Purpose: The purpose of the present study was to illuminate how individuals living with SHR, experience its impact on accessibility, financial security and social relationships. Method: A qualitative approach was used. The participants were recruited by advertising on the website for “The network for people with odor intolerance”. The data was collected by written descritive texts from the participants and analysed with qualitative content analysis. Results: The results showed that the informants experienced an extensive lack of accessibility in society. It was difficult to move around in society, to visit public buildings and facilities and it was almost impossible to find a suitable place to live. Regarding financial security they had a reduced income due to difficulties to earn their living in combination with increased expenses because of the disease and they had difficulties to get the support they needed from authorities. This created an insecure financial situation. Further, the findings showed that their social relationships had been affected. Socializing with others had become hard and troublesome, they had become limited in doing social activities and they got support from some but these persons became limited. Six themes permeated the categories in all three content areas: “Being limited”, “Being forced to behave incompatible with your true personality”, “Experiencing a lack of understanding and respect from others”, “Experiencing insecurity”, “Being dependent on others” and “Being forced to choose between the plague and cholera”. / Syfte: Syftet med denna studie var att belysa hur individer som lever med sensorisk hyperreaktivitet (SHR) upplever dess påverkan på tillgänglighet, ekonomisk trygghet och sociala relationer. Metod: Kvalitativ metod användes och deltagarna rekryterades via Internet genom annonsering på nätverket för doftöverkänsligas hemsida. Datainsamlingen skedde genom skrivna berättelser från deltagarna och data analyserades sedan med kvalitativ innehållsanalys. Resultat: Resultatet visade att informanterna upplevde en omfattande brist på tillgänglighet i samhället. Det var svårt att röra sig i samhället, att besöka offentliga lokaler och inrättningar samt att det var nästan omöjligt att hitta en lämplig bostad. Deras ekonomiska trygghet var påverkad genom att de hade minskad inkomst på grund av svårigheter att försörja sig i kombination med ökade utgifter orsakade av sjukdomen samt att de hade svårigheter att få det stöd de behövde från myndigheter. Detta skapade en otrygg ekonomisk situation. Deras sociala relationer hade blivit påverkade av sjukdomen. Att umgås med andra hade blivit jobbigt och besvärligt, deras sociala aktiviteter hade blivit begränsade och de fick stöd av vissa men dessa personer blev då begränsade. Sex teman genomsyrade kategorierna i alla tre innehållsområdena: "Vara begränsad", "Vara tvungen att bete sig oförenligt med sin rätta personlighet", "Uppleva brist på förståelse och respekt från andra", "Uppleva otrygghet", "Vara beroende av andra" och "Vara tvungen att välja mellan pest eller kolera"

Introdução: A asma é caracterizada por um processo inflamatório crônico que está associado ao desenvolvimento da hiperresponsividade brônquica (HRB). O exercício físico regular proporciona inúmeros benefícios aos pacientes com asma porém, os efeitos do treinamento físico na HRB permanecem pouco compreendidos. Objetivo: Avaliar o efeito do treinamento físico aeróbio na hiperresponsividade brônquica, inflamação pulmonar, controle clínico e fatores relacionados à qualidade de vida de pacientes adultos com asma persistente moderada a grave. Métodos: Cinquenta e oito adultos com asma moderada a grave foram divididos aleatoriamente, em dois grupos: Controle (GC, n=28) e Treinado (GT, n=30). Os pacientes do GC foram submetidos a um programa educacional e a um programa de exercícios respiratórios, enquanto os pacientes do GT foram submetidos a todos os procedimentos do GC e a um programa de condicionamento físico aeróbio. A hiperresponsividade brônquica foi avaliada através do teste de broncoprovocação inespecífica com histamina antes e após a intervenção. Nestas ocasiões, todos os pacientes também realizaram, análise do escarro induzido e da fração exalada de óxido nítrico, espirometria, teste ergoespirométrico e responderam aos questionários de controle clínico, fatores de saúde relacionados à qualidade de vida (FSRQV) e níveis de depressão. Além disso, foi coletada uma amostra do sangue venoso dos pacientes para quantificação do IgE total e de IgE específica. Resultados: Após três meses de intervenção, os pacientes do GT aumentaram 1 dupla dose de concentração (dd) (1 dd; 0,3-1,7 dd, 95% CI) (p < 0,05) enquanto o GC (0,06 dd; -0,6dd a 0,7 dd, 95% CI) não apresentou mudança significativa na hiperresponsividade brônquica. A inflamação pulmonar reduziu apenas nos pacientes do GT que apresentaram níveis elevados de eosinófilos (> 3%) e FeNO (> 26ppb) (p < 0,05). O condicionamento aeróbio melhorou os FSRQV, controle clínico da asma e níveis de depressão (p < 0,05). Conclusão: Nossos resultados demonstram que o treinamento aeróbio tem um efeito anti-inflamatório importante