No description available.

Bibliography: leaves 363-416. / v, 416 leaves ; / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / A longitudinal observational study of hospital asthma patients, recruited from two different settings, has been conducted. The results show that failing to look at the patient in the context of their whole life and considering the socio-economic, psychological and attitudes and beliefs of patients, the current reductions in reductions in asthma morbidity and mortality may not continue. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1999

There are approximately 22.2 million Americans’ who are living with asthma and of those 18.4 million are adults. African Americans’ are more likely to be diagnosed with asthma compared to Caucasians, and experience more asthma attacks. In this study, the Social Cognitive Theory was used to examine the relationships among personal characteristics, environmental factors, asthma self-efficacy, self-management behaviors, and quality of life (QOL) in African American adults with asthma. A correlational design was used. Data were collected from a non-random sample of adult African Americans’ with asthma (N = 39) using the following self-report questionnaires: the Knowledge, Attitude, and Self-Efficacy of Asthma Questionnaire (KASE), the short form of the Rapid Estimate of Adult Literacy in Medicine (REALM-SF), the Medical Outcomes Study (MOS) for social support, the Asthma Trigger Inventory (ATI), the Morisky Medication Adherence Questionnaire, Asthma Self-Management Questionnaire (ASMQ), the Modified Pittsburgh Sleep Quality Index (PSQI), the Asthma Control Test (ACT), and the Asthma Quality of Life Standardized (AQLQ-S). Data analyses included descriptive statistics, Pearson Product correlations, and hierarchical multiple regression. On average, participants (N = 39) were middle aged (M = 55.9 ± 7.9) years, female (65%), did not smoke (87%), did not use a peak flow meter (PEFR) to self-manage their asthma (72%), and were obese (M = 34.06, SD = 10.78). Participants reported high confidence in asthma self-management; however, had low medication adherence and scores indicating uncontrolled asthma (M = 16.10, SD = 4.29). More than half (67%) of the participants reported poor sleep quality (PSQI). BMI and sleep quality accounted for significant variance (38%) in asthma QOL (F (2, 38) = 7.08, p = .001). Social support was an independent predictor of asthma self-efficacy (F (2, 38) = 5.65, p = .02). Better control of weight and asthma symptoms may improve sleep quality. Health care providers need to address the ongoing challenges of asthma self-management and monitor sleep quality. Encouraging the use of peak flow meters, which have been shown to improve self-management and asthma control, may result in better quality of life for African Americans’ with asthma.

Asthma affects over 2.2 million people in Australia. Asthma morbidity is increasing while mortality is decreasing. People with asthma experience shortness of breath as their airways narrow and become inflamed. After an episode of acute asthma many patients experience a relapse requiring further emergency department care. Numerous studies have been undertaken to identify the determinants of asthma morbidity and these studies have primarily used asthma oriented and co-morbidity scales such as anxiety and depression indices. Other studies in this area have indicated psychosocial factors such as coping, asthma attitudes and beliefs that may be linked to people with asthma who are non-compliant or adherent to treatment. Currently, there is no research available that has examined the link between general health promoting behaviours, an individual’s risk behaviour assessment and a brief asthma education encounter that is patient-centred. This study provides a description of the health promoting and risk taking behaviours of people who attend the emergency department with acute asthma. Secondly, it examines the effectiveness of patient-centred education compared with standard education. One hundred and forty-six people with acute asthma who attended the emergency departments of the Princess Alexandra and Mater Adult Public Hospitals were enrolled in this study. Participants self-reported health promoting and risk taking behaviours by completing the questionnaire that contained the Health Promoting Lifestyle Profile (HPLPII) and the Health Risk Appraisal (HRA) instruments. The Hospital Anxiety and Depression Scale (HADS) was also incorporated into the questionnaire to ascertain levels of anxiety and depression in this acute asthma group of people. The asthma education curriculum had the same topics for both the standard education and the patient-centred groups. However, the patient-centred group were able to prioritise the order of the topics according to their