Karolinska Inst, Dept Med, Clin Immunol & Allergy Unit, Stockholm, Sweden.;Karolinska Hosp, S-10401 Stockholm, Sweden..
    Johansson, S. G. O.
    Karolinska Inst, Dept Med, Clin Immunol & Allergy Unit, Stockholm, Sweden.;Karolinska Hosp, S-10401 Stockholm, Sweden..
    Lilja, G.
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, S-11883 Stockholm, Sweden..
    Sundqvist, A. -C
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Uppsala, Sweden..
    Nilsson, C.
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, S-11883 Stockholm, Sweden..
    Basophil allergen threshold sensitivity and component-resolved diagnostics improve hazelnut allergy diagnosis2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 9, p. 1412-1418Article in journal (Refereed)
    Abstract [en]

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

  • 8.
    Brew, Bronwyn K.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Soderberg, Joakim
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lundholm, Cecilia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Afshar, Soren
    Karolinska Univ Hosp, Dept Med, Div Resp Med, Stockholm, Sweden.
    Holmberg, Kirsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social medicine/CHAP.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Pediat Allergy & Pulmonol Unit, Stockholm, Sweden.
    Academic achievement of adolescents with asthma or atopic disease2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 892-899Article in journal (Refereed)
    Abstract [en]

    Background

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

    Objective

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

    Methods

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

    Results

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

    Conclusion and clinical relevance

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

  • 9.
    Brough, H. A.
    et al.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Guys & St Thomass NHS Fdn Trust, Childrens Allergy Serv, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Kull, I.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden;Soder Sjukhuset, Sachs Childrens Hosp, Stockholm, Sweden.
    Richards, K.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Hallner, E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Söderhäll, C.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Douiri, A.
    Kings Coll London, Div Hlth & Social Care Res, London, England.
    Penagos, M.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Melen, E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Soder Sjukhuset, Sachs Childrens Hosp, Stockholm, Sweden.
    Bergström, A.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.
    Turcanu, V.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Wickman, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Lack, G.
    Kings Coll London, Guys Hosp, Sch Life Course Sci, Paediat Allergy Grp,Dept Women & Childrens Heath, London, England;Guys & St Thomass NHS Fdn Trust, Childrens Allergy Serv, London, England;Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Paediat Allergy Grp, London, England.
    Environmental peanut exposure increases the risk of peanut sensitization in high-risk children2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 5, p. 586-593Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

  • 11.
    Byström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Garcia, R. C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Håkansson, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karawajczyk, Malgorzata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Soukka, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eosinophil cationic protein is stored in, but not produced by, peripheral blood neutrophils2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 7, p. 1082-1091Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 12.
    Byström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Garcia, Rodolfo
    Håkansson, Lena
    Karawajczyk, Malgorzata
    Moberg, Lena
    Soukka, Juri
    Venge, Per
    Eosinophil Cationic Protein is stored in, but not produced by, peripheral blood neutrophils2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 7, p. 1082-1091Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 13.
    Courbis, Anne-Lise
    et al.
    Univ Montpellier, IMT Mines Ales, LGI2P, Ales, France.
    Murray, Ruth Brigid
    Medscript NZ Ltd, Dept Allerg Dis, Kapiti Coast, New Zealand.
    Arnavielhe, Sylvie
    Kyomed, Montpellier, France.
    Caimmi, Davide
    Montpellier Univ Hosp, Dept Resp Dis, Montpellier, France.
    Bedbrook, Anna
    Contre Malad Chron Vleillissement Actif France Eu, Montpellier, France.
    Van Eerd, Michiel
    Peercode BV, Geldermalsen, Netherlands.
    De Vries, Govert
    Peercode BV, Geldermalsen, Netherlands.
    Dray, Gerard
    Univ Montpellier, IMT Mines Ales, LGI2P, Ales, France.
    Agache, Ioana
    Transylvania Univ Brasov, Brasov, Romania.
    Morais-Almeida, Mario
    CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal.
    Bachert, Claus
    Ghent Univ Hosp, Upper Airways Res Lab, ENT Dept, Ghent, Belgium.
    Bergmann, Karl Christian
    Charite Univ Med Berlin, Dept Dermatol & Allergy, Allergy Ctr Charite, Berlin, Germany.
    Bosnic-Anticevich, Sinthia
    Univ Sydney, Woolcock Inst Med Res, Glebe, NSW, Australia;Sydney Local Hlth Dist, Glebe, NSW, Australia.
    Brozek, Jan
    McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
    Bucca, Caterina
    Univ Pneumol Unit AOU Molinette, Hosp City Hlth & Sci Torino, Turin, Italy.
    Camargos, Paulo
    Univ Fed Minas Gerais, Med Sch, Dept Pediat, Belo Horizonte, MG, Brazil.
    Canonica, Giorgio Walter
    Humanitas Univ & Res Hosp, Personalized Med Asthma & Allergy Clin, Milan, Italy.
    Carr, Warner
    Allergy & Asthma Associates Southern Calif, Mission Viejo, CA USA.
    Casale, Thomas
    Univ S Florida, Morsani Coll Med, Div Allergy & Immunol, Tampa, FL USA.
    Fonseca, Joao A.
    Univ Porto, Fac Med, CINTESIS, Porto, Portugal;LDA, MEDIDA, Porto, Portugal.
    Haahtela, Tari
    Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland.
    Kalayci, Omer
    Hacettepe Univ, Sch Med, Dept Pediat Allergy, Ankara, Turkey.
    Klimek, Ludger
    Ctr Rhinol & Allergol, Wiesbaden, Germany.
    Kuna, Piotr
    Med Univ Lodz, Barlicki Univ Hosp, Lodz, Poland.
    Kvedariene, Violeta
    Vilnius Univ, Inst Biomed Sci, Clin Infect Chest Dis Dermatol & Allergol, Dept Pathol,Fac Med, Vilnius, Lithuania.
    Larenas Linnemann, Desiree
    Hosp Med Sur, Clin Alergia Asma & Pediat, Mexico City, DF, Mexico.
    Lieberman, Phil
    Univ Tennessee, Coll Med, Dept Internal Med & Pediat, Div Allergy & Immunol, Germantown, TN USA.
    Mullol, Joaquim
    Univ Barcelona, Hosp Clin Clin & Expt Resp Immunoallergy, ENT Dept, IDIBAPS,CIBERES, Barcelona, Spain.
    Ohehir, Robyn
    Monash Univ, Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia;Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia.
    Papadopoulos, Nikolaos
    Univ Manchester, Div Infect Immun & Resp Med, Manchester, Lancs, England;Univ Athens, Pediat Clin 2, Allergy Dept, Athens, Greece.
    Price, David
    Observat & Pragmat Res Inst, Singapore, Singapore.
    Ryan, Dermot
    Univ Edinburgh, Med Sch, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Samolinski, Boleslaw
    Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland.
    Simons, F. Estelle
    Univ Manitoba, Fac Med, Dept Immunol, Dept Pediat & Child Hlth, Winnipeg, MB, Canada.
    Tomazic, Peter
    Med Univ Graz, Dept ENT, Graz, Austria.
    Triggiani, Massimo
    Univ Salerno, Div Allergy & Clin Immunol, Salerno, Italy.
    Valiulis, Arunas
    Vilnius Univ, Inst Clin Med Dis, Clin Childrens Dis, Dept Publ Hlth,Inst Hlth Sci,Fac Med, Vilnius, Lithuania.
    Valovirta, Erkka
    Univ Turku, Dept Lung Dis & Clin Allergol, Turku, Finland;Terveystalo, Allergy Clin, Turku, Finland.
    Wagenmann, Martin
    Univ Klinikum Dusseldorf, HNO Klin, Dept Otorhinolaryngol, Dusseldorf, Germany.
    Wickman, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Yorgancioglu, Arzu
    Celal Bayar Univ, Fac Med, Dept Pulmonol, Manisa, Turkey.
    Bousquet, Jean
    Contre Malad Chron Vleillissement Actif France Eu, Montpellier, France;VIMA Ageing & Chron Dis Epidemiol & Publ Hlth App, INSERM, U 1168, Villejuif, France;Univ Versailles St Quentin en Yvelines, UMRS 1168, Montigny Le Bretonneux, France;CHU Montpellier, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France.
    Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 12, p. 1640-1653Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 14. Darsow, U.
    et al.
    Brockow, K.
    Pfab, F.
    Jakob, T.
    Petersson, C. J.
    Borres, M. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ring, J.
    Behrendt, H.
    Huss-Marp, J.
    Heterogeneity of molecular sensitization profiles in grass pollen allergy - implications for immunotherapy?2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 5, p. 778-786Article in journal (Refereed)
    Abstract [en]