na asma e deve ser considerado como um tratamento complementar para o manejo da doença / Introduction: Asthma is characterized by a chronic inflammatory process that is associated with the development of bronchial hyperresponsiveness (BHR). Regular exercise provides numerous benefits in patients with asthma; however, the effects of exercise training on BHR remain poorly understood. Objective: To evaluate the effect an aerobic training on bronchial hyperresponsiveness, pulmonary inflammation, clinical control and health related quality of life (HRQoL) in adults patients with moderate to severe asthma. Methods: Fifty-eigth patients adults with moderate to severe asthma were randomly assigned into two groups: Control (CG, n = 28) and Trained (TG, n = 30).The GC patients undertake an educational program and performed breathing exercises, while the TG patients underwent the same procedures than CG plus an aerobic training program. Bronchial hyperresponsiveness was assessed by nonspecific bronchial provocation test with histamine before and after the intervention. On these occasions, all patients also performed induced sputum analysis and fractional exhaled nitric oxide (FeNO), spirometry, cardiopulmonary exercise testing and fulfilled questionnaires to evaluate clinical control test, HRQoL and depression levels. In addition, blood samples were collect in order to quantify total serum immunoglobulin (IgE) and specific IgE. Results: After 3 months of intervention, the TG increased 1 double dose of concentration (dd) (0.3 to 1.7 dd, 95% IC) and CG did not change significantly on bronchial hyperresponsiveness 0.06 dd (-0.6 to 0.7 dd, 95% IC) (p < 0.05).The pulmonary inflammation reduced only in the GT patients with high levels of eosinophils (> 3%) and FeNO (> 26ppb) (p < 0.05). Aerobic training also improved HRQoL, clinical control and depression levels (p < 0.05).Conclusion: Our results demonstrate that aerobic training exercise has a significant anti-inflammatory effect on asthma and should be considered as a complementary treatment for disease management

Mais de 60% dos pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC) podem apresentar hiper-responsividade brônquica. Entretanto, não se sabe se, além das vias aéreas, o tecido pulmonar periférico também apresenta uma resposta exagerada a um agonista na DPOC. No presente estudo foi investigado o comportamento mecânico in vitro e as alterações estruturais e inflamatórias do tecido pulmonar periférico de 10 pacientes com DPOC comparados com 10 controles não fumantes. Foram realizadas medidas de resistência (R) e elastância (E) de fatias pulmonares em situação basal e após desafio com Acetilcolina. Também foram analisados no tecido alveolar as densidades de neutrófilos, eosinófilos, macrófagos, mastócitos e linfócitos CD8+ e CD4+, além do conteúdo de células positivas para -actina de músculo liso, fibras elásticas e colágenas. Os valores de R após o tratamento com Acetilcolina (RACh) e a porcentagem de aumento de resistência (%R) foram significativamente maiores no grupo DPOC comparado ao grupo controle (p0,03). O grupo DPOC também apresentou densidade de macrófagos (p=0,04) e linfócitos CD8+ (p=0,017) significativamente maior e conteúdo de fibras elásticas significativamente menor (p=0,003) comparado ao grupo controle. Foi observada uma correlação positiva significativa entre a %R e a densidade de eosinófilos e linfócitos CD8+ (r=0,608, p=0,002; e r=0,581, p=0,001, respectivamente), e também uma correlação negativa significativa entre a %R e a relação VEF1/ CVF (r=-0,451, p<0,05). Concluímos que a resposta colinérgica de fatias de parênquima pulmonar está aumentada em pacientes com doença pulmonar obstrutiva crônica e parece estar relacionada tanto à densidade de eosinófilos e de linfócitos CD8+ no tecido alveolar quanto ao grau de obstrução determinado pela prova de função pulmonar. / Up to 60% of COPD patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also presents an exaggerated response to agonists in COPD. In this study we investigated the in vitro mechanical behavior and structural and inflammatory changes of peripheral lung tissue of 10 COPD patients and compared to 10 non-smoking controls. We measured resistance (R) and elastance (E) of lung strips at baseline and after acetylcholine (ACh) challenge. We further assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, and the content of -smooth muscle actin+ cells, elastic fibers and collagen fibers. Values of R after ACh treatment (RACh) and percent increase of tissue resistance (%R) were significantly higher in COPD group compared to controls (p0.03). There was a significantly higher density of macrophages (p=0.04) and CD8+ cells (p=0.017) and a lower elastic fiber content (p=0.003) in COPD group compared to controls. We observed a significant positive correlation between %R and eosinophil and CD8+ cells density (r=0.608, p=0.002; and r=0.581, p=0.001, respectively), and also a negative correlation between %R and FEV1/FVC (r=-0.451, p<0.05). We conclude that the cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and also to the degree of airway obstruction at pulmonary function test.