identified need. Secondly, the patient-centred group were asked two questions to ascertain the most important issue and asthma issue for them at that point in time. Both groups of participants were educated using the Asthma Foundation Leaflet “Asthma - Basic Facts” during the individual education session. There were 56% females and 44% males with a mean age (+SD) of 34 (13.8) years with 70.3% reported year 12 or above education and 49% of participants earned less that $20,000. Nearly half of the participants were admitted to a hospital ward following emergency department assessment and care. A large proportion of the participants had either moderate or severe asthma. The health behaviour findings from this study suggest people with acute asthma follow preventive health recommendations and safety guidelines more so than the wider community. However, they did not self-initiate home based health actions such as breast self-examination. At the time of attendance to the emergency department with acute asthma there were no statistical difference between the patient-centred education and standard format education groups for age, gender, education, income, asthma control and previous emergency department attendances. The patient-centred education group had fewer re-attendances in the four months after the education intervention when compared with prior emergency department attendances than the control group (p=0.057; p=0.486). In conclusion, people with acute asthma report undertaking a number of preventive health behaviours and actions according to national guidelines and safety recommendations. They report a lack of self-initiated home based health behaviours. Further research is required to investigate the impact on the National Asthma Council’s recommendations of the importance of asthma action plans on people who follow preventive health guidelines and who lack self-initiative abilities. In terms of asthma education, patient-centred education when compared to standard format education may be useful in reducing further emergency department attendances for acute asthma. More research is required to identify other key education issues for people with acute asthma.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Includes CD-ROM inside back cover of volume 2. Bibliography: p. 178-222. Aims to identify current risk factors for asthma and to determine which of these factors, at the population level, is associated with asthma prevalence in children in South Australia. In addition, modelling techniques are used to determine which factors are significant predictors of asthma prevalence in 4 to 5 year old children in S.A. Study results show that at the population level, 9 risk factors are significantly associated with lifetime prevalence and 24 factors with period prevalence. Study findings are generally consistent with existing literature.

Asthma is an inflammatory airways disease affecting over 339 million people of all ages worldwide. More than 10% of asthmatics have uncontrolled severe disease which is insensitive to high doses of oral corticosteroid treatment. Type 2 innate lymphoid cells (ILC2) are pro-inflammatory lymphomononuclear cells proposed as critical drivers of eosinophilic inflammatory disease of the upper and lower airways. Controlling this activity may provide novel therapies for asthma. This thesis aimed to investigate factors that affect the local activation and expansion of ILC2 in the airways including anti-inflammatory medications such as (i) corticosteroids, (ii) neuro-immune regulation of ILC2, and (iii) effect of locally generated cytokines on ILC phenotypes and the relationship to the ongoing airway inflammatory profile. We firstly investigated the effect of intranasal corticosteroids on activation levels of ILC2 in the upper airway of allergic rhinitics with mild asthma following controlled nasal allergen challenge (Chapter 2). Following pre-treatment with intranasal corticosteroid there was an attenuation in the allergen-induced increase in total ILC2 and IL-5/13+ ILC2 in the nasal mucosa. In addition, HLA-DR expression on ILC2 in the nasal mucosa was down-regulated. Overnight culture with IL-2, TSLP or IFN-γ up-regulated HLA-DR expression on ILC2, in vitro; an effect that is inhibited in the presence of corticosteroids. Attenuation of HLA-DR expression by ILC2 may be an additional mechanism by which corticosteroids modulate adaptive immune responses in the airways. We have previously reported that lung ILC2 are activated within 7h following allergen-inhalation challenge. Since airway mucosal tissue is highly innervated, we investigated whether neuroimmune interactions may trigger early and rapid host immune responses (Chapter 3). In a diluent-controlled allergen-inhalation challenge cross-over study, where mild asthmatics developed early and late