Background & Objectives: There has been few investigation of the association between the farming related activities or specific characteristics and atopic disease in rural Canadian children. In population-based studies, assuring the quality of information from questionnaires is of concern. We conducted this study in order to: first, identify the prevalence and risk factors of atopy and allergic conditions among school-age children in a rural region of Canada. Also, we sought to evaluate the validity and reliability of a questionnaire report of allergy to assess in this population. Methods: As part of a longitudinal study of lung health in rural residents, we conducted a cross-sectional baseline study in rural Saskatchewan, Canada. This included an initial survey phase followed by a clinical testing phase. A sub-sample of 584 children (grades 1-8) completed skin prick testing to assess atopic status. Of these, 480 children completed a questionnaire report of allergy and atopic outcomes and participated in skin prick testing (SPT). Atopy was defined as a positive reaction to any of 6 allergens (local grasses, wheat dust, cat dander, house dust mite, Alternaria, Clasdosporium)≥3mm compared to the negative control. Agreement between questionnaire report and objective measures of atopy was considered overall and between the specific allergens tested on SPT and those assessed on questionnaire. We considered percent concordance, Kappa, sensitivity, specificity, and the positive and negative predictive values of reported allergies or allergic conditions in comparison to SPT as the gold standard. Results: The prevalence of atopy as well as allergen-specific sensitizations was similar between farm and non-farm children but supported the notion that livestock farming is protective against atopy. Also, we found that 25.0% of children reported a history of allergic conditions by questionnaire and 19.4% were atopic detected by skin pick test. In our study, the agreement between questionnaire report of specific allergic triggers and atopy measured by SPT was high (83.0% - 89.5%). Conclusion: In children, livestock exposure has a protective effect on SPT positivity.The agreement between questionnaire report of allergic symptoms and atopy measured by SPT was high and the agreement between atopy and report of allergic conditions was moderate.

[Truncated abstract] The last few decades have witnessed an increase in the prevalence, morbidity and economic burden associated with asthma and allergic disease. This rising incidence cannot be completely explained by changes in genetic factors or by improvements in diagnostic procedures. Environmental factors, particularly those associated with a westernised lifestyle, are considered to be involved in this increase. In the late 1980’s Strachan was the first to link environmental factors with allergic disease, this theory became to be known as the ‘hygiene hypothesis’. This hypothesis links the “cleaner” more “healthy ” environment we now live in, with an increased risk of developing allergic disease. This effect is highlighted by studies linking farm and animal exposure (rich in microbial compounds) during early life with a decrease in allergic disease. Since then numerous studies have been undertaken to ascertain the factors present in the microbe rich environment, which elicit this protective effect. Many studies have revolved around endotoxin, however microbial components (mainly from Gram-positive bacteria) which signal through Toll-like receptor 2 (TLR2), have also shown that they can alter the allergic immune response. In mice models TLR2 has been shown to both exacerbate and inhibit allergic disease. The above research highlights the need for further studies into the effect of TLR2 ligands, and to define the mechanisms by which they exert their effects in human allergic disease. These mechanisms will be relevant to understanding the pathogenesis of allergy, but also might provide novel ways to treat allergy. The aims of the study outlined in this thesis were to determine whether in vitro exposure to TLR2 ligands could modify the established immune response to house dust mite allergen (HDM), and to examine the mechanisms by which this occurs. ... The addition of glucocorticoids to LTA enhanced the ability of this TLR2 ligand to inhibit IL-5 and IL-13 production by HDM-activated blood mononuclear cells. In conclusion, this study shows that TLR2 ligands have the ability to inhibit the Th2 response to mite allergen in previously sensitized individuals by an as yet unknown mechanism. However the findings described herein do provide an impetus for future studies designed to uncover novel mechanisms by which allergic responses can be ameliorated, and may open new treatment modalities.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2007. / Härtill 4 uppsatser.