L’asthme équin est une condition inflammatoire fréquente affectant les voies respiratoires inférieures. Cette maladie est caractérisée par une bronchoconstriction, une hyperréactivité bronchique, ainsi que des changements des différentes couches tissulaires des voies respiratoires que l’on regroupe sous le terme de remodelage pulmonaire. Le remodelage du muscle lisse bronchique dans l’asthme comprend une hyperplasie, une hypertrophie, ainsi qu’une altération des propriétés contractiles des myocytes. Bien que ces changements aient été décrits dans la forme sévère de l’asthme équin, la présence de telles altérations chez les chevaux atteints des formes légères à modérées de l’asthme demeure incertaine. L’objectif de notre étude est donc de déterminer si le muscle lisse bronchique présente un remodelage chez les chevaux asthmatiques légers à modérés. Des biopsies endobronchiques provenant de 18 chevaux asthmatiques et de 7 chevaux contrôles ont été étudiées. Le diagnostic était basé sur les signes cliniques et confirmé par cytologie du lavage bronchoalvéolaire. La prolifération des cellules du muscle lisse bronchique était évaluée par l’expression du proliferating cell nuclear antigen marqué par immunohistochimie, et l’expression génique de l’isoforme rapide de la myosine, une protéine hypercontractile, a été mesurée par RT-qPCR. Cette étude a permis de mettre en évidence une surexpression de l’isoforme rapide de la myosine chez les chevaux asthmatiques légers à modérés. Malgré l’absence de différence dans le taux de prolifération cellulaire du muscle lisse bronchique entre les groupes, le pourcentage de myocytes en prolifération était corrélé à l’inflammation pulmonaire neutrophilique ainsi qu’à l’expression de l’isoforme rapide de la myosine chez les chevaux asthmatiques. Cette première étude évaluant le remodelage du muscle lisse bronchique chez les chevaux asthmatiques légers à modérés a démontré une altération fonctionnelle du muscle lisse bronchique dans les formes légères de l’asthme équin, une possible influence de la neutrophilie pulmonaire sur la prolifération du muscle lisse, ainsi qu’une association entre les phénotypes prolifératifs et contractiles. Les altérations identifiées pourraient servir de biomarqueurs potentiels dans l’évolution de la maladie et de la réponse aux traitements. / Equine asthma is a common inflammatory condition affecting the lower airways. This disease is characterised by bronchoconstriction, airway hyperreactivity, and changes in the different tissue layers of the airways, which are referred to as airway remodelling. Remodelling of the smooth muscle in asthma includes hyperplasia, hypertrophy, and altered contractile properties of the myocytes. Although these changes have been described in severe equine asthma, their presence in horses with milder forms of asthma remains unclear. The aim of our study was therefore to determine whether airway smooth muscle remodelling occurs in horses with mild to moderate asthma. Endobronchial biopsies from 18 asthmatic horses and 7 control horses were studied. The diagnosis was based on clinical signs and confirmed by bronchoalveolar lavage cytology results. Airway smooth muscle cell proliferation was assessed by the expression of immunohistochemically labelled proliferating cell nuclear antigen, and the gene expression of the fast contracting myosin isoform, a hypercontractile protein, was measured by RT-qPCR. This study showed overexpression of the fast contracting myosin isoform in horses with mild to moderate asthma. Although there was no difference in the proliferation rate of airway smooth muscle myocyte between groups, it was correlated with neutrophilic lung inflammation as well as with the expression of the fast myosin isoform in asthmatic horses. This first study evaluating airway smooth muscle remodelling in mild to moderate asthmatic horses has demonstrated a functional alteration of airway smooth muscle in mild equine asthma, as well as a possible influence of pulmonary neutrophilia on smooth muscle proliferation, and an association between proliferative and contractile phenotypes. The identified alterations could eventually serve as biomarkers in the evolution of the disease and the response to treatments.