bronchoconstrictor responses with sputum eosinophilia (>3%), NMUR1, a receptor for the neuropeptide, neuromedin-U, was up-regulated on sputum ILC2 in 7h post allergen challenge. This was associated with increased expression of IL-5/IL-13 by sputum ILC2 post-allergen and following in vitro culture. ILC2 activation was mediated through a MAPK/PI3 kinase dependent-signaling pathway that was attenuated in the presence of dexamethasone. Co-culture with IL-33 and TSLP, in vitro up-regulated NMUR1 expression on ILC2 at the protein and transcriptomic level which was attenuated by dexamethasone. The close interplay between neuropeptide signalling and tissue-derived alarmin cytokines may be important interactions for rapid ILC2 activation in airway inflammatory responses in asthma. We have reported increased ILC2 with the highest level of IL-5/13+ ILC2 in the airways of severe asthma with uncontrolled eosinophilia (>3%). The prevalence and phenotypic analyses of innate lymphoid cells subsets in severe asthma with neutrophilic or mixed granulocytic airway inflammatory endotypes remains unclear and was investigated in Chapter 4. Sputum ILC3 were most abundant in severe asthma with neutrophilic airway inflammation where IL-17A+ ILC3 correlated with airway neutrophilia. ILC2 were predominant in severe asthma with airway eosinophilia. Importantly, we identified an intermediate ILC2 phenotype displaying ILC3-like markers (c-kit and IL-17A) in severe asthma with neutrophilic and mixed granulocytic airway inflammation. Inflammasome related cytokines, IL-1β and IL-18 were significantly increased in the airways of these patients. At both proteomic and transcriptomic levels, flow sort-purified ILC2 trans-differentiated to the intermediate phenotype when co-cultured with IL-1β+IL-18. Blocking inflammasome-related cytokines may control T2-low severe asthma exacerbations. Collectively, the findings of this thesis highlight the role of corticosteroids, neuropeptides and airway inflammasome related cytokines as modulators of ILC fate and activity in asthma. / Thesis / Doctor of Philosophy (PhD) / Asthma is a disease of the airways that makes breathing difficult. About 10% of asthma patients have uncontrolled severe symptoms despite treatment with high doses of corticosteroids which imposes many unwanted side effects. Investigating processes that worsen the disease will help to discover new treatments for asthma. Type 2 innate lymphoid cells (ILC2) are novel cells that produce large quantities of factors which attract and activate effector cells to the lungs which in turn make breathing difficult. This thesis investigated whether controlling ILC2 activity reduces asthma symptoms by studying i) responsiveness of ILC2 to corticosteroids using a controlled allergen exposure through the nose in people with allergic rhinitis and mild asthma, ii) the role of airway nerves and mediators on ILC2 activation, and iii) the ability of signals produced by the lungs to impact factors released by ILC2 and the relationship to effector cells found in the airways of severe asthma. Overall, ILC2 activation can be modulated by corticosteroids, nerve derived factors and lung tissue derived cytokines, and this is associated with changes in the number and type of effector cells in the lungs.

Asthma, a chronic respiratory disease affecting millions of people worldwide, can vary in severity depending on individual triggers such as Carbon Dioxide, Particulate Matter, dust mites, tobacco smoke, and indoor household activities such as cooking, cleaning, use of heating, and window opening, which can have a negative impact on indoor air quality (IAQ) and exacerbate asthma symptoms. Investigating the relationship between IAQ and asthma severity, a case study was conducted on five asthmatic participants from Bradford, UK. IAQ was measured using IoT indoor air quality monitoring devices. Indoor activities were recorded using a daily household activities questionnaire, and asthma severity was assessed using the Asthma Control Questionnaire (ACQ). Machine learning prediction models were used to analyse various IAQ parameters, such as particulate matter, carbon dioxide, and humidity levels, to identify the most significant predictors of asthma severity with IAQ. The study aimed to develop targeted interventions to improve IAQ and reduce the burden of asthma. Results showed that higher asthma severity scores were associated with increased indoor activity and higher levels of indoor air pollution. Some interventions were implemented to improve ventilation hours, significantly improving IAQ and reducing asthma symptoms, particularly those with more severe asthma. The findings indicate that interventions targeting IAQ, and indoor activities can effectively reduce asthma severity, with up to a 60% reduction in symptoms for asthma patients.

