Asthma and allergy in teenagers and young adults, risk-factors and T-cell regulation

Asthma is one of the most common chronic diseases among teenagers and young adults. The prevalence of asthma among young adults in Sweden is approximately 7- 10%. Despite this, only a limited number of studies have focused on asthma, allergy and allergic inflammation in this age group. The aims of this thesis are to study the consequences of asthma and allergy in teenagers and young adults, incidence and riskfactors for death due to asthma, and deterioration in asthma prior and following transfer from pediatric to adult health care. As allergic inflammation is involved in a majority of asthma patients in this age-group we have further investigated a T cell mediated inflammatory mechanism with possible implications in monitoring and modulating autoimmune and allergic diseases. PAPER I During the 1994-2003 period 37 deaths due to asthma were identified. The incidence of asthma in 1-34 year-olds decreased during the period from 1.54 to 0.53 per million. Common risk-factors were under-treatment, poor adherence to prescribed treatment and adverse psychosocial situation. An alarming finding was that 11/37 deaths was probably caused by food allergy and 8/37 were associated with exposure to pet dander. PAPER II In a 5-year prospective follow-up study to identify risk factors for deterioration of asthma following transfer from pediatric to adult health care 150 teenagers with asthma were enrolled. Skin prick test at entrance revealed that 89% were sensitized towards at least one of tested allergens. A minority performed with impaired lung function without deterioration during the five-year follow up, while bronchial hyper responsiveness (BHR) was present in 71% of the subjects at entrance and among 59% at follow-up. Risk for persistence of BHR after five years was elevated by poor adherence and attenuated by regular physical activity. Working capacity decreased significantly during the study period without any correlation to risk factors examined. Paper III Interactions between the low-density lipoprotein receptor-related protein 1(LRP1) and thrombospondin-1 (TSP-1) is necessarily for T cell motility and that the motogenic LRP/TSP-1 mechanism antagonizes adhesion to ICAM-1 and fibronectin as well as TCR induced proliferative responses. This cascade mediates regulatory effects of IL-2 and IL-4. In addition expression of TSP-1, with known ability to protect against inflammation, was increased by IL-2. Paper IV T cell activation induces arrest of T cell motility through down-regulation of LRP1 synthesis a concomitant up-regulation of TSP-1 synthesis providing a mechanism for enhancement of adhesion of T cells to APC´s stimulating proliferative responses. Despite this arrest of motility, co-ligation with CD28 maintains a basal motility level by enhancing transport of LRP1 to the cell surface. Paper V Patients with allergy and psoriasis showed impaired T cell motility and decreased TSP- 1 expression compared to healthy controls. IL-2 was shown to up-regulate the impaired motility in patient to the same level as in controls indicating a reversible state probably excluding a constitutional defect

Global economic drivers in the development of different industrial hubs in the European Arctic

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Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.Original Publication: Johanna Sjöwall, Linda Fryland, Marika Nordberg, Florence Sjögren, Ulf Garpmo, Christian Jansson, Sten-Anders Carlsson, Sven Bergstrom, Jan Ernerudh, Dag Nyman, Pia Forsberg and Christina Ekerfelt, Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans, 2011, PLOS ONE, (6), 3, 0018220. http://dx.doi.org/10.1371/journal.pone.0018220 Copyright: Public Library of Science (PLoS) http://www.plos.org

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

Parametervärden för HBV-modellen i Sverige : Erfarenheter från modellkalibreringar under perioden 1975-1989

HBV-modellen utvecklades vid SMHI i början av 1970-talet och har sedan dess funnit ett stort antal tillämpningar i landet. Inledningsvis var intresset mest knutet till hydrologisk prognosering åt vattenkraftindustrin och översvämningsvarningar till allmänheten, men under senare år har modellen fått spela en allt större roll för beräkning av dimensionerande flöden. Modellen finns i ett antal versioner, HBV-3, HBV-6 och HBV-TL samt ytterligare några för speciella tillämpningar. Dessutom finns ett antal versioner av modellen vid institutioner utanför SMHI såväl i Sverigesom utomlands

Utveckling och tillämpning av en begreppsmässig avrinningsmodell för Skandinaviska nederbördsområden

The experiences of conceptual runoff modelling at the Swedish Meteorological and Hydrological Institute are surnmarized in the present work. The basic philosophy and the methodology when developing the HBV-model are discussed. The structure of the model is described with a discussion of its physical relevance and examples of alternatives. The sensitivity of the model to changes in parameter values is studied through reappings of the response surfaces of a sum of squares criterion of fit. Applications to a variety of catchments in Sweden and Norway are presented and the performance of the model is verified by a numerical criterion of fit, plottings of computed hydrographs and recorded ones, scatter diagrams of peak flows and flow duration curves. Examples of both short range and longrange hydrological forecasting are given. A general conclusion is that the HBV-model can be used for the reconstructionof the discharge in catchments of the presented type, if it is properly calibrated. The model can also be used for hydrological forecasting, if combined with meteorological forecasts or recorded climatic series.Erfarenheterna av begreppsmässiga avrinningsmodeller vid Sveriges Meteorologiskaoch Hydrologiska Institut summeras i föreliggande arbete. Den grundläggande filosofin och metodiken vid utvecklingen av HBV-modellen diskuteras. Modellstrukturen beskrives med en presentation av den fysikaliska bakgrunden och exempel på alternativ. Modellens känslighet förstörningar av parametervärden studeras genom kartläggning av ett minsta kvadratkriteriums responsytor. Tillämpningar av modellen på ett antal avrinningsområden i Sverige och Norge redovisas och simuleringen utvärderas med ett numeriskt anpassningskriterium, uppritningar av den beräknade och observerade hydrografen, jämförelser mellan simulerade och beräknade flödestoppar samt varaktighetsdiagram. Exempel ges på hydrologiska lång- och korttidsprognoser. En allmän slutsats är att HBV-modellen är användbar för rekonstruktion av vattenföringsserier i den typ av områden, där den tillämpats, under förutsättning att den kalibreras på ett riktigt sätt. Modellen kan också användas för hydrologiska prognoser med hjälp av meteorologiska prognoser eller observerade klimatserier

The colonization of state forest areas in Norrbotten in the period 1894-1950

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