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

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

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

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

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

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

  • 2. Alcocer, M. J. C.
    et al.
    Murtagh, G. J.
    Mirotti, L.
    Brans, A.
    Harnett, W.
    Rundqvist, Louise
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    The allergenicity of 2S plant albumins2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 12, p. 1827-1827Article in journal (Refereed)
  • 3. Al-Shamkhi, N.
    et al.
    Alving, K.
    Dahlen, S. E.
    Hedlin, G.
    Middelveld, R.
    Bjerg, A.
    Ekerljung, L.
    Olin, A. C.
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Janson, C.
    Malinovschi, A.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma: results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

  • 5.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Räisänen, Petri
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Health Sciences, Luleå University, Luleå, Sweden.
    Stridsman, Caroline
    Department of Health Sciences, Luleå University, Luleå, Sweden.
    Andersson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundbäck, Bo
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016: results from three population surveys2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1426-1435Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  • 8.
    Bjerg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Perzanowski, Matthew
    Wennergren, Göran
    Lundbäck, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Decreased importance of environmental risk factors for childhood asthma from 1996 to 20062015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 1, p. 146-153Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 9.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Holgate, Stephen
    Kelly, Frank
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan
    Frew, Anthony
    Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 6, p. 777-782Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 10.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Vogt, H.
    Hjern, A.
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

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

  • 11. Eriksson, Jonas
    et al.
    Ekerljung, Linda
    Bossios, Apostolos
    Bjerg, Anders
    Wennergren, Göran
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå.
    Torén, Kjell
    Lötvall, Jan
    Lundbäck, Bo
    Aspirin-intolerant asthma in the population: prevalence and important determinants2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 1, p. 211-219Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Population-based studies on aspirin-intolerant asthma are very few and no previous population study has investigated risk factors for the condition.

    OBJECTIVE: To investigate the prevalence and risk factors of aspirin-intolerant asthma in the general population.

    METHODS: A questionnaire on respiratory health was mailed to 30 000 randomly selected subjects aged 16-75 years in West Sweden, 29 218 could be traced and 18 087 (62%) responded. The questionnaire included questions on asthma, respiratory symptoms, aspirin-induced dyspnea and possible determinants.

    RESULTS: The prevalence of aspirin-intolerant asthma was 0.5%, 0.3% in men and 0.6% in women (p=0.014). Sick leave, emergency visits due to asthma and all investigated lower respiratory symptoms were more common in aspirin-intolerant asthma than in aspirin-tolerant asthma. Obesity was a strong risk factor for aspirin-intolerant asthma (BMI>35: OR 12.1; 95% CI 2.49-58.5) and there was a dose-response relationship between increasing body mass index and risk of aspirin-intolerant asthma. Obesity, airborne occupational exposure and visible mold at home were considerably stronger risk factors for aspirin-intolerant asthma than for aspirin-tolerant asthma. Current smoking was a risk factor for aspirin-intolerant asthma (OR 2.55; 95% CI 1.47-4.42), but not aspirin-tolerant asthma.

    CONCLUSION: Aspirin-intolerant asthma identified in the general population was associated with a high burden of symptoms, uncontrolled disease and a high morbidity. Increasing body mass index increased the risk of aspirin-intolerant asthma in a dose-response manner. A number of risk factors, including obesity and current smoking, were considerably stronger for aspirin-intolerant asthma than for aspirin-tolerant asthma.

  • 12. Forsberg, A.
    et al.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. International Inflammation (in-FLAME) network of the World Universities Network, Umeå, Sweden.
    Prescott, S. L.
    Jenmalm, M. C.
    Pre- and probiotics for allergy prevention: time to revisit recommendations?2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 12, p. 1506-1521Article, review/survey (Refereed)
    Abstract [en]

    Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more affluent regions. Quantitatively, the largest important source of early immunemicrobial interaction, the gut microbiota, is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the ` dysbiotic drift' in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo-controlled trials. In this review, we provide an overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high-risk infants. It is however stressed that these recommendations are conditional, based on very low-quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition. Furthermore, we propose strategies to potentially improve allergy-preventive effects and enable future evidence-based implementation.