Aims. The overall aim was to examine the severity, treatment and level of control in patients with asthma in primary care in Sweden. The specific aims were to assess what matters to asthma patients, evaluate symptoms, medication and identify factors related to asthma severity, compare the extent of asthma control in 2001 and 2005, and investigate the development of asthma and degree of asthma control in adolescents and young adults who had reported asthma six years earlier. Methods. The first study was a telephone interview of a representative sample of Swedish asthmatics. In the second study a random sample of 1,136 patients answered two questionnaires. A classification of the asthma severity similar to that in the GINA guidelines was made. In the third study two surveys were performed, in 2001 and in 2005, with a random sample of 1,012 and 224 asthma patients, respectively, and a classification of asthma control similar to the recent GINA guidelines was made. In the fourth study 71 individuals who reported physician-diagnosed asthma in a population-based survey in 1997 and were defined as current asthmatics, were reinvestigated in 2003 with a skin prick test, methacholine challenge test, eucapnic voluntary hyperventilation test and measurement of exhaled nitric oxide. Results. Common situations causing symptoms of asthma were physical exertion and contact with pets. Nocturnal symptoms were frequent. In primary care 35% of the women and 24% of the men were classified as having severe asthma. Female sex, increasing age, not filling the asthma prescription owing to cost, daily smoking, and pollen allergy increased the odds of having severe asthma. In 2001, 37% had achieved asthma control, as compared with 40% in 2005. Uncontrolled asthma was more common in women and smokers. In the 2003 study of adolescents and young adults with asthma six years earlier, the definition of current asthma was fulfilled by 50 of the 71 subjects and one third had achieved asthma control. Conclusions. The majority of the asthmatics reported a large number of symptoms and limitations in their daily living. Many asthma patients in primary care have insufficient asthma control. One reason for lack of control might be undertreatment with inhaled corticosteroids.

INTRODUÇÃO: A asma grave acomete menos de 10% dos asmáticos, mas tem um impacto desproporcional sobre a utilização de recursos de saúde, contribuindo para, pelo menos, metade dos custos diretos e indiretos da doença. A proporção de indivíduos obesos ou com sobrepeso é elevada em pacientes com asma grave. Na verdade, a obesidade é um fator de risco para a asma, está associada com a gravidade da doença, com pior resposta a corticosteroides e pior controle clínico. Estudos sobre os efeitos da perda de peso em pacientes com asma ainda são escassos. OBJETIVOS: Avaliar o impacto da perda de peso com medidas clínicas em pacientes com asma grave e obesidade. MÉTODOS: Este é um estudo prospectivo randomizado aberto com dois grupos paralelos. Os participantes eram obesos e com asma grave e que, depois de um período de run-in de três meses, não estavam controlados de acordo com critérios da GINA. Os pacientes elegíveis foram randomizados em uma proporção de 2:1 (perda de peso: controle). Todos os participantes passaram por consultas bimensais no ambulatório de asma e foram acompanhados por seis meses. O desfecho primário foi o nível de controle da asma seis meses após o início do programa de redução de peso medido pelo Questionário de Controle da Asma (ACQ). Os desfechos secundários incluíram o Teste de Controle da Asma (ACT), resultados de função pulmonar, o Questionário Respiratório de St. George (SGRQ), a mudança na reatividade brônquica à metacolina, o uso diário de medicação de alívio para asma, percentagem de dias livres de sintomas, número de visitas ao pronto-socorro e exacerbações, marcadores de inflamação das vias aéreas medidos pelo escarro induzido e pelo óxido nítrico exalado (FeNO). IgE, proteína C reactiva, eotaxina, leptina e Transforming Growth Factor beta 1 (TGF 1) também foram medidos. RESULTADOS: Trinta e três foram randomizados. O grupo era composto predominantemente de mulheres com obstrução moderada, aprisionamento de ar, aumento da resistência das vias aéreas e marcada eosinofilia no escarro. O aumento dos níveis séricos de IgE foram consistentes com uma predominância de asma atópica. Dos 22 pacientes randomizados para submeterem-se a tratamento para a obesidade, 12 atingiram a meta de perda de peso de, pelo menos, 10% do peso corporal. A redução de peso no grupo de tratamento foi associada com melhor controle da asma medido pelo ACQ, ACT e SGRQ. Houve aumento de dias sem