    BackgroundData on molecular allergy diagnostics in adults with grass pollen allergy with regard to conjunctival and nasal provocation test outcome and specific immunotherapy are lacking to date. ObjectiveTo assess whether molecular allergy diagnostics for grass pollen allergens could help with predicting provocation test outcomes and serve as a basis for future component-resolved specific immunotherapy. MethodsSera of 101 adults with grass pollen allergy was analysed for IgE against timothy grass pollen (Phleum pratense), rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11 and rPhl p12 and correlated with the individuals' outcome in the nasal and conjunctival provocation tests and investigated in regard to a potential component-resolved specific immunotherapy. ResultsAn increasing number of sensitizations to timothy grass allergens was correlated to a positive reaction in the conjunctival (4.9 vs. 3.6, P=0.003) and nasal provocation tests (4.5 vs. 2.2, P=0.0175). In molecular sensitization profiles, a substantial heterogeneity was detected, with none of the patients exactly matching the allergen composition of a previously published component-resolved specific immunotherapy containing Phl p 1, Phl p 2, Phl p 5a/b and Phl p 6. The results indicate that in 95% of the patients, a proportion of 50% of timothy-IgE would be targeted with such a specific immunotherapy, while in 50% and 10% of patients, 80% and 90% of timothy-IgE would be targeted, respectively. Conclusion and Clinical RelevanceMolecular allergy diagnostics is a prerequisite for future component-resolved specific immunotherapy due to the high heterogeneity of sensitization profiles. However, of current clinical relevance is the observed correlation between the number of sensitizations and provocation test outcome.

  • 15. Gore, C.
    et al.
    Custovic, A.
    Tannock, G. W.
    Munro, K.
    Kerry, G.
    Johnson, K.
    Peterson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Morris, J.
    Chaloner, C.
    Murray, C. S.
    Woodcock, A.
    Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema: randomized controlled trial with follow-up until age 3 years2012In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 42, no 1, p. 112-122Article in journal (Refereed)
    Abstract [en]

    Background Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema.

    Objective We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I3446 had a treatment effect or altered allergic disease progression.

    Methods Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen- sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD >= 10, consuming >= 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). Trial number: ISRCTN41490500.

    Results Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.416.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups.

    Conclusion and Clinical Relevance We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.

  • 16. Gref, A
    et al.
    Rautiainen, S
    Gruzieva, O
    Håkansson, N
    Kull, I
    Pershagen, G
    Wickman, M
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melén, E
    Bergström, A
    Dietary total antioxidant capacity in early school age and subsequent allergic disease.2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 6, p. 751-759Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dietary antioxidant intake has been hypothesized to influence the development of allergic diseases; however, few prospective studies have investigated this association.

    OBJECTIVE: Our aim was to study the association between total antioxidant capacity (TAC) of the diet at age 8 years and the subsequent development of asthma, rhinitis and sensitization to inhalant allergens between 8 and 16 years, and to assess potential effect modification by known risk factors.

    METHODS: A total of 2359 children from the Swedish birth cohort BAMSE were included. Dietary TAC at age 8 years was estimated by combining information on the child's diet the past 12 months from a food frequency questionnaire with a database of common foods analysed with the oxygen radical absorbance capacity method. Classification of asthma and rhinitis was based on questionnaires, and serum IgE antibodies were measured at 8 and 16 years.

    RESULTS: A statistically significant inverse association was observed between TAC of the diet and incident sensitization to inhalant allergens (adjusted odds ratio: 0.73, 95% confidence interval: 0.55-0.97 for the third compared to the first tertile, P-value for trend = 0.031). Effect modification by traffic-related air pollution exposure was observed, with a stronger association between dietary TAC and sensitization among children with low traffic-related air pollution exposure (P-value for interaction = 0.029). There was no evidence for effect modification by GSTP1 or TNF genotypes, although these results should be interpreted with caution. No clear associations were observed between TAC and development of rhinitis or asthma, although a significant inverse association was observed for allergic asthma (ORadj 0.57, 95% CI 0.34-0.94).

    CONCLUSIONS AND CLINICAL RELEVANCE: Higher TAC of the diet in early school age may decrease the risk of developing sensitization to inhalant allergens from childhood to adolescence. These findings indicate that implementing an antioxidant-rich diet in childhood may contribute to the prevention of allergic disease.

  • 17. Gülen, T
    et al.
    Hägglund, Hans
    astocytosis Centre Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Dahlén, B
    Nilsson, G
    High prevalence of anaphylaxis in patients with systemic mastocytosis: a single-centre experience2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 1, p. 121-129Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Systemic mastocytosis (SM) is a clonal mast cells disorder characterized by the proliferation, accumulation and activation of mast cells in extracutaneous tissues. The clinical picture is heterogeneous and may range from asymptomatic to potentially fatal anaphylactic reactions due to excessive mast cell mediator release.

    OBJECTIVE: The aim of this study was to investigate the prevalence and trigger factors of anaphylactic reactions among adult SM patients. We also explored the clinical spectrum of mast cell mediator-related symptoms in patients with SM.

    METHODS: This descriptive study was performed among 84 consecutive adult (≥ 18 years) patients those were diagnosed with SM according to WHO criteria. Sixty-six of the patients also underwent a comprehensive allergy work-up.

    RESULTS: Sixty of 84 patients with SM (71%) had bone marrow mast cell aggregates and fulfilled the major criteria for SM and 76 patients (91%) had indolent disease. Simultaneous occurrence of cutaneous mastocytosis was observed in 59 patients (70%). Thirty-six patients (43%) had had at least one episode of an anaphylactic reaction. The clinical courses of the reactions were usually severe and patients often presented with syncope attacks (72%). Most patients reacted after hymenoptera venom stings (19/36; 53%). In 39% (14/36), a clear aetiology could not be determined. While males and females were equally frequent among the patients with SM, anaphylaxis patients showed a male predominance (61%). Anaphylactic reactions occurred more frequently in patients without cutaneous engagement. The rate of allergy sensitization was significantly higher in SM patients with anaphylaxis as compared with non-anaphylaxis SM patients, 70% vs. 23%, respectively (P = 0.0002).

    CONCLUSIONS AND CLINICAL RELEVANCE: Anaphylaxis is more prevalent in patients with SM, predominantly in patients with atopic SM. Hymenoptera venom-induced and idiopathic anaphylaxis were the most frequent elicitors. Our findings implicate that all mastocytosis patients with anaphylaxis should undergo detailed allergological assessment before considering treatment and preventive measures.

  • 18. Gülen, T
    et al.
    Hägglund, Hans
    Mastocytosis Centre Karolinska, Karolinska University Hospital and Karolinska Institutet, Stockholm.
    Sander, B
    Dahlén, B
    Nilsson, Gunnar
    Department of Medicine Solna, Clinical Immunology and Allergy Research Unit, Karolinska Institutet, Stockholm.
    The presence of mast cell clonality in patients with unexplained anaphylaxis2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 9, p. 1179-1187Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The mechanisms by which mast cells in patients with unexplained anaphylaxis (UEA) are triggered remain elusive. Onset of episodes is unpredictable and often recurrent. The substantial overlap between the clinical manifestations of UEA and clonal mast cell disorders (CMD) suggests an association between these rare disorders. The two forms of CMD characterized to date are systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS).

    OBJECTIVE: To examine the hypothesis that the pathogenesis of UEA reflects the presence of aberrant subpopulations of mast cells.

    METHODS: Thirty (14 men, 16 women) patients (≥ 18 years) suffering from UEA and with no signs of cutaneous mastocytosis were recruited. Patients underwent an initial complete allergy work-up to confirm the diagnosis of UEA. Level of baseline serum tryptase (sBT) and total IgE were determined. In addition, a bone marrow examination was performed on all 30 patients to investigate possible underlying CMD.

    RESULTS: Fourteen (47%) of our cases (nine men, five women) were diagnosed with CMD: 10 with SM and four with MMAS. Four of the 10 patients with SM had mast cell aggregates in their bone marrow. All patients with SM exhibited a sBT level > 11.4 ng/mL, whereas this level was elevated in only two of those with MMAS and four with UAE but not diagnosed with CMD. Total IgE levels were lower in the group of patients with CMD (P < 0.03).