  • 13.
    Hedman, Linnéa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Andersson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bjerg, Anders
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundbäck, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Environmental risk factors related to the incidence of wheeze and asthma in adolescence2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 1, p. 184-191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma is common among adolescents, but there are few population-based studies on the risk factors for incident asthma and wheeze at this age group OBJECTIVE: To study risk factors for incident asthma and wheeze in adolescence.

    METHOD: Within the Obstructive Lung Disease In Northern Sweden (OLIN) studies, a cohort of 3430 school children (age 7-8y) was recruited in 1996. In the present study, this cohort was followed from age 12 to 19y. At baseline (age 12y), 3151 participated and skin prick tests (SPT) were performed. The cohort was resurveyed annually and risk factors for the cumulative incidence of asthma and wheeze from age 12 to19y were analysed using multivariate Cox regression.

    RESULTS: Female sex (wheeze: HR1.4 95%CI 1.2-1.6; asthma: HR1.8 95%CI1.2-2.5) and a positive SPT to cat, dog or horse at baseline (wheeze: HR 1.6 95%CI 1.2-2.1; asthma: HR2.3 95%CI 1.4-4.0) were significantly associated with the cumulative incidence of wheeze and asthma. Increasing numbers of siblings were inversely related to the incidence of wheeze (HR0.9 95%CI 0.8-0.97) and asthma (HR0.8 95%CI 0.7-0.97). Parental asthma was related to the incidence of asthma (HR 1.8 95%CI 1.2-2.6) while ever smoking (HR 2.0 95%CI 1.6-2.4) and house dampness (HR 1.3 95%CI 1.1-1.6) were risk factors for the incidence of wheeze. Maternal ETS exposure increased the risk of incident asthma in non-sensitized subjects (HR 1.9 95%CI 1.0-3.7).

    CONCLUSION AND CLINICAL RELEVANCE: Several environmental risk factors related to the incidence of asthma and wheeze in adolescence were identified and may be possible targets for intervention and prevention.

  • 14.
    Lodge, Caroline J.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Vic., Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Vic., Australia.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lowe, Adrian J.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Vic., Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Vic., Australia.
    Dharmage, S. C.
    Olsson, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Grandmaternal smoking increases asthma risk in grandchildren: a nationwide Swedish cohort2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 2, p. 167-174Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is growing interest in exposures prior to conception as possible risk factors for offspring asthma. Although partially supported by evidence from limited human studies, current evidence is inconsistent, and based on recall of exposure status.

    OBJECTIVE: We aimed to investigate grandmaternal smoking during pregnancy and the risk of asthma in grandchildren using prospectively collected population-based data.

    METHODS: Information on grandmaternal and maternal smoking during pregnancy and grandchild use of asthma medications was collected from national Swedish registries. Associations between grandmaternal smoking during pregnancy (10-12 weeks), and asthma medication use in grandchildren were investigated using generalized estimating equations. Ages at which asthma medications were prescribed classified childhood asthma into never, early transient (0-3years), late onset (3-6 years) and early persistent (0-3 and 3-6 years) phenotypes.

    RESULTS: From 1982 to 1986, 44,583 grandmothers gave birth to 46,197 mothers, who gave birth to 66,271 grandchildren (born 1996-2010). Children aged 1-6 years had an increased asthma risk if their grandmothers had smoked during pregnancy, with a higher risk for more exposure (10+ cigs/day; adjusted OR 1·23; 1·17, 1·30). Maternal smoking did not modify this relationship.

    CONCLUSIONS & CLINICAL RELEVANCE: Children had an increased risk of asthma in the first six years of life if their grandmothers smoked during early pregnancy, independent of maternal smoking. Importantly this exhibited a dose-response relationship and was associated with a persistent childhood asthma phenotype. These findings support possible epigenetic transmission of risk from environmental exposures in previous generations. 

