Browsing by Subject "ATOPIC SENSITIZATION"

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  • Haahtela, Tari (2019)
    Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.
  • PASTURE EFRAIM Study Grp; Metzler, Stefanie; Frei, Remo; Schmausser-Hechfellner, Elisabeth; Pekkanen, Juha; Karvonen, Anne M.; Kirjavainen, Pirkka V.; Roduit, Caroline (2019)
    Background: Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain inconsistent. The aim of this study was to investigate the association between pre-and post-natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis). Methods: A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6 years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded. Results: Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11-2.48 and for food allergy: aOR 3.01, 95% CI 1.22-7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4 years (aOR 2.73, 95% CI 1.66-4.49) and also suggested a dose-response relationship. A tendency was observed with asthma between 3 and 6 years (aOR 1.65, 95% CI 0.95-2.86). Conclusions: Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post-natal exposure to antibiotics in children born in rural settings.
  • Ruokolainen, Lasse; Parkkola, Anna; Karkman, Antti; Sinkko, Hanna; Peet, Aleksandr; Hämäläinen, Anu-Maaria; von Hertzen, Leena; Tillmann, Vallo; Koski, Katriina; Virtanen, Suvi M.; Niemelä, Onni; Haahtela, Tari; Knip, Mikael (2020)
    Background Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures. Methods We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children. Results Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genusAcinetobacterwas more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile ofAcinetobacter lwoffiiwas more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genusAcinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization. Conclusions In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genusAcinetobacterin the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.
  • Frei, Remo; Ferstl, Ruth; Roduit, Caroline; Ziegler, Mario; Schiavi, Elisa; Barcik, Weronika; Rodriguez-Perez, Noelia; Wirz, Oliver F.; Wawrzyniak, Marcin; Pugin, Benoit; Nehrbass, Dirk; Jutel, Marek; Smolinska, Sylwia; Konieczna, Patrycja; Bieli, Christian; Loeliger, Susanne; Waser, Marco; Pershagen, Goeran; Riedler, Josef; Depner, Martin; Schaub, Bianca; Genuneit, Jon; Renz, Harald; Pekkanen, Juha; Karvonen, Anne M.; Dalphin, Jean-Charles; van Hage, Marianne; Doekes, Gert; Akdis, Mubeccel; Braun-Fahrlander, Charlotte; Akdis, Cezmi A.; von Mutius, Erika; O'Mahony, Liam; Lauener, Roger P.; Prevention Allergy Risk Factors Se; Protection Against Allergy Study R (2018)
    Background: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. Objective: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. Methods: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. Results: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17(+) T-cell numbers and supported differentiation of regulatory T cells. Conclusions: In addition to microbial exposure, increased exposure to non microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
  • Haahtela, T.; Laatikainen, T.; Alenius, H.; Auvinen, P.; Fyhrquist, N.; Hanski, I.; von Hertzen, L.; Jousilahti, P.; Kosunen, T. U.; Markelova, O.; Mäkelä, M. J.; Pantelejev, V.; Uhanov, M.; Zilber, E.; Vartiainen, E. (2015)
    The Finnish and Russian Karelia are adjacent areas in northern Europe, socio-economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non-existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti-inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10-year National Allergy Programme was started in 2008 to combat the epidemic in Finland.
  • Bornelov, Susanne; Saaf, Annika; Melen, Erik; Bergstrom, Anna; Moghadam, Behrooz Torabi; Pulkkinen, Ville; Acevedo, Nathalie; Pietras, Christina Orsmark; Ege, Markus; Braun-Fahrlaender, Charlotte; Riedler, Josef; Doekes, Gert; Kabesch, Michael; van Hage, Marianne; Kere, Juha; Scheynius, Annika; Soderhall, Cilla; Pershagen, Goran; Komorowski, Jan (2013)