    CONCLUSION AND CLINICAL RELEVANCE: The pathogenic mechanism underlying UEA could be explained by the presence of immunophenotypically aberrant mast cells with clonal markers in 47% of our subjects, indicating that clonal mast cell disorders are present in a substantial subset of these patients. Thus, the presence of CMD should be considered in patients with UEA if they have an elevated level of sBT (≥ 11.4 ng/mL) and cardiovascular symptoms such as syncope.

  • 19. Gülen, T
    et al.
    Möller Westerberg, C
    Lyberg, K
    Ekoff, M
    Kolmert, J
    Bood, J
    Öhd, J
    James, A
    Dahlén, S-E
    Nilsson, G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Department of Medicine, Clinical Immunology and Allergy Research Unit, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden; Mastocytosis Centre Karolinska, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Centre for Allergy research (CfA), Karolinska Institutet, Stockholm, Sweden .
    Dahlén, B
    Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis.2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 7, p. 909-917Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.

    OBJECTIVE: To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.

    METHODS: were measured, as well as ex vivo basophil histamine release.

    RESULTS: Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end-organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.

    CONCLUSIONS AND CLINICAL RELEVANCE: Mast cells in the skin and airways of subjects with SM do not exhibit hyper-reactivity towards the MC-activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.

  • 20. Harrop, J.
    et al.
    Chinn, S.
    Verlato, G.
    Olivieri, M.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Wjst, M.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Zock, J-P
    Leynaert, B.
    Gislason, D.
    Ponzio, M.
    Villani, S.
    Carosso, A.
    Svanes, C.
    Heinrich, J.
    Jarvis, D.
    Eczema, atopy and allergen exposure in adults: a population-based study2007In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 37, no 4, p. 526-535Article in journal (Refereed)
    Abstract [en]

    Background: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. Objective: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. Methods: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. Results: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. Conclusions: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.

  • 21.
    Heijkenskjöld Rentzhog, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Berglund, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control.2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 12, p. 1546-1554Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Classic spirometry is effort dependent and of limited value in assessing small airways. Peripheral airway involvement, and relation to poor control, in asthma, has been highlighted recently. Forced oscillation technique (FOT) offers an effort-independent assessment of overall and peripheral lung mechanics. We studied the association between lung function variables, obtained either by spirometry or multifrequency (5, 11 and 19 Hz) FOT, and asthma diagnosis and control.

    METHODS: ), resistance difference between 5-19 Hz (R5-R19) and Asthma Control Test scores were determined in 234 asthmatic and 60 healthy subjects (aged 13-39 years). We used standardized lung function variables in logistic regression analyses, unadjusted and adjusted for age, height, gender and weight.

    RESULTS: and R5-R19) were associated with uncontrolled asthma (P-values < .05).

    CONCLUSIONS: /FVC, supporting a complementary role for FOT. Asthma control was related to FOT measures of peripheral airways, suggesting a potential use in identifying such involvement. Further studies are needed to determine a clinical value and relevant reference values in children, for the multifrequency FOT measurements.

  • 22.
    Håkansson, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Heinrich, Christina
    Rak, Sabina
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Activation of B-lymphocytes during birch pollen season: Effect of immunotherapy1998In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 7, p. 791-798Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: B-lymphocytes play an important part in the allergic reaction as producers of IgE antibodies.

    OBJECTIVE: To investigate the cell surface expression of the activation antigens CD23, CD40 and HLA-DR on B-lymphocytes in birch pollen allergic patients before and during birch pollen season and to study the effect of immunotherapy.

    METHODS: The study included 24 birch pollen allergic patients half of whom were treated with immunotherapy against birch pollen before the start of the season. Eleven of the 24 patients had asthma. Blood samples were taken and lung function was registered before the season began and before the immunotherapy treatment in January to February and during the season in May. The relative number of B-lymphocytes (CD19+) of the lymphocyte population and the cell surface expression of CD23, CD40 and HLA-DR on B-lymphocytes was measured by the use of flow cytometry.

    RESULTS: In the control group of patients the relative number and concentration of B-lymphocytes, the cell surface expression of CD23, CD40 and HLA-DR on B cells, and the serum concentration of IgE increased during season compared with before season. In contrast, in the immunotherapy treated patients no changes in the number of B cells or cell surface expression of CD23, CD40 and HLA-DR were demonstrated.

    CONCLUSION: The elevated expression of CD23, CD40 and HLA-DR on B cells, combined with increased levels of IgE in allergic patients during season could be explained by the effect of cytokines produced by activated TH2 cells. A shift from TH2 to TH1 cells might be the mechanism after the absence of signs of B-cell activation in immunotherapy treated patients. The prevention of increased cell surface expression on B cells by immunotherapy may constitute a significant mechanism behind the beneficial effects of immunotherapy in the treatment of pollen atopy.

  • 23. Jönsson, Ulla-Britt
    et al.
    Byström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stålenheim, Gunneamar
    Venge, Per
    Polymorphism of the eosinophil cationic protein-gene is related to the expression of allergic symptoms2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 7, p. 1092-1095Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have found a polymorphism in the ECP (eosinophil cationic protein)-gene at position 434 according to GenBank accession number NM 002935. This polymorphism would cause the change of the amino acid arginine (base at position 434 is G) at position 97 to threonine (base at position 434 is C).

    OBJECTIVE: To investigate the prevalence of the ECP-polymorphism and to screen for disease associations.

    METHODS: DNA of 209 medical students and 76 asthmatic subjects was analysed. The 434 genotype in the ECP-gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis.

    RESULTS: The prevalences of the polymorphism in the student population were 53%, 39% and 8% for the 434GG, the 434GC and the 434CC genotype, respectively, with allele frequencies of 72% (434G) and 28% (434C). Subjects reporting allergy had a higher prevalence of the 434G allele than non-allergic subjects (P = 0.0056). Of the students who were Phadiatop-positive and had allergic symptoms, 79% had the 434GG genotype, whereas the 434GC and 434CC genotypes were present in 82% of those who did not express allergic symptoms (P < 0.001). Among the 76 patients with asthma, patients with allergic asthma had a significantly higher proportion of 434GG compared with patients with non-allergic asthma (P = 0.04). None of the 18 subjects of the two groups with the 434CC genotype had allergy.

    CONCLUSION: The 434(G > C) polymorphism in the ECP-gene is related to the development of allergic symptoms, suggesting a central role for the ECP molecule in the process.

  • 24.
    Karawajczyk, G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Peterson, C.G.
    Eklund, E.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The differential release of eosinophil granule proteins: Studies on patients with acute bacterial and viral infections1995In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 25, no 8, p. 713-719Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Earlier in vitro studies have suggested that the eosinophil may release its granule proteins selectively depending on the stimulus to which the cell is exposed.

    OBJECTIVE: The object of the present study was to study the question of selective release in vivo by means of serum measurements of the two eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in acute infections.

    METHODS: Fourty-six subjects with acute infections were studied before treatment, 20 with bacterial infections and 26 with viral infections. Serum ECP, EPO and MPO were measured by specific RIA.

    RESULTS: In acute bacterial infections ECP, but not EPO, was significantly raised in serum (P < 0.0001) compared with non-infected healthy subjects. In acute bacterial infections ECP was significantly correlated to the levels of the neutrophil marker myeloperoxidase (MPO) (rs = 0.96, P < 0.0001) but not to EPO. In acute viral infections neither ECP nor EPO were on average raised. However, almost 20% the patients had elevated levels of bot proteins. In the viral infections the serum-levels of ECP and EPO were correlated (rs = 0.63, P < 0.001), but no correlation was found with MPO.

    CONCLUSION: It is concluded that eosinophils are activated during acute bacterial infections and that this activation results in the preferential mobilisation of ECP. The simultaneous assay of the two eosinophil proteins, ECP and EPO, may give new insight into the role of the eosinophil in disease.

  • 25. Laerum, B. N.
    et al.
    Wentzel-Larsen, T.
    Gulsvik, A.
    Omenaas, E.
    Gíslason, T.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svanes, C.
    Relationship of fish and cod oil intake with adult asthma2007In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 37, no 11, p. 1616-1623Article in journal (Refereed)
    Abstract [en]

    Background A diet rich in fish or cod oil might possibly reduce the risk for asthma and atopic diseases. However, previous studies show conflicting results and no studies have assessed the potential long-term effects of childhood fish intake on adult asthma.