  • 15. Metcalfe, J. R.
    et al.
    D'Vaz, N.
    Makrides, M.
    Gold, M. S.
    Quinn, P.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. School of Paediatrics and Child Health, The University of Western Australia, Perth.
    Loh, R.
    Prescott, S. L.
    Palmer, D. J.
    Elevated IL-5 and IL-13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 2, p. 308-316Article in journal (Refereed)
    Abstract [en]

    Background

    Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure.

    Objective

    To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy.

    Methods

    Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive ‘early egg’ or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge.

    Results

    In 4–month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by ‘early’ introduction of egg.

    Conclusions & Clinical Relevance

    Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.

  • 16. Mogensen, Ida
    et al.
    Alving, Kjell
    Bjerg, Anders
    Borres, Magnus P
    Hedlin, Gunilla
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Dahlén, Sven-Erik
    Janson, Christer
    Malinovschi, Andrei
    Simultaneously elevated exhaled nitric oxide and serum-ECP relate to recent asthma events in asthmatics in a cross sectional population based study2016In: 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 done 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 was independently associated to asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8).

    CONCLUSIONS: Simultaneous elevated FeNO and S-ECP 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 in order to identify individuals at high risk of exacerbations.

  • 17. Newson, R. B.
    et al.
    Jones, M.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Janson, C.
    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.
    Krämer, 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]

    BACKGROUND: Cross-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.

    OBJECTIVE: We 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.

    METHODS: The 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.

    RESULTS: One thousand nine hundred and fifty-five subjects aged 16-77 years 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 RELEVANCE: Asthma 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.

  • 18.
    Patelis, Antonios
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Uppsala University, Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala, Sweden; Uppsala University , Department of Medical Sciences: Clinical Physiology, Uppsala, Sweden.
    Alving, K
    Middelveld, R
    James, A
    Ono, J
    Ohta, S
    Izuhara, K
    Borres, M P
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Janson, C
    Malinovschi, A
    IgE sensitisation 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 1365-2222Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have recently reported that sensitisation to food allergens and sensitisation 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 sensitisation 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 17-76 years, from the Swedish GA2LEN study. Sensitisation to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitisation to food allergens with measurement of specific IgE (≥0.35kU/L).

    RESULTS: Asthmatics sensitised to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs. 16.1 ppb (14.2, 18.2) (p=0.005), S-ECP, 17.7 mg/L (14.8, 21.1) vs. 12.8 mg/L (10.9, 14.9) (p=0.01), and periostin, 73.7 (67.5, 80.3) ng/mL vs. 59.9 (55.8, 64.2) ng/mL (p=0.003), than non-sensitised subjects. Periostin levels in this group were also significantly higher than in the group sensitised only to airborne allergens (p=0.01). Sensitisation to food allergens related independently to FeNO (p=0.02), S-ECP (p=0.006) and periostin (p=0.004), whereas sensitisation only to airborne allergens related only to FeNO (p=0.02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r=0.17, p<0.001), periostin (r=0.19, p<0.001) and U-EDN (0.16, p<0.001). S-ECP also correlated weakly with U-EDN (r=0.12, p=0.02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant.

    CONCLUSIONS & CLINICAL RELEVANCE: Sensitisation 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 sensitisation, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management. This article is protected by copyright. All rights reserved.

  • 19.
    West, C E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Videky, D J
    School of Paediatrics and Child Health Research (SPACH), University of Western Australia, Perth, WA, Australia.
    Prescott, S L
    School of Paediatrics and Child Health Research (SPACH), University of Western Australia, Perth, WA, Australia.
    Dietary polyunsaturated fatty acids in the prevention of allergic inflammatory conditions: progress and perspectives2010In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 40, no 8, p. 1113-1115Article in journal (Refereed)
  • 20.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöstedt, M
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Probiotic effects on T-cell maturation in infants during weaning.2012In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 42, no 4, p. 540-549Article in journal (Refereed)
    Abstract [en]

    Background: We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema.

