Tesi sul tema "Asthma"

Thèse (M.Med.Exp.) -- Université du Québec à Chicoutimi, programme extensionné de l'Université Laval, 2004.
Bibliogr.: f. [78]-95. Document électronique également accessible en format PDF. CaQCU

The hypothesis underlying this thesis was that abnormal, dysfunctional breathing may occur commonly in people with asthma, and when identified and treated using a breathing training programme supervised by a physiotherapist, will result in improved asthma control.  The thesis is based around four original research papers published in peer-reviewed journals.  These papers present epidemiological surveys quantifying the extent of symptoms attributable to dysfunctional breathing in adults with asthma in comparison with the non-asthmatic adult population, and randomised controlled trials investigating the effectiveness of a breathing training programme in improving asthma control. Initially, a review of the existing evidence of co-morbidity between asthma and dysfunctional breathing is presented, together with that of effectiveness of breathing training interventions.  In subsequent chapters, two epidemiological surveys are presented, showing that symptoms consistent with dysfunctional breathing were more common in the asthmatic than the non-asthmatic adult population.  Data from a pilot and a subsequent full randomised controlled trial are then presented.  These show that breathing training was associated with improved patient-reported outcomes in comparison with a control intervention of asthma education (chosen to control for the non-specific effects of professional contact and interest on a symptomatic patient). The thesis shows that in a clinical trial situation, many people with asthma can benefit from breathing training.

The aim of my master degree project of Advanced Product Design was to develop a monitoring and medication device to empower people who are suffering from asthma. Asthma is a major non-communicable disease characterized by recurrent attacks of breathlessness and wheezing. It is not possible to cure asthma, but appropriate management can control the disease and enable people to enjoy a good quality of life. Asthma varies in severity and frequency from person to person and not every asthmatic will require the same level of treatment. Also asthma conditions can vary over time and the level of airways inflammation has to be reviewed and medication has to be adjusted. Asthma diagnostic takes place at a point-of-care environment and is usually based on the pattern of symptoms, response to therapy over time and by objective parameters like lung function tests. My degree project was focused on a home used diagnostic and medication system in order to adjust the dosage of asthma medication on a more frequently basis.

Background: Asthma is an illness that many adolescents have today. The symtom can prevent them to live like contemporaries and the development phase they experience makes asthma difficult to get control of. Aim: The aim of this study was to describe adolescent’s experience of living with asthma. Method: The literature review was performed by reviewing nine scientific articles. Results: The categories which developed were social, physical and psychical experiences. Adolescents experienced poor quality of life and their feelings were described with words like fear, anxiety, anger and depression. Physical activities experience troublesome by the adolescents and they experienced support from friends and teachers were not enough. To be like everyone else and experience ego became an expression from the adolescents. Discussion: Experience of physical activities, quality of life, enhanced understanding and adolescents view at the future were discussed with Antonovskys concept of KASAM and integrated with the nurse competence. Conclusion: Adolescents experience of living with asthma is frustration, fear and anxiety. They sometimes don’t medicate because they want to be like their friends. Understanding from friends and teachers could be better. Suggestions for new reaserch are teachers understanding and friend’s apprehension about the person which is suffering from asthma.

Part I of the thesis contains a brief review of the clinical importance of nocturnal asthma, and an account of the methods used to study breathing during sleep. The original work of the thesis is divided into three further parts: In Part II are described studies of breathing and oxygenation during sleep in normal subjects. These studies were performed to establish a normal range of apnoea, hypopnoea and oxygenation during sleep and to determine the effects of age and sex on these variables. Part III contains the results of similar studies in patients with asthma. Breathing patterns and oxygenation during sleep in asthmatic patients were compared with those of normal subjects and those of patients with chronic bronchitis and emphysema. The studies described in Part IV were designed to explore the relationship between sleep and bronchoconstriction. I wished to establish whether sleep was essential for nocturnal bronchoconstriction and to determine whether bronchoconstriction was associated with one particular stage of sleep. The results are summarised at the end of each section, and the clinical implications of the results are discussed in Part V.