    Objective To investigate whether childhood and adult fish and cod oil intake was related to adult asthma.

    Methods In a large population-based study, Respiratory Health in Northern Europe (RHINE), 16 187 subjects aged 23–54 years answered a postal questionnaire. The relations of fish and cod oil intake with asthma symptoms and asthma were analysed using multiple logistic and Cox regression analyses, with adjustment for gender, adult hayfever, smoking, age, body mass index, household size, dwelling, parental education and centre, and for maternal smoking and family history of hayfever and asthma in a subsample (n=2459).

    Results Subjects from Iceland and Norway reported much more frequent intake of fish both in childhood and adulthood as compared with subjects from Sweden, Estonia and Denmark. Current fish intake less than weekly in adults was associated with more asthma symptoms, while more frequent fish intake did not appear to decrease the risk further. No dose–response association was found between childhood fish intake and adult asthma, but those who never ate fish in childhood had an increased risk for asthma and earlier asthma onset. Adult consumption of cod oil had a u-shaped association with asthma, with the highest risks in those taking cod oil never and daily.

    Conclusion A minimum level of weekly fish intake in adulthood was associated with protection against asthma symptoms in this large North-European multi-centre study. Subjects who never ate fish in childhood were at an increased risk for asthma. Both indicate a possible threshold effect of fish on asthma.

  • 26.
    Lidén, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kristjánsson, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Valtysdottir, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hällgren, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cow's milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren's syndrome2008In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 38, no 6, p. 929-935Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)-like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed. OBJECTIVE: This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms. Methods: A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique. RESULTS: Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM-free diet. CONCLUSION: A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS-like symptoms were common in pSS, linked to CM sensitivity.

  • 27.
    Lindvik, H.
    et al.
    Oslo Univ Hosp.
    Carlsen, K. C. Lodrup
    Oslo Univ Hosp; Univ Oslo.
    Mowinckel, P.
    Oslo Univ Hosp.
    Navaratnam, J.
    Oslo Univ Hosp.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Thermo Fisher Sci.
    Carlsen, K. -H
    Oslo Univ Hosp; Univ Oslo.
    Conjunctival provocation test in diagnosis of peanut allergy in children2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 6, p. 785-794Article in journal (Refereed)
    Abstract [en]

    Background Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy. Objective To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy. Methods This cross-sectional case-control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut-tolerant control group of 28 children of similar age was recruited locally. A double-blind placebo-controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double-blind placebo-controlled challenge in children with suspected peanut allergy and as an open challenge in the control children. Results All 81 children with a positive double-blind placebo-controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC. Conclusion and Clinical Relevance Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.

  • 28. Magnusson, J
    et al.
    Gellerstedt, M
    Ahlstedt, S
    Andersson, B
    Bengtsson, U
    Telemo, E
    Hansson, Tony
    Department of Rheumatology, Karolinska Institute.
    Peterson, C G B
    A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 8, p. 1052-1059Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Immune-mediated food hypersensitivity affecting the gut is difficult to evaluate, and objective tools to diagnose local gastrointestinal (GI) inflammatory reactions are lacking.

    OBJECTIVES: To determine whether allergic manifestations in adults with a history of food-related GI symptoms could be assessed in feces during symptomatic and non-symptomatic periods, using the surrogate markers, eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO).

    METHODS: Thirteen subjects with food hypersensitivity-related GI symptoms, confirmed by a positive double-blind placebo-controlled food challenge (DBPCFC), were subjected to an open kinetic food challenge design for 6 weeks. Symptoms were recorded and scored during the 3-week study period and stool samples were obtained every day. The surrogate markers ECP, EPX and MPO were measured in the supernatants from feces samples.

    RESULTS: A significant increase in abdominal pain, distension and flatulence was observed during challenge, with a gradual decrease during elimination diet. Both between days and subjects, EPX levels were more frequently increased compared to ECP and MPO. Individuals with a history of a short duration of symptoms had significantly higher mean levels of EPX and MPO than those with a longer duration of symptoms.

    CONCLUSIONS: An overall increase in levels of eosinophil markers, in particular EPX, was observed in feces from patients with food-related GI symptoms. However, rather than being a tool to differentiate symptomatic from non-symptomatic periods, EPX might be used for detecting an ongoing clinical or subclinical chronic inflammation, that may have an impact on the patient's clinical course of GI symptoms.

  • 29.
    Malinovschi, Andrei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kalm-Stephens, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Increased exhaled nitric oxide predicts new-onset rhinitis and persistent rhinitis in adolescents without allergic symptoms2012In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 42, no 3, p. 433-440Article in journal (Refereed)
    Abstract [en]

    Background: The fraction of nitric oxide in exhaled air (FENO) is increased in rhinitis and asthma. We have previously suggested that elevated FENO levels in the absence of asthma symptoms may be a sign of 'early asthma'. In the present study, we hypothesize that elevated exhaled NO levels may also precede rhinitis symptoms.

    Objective: To investigate in a cohort of adolescents whether or not increased exhaled NO levels at the age of 13-14 years predicted new-onset or persistent rhinitis within a 4-year period.

    Methods: A total of 959 randomly selected adolescents (13-14 years) completed a questionnaire on respiratory symptoms at baseline and follow-up, 4 years later. Exhaled NO was measured at baseline. After exclusion of subjects with asthma diagnosis or asthma symptoms at baseline, 657 participants were eligible for the present study.

    Results: Higher FENO levels at baseline were associated with increased risk for new-onset (P = 0.009) and persistent rhinitis (P = 0.03) within a 4-year period. The risk of new-onset rhinitis was 2.32 (1.23, 4.37) [OR (95% CI)] times higher if FENO > 90th percentile of the group without rhinitis at baseline. This increased risk for new-onset rhinitis was significant [2.49 (1.24, 5.01)] after excluding subjects with allergic symptoms. The risk of persistent rhinitis was 5.11 (1.34, 19.57) times higher if FENO > 90th percentile of the group without rhinitis at baseline.

    Conclusion: Elevated exhaled nitric oxide levels predicted incident and persistent rhinitis in this population-based study of adolescents. Moreover, these findings were consistent after excluding subjects with allergic symptoms. Thus, it appears that elevation of exhaled NO precedes airway symptoms and predicts development of rhinitis in subjects without allergic symptoms or family history of allergic disease.

  • 30.
    Maruyama, N.
    et al.
    Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Uji, Kyoto 6110011, Japan..
    Nakagawa, T.
    Aichi Childrens Hlth & Med Ctr, Dept Allergy, Obu, Aichi, Japan..
    Ito, K.
    Aichi Childrens Hlth & Med Ctr, Dept Allergy, Obu, Aichi, Japan..
    Cabanos, C.
    Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Uji, Kyoto 6110011, Japan..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Uppsala, Sweden..
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Thermo Fisher Sci, Uppsala, Sweden..
    Tanaka, A.
    Thermo Fisher Sci, Tokyo, Japan..
    Sato, S.
    Sagamihara Natl Hosp, Clin Res Ctr Allergol & Rheumatol, Dept Allergy, Sagamihara, Kanagawa, Japan..
    Ebisawa, M.
    Sagamihara Natl Hosp, Clin Res Ctr Allergol & Rheumatol, Dept Allergy, Sagamihara, Kanagawa, Japan..
    Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of sesame allergy2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 1, p. 163-171Article in journal (Refereed)
    Abstract [en]

    Background The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. Objective The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. Methods Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Results Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA/L) were 86.1% and 85.7%, respectively. Conclusion and Clinical Relevance Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.