    Objective: To investigate the impact of feeding LF19 on T-cell maturation.

    Methods: One hundred and seventy-nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 10colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T-cell stimulation by anti-CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN-γ, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T regulatory lineages.

    Results: There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the placebo group (P < 0.05), whereas the IFN-γ/IL-2 (P < 0.01) and IL-17A/IL-2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the IFN-γ and IL-4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P > 0.05).

    Conclusion and Clinical Relevance: Our findings suggest modest effects by probiotics on T-cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.

  • 21.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jenmalm, M. C.
    Prescott, S. L.
    The gut microbiota and its role in the development of allergic disease: a wider perspective2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 1, p. 43-53Article, review/survey (Refereed)
    Abstract [en]

    The gut microbiota are critical in the homoeostasis of multiple interconnected host metabolic and immune networks. If early microbial colonization is delayed, the gut-associated lymphoid tissues (GALT) fail to develop, leading to persistent immune dysregulation in mice. Microbial colonization has also been proposed as a major driver for the normal age-related maturation of both Th1 and T regulatory (Treg) pathways that appear important in suppressing early propensity for Th2 allergic responses. There is emerging evidence that resident symbionts induce tolerogenic gut-associated Treg cells and dendritic cells that ensure the preferential growth of symbionts; keeping pathogenic strains in check and constraining proinflammatory Th1, Th2, and Th17 clones. Some effects of symbionts are mediated by short-chain fatty acids, which play a critical role in mucosal integrity and local and systemic metabolic function and stimulate the regulatory immune responses. The homoeostatic IL-10/TGF- dominated tolerogenic response within the GALT also signals the production of secretory IgA, which have a regulating role in mucosal integrity. Contrary to the sterile womb' paradigm, recent studies suggest that maternal microbial transfer to the offspring begins during pregnancy, providing a pioneer microbiome. It is likely that appropriate microbial stimulation both pre- and postnatally is required for optimal Th1 and Treg development to avoid the pathophysiological processes leading to allergy. Disturbed gut colonization patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a healthy gut microbiome' that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks, using harmonized outcomes and methodologies, are needed to advance our understanding in this field.

  • 22.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ryden, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Lundin, D.
    Engstrand, L.
    Tulic, M. K.
    Prescott, S. L.
    Gut microbiome and innate immune response patterns in IgE-associated eczema2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 9, p. 1419-1429Article in journal (Refereed)
    Abstract [en]

    BackgroundGut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling. ObjectiveWe examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5years in predisposed children due to maternal atopy [, trial ID ACTRN12606000280505]. MethodsMicrobial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1week, 1month and 12months in infants (n=10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5years of age (n=10). Microbiome data at 1week and 1month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6months of age. ResultsThe relative abundance of Gram-positive Ruminococcaceae was lower at 1week of age in infants developing IgE-associated eczema, compared with controls (P=0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, P=0.042) and TNF- (-0.597, P=0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF- (rs=-0.629, P=0.024). This relationship persisted at 1month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4-induced TNF- (rs=-0.697, P=0.038) and Enterobacteriaceae and IL-6 (rs=-0.709, P=0.035). Mothers whose infants developed IgE-associated eczema had lower -diversity of Bacteroidetes (P=0.04) although this was not seen later in their infants. At 1year, -diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (P=0.002). Conclusion and clinical relevanceOur findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated inflammatory cytokine responses to TLR-ligands and subsequent development of IgE-associated eczema.

  • 23.
    Österlund, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Grönlund, H
    Polovic, N
    Sundström, S
    Gafvelin, G
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells2009In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 39, no 8, p. 1199-1208Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: House dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens.

    OBJECTIVE: To investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation.

    METHODS: The human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors.

    RESULTS: Der p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappaB and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappaB activation.

    CONCLUSION: These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.

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