O aumento da prevalência de doenças alérgicas como a asma, tem sido atribuído à falta de estímulos infecciosos. A atopia, que embasa as manifestações alérgicas, caracteriza-se por uma disfunção imune com predomínio da resposta do tipo Th2. Experimentos em modelos animais com micobactérias e seus produtos têm demonstrado resultados promissores na proteção e reversão de resposta imune do tipo Th2. A imunoterapia para alérgenos inalatórios tem mostrado resultados positivos e o uso do BCG como adjuvante poderia trazer benefícios adicionais. Em estudo randomizado duplo cego foram avaliados 21 indivíduos de ambos os sexos, com idades de 8 a 17 anos sensibilizados ao Dermatophagoides pteronissynus (Dpt) e portadores de asma leve ou moderada persistentes. Os pacientes foram divididos em dois grupos e tratados com imunoterapia específica (ITE) para Dpt. O Grupo A recebeu como adjuvante, no início da ITE, uma aplicação do diluente do BCG e o Grupo B uma dose da vacina BCG. Na avaliação realizada após o período de indução da ITE constatou-se nos dois grupos diminuição significativa dos sintomas, da necessidade de medicação para asma, da hiperreatividade brônquica inespecífica, da reatividade cutânea ao Dpt juntamente com a melhora da função pulmonar. Houve uma redução no índice de estimulação da cultura de células mononucleares do sangue periférico estimuladas com Dpt, acompanhada de uma elevação da IL-10 no sobrenadante e dos níveis da IgG específica para Dpt e da IgE total. Os eosinófilos, a IgE específica para Dpt do sangue e o óxido nítrico no ar exalado não se alteraram. Não houve diferença na comparação dentre os grupos, exceto na proliferação das células mononucleares do sangue periférico estimuladas com PPD, que foi maior no Grupo B. Conclusão: a ITE levou a resultados satisfatórios com melhora clínica e alterações imunológicas já ao final do período de indução. A avaliação do uso do BCG como adjuvante, não mostrou benefícios adicionais. / The increase of allergic diseases, such as asthma, has often been explained by a decline in infectious stimulation. Atopy that is characterized as an immune dysfunction promotes a strong type Th2 immune response and underlines allergic diseases. Experimental animal models researches with mycobacteria and its products had led to promising results in prevention or reversion of type Th2 response. Positive results have been obtained to allergens specific immunotherapy (SIT) and its association with BCG vaccine, as an adjuvant, could promote additional benefits. In a randomized double blind study 21 patients sensitized to mite Dermatophagoides pteronyssinus (Dpt) with mild or moderate persistent asthma, aged 8 to 17 years of both sex were evaluated. Patients were divided in two groups. Group A received at the beginning of SIT one dose of BCG diluent and Group B one dose of BCG vaccine. After the SIT induction period we observed in both groups a significant decrease in asthma symptoms, bronchial hyperreactivity, immediate cutaneous reactivity to Dpt and the necessity of drugs intake. Specific lymphoproliferation against Dpt significantly decreased while IL-10 levels, specific IgG and total IgE increased. Blood eosinophils, specific IgE, others immunoglobulins levels and nitric oxide in exhaled air didn\'t change. There were no differences in all parameters evaluated between the two groups except on specific lymphoproliferation against PPD that was higher in Group B. Conclusions: improvement in symptoms and immunologicals changes where observed at the end of SIT induction period. BCG as adjuvant didn\'t add additional benefits.

O aumento da prevalência de doenças alérgicas como a asma, tem sido atribuído à falta de estímulos infecciosos. A atopia, que embasa as manifestações alérgicas, caracteriza-se por uma disfunção imune com predomínio da resposta do tipo Th2. Experimentos em modelos animais com micobactérias e seus produtos têm demonstrado resultados promissores na proteção e reversão de resposta imune do tipo Th2. A imunoterapia para alérgenos inalatórios tem mostrado resultados positivos e o uso do BCG como adjuvante poderia trazer benefícios adicionais. Em estudo randomizado duplo cego foram avaliados 21 indivíduos de ambos os sexos, com idades de 8 a 17 anos sensibilizados ao Dermatophagoides pteronissynus (Dpt) e portadores de asma leve ou moderada persistentes. Os pacientes foram divididos em dois grupos e tratados com imunoterapia específica (ITE) para Dpt. O Grupo A recebeu como adjuvante, no início da ITE, uma aplicação do diluente do BCG e o Grupo B uma dose da vacina BCG. Na avaliação realizada após o período de indução da ITE constatou-se nos dois grupos diminuição significativa dos sintomas, da necessidade de medicação para asma, da hiperreatividade brônquica inespecífica, da reatividade cutânea ao Dpt juntamente com a melhora da função pulmonar. Houve uma redução no índice de estimulação da cultura de células mononucleares do sangue periférico estimuladas com Dpt, acompanhada de uma elevação da IL-10 no sobrenadante e dos níveis da IgG específica para Dpt e da IgE total. Os eosinófilos, a