  • 31. Menditto, Enrica
    et al.
    Costa, Elisio
    Midão, Luis
    Bosnic-Anticevich, Sinthia
    Novellino, Ettore
    Bialek, Slawomir
    Briedis, Vitalis
    Mair, Alpana
    Rajabian-Soderlund, Rojin
    Arnavielhe, Sylvie
    Bedbrook, Anna
    Czarlewski, Wienczyslawa
    Annesi-Maesano, Isabella
    Anto, Josep M.
    Devillier, Philippe
    De Vries, Govert
    Keil, Thomas
    Sheikh, Aziz
    Orlando, Valentina
    Larenas-Linnemann, Désirée
    Cecchi, Lorenzo
    De Feo, Giulia
    Illario, M.
    Stellato, Christiana
    Fonseca, Joao
    Malva, Joao
    Morais-Almeida, Mario
    Pereira, Ana Maria
    Todo-Bom, Ana Maria
    Kvedariene, Violeta
    Valiulis, Arunas
    Bergmann, Karl Christian
    Klimek, Ludger
    Mösges, Ralph
    Pfaar, Oliver
    Zuberbier, Torsten
    Cardona, Vicky
    Mullol, Joaquim
    Papadopoulos, Nikos G.
    Prokopakis, Emmanuel P.
    Bewick, Mike
    Ryan, Dermot
    Roller-Wirnsberger, Regina E.
    Tomazic, Peter Valentin
    Cruz, Alvaro A.
    Kuna, Piotr
    Samolinski, Boleslaw
    Fokkens, Wytske J.
    Reitsma, Sietze
    Bosse, Isabelle
    Fontaine, Jean-François
    Laune, Daniel
    Haahtela, Tari
    Toppila-Salmi, Sanna
    Bachert, Claus
    Hellings, Peter W.
    Melén, Erik
    Wickman, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Bindslev-Jensen, Carsten
    Eller, Esben
    O'Hehir, Robyn E.
    Cingi, Cemal
    Gemicioğlu, Bilun
    Kalayci, Omer
    Ivancevich, Juan Carlos
    Bousquet, Jean
    Adherence to treatment in allergic rhinitis using mobile technology: the MASK Study2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 4, p. 442-460Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mobile technology may help to better understand the adherence to treatment MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centered ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries.

    OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App.

    METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from January 1, 2016 to August 1, 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach.

    RESULTS: 12,143 users were registered. 6,949 users reported at least one VAS data recording. Among them, 1,887 users reported ≥ 7 VAS data. 1,195 subjects were included in the analysis of adherence. 136 (11.28%) users were adherent (MPR ≥70% and PDC ≤ 1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC =1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR<70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users.

    CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous versus on-demand treatment for AR symptoms is still a matter of debate.This study shows an approach for measuring retrospective adherence based on a mobile app. This represent a novel approach also for analyzing medication taking behavior in a real-world setting. This article is protected by copyright. All rights reserved.

  • 32.
    Mogensen, Ida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bjerg, A.
    Karolinska Inst, Dept Womens & Childrens Hlth Clin Paedi, Stockholm, Sweden.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hedlin, G.
    Karolinska Inst, Dept Womens & Childrens Hlth Clin Paedi, Stockholm, Sweden.
    Sommar, J.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat Med, Umea, Sweden.
    Dahlén, S-E
    Karolinska Inst, Expt Asthma & Allergy Res Unit, Inst Environm Med, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Simultaneously elevated exhaled nitric oxide and serum-eosinophil cationic protein relate to recent asthma events in asthmatics in a cross-sectional population-based study.2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 12, p. 1540-1548Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2 -driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population-based study.

    OBJECTIVE: To investigate the relation between simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels and asthma events among asthmatics.

    METHODS: Measurements of FeNO (elevated ≥ 25 ppb) and S-ECP (elevated ≥ 20 ng/mL) were performed in 339 adult asthmatics. Asthma events (attacks and symptoms) were self-reported.

    RESULTS: Simultaneously normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs. 25%, P = 0.001). This was not found for subjects with singly elevated S-ECP (P = 0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and FeNO levels were independently associated with asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8).

    CONCLUSIONS: Simultaneously elevated FeNO and S-ECP levels were related to a higher likelihood of asthma attacks in the preceding 3 months. This indicates that there is a value in measuring both FeNO and systemic eosinophilic inflammation in patients with asthma to identify individuals at high risk of exacerbations.

    CLINICAL RELEVANCE: FeNO and S-ECP are markers for inflammation in asthma, but are dependent on different inflammatory pathways and weakly correlated. Simultaneous measurements of both offer better risk characterization of adult asthmatics.

  • 33.
    Mogensen, Ida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlen, Sven-Erik
    James, Anna
    Forsberg, Bertil
    Ono, Junya
    Ohta, Shoichiro
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Izuhara, Kenji
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Fixed airflow obstruction relates to eosinophil activation in asthmatics2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 2, p. 155-162Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO.

    OBJECTIVES: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.

    METHODS: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).

    RESULTS: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06 (2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO.

    CONCLUSIONS AND CLINICAL RELEVANCE: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO. This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

  • 34.
    Mogensen, Ida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Jacinto, T.
    CINTESIS, Inst & Hosp CUF, Porto, Portugal;Univ Porto, Fac Med, Porto, Portugal.
    Fonseca, J.
    CINTESIS, Inst & Hosp CUF, Porto, Portugal;Univ Porto, Fac Med, Porto, Portugal.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Simultaneously elevated FeNO and blood eosinophils relate to asthma morbidity in asthmatics from NHANES 2007-122018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 8, p. 935-943Article in journal (Refereed)
    Abstract [en]

    BackgroundFraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count are biomarkers for type 2 inflammation. However, they signal different inflammatory pathways. Simultaneously elevated, they are related to more asthma events in a general population and among younger asthmatics. ObjectiveTo investigate if simultaneously elevated FeNO and B-Eos relate to asthma outcomes and lung function among subjects with asthma at a wide age span, and how different cut-offs for the markers affect these relations. MethodFeNO, B-Eos and forced expiratory volume in 1 second (FEV1) were assessed in 1419 subjects with asthma, aged 6-79 years old, from the National Health and Nutrition Examination Survey (NHANES) 2007-12. Elevated levels were defined as FeNO 20 p.p.b. for children <12 years and 25 p.p.b. for subjects 12 years and B-Eos count 300 cells/L. Additional analyses were performed for the cut-offs FeNO >35/30 and >50/35 p.p.b., and for B-Eos 400 and 500 cells/L, as well as for different age subgroups (6-17, 18-44, >44 years old). Asthma events during the past year were self-reported. ResultsSubjects with simultaneously elevated FeNO and B-Eos compared with normal levels of both markers had a higher adjusted odds ratio (aOR (95%CI)) for having FEV1 <80% of predicted (2.15 (1.28-3.59), wheeze disturbing sleep (1.88 (1.27, 2.78)) but did not differ regarding asthma attacks past year. Elevated B-Eos, but not FeNO, was related to higher aOR for asthma attack (1.57 (1.14, 2.18) or emergency room (ER) visit due to asthma (1.88 (1.33, 2.64) when elevated FeNO and elevated B-Eos were studied as independent predictors. ConclusionSimultaneously elevated FeNO and B-Eos related to reduced lung function in asthmatics, wheezing symptoms, but not to a history of asthma attacks. Asthma attacks and ER-visit due to asthma were related to increased B-Eos levels.

  • 35.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Dalarna Univ, Dept Med Hlth & Social Studies, Falun, Sweden.
    Olivieri, Mario
    Univ Verona, Unit Occupat Med, Verona, Italy.
    Gislason, Thorainn
    Landspitali Univ Hosp, Dept Sleep, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Olin, Anna C.
    Univ Gothenburg, Inst Med, Sect Occupat & Environm Med, Gothenburg, Sweden.
    Nielsen, Rune
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Thorac Med, Bergen, Norway.
    Johannessen, Ane
    Univ Bergen, Ctr Int Hlth, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Haukeland Hosp, Dept Occupat Med, Bergen, Norway.
    Ferreira, Diogenes S.
    Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic, Australia;Univ Fed Paran, Complexo Hosp Clin, Alergia & Imunol, Curitiba, Parana, Brazil.
    Marcon, Alessandro
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Cazzoletti, Lucia
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Accordini, Simone
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Pin, Isabelle
    CHU Grenoble Alpes, Dept Pediat, Grenoble, France;INSERM, Inst Adv Biosci, Grenoble, France;Univ Grenoble Alpes, Grenoble, France.
    Corsico, Angelo
    IRCCS Policlin San Matteo Fdn, Div Resp Dis, Pavia, Italy;Univ Pavia, Dept Internal Med & Therapeut, Pavia, Italy.
    Demoly, Pascal
    Univ Montpellier, CHU Montpellier, Hop Arnaud de Villeneuve, Dept Pneumol & Addictol, Montpellier, France;Sorbonne Univ, INSERM, Inst Pierre Louis Epidemiol & Sante Publ, Equipe EPAR, Paris, France.
    Weyler, Joost
    Univ Antwerp, Univ Antwerp StatUA Stat Ctr, Epidemiol & Social Med, Antwerp, Belgium.
    Nowak, Dennis
    Ludwig Maximilians Univ Munchen, Hosp Ludwig Maximilian Univ Munich, Munich, Germany;German Ctr Lung Res DZL, CPC M, Munich, Germany.
    Jogi, Rain
    Tartu Univ Hosp, Lung Clin, Tartu, Estonia.
    Forsberg, Bertil
    Umea Univ, Dept Publ Hlth & Clin Med, Occupat & Environm Med, Umea, Sweden.
    Zock, Jan P.
    ISGlobal, Barcelona, Spain;UPF, Barcelona, Spain;CIBERESP, Madrid, Spain.
    Sigsgaard, Torben
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.
    Heinric, Joachim
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany;Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic, Australia.
    Bono, Roberto
    Univ Turin, Dept Publ Hlth & Pediat, Turin, Italy.
    Leynaert, Benedicte
    INSERM, UMR1152, Paris, France;Univ Paris Diderot, DHU FIRE, Paris, France.
    Jarvis, Deborah
    Imperial Coll, Natl Heart & Lung Inst, London, England.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 7, p. 969-979Article in journal (Refereed)
    Abstract [en]