Abstract An excess of atopic allergies has been found in patients with depression, and conversely, increased amounts of depressive symptoms have been reported in patients with atopic disorders. Thus far, however, the findings have mainly been based on clinical samples. In this thesis, the association between atopic disorders and depression was investigated at epidemiological level by using data from the Northern Finland 1966 Birth Cohort. An unselected cohort of 12058 liveborn children was followed prospectively from prenatal stages until 1997. During the 31-year follow-up, 6025 cohort members underwent skin prick tests. Data on lifetime depression diagnoses and atopic conditions were obtained from postal questionnaires and Finnish Hospital Discharge Registers, and the severity of the depressive symptoms was assessed with Hopkins Symptom Checklist-25. Information on the family histories of the atopic disorders was obtained from questionnaires of the 31-year follow-up. Females with positive skin prick test responses and self-reported histories of allergic symptoms exhibited a 2.7-fold probability of developing lifetime depression. The corresponding probability increased in line with the increased severity of depressive symptoms in atopic but not in non-atopic females, ranging from 3.0 to 4.7-fold. Among males, the atopy-depression association was seen only in the highest depression scores, the odds ratio being up to 6.3-fold. While the most severe, hospital-treated manifestations of both disorders were considered, atopic disorders increased the risk of depression 3-fold independently of the subject's gender and sociodemographic characteristics. When investigating the effect of familial atopy on a child's depression, maternal atopy increased the probability of lifetime depression nearly 2-fold in females, and over 4-fold, when a female cohort member's own atopy was also present. At epidemiological level, the presence of atopic conditions seemed to increase the probability of lifetime depression especially in females. Since both atopic disorders and depression are illnesses of major public health importance in Western countries, also the co-morbidity between these disorders should be seriously taken into account in clinical practice. Further investigations are called for in evaluating whether this association is specific to atopic disorders, since increased risks of depression have been noted in connection with many other physical diseases as well.

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden (n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63–0.96; p = 0.017) and for 280Met an odds ratio of 0.71 (95% confidence interval 0.56–0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

No description available.

[pt] Esta tese parte de uma provocação enunciada pela personagem Alcibíades em seu discurso no diálogo Banquete de Platão: Nenhum de vocês o conhece bem. Esta frase versa a respeito da ininteligibilidade e consequente incomparabilidade de Sócrates, identificada pelo simposiasta como atopía, um não-lugar. Partindo, então, deste termo, buscamos aqui analisar as pistas que a personagem que discursa sobre o filósofo apresenta acerca dele, correlacionandoas a outras que ocorrem na obra platônica em geral e que consolidam a atopia de Sócrates. Assim, desenvolvemos uma análise de Sócrates enquanto um ser atópico tanto em sua fisionomia, como em seu comportamento e palavras, sendo estas três áreas da vida do filósofo o que chamamos nesta tese de eixos, bases metodológicas segundo as quais desenvolveremos a análise da sua atopia. Como fio condutor principal de todos estes eixos, teremos a presença central das figuras divinas de Eros e Dioniso, ambas apresentadas no Banquete como sendo os principais referenciais a partir dos quais Sócrates viverá a sua atopia. No campo de Eros, analisaremos o fundamento da narrativa de Diotima acerca deste deus, com seu caráter intermediário e daimônico, que será associado a Sócrates de forma evidente na fala da sacerdotisa de Mantineia. Já quanto ao aspecto dionisíaco, ele surgirá permeando todo o diálogo, mas será encontrado, em especial, na figura dos sátiros e silenos, seres mitológicos do círculo dionisíaco que serão associados a Sócrates por Alcibíades. Postulamos, assim, como tese central deste trabalho, que Sócrates é atópos porque a sua filosofia será um exercício integrado de seu corpo, de seus atos e de suas palavras, como partes de seu ser erótico e dionisíaco. / [en] This thesis is part of a provocation enunciated by the character Alcibiades in his speech in Plato s Symposium dialogue: None of you know him well. This phrase concerns the unintelligibility and consequent incomparability of Socrates, identified by the symposiasta as atopy, a non-place. Beginning from this term, we reach to analyze the clues that the character speeches about the philosopher presents about him, correlating them to others, that occurs in the Platonic piece in general and that consolidates the atopy of Socrates. Thus, we developed an analysis of Socrates as an atopic being both in his physiognomy as in his behavior and words, these three areas of the philosopher s life being what we call this thesis of axes, methodological bases according to which we ll develop the analysis of his atopy. As the main thread of all these axes, we will have the central presence of the divine figures of Eros and Dionysus, both presented at the Symposium as the main references from which Socrates will live his atopy. In Eros field, we will analyze the foundation of Diotima s narrative about this god, with his intermediate and daimonic character, which will be associated with Socrates in an evident way in the speech of the priestess of Mantineia. In the matter of the Dionysian aspect, it will appear permeating the whole dialogue, but will be found, in particular, in the figure of the satyrs and silenos, mythological beings of the Dionysian circle that will be associated with Socrates by Alcibiades. We postulate, therefore, as the central thesis of this work, that Socrates is atomic because his philosophy will be an integrated exercise of his body, his acts and his words, as parts of his erotic and Dionysian being.