IgE específica para Dpt do sangue e o óxido nítrico no ar exalado não se alteraram. Não houve diferença na comparação dentre os grupos, exceto na proliferação das células mononucleares do sangue periférico estimuladas com PPD, que foi maior no Grupo B. Conclusão: a ITE levou a resultados satisfatórios com melhora clínica e alterações imunológicas já ao final do período de indução. A avaliação do uso do BCG como adjuvante, não mostrou benefícios adicionais. / The increase of allergic diseases, such as asthma, has often been explained by a decline in infectious stimulation. Atopy that is characterized as an immune dysfunction promotes a strong type Th2 immune response and underlines allergic diseases. Experimental animal models researches with mycobacteria and its products had led to promising results in prevention or reversion of type Th2 response. Positive results have been obtained to allergens specific immunotherapy (SIT) and its association with BCG vaccine, as an adjuvant, could promote additional benefits. In a randomized double blind study 21 patients sensitized to mite Dermatophagoides pteronyssinus (Dpt) with mild or moderate persistent asthma, aged 8 to 17 years of both sex were evaluated. Patients were divided in two groups. Group A received at the beginning of SIT one dose of BCG diluent and Group B one dose of BCG vaccine. After the SIT induction period we observed in both groups a significant decrease in asthma symptoms, bronchial hyperreactivity, immediate cutaneous reactivity to Dpt and the necessity of drugs intake. Specific lymphoproliferation against Dpt significantly decreased while IL-10 levels, specific IgG and total IgE increased. Blood eosinophils, specific IgE, others immunoglobulins levels and nitric oxide in exhaled air didn\'t change. There were no differences in all parameters evaluated between the two groups except on specific lymphoproliferation against PPD that was higher in Group B. Conclusions: improvement in symptoms and immunologicals changes where observed at the end of SIT induction period. BCG as adjuvant didn\'t add additional benefits.

L'asma és una malaltia d'etiologia complexa, formada per factors genètics i ambientals, on la interrelació de ambdós factors mitjançant interaccions gen-ambient juga un paper clau. L'objectiu d'aquesta tesi ha sigut aprofundir en el coneixement del paper dels polimorfismes genètics, i la seva interacció amb factors ambientals, en la ocurrència d'asma, atòpia i hiperreactivitat bronquial. Aquest objectiu ha estat desenvolupat a través de la replicació de variants genètiques prèviament identificades, l'avaluació d'interaccions gen-ambient i la identificació de nous gens de susceptibilitat mitjançant un disseny basat en el genotipatge de variants genètiques all llarg del genoma en pools d'ADN. La tesi ha estat majoritàriament duta a terme dins l'estudi European Community Respiratory Health Survey (ECRHS) que està comprès per 5.000 individus seguits durant 9 anys, pels quals es disposa d'un qüestionari complet sobre símptomes respiratoris, avaluacions clíniques, informació sobre exposicions ambientals i mostres de ADN. Aquesta tesi a replicat l'associació del polimorfismes dels gens TNFA i NPSR1 amb asma. A més s'han establert les interaccions entre TNFA i obesitat, NQO1 i contaminació atmosfèrica, i NPSR1 i edat d'inici d'asma. L'anàlisi de pools d' ADN ha permès associar la regió on es situa el gen SGK493 amb atòpia. Aquesta tesi contribueix al coneixement de l'etiologia d'asma amb la identificació i replicació d'associacions genètiques i interaccions gen-ambient. / Asthma is a disease with a complex etiology, involving multiple genetic and environmental factors, and with an important role of the interplay of these factors through gene-environment interactions. In this thesis I aimed to advance our knowledge on the importance of genetic polymorphisms and their interaction with environmental data for the occurrence of asthma and related phenotypes (atopy and bronchial hyperreactivity). This objective was developed through the replication of genetic associations previously reported, the assessment of gene-environment interactions and the identification of new susceptibility genes using genome-wide analysis based on a pooling DNA strategy. The thesis was, mostly, performed within the European Community Respiratory Health Survey (ECRHS). This cohort has information and DNA samples from approximately 5,000 adult subjects followed-up for 9 years, with extensive questionnaires on respiratory symptoms, clinical evaluations and information on environmental exposures. This thesis replicates previous effects on asthma of polymorphisms in TNFA and NPSR1 genes. In addition, interactions have been established between TNFA and obesity, NQO1 and air-pollution, and NPSR1 and age at onset of asthma. The approach based on genome-wide analysis of DNA pools identified the SGK493 region being associated with atopy. This thesis contributes to the understanding of the etiology of asthma through the identification and replication of genetic associations and gene-environment interactions.