    Introduction

    The fractional exhaled nitric oxide (FENO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FENO as a reliable biomarker, it is important to investigate factors that influence FENO in healthy individuals. Men have higher levels of FENO than women, but it is unclear whether determinants of FENO differ by sex.

    Objective

    To identify determinants of FENO in men and women without lung diseases. Method Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease.

    Results

    Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FENO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = FENO, compared with the lowest age quartile. Height was related to 8% higher FENO level in men (P < 0.001) and 5% higher FENO levels in women (P = 0.008). Men who smoked had 37% lower FENO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FENO levels compared with non-sensitized subjects 26% and 29%, P Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FENO started increasing at lower age in women than in men, suggesting that interpretation of FENO levels in adults aged over 50 years should take into account age and sex.

  • 36. Newson, R. B.
    et al.
    Jones, M.
    Forsberg, B.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Bossios, A.
    Dahlen, S. -E
    Toskala, E. M.
    Al-Kalemji, A.
    Kowalski, M. L.
    Rymarczyk, B.
    Salagean, E. M.
    van Drunen, C. M.
    Bachert, C.
    Wehrend, T.
    Kraemer, U.
    Mota-Pinto, A.
    Burney, P.
    Leynaert, B.
    Jarvis, D.
    The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 2, p. 250-260Article in journal (Refereed)
    Abstract [en]

    BackgroundCross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. ObjectiveWe wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. MethodsThe Global Asthma and Allergy Network of Excellence (GA(2)LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. ResultsOne thousand nine hundred and fifty-five subjects aged 16-77years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P=0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. Conclusions and Clinical RelevanceAsthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.

  • 37.
    Norbäck, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Cai, Guihong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dampness, indoor mould, fungal DNA and respiratory health - molecular methods in indoor epidemiology2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 5, p. 840-843Article in journal (Other academic)
  • 38.
    Patelis, Antonios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Umea Univ, Div Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Middelveld, R.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    James, A.
    Karolinska Inst, Natl Inst Enviromental Med, Expt Asthma & Allergy Res, Stockholm, Sweden.
    Ono, J.
    Shino Test Corp, Tokyo, Kanagawa, Japan.
    Ohta, S.
    Saga Med Sch, Dept Lab Med, Saga, Japan.
    Izuhara, K.
    Saga Med Sch, Div Med Biochem, Dept Biomol Sci, Saga, Japan.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Forsberg, B.
    Umea Univ, Div Occupat & Environm Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    IgE sensitization to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 9, p. 1147-1154Article in journal (Refereed)
    Abstract [en]

    Background: We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle-aged adults and in young subjects with asthma.

    Objective: To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics.

    Methods: FeNO, urinary eosinophil-derived neurotoxin (U-EDN), serum eosinophil cationic protein (S-ECP) and periostin were measured in 396 asthmatics, aged 17-76years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (3mm wheal) and sensitization to food allergens with measurement of specific IgE (0.35kU/L).

    Results: Asthmatics sensitized to food allergens had higher FeNO, 22.3ppb (18.6, 26.7) vs 16.1ppb (14.2, 18.2) (P=.005), S-ECP, 17.7mg/L (14.8, 21.1) vs 12.8mg/L (10.9, 14.9) (P=.01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P=.003), than non-sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P=.01). Sensitization to food allergens related independently to FeNO (P=.02), S-ECP (P=.006) and periostin (P=.004), whereas sensitization only to airborne allergens related only to FeNO (P=.02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r=.17, P<.001), periostin (r=.19, P<.001) and U-EDN (0.16, P<.001). S-ECP also correlated weakly with U-EDN (r=.12, P=.02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant.

    Conclusions & Clinical Relevance: Sensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S-ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management.

  • 39.
    Patelis, Antonios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Immunodiagnost, Uppsala, Sweden.
    Kober, A.
    Thermo Fisher Sci, Immunodiagnost, Uppsala, Sweden.
    Berthold, M.
    Thermo Fisher Sci, Immunodiagnost, Uppsala, Sweden.
    Multiplex component-based allergen microarray in recent clinical studies2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 8, p. 1022-1032Article in journal (Refereed)
    Abstract [en]

    During the last decades component-resolved diagnostics either as singleplex or multiplex measurements has been introduced into the field of clinical allergology, providing important information that cannot be obtained from extract-based tests. Here we review recent studies that demonstrate clinical applications of the multiplex microarray technique in the diagnosis and risk assessment of allergic patients, and its usefulness in studies of allergic diseases. The usefulness of ImmunoCAP ISAC has been validated in a wide spectrum of allergic diseases like asthma, allergic rhinoconjunctivitis, atopic dermatitis, eosinophilic esophagitis, food allergy and anaphylaxis. ISAC provides a broad picture of a patient's sensitization profile from a single test, and provides information on specific and cross-reactive sensitizations that facilitate diagnosis, risk assessment, and disease management. Furthermore, it can reveal unexpected sensitizations which may explain anaphylaxis previously categorized as idiopathic and also display for the moment clinically non-relevant sensitizations. ISAC can facilitate a better selection of relevant allergens for immunotherapy compared with extract testing. Microarray technique can visualize the allergic march and molecular spreading in the preclinical stages of allergic diseases, and may indicate that the likelihood of developing symptomatic allergy is associated with specific profiles of sensitization to allergen components. ISAC is shown to be a useful tool in routine allergy diagnostics due to its ability to improve risk assessment, to better select relevant allergens for immunotherapy as well as detecting unknown sensitization. Multiplex component testing is especially suitable for patients with complex symptomatology.

  • 40.
    Patelis, Antonios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gunnbjörnsdottir, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Thermo Fisher Sci, Immunodiagnost, Uppsala, Sweden.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Allergen extract vs component sensitisation and airway inflammation, responsiveness and new-onset respiratory disease.2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 5, p. 730-740Article in journal (Refereed)
    Abstract [en]

    Background: The absence of IgE sensitization to allergen components in the presence of sensitization to the corresponding extract has been reported, but its clinical importance has not been studied.

    Objective: To evaluate the clinical significance of IgE sensitization to three aeroallergen extracts and the corresponding components in relation to the development of respiratory disease.

    Methods: A total of 467 adults participated in the European Community Respiratory Health Survey (ECRHS) II and 302 in ECRHS III, 12years later. IgE sensitization to allergen extract and components, exhaled nitric oxide (FeNO) and bronchial responsiveness to methacholine were measured in ECRHS II. Rhinitis and asthma symptoms were questionnaire-assessed in both ECRHS II and III.

    Results: A good overall correlation was found between IgE sensitization to extract and components for cat (r=0.83), timothy (r=0.96) and birch (r=0.95). However, a substantial proportion of subjects tested IgE positive for cat and timothy allergen extracts but negative for the corresponding components (48% and 21%, respectively). Subjects sensitized to both cat extract and components had higher FeNO (P=0.008) and more bronchial responsiveness (P=0.002) than subjects sensitized only to the extract. Further, subjects sensitized to cat components were more likely to develop asthma (P=0.005) and rhinitis (P=0.007) than subjects sensitized only to cat extract.

    Conclusion: Measurement of IgE sensitization to cat allergen components would seem to have a higher clinical value than extract-based measurement, as it related better to airway inflammation and responsiveness and had a higher prognostic value for the development of asthma and rhinitis over a 12-year period.