Résumé : PROBLÉMATIQUE: L’exposition résidentielle à l’humidité excessive ou aux moisissures est maintenant reconnue comme un facteur important influençant la santé respiratoire. Cette problématique a été peu étudiée chez les étudiants universitaires, bien que vulnérables par leur faible revenu et leur statut de locataire. OBJECTIFS: Cette maîtrise vise à décrire la prévalence (a) de l’exposition résidentielle à l’humidité excessive ou aux moisissures et (b) des maladies respiratoires chez les étudiants universitaires, ainsi qu’à (c) examiner l’association entre l’exposition résidentielle à l’humidité excessive ou aux moisissures et ces maladies. MÉTHODES: En 2014, une enquête électronique a été réalisée auprès de 2097 étudiants enregistrés à l’Université de Sherbrooke (Québec, Canada). Lorsque possible, des questions et des scores validés ont été utilisés pour estimer les prévalences des maladies respiratoires (rhinite allergique, asthme et infections respiratoires), de l’exposition résidentielle à l’humidité excessive ou aux moisissures et des covariables (ex. : revenu annuel familial, statut tabagique, atopie familiale, caractéristiques de l’étudiant). Les associations entre cette exposition et ces maladies ont d’abord été examinées par des tests de chi-carré en utilisant un seuil alpha de 0,05. Des régressions logistiques multivariées ont ensuite été utilisées pour déterminer les associations brutes et ajustée entre cette exposition et les maladies respiratoires. Les analyses descriptives ont été pondérées pour le sexe, l’âge et le campus d’étude. RÉSULTATS: L’exposition à l’humidité excessive ou aux moisissures était fréquente parmi les participants (36,0%; Intervalle de confiance (IC)95% : 33,9-38,1). Ceux-ci ont également été nombreux à rapporter une rhinite allergique (23,9%; IC95% :22,0-25,8), de l’asthme (32,6%; IC95% : 30,5-34,7) et des infections respiratoires (19,4%; IC95% :17,7-21,2) au cours de la dernière année. Après ajustement, les associations demeuraient significatives entre l’exposition à l’humidité excessive ou aux moisissures et la rhinite allergique (Rapport de cote (RC) : 1,30; IC95% : 1.05-1.60), l’asthme RC : 1,75; IC95% : 1,42-2,16), mais pas les infections respiratoires (RC : 1,07; IC95% : 0,85-1.35). CONCLUSIONS: La prévalence élevée de l’exposition résidentielle des étudiants universitaires à l’humidité excessive ou aux moisissures, de même que son association avec l’asthme et la rhinite allergique, mettent en lumière sa contribution potentielle à la forte prévalence des maladies respiratoires ayant une composante allergique dans cette population. Cette étude fournit un nouveau levier pour les organisations de santé publique et leurs partenaires afin d’adapter les stratégies préventives ciblant les logements insalubres, particulièrement chez les populations vulnérables. / Abstract : PROBLEMATIC: Indoor residential dampness and mold is now recognised as a major respiratory health determinant. University students are vulnerable to such exposure by their low income and high mobility, but few studies have assessed their exposure. OBJECTIVES: This project aims to describe prevalence of (a) residential dampness or mold exposure and (b) respiratory diseases in University students as well as to (c) examine the independent contribution of residential excessive dampness and mold to these diseases. METHODS: In 2014, an online survey was conducted among 2097 students registered at the University of Sherbrooke (Quebec, Canada). Validated questions, and scores when possible, were used to assess respiratory diseases (allergic rhinitis, asthma-like symptoms, respiratory infections), residential excessive dampness and mold, and covariates (e.g. family annual income, smoking status, parental atopy, student characteristics). Associations between exposure and diseases were first evaluated using bivariate analyses (khi-square tests) with an alpha value of 0.05. Using logistic regressions, the crude and adjusted relationships between residential excessive dampness or mold and respiratory diseases were examined. Results were weighted for sex, age and campus affiliation. RESULTS: Residential dampness or mold exposure was frequent (36.0%; 95%Confidence Interval (CI) : 33.9-38.1). Respondents also reported high prevalence of allergic rhinitis (32.6%; 95%CI : 30.5-34.7), asthma-like symptoms (23.9%; 95%CI : 22.0-25.8) and respiratory infections (19.4%; 95%CI : 17.7-21.2). After adjustment, associations with residential excessive dampness or mold were significant for allergic rhinitis (Odd Ratio(OR) : 1.30; 95%CI : 1.05-1.60) and asthma-like symptoms (OR : 1.75; 95%CI : 1.42-2.16), but not for respiratory infections (OR : 1.07; 95%CI : 0.85-1.35). CONCLUSIONS: High frequency of residential excessive dampness and mold, as well as its associations with asthma and allergic rhinitis highlight this exposure’s potential contribution to high atopy prevalence among university students. These results emphasize the importance for public health organizations to tackle poor housing, especially for vulnerable populations.

Atopische Erkrankungen wie Asthma, atopische Dermatitis und allergische Rhinitis sind komplexe, multifaktorielle Erkrankungen. Diese Arbeit untersuchte Gen-Gen- und Gen-Umweltinteraktionen von insgesamt acht Polymorphismen in fünf Kandidatengenen. In einer großen deutschen Geburtskohorte (Multizentrische Allergie Studie, MAS 90) mit longitudinalen klinischen und serologischen Daten wurde der Effekt von Polymorphismen in Genen, die für Interleukin-13 (IL-13), Interleukin-4 (IL-4) und dessen gemeinsamer Rezeptoruntereinheit IL4R-a kodieren, auf Atopie-assoziierte Merkmale untersucht. Zwei Polymorphismen im IL13-Gen (Arg130Gln, C-1055T) zeigten über den gesamten Beobachtungszeitraum von sieben Jahren eine signifikante Assoziation mit erhöhten Gesamt-IgE-Werten. Weiterhin konnte diese Untersuchung zeigen, dass mütterliches Rauchen diesen Effekt auf die IgE-Werte noch verstärkt. Ein Polymorphismus des Komplementfaktor-C5-Rezeptors, der im Mausmodell als Suszeptibilitätslokus für Asthma identifiziert wurde, wurde in der MAS-Kohorte wie auch in einer afro-karibischen Population auf Assoziation mit Atopie-relevanten Merkmalen untersucht. Eine Assoziation konnte zwar nicht gefunden werden, jedoch waren hochsignifikante Unterschiede in der Allelfrequenz in den zwei ethnischen Gruppen auffällig; ein Phänomen, welches auch bei anderen genetischen Varianten in proinflammatorischen Genen beobachtet wurde. Ein funktioneller Polymorphismus des histaminabbauenden Enzyms Histamin-N-Methyl-Transferase wurde auf eine Assoziation mit bronchialer Hyperreagibilität und Asthma in der MAS-Kohorte sowie in einer weiteren kaukasischen Population von asthmatischen Kindern überprüft. Weder eine Assoziation mit Asthma noch eine modulierende Wirkung auf den Schweregrad der bronchialen Hyperreagibilität konnte in den Studienpopulationen gefunden werden. Im Gegensatz zu Untersuchungen bei erwachsenen Asthmatikern scheint diese Variante bei kindlichem Asthma keine entscheidende Rolle zu spielen. / Atopic diseases like asthma, atopic dermatitis and allergic rhinitis are complex traits of multifactorial origin. This study aimed to reveal gene-gene- and gene-environmental interactions of eight polymorphisms in five candidate genes. We examined whether 6 genetic variants of the genes coding for Interleukin-4 (IL-4), Interleukin-13 (IL-13) and their common receptor unit IL4R-alpha had genotypic effects on atopy-related traits such as total serum IgE levels in a large German birth cohort study (Multicenter Atopy Study, MAS 90) with longitudinally well defined phenotypes. Two single nucelotide polymorphisms (SNP) in the IL-13 gene (Arg130Gln, C-1055T) showed a significant association with increased serum IgE levels over the whole period of seven years. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. We tested the association of atopy-related traits and a SNP of the complement factor 5 receptor (-245T) in the MAS cohort and in an afro-caribbean population. Although we could not observe any association, there was a highly significant difference in the frequency of the -245T allele between the two ethnic populations, a phenomenon previously described for other genetic variants. Histamine N-Methyltransferase (HNMT) catalyses the major pathway of histamine metabolism in the human lung. We tested the functional polymorphism C314T of HNMT for association with asthma and bronchial hyperresponsiveness in two German pediatric populations (MAS, Astmatic children from Freiburg). No association of the T314 Allele with asthma, BHR and other asthma related phenotypes could be observed. We concluded that this SNP might not play a major role in the pathogenesis of asthma or BHR in German children.

Individual and environmental risk factors in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospital workers with a follow-up time of 20 months. Current hand eczema was analyzed in 142 wet hospital workers from this cohort with respect to the etiologic importance of irritants, allergens and contact urticants. The density of the microflora and the effect on the microflora of topical treatment with a potent corticosteroid were studied in 20 patients with hand eczema. ’Wet’ hospital work was found to increase the odds of developing hand eczema only twice compared to 'dry' office work. Nursing children under four years old and the lack of a dish-washing machine significantly increased the risk of contracting hand eczema. Unfavourable combinations of these domestic factors increased the risk as much as wet work. A history of atopic dermatitis approximately tripled the odds both in wet as well as in dry work. Histories of earlier hand eczema (HHE), metal dermatitis (HMD) and of atopy were analyzed as risk factors for hand eczema in 1857 women in wet work. HHE increased the odds by a factor of 12.9 and created a subdivision of the population into high risk individuals and normal risk individuals. HHE was found in half of the subjects with atopic dermatitis, in one quarter of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics. A HMD increased the odds by a factor of 1.8. This increase was seen as a high risk level in subjects with HHE and as a normal risk level in subjects with no HHE. A history of atopic disease as a complement to information about HHE and HMD increased the odds by another 1.3 times. The predicted probability of developing hand eczema ranged from 91 % in subjects with a combination of HHE, HMD and atopy to 24% in subjects with none of these risk factors. Subjects with AD were found to suffer a more severe form of hand eczema with significantly higher figures for medical consultation, sick- leave, termination due to hand eczema, early debut, permanent symtoms and vesicular lesions. Amongst the patients investigated for current hand eczema high risk individuals were overrepresented. It was claimed in 92.3% of the cases that trivial irritant factors had elicited the current episodes of hand eczema. In 35% of the cases the exposure to the irritant took place largely at home. Although contact sensitivity and contact urticaria were fairly common, they mostly seemed to be of minor importance in the etiology of the current hand eczema. Staphylococcus aureus colonized eczematous lesions of the hands in 18/20 patients. The density exceeded 105 colony forming units/cm2 in 15/20 patients. Only three of these patients showed signs of clinical infection. Successful topical treatment with a potent corticosteroid significantly reduced the colonization of S. aureus. / <p>Härtill 4 uppsatser</p> / digitalisering@umu