sintomas, menor uso de medicação de resgate e menos visitas ao serviço de emergência durante o período de estudo. Não houve diferença no número de exacerbações. A capacidade vital forçada (CVF) aumentou significativamente no grupo de tratamento e permaneceu inalterada no grupo de controle. As outras medidas da função pulmonar não mostraram diferenças entre os grupos. A hiperreatividade das vias aéreas, níveis de óxido nítrico exalado e celularidade do escarro induzido não se alterou ao longo do estudo. Os níveis de leptina diminuíram em ambos os grupos. Os níveis séricos de IgE, proteína C-reactiva, eotaxina, e TGF-1 não se alteraram. CONCLUSÃO: Nosso estudo adiciona informações à controvérsia sobre o impacto da obesidade e seu tratamento no controle da asma. Nossos resultados sugerem que a redução de peso em pacientes obesos com asma grave melhore os resultados de asma por mecanismos não relacionados com a inflamação das vias aéreas e que o controle da asma pobre em pessoas obesas é, pelo menos em parte, o resultado de fatores relacionados com a obesidade. A abordagem terapêutica para pacientes obesos com dificuldade de tratar a asma deve ser destinada à redução de peso, bem como à intensificação do tratamento anti-inflamatório / INTRODUTION: Severe asthma affects less than 10% of asthmatics, but has a disproportionate impact on the use of health resources, contributing to at least half of the direct and indirect costs of the disease. The proportion of obese or overweight individuals is elevated in patients with severe asthma. In fact, obesity is a risk factor for asthma, is associated with the severity of the disease, a poor response to corticosteroids and worse clinical control. Studies on the effects of weight loss in patients with asthma are still scarce. OBJECTIVES: Assess the impact of weight loss with a medical weight loss program in patients with severe asthma associated with obesity. METHODS: This is a prospective open study with two randomized parallel groups. The participants were obese and with severe asthma and, after a three month run-in period, were not controlled according to GINA criteria. Eligible patients were randomized in a 2:1 ratio (weight loss:control). All participants attended bimonthly consultations in the asthma clinic and were followed for six months. The primary outcome measure was the level of asthma control 6 months after initiation of the weight reduction program quantified by using the Asthma Control Questionnaire (ACQ). Secondary clinical outcomes included the Asthma Control Test (ACT), lung function results, score on the St. Georges Respiratory Questionnaire (SGRQ), change in metacholine reactivity, daily use of asthma reliever medication, percentage of asthma symptom free days, number of visits to emergency room and exacerbations, markers of airway cellular inflammation measured in induced sputum and with exhaled nitric oxide (FeNO). IgE, C reactive protein, leptin, eotaxin and Transforming Growth Factor beta 1 (TGF1) levels in serum were also measured. RESULTS: Thirty-three patients were randomized. The group consisted predominantly of women with moderate airflow obstruction, air trapping, increased airway resistance and marked eosinophilia in the sputum. The increased serum levels of IgE were consistent with a predominance of atopic asthma. Of the 22 patients randomized to undergo treatment for obesity, 12 achieved the weight loss goal of at least 10% of body weight. The reduction in weight in the treatment group was associated with improvement in the control as measured by ACQ, ACT and SGRQ. There was increase of symptom-free days, less use of rescue medication and fewer visits to the emergency room during the study period. There were no differences in the number of exacerbations. The forced vital capacity (FVC) increased significantly in the treatment group and remained unchanged in the control group. The other measures of the pulmonary function showed no differences between groups. The airway hyperresponsiveness, exhaled nitric oxide levels and induced sputum cellularity did not change throughout the study. Leptin levels decreased in both groups. Serum levels of IgE, C-reactive protein, eotaxin, and TGF-1 did not change. CONCLUSION: Our study adds information to the controversy about the impact of obesity and its treatment on asthma control. Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation and that poor asthma control in people who are obese is at least in part the result of obesity-related factors. The therapeutic approach for obese patients with difficult-to-treat asthma should therefore be aimed at weight reduction as well as on intensifying antiinflammatory treatment