  • 41.
    Patelis, Antonios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gunnbjörnsdottir, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Allergen extract vs component sensitisation and airway inflammation, responsiveness and new-onset respiratory diseaseIn: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222Article in journal (Other academic)
    Abstract [en]

    Background: The absence of IgE sensitization to allergen components in the presence of sensitization to the corresponding extract has been reported, but its clinical importance has not been studied.

    Objective: To evaluate the clinical significance of IgE sensitization to three  aeroallergen extracts and the corresponding components in relation to the development of respiratory disease.

    Methods: A total of 467 adults participated in the European Community Respiratory Health Survey (ECRHS) II and 302 in ECRHS III, 12 years later. IgE sensitization to allergen extract and components, exhaled nitric oxide (FeNO) and bronchial responsiveness to methacholine were measured in ECRHS II. Rhinitis and asthma symptoms were questionnaire-assessed in both ECRHS II and III.

    Results: A good overall correlation was found between IgE sensitization to extract and components for cat (r=0.83), timothy (r=0.96) and birch (r=0.95). However, a substantial proportion of subjects tested IgE-positive for cat and timothy allergen extracts but negative for the corresponding components (48% and 21%, respectively). Subjects sensitized to both cat extract and components had higher FeNO (p=0.008) and more bronchial responsiveness (p=0.002) than subjects sensitized only to the extract. Further, subjects sensitized to cat components were more likely to develop asthma (p=0.005) and rhinitis (p=0.007) than subjects sensitized only to cat extract.

    Conclusion: Measurement of IgE sensitization to cat allergen components would seem to have a higher clinical value than extract-based measurement, as it related better to airway inflammation and responsiveness and had a higher prognostic value for the development of asthma and rhinitis over a 12-year period.

  • 42.
    Reier-Nilsen, T.
    et al.
    Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Michelsen, M. M.
    Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Carlsen, K. C. Lodrup
    Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Carlsen, K. -H
    Mowinckel, P.
    Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Nygaard, U. C.
    Norwegian Inst Publ Hlth, Div Infect Control & Environm Hlth, Oslo, Norway.
    Namork, E.
    Norwegian Inst Publ Hlth, Div Infect Control & Environm Hlth, Oslo, Norway.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Thermofisher Sci, Uppsala, Sweden.
    Håland, G.
    Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Predicting reactivity threshold in children with anaphylaxis to peanut2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 4, p. 415-423Article in journal (Refereed)
    Abstract [en]

    Background: Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy.

    Objective: We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC.

    Methods: A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] 3 mm or specific immunoglobulin E [s-IgE] 0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG(4)), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC.

    Results: During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63(+) basophils 15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (<3 mg of peanut protein), with an optimal cut-off of 75.8% giving a 93.5% negative predictive value. None of the characteristics were significantly associated with the severity of allergic reaction.

    Conclusion and Clinical Relevance: In children with anaphylaxis to peanut, basophil activation, peanut SPT and the ratio of peanut s-IgE/total IgE were associated with reactivity threshold and LOAEL, but not with allergy reaction severity.

  • 43.
    Salomonsson, Maya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kalm-Stephens, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation, Metabolism and Child Health Research.
    Dahlin, Joakim S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation, Metabolism and Child Health Research.
    Hallgren, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Circulating mast cell progenitors correlate with reduced lung function in allergic asthma2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 874-882Article in journal (Refereed)
    Abstract [en]

    Background

    Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to the lung during acute allergic airway inflammation. The discovery of a corresponding human mast cell progenitor population in the blood has enabled to study the relation of circulating mast cell progenitors in clinical settings.

    Objectives

    To explore the possible association between the frequency of mast cell progenitors in the blood circulation and allergic asthma, we assessed the relation of this recently identified cell population with asthma outcomes and inflammatory mediators in allergic asthmatic patients and controls.

    Methods

    Blood samples were obtained, and spirometry was performed on 38 well‐controlled allergic asthmatic patients and 29 controls. The frequency of blood mast cell progenitors, total serum IgE and 180 inflammation‐ and immune‐related plasma proteins were quantified.

    Results

    Allergic asthmatic patients and controls had a similar mean frequency of blood mast cell progenitors, but the frequency was higher in allergic asthmatic patients with reduced FEV1 and PEF (% of predicted) as well as in women. The level of fibroblast growth factor 21 (FGF‐21) correlated positively with the frequency of mast cell progenitors, independent of age and gender, and negatively with lung function. The expression of FcεRI on mast cell progenitors was higher in allergic asthmatic patients and correlated positively with the level of total IgE in the controls but not in the asthmatic patients.

    Conclusion

    Elevated levels of circulating mast cell progenitors are related to reduced lung function, female gender and high levels of FGF‐21 in young adults with allergic asthma.

  • 44.
    Suzuki, Shintaro
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden; Showa Univ, Sch Med, Dept Med, Div Allergol & Resp Med, Tokyo, Japan.
    Nwaru, Bright I.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden; Univ Gothenburg, Inst Med, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden.
    Ekerljung, Linda
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden.
    Sjölander, Sigrid
    Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden.
    Mincheva, Roxana
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden.
    Rönmark, Erik P.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå Univ, OLIN Unit, Dept Publ Hlth & Clin Med, Occupat & Environm Med, Umeå, Sweden.
    Lundbäck, Bo
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research. Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden.
    Lotvall, Jan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden.
    Characterization of sensitization to furry animal allergen components in an adult population2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 4, p. 495-505Article in journal (Refereed)
    Abstract [en]

    Background: There are paucity of data on sensitization to furry animal allergen components in adults. Furry animals are major sensitizers and contributors to asthma burden in northern Europe and North America.

    Objective: To characterize sensitization patterns to furry animal allergen components in Swedish adults.

    Methods: Based on the West Sweden Asthma Study, a random population (n = 1103) and an asthma sample (n = 769) were tested for allergen sensitization using Phadiatop®. Those with IgE ≥ 0.35 kUA/L were tested for cat (Fel d 1, 2, and 4), dog (Can f 1, 2, 3, and 5), and horse (Equ c 1) allergen component sensitization. We defined allergen component poly‐sensitization patterns, identified data‐driven sensitization clusters, described component sensitization overlaps, and assessed determinants of sensitization patterns.

    Results: The prevalence of allergen component sensitization ranged from 0.8% for Fel d 2 and Can f 3 to 8.9% for Fel d 1. The most common dog component was Can f 5 (3.6%); 2.1% were sensitized to Equ c 1. Those sensitized to Fel d 2 and Fel d 4 were commonly sensitized to Fel d 1. The most common dog component overlap was between Can f 1/Can f 2 and Can f 5. Mono‐sensitization was 5.6%, double sensitization 1.5% and poly‐sensitization 2.1%. Sensitization was always higher in the asthma than in the random sample. Three sensitization clusters were derived, namely non‐sensitized (90% in random vs 66% in asthma sample); Fel d 1‐driven sensitized (7% vs 19%); and multi‐sensitized (3% vs 15%). Key determinants of sensitization were gender, age, raised on a farm, family history of allergy or asthma, smoking, and occupational exposure to dust or fumes.

    Conclusions & Clinical Relevance: Fel d 1 and Can f 5 are the most common cat and dog components sensitization in this adult Swedish population. Mono‐sensitization is more common than poly‐sensitization. This detailed characterization highlights the current distribution of furry animal allergen components in Swedish adults, and their impact on clinical outcomes of asthma will be further explored.

  • 45.
    Trulson, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Byström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Engström, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The functional heterogeneity of eosinophil cationic protein is determined by a gene polymorphism and post-translational modifications2007In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 37, no 2, p. 208-218Article in journal (Refereed)
    Abstract [en]

    Background

    The eosinophil is a cytotoxic cell and takes part in parasite killing and tissue-destructive processes by secretion of proteins such as eosinophil cationic protein (ECP). A polymorphism was demonstrated in the ECP gene, giving rise to a substitution of arginine at position 97 with threonine. This polymorphism is related to disease development.

    Objective

    To investigate the functional and molecular heterogeneity of native ECP and the functional consequences of the replacement of arginine with a threonine.

    Methods

    ECP was purified from healthy blood donors by gel filtration, ion-exchange chromatography and reversed-phase chromatography. Recombinant ECPs i.e. rECP 97arg and rECP 97thr were produced by the pFASTBAC baculovirus expression system. The cytotoxic activity was determined against an erythroleukaemia or a small cell lung cancer cell line.

    Results

    Native ECP was purified to apparent homogeneity and showed a considerable molecular heterogeneity and a corresponding functional heterogeneity with respect to cytotoxic activity. After reduction, the native cytotoxic ECP showed three bands on sodium dodecylsulphate polyacrylamide gel electrophoresis: one major band at 18-20 kDa and two minor bands at about 10 and 5 kDa, respectively. The 5 kDa contained two masses differing with 56.2 Da, which corresponds to the difference in molecular masses of arginine and threonine. rECP 97arg was cytotoxic in contrast to rECP97thr. Deglycosylation with N-glycosidase F did not affect the cytotoxic activity of native ECP to any measurable extent nor the activity of rECP 97arg, whereas rECP 97thr achieved cytotoxic activity. The RNase activities of the recombinant and native ECPs were similar.

    Conclusion

    We conclude that ECP is present in several molecular forms with varying biological activities. Some of this functional heterogeneity is based on the genetic polymorphism of the ECP gene and some on post-translational modifications. In subjects carrying the ECP 97thr variant, the cytotoxic activity may be disguised by N-linked glycosylation of the active site.

  • 46.
    Tsolakis, Nikolaos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    The absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 6, p. 722-730Article in journal (Refereed)
    Abstract [en]

    Background:

    Atopic asthma is associated with elevated type-2 biomarkers such as fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count. However, increased type 2 markers have also been reported in traditionally defined non-atopic asthma.

    Objective:

    To determine a clinically useful level of IgE sensitization for ruling out type 2 asthma. Methods: Asthmatics (N=408; age 10-35years) were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: 0.35kU(A)/L for at least one test (n=326) or <0.35kU(A)/L for both tests (n=82). he latter group was subsequently divided into 2 groups: IgE 0.10-0.34kU(A)/L (n=34) and IgE<0.10kU(A)/L (n=48). The relationships between type 2 biomarkers, and inadequate asthma control (ACT<20), reduced lung function (FEV1<80%), recent asthma attacks and airway hyperresponsiveness (AHR) to methacholine were determined.

    Results:

    In univariate analyses, at least one type 2 marker related to each asthma outcome in subjects with IgE 0.35kU(A)/L. In subjects with IgE 0.10-0.34kU(A)/L, elevated FeNO related to reduced lung function (P=.008) and B-Eos to AHR (P=.03). No associations were found in subjects with IgE<0.10kU(A)/L. In multivariate analysis, a relationship between FeNO and reduced lung function remained in subjects with IgE<0.35kU(A)/L (P=.03).

    Conclusion and Clinical Relevance:

    Clinically relevant elevation of type 2 biomarkers was seen in young asthmatics with IgE antibodies <0.35kU(A)/L, but not those with IgE<0.10kU(A)/L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement.

  • 47.
    Tsolakis, Nikolaos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Mattsson, Lars
    Thermo Fisher Sci, Uppsala, Sweden.
    Lidholm, Jonas
    Thermo Fisher Scientific, Uppsala, Sweden.
    Pedroletti, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Sensitization to minor cat allergen components is associated with type-2 biomarkers in young asthmatics2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 9, p. 1186-1194Article in journal (Refereed)
    Abstract [en]

    Background: Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied.

    Objective: To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals.

    Methods: Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders.

    Results: The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with B-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51).

    Conclusions: Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics.

    Clinical relevance: We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects.

  • 48.
    Victor, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Binnmyr, Jonas
    Karolinska Inst, Dept Clin Neurosci, Therapeut Immune Design Unit, Stockholm, Sweden.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rask-Andersen, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Elfman, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Levels of horse allergen Equ c 4 in dander and saliva from ten horse breeds2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 5, p. 701-711Article in journal (Refereed)
    Abstract [en]

    Background: Horses are an important source of allergens, but the distribution of horse allergens is poorly understood. Five horse allergens have been identified, Equ c 1-4 and 6. Equ c 4 seems to be an important allergen, with an IgE-binding frequency of 77% in horse-sensitized individuals.0000 Objectives: The aim of this study was to investigate levels of horse allergen Equ c 4 in dander, saliva and urine from ten horse breeds. Method: The study population included 170 horses (87 mares, 27 stallions, 56 geldings) from ten breeds. Horse dander, saliva and urine samples were collected. Levels of horse allergen Equ c 4 were quantified using a two-site sandwich ELISA (mAb 103 and 14G4) and were expressed as Equ c 4 U/mu g protein. Results: The horse allergen Equ c 4 was present in all dander and saliva samples from ten horse breeds, with high within-breed and inter-breed variations; GM values were 639 Equ c 4 U/mu g protein (range 5-15 264) for dander and 39.5 (4-263) for saliva. Equ c 4 was found in 19/21 urine samples. Adjusted for age, sex and changes over time, no differences between breeds could be seen in dander, while in saliva the North Swedish horse showed lower levels of Equ c 4 than any other breed. The levels of Equ c 4 protein in dander and saliva were significantly higher in samples from stallions compared to mares and geldings, independent of breed. Conclusions and Clinical Relevance: The results show a high variability in allergen levels of Equ c 4 in dander and saliva both within and between breeds. Significantly higher levels were found in stallions compared to mares and geldings, independent of breed. Results suggest that none of the horse breeds studied can be recommended for individuals allergic to Equ c 4.

  • 49.
    Villalta, D.
    et al.
    S Maria Angeli Hosp, Allergy & Clin Immunol Unit, Via Montereale 24, I-33170 Pordenone, Italy..
    Pantarotto, L.
    S Maria Angeli Hosp, Allergy & Clin Immunol Unit, Via Montereale 24, I-33170 Pordenone, Italy..
    Da Re, M.
    S Maria Angeli Hosp, Allergy & Clin Immunol Unit, Via Montereale 24, I-33170 Pordenone, Italy..
    Conte, M.
    S Maria Angeli Hosp, Allergy & Clin Immunol Unit, Via Montereale 24, I-33170 Pordenone, Italy..
    Sjölander, S.
    Uppsala Univ, Thermo Fisher Sci, Uppsala, Sweden..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala Univ, Thermo Fisher Sci, Uppsala, Sweden..
    Martelli, P.
    S Maria Angeli Hosp, Allergy & Clin Immunol Unit, Via Montereale 24, I-33170 Pordenone, Italy..
    High prevalence of sIgE to Galactose--1,3-galactose in rural pre-Alps area: a cross-sectional study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 2, p. 377-380Article in journal (Refereed)
  • 50. Woschnagg, Charlotte
    et al.
    Garcia, R.
    Rak, S.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    IL-5 priming of the PMA-induced oxidative metabolism of human eosinophils from allergic and normal subjects during a pollen season2001In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, no 4, p. 555-564Article in journal (Refereed)
    Abstract [en]

    AIM: To study the effect of IL-5 priming on the PMA-induced oxidative metabolism of blood eosinophils from allergic patients and healthy controls, during pollen exposure.

    METHODS: Twenty birch pollen allergic patients with seasonal symptoms of rhinitis or rhinitis plus asthma were studied during the birch pollen season of Sweden. Eosinophils were purified to > 95% by Percoll gradients followed by the MACS system. Oxidative metabolism was measured by a lucigenin enhanced chemiluminescence (CL) assay. Eosinophils were primed with IL-5 and subsequently stimulated with PMA. The signal transduction mechanisms of IL-5 priming were studied using the MEK inhibitor PD 98059, the PkC inhibitors Staurosporine, Ro 318220, Gö 6983 and the PI3kinase inhibitor Wortmannin.

    RESULTS: During the season, the eosinophils from the allergic patients showed a reduced t(1/2)rise compared to the non-allergic controls (P = 0.019) after stimulation. IL-5 reduced the total PMA CL response both in control and patients' cells (P = 0.012 and 0.0054 resp.), whereas it primed it in terms of the t(1/2)rise of the curves, in both groups (P = 0.012 and 0.0015 resp.). The PMA-induced CL reactions were inhibited by PD 98059, all PkC-inhibitors and Wortmannin. IL-5 priming counteracted only the MEK inhibition significantly.

    CONCLUSIONS: Blood eosinophils from allergic patients are primed in vivo, as compared to eosinophils from non-allergic controls, during a pollen season. Interleukin-5 primes equally the PMA-induced oxidative metabolism of human eosinophils from healthy or allergic subjects. The mechanism of IL-5 priming after PMA stimulation of oxygen radical production is MEK independent.

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