Asthma is one of the most common chronic diseases among children. Asthma affects children’s quality of life, sleep, social and physical activities, and academic performance at school. This effect on children’s quality of life places a burden on their caregivers (parents) and the family milieu. These facts suggest that schools are and should be an important setting for asthma care. While children attend school, the caregiving role is partly transferred from parents to teachers, and peers can also play a pivotal role by creating a supportive environment, despite not being involved in care provision. Given the significant effects of asthma, it is important that all teachers have working knowledge of asthma in order to be able to understand asthma symptoms, help children with asthma use their medications when needed, and assist in emergency situations, as, in most cases, teaching occurs with a single teacher educating a given class. Unfortunately, a review of the literature revealed that teachers’ asthma knowledge and symptom management skills are suboptimal. With such research findings emanating from various countries, many programs have been developed in Australia, Europe, and the United States to improve awareness about childhood asthma and to provide trainees (teachers) with the skills necessary to recognise and provide appropriate first aid to children experiencing a worsening of symptoms in the school setting. Many other programs were also conducted in the school setting, which focused on children with asthma, school resources (such as nurses/medical staff), and the entire school community. The majority of research in this field and program development is reported from developed, English-speaking countries with a traditionally high prevalence of asthma and allergies in children. However, current epidemiological data indicate that the burden of asthma is shifting globally, with many developed countries demonstrating static trends in prevalence and developing countries exhibiting an increase in the prevalence of asthma, particularly among children. These data may or may not reflect a “true” increase, but they do reflect an increasing understanding asthma and recognition, and parallel changes in public health focus from communicable to non-communicable diseases in these countries. For example, in Saudi Arabia, there seems to be an increase in asthma prevalence in recent years, even though it has not been a country with a historically high prevalence of asthma. Given that asthma is only recently assuming importance because of its increasing prevalence, programs and investment in public awareness and education are likely to be lower in Saudi Arabia. Indeed, research suggests that Saudi Arabia’s school health infrastructure is not well developed and that there are no national-level policies on managing asthma in Saudi schools. Furthermore, research in this area is quite limited. To the best of my knowledge, the only published study on the topic suggested that most Saudi school staff have low levels of general asthma awareness and that misconceptions regarding asthma medications are common among Saudi school teachers. This situational context formed the basis for this research. Aim The overarching aim of this thesis was to develop, implement and evaluate an asthma education program for primary school teachers in Saudi Arabia. This aim will be achieved via successive phases, which included initially assessing the needs and preferences for educational programs (from both the school teachers and parents of school children with asthma) and culminated in implementing a pilot program that was constructed based on the identified needs. Methods This thesis used a comprehensive literature review as a building block for the research. This review explored the literature on asthma interventions provided in primary schools and targeted school teachers, personnel, nurses with or without children, children’s peers, and children’s parents. Medline, PubMed, ERIC, CINAHIL, IPA, Embase, and Informit were searched to identify studies on school-based asthma interventions published during the previous five years (2007 to 2012), in order to identify the gaps in this research area. The review was followed by the use of quantitative and qualitative methods to investigate the needs and preferences for school-based asthma support. The quantitative method used to assess the needs and preferences of school teachers was a cross-sectional questionnaire. This questionnaire included items related to asthma awareness (knowledge), attitudes towards roles in asthma, and the efficiency of school-based asthma policies. Data from this survey were tested for the reliability of responses and descriptively analysed. The survey was prepared in Arabic and administered to a random sample of primary school teachers working in Riyadh, Saudi Arabia. Qualitative methods (in-depth semi-structured interviews) were used to assess the needs and preferences of Saudi Arabian parents of children with asthma. School notice boards were used to inform Saudi parents about the study and request their participation; subsequently, interviews were conducted with the parents recruited via convenience sampling and passive snowballing approaches. The interviews were recorded, transcribed verbatim, and thematically analysed using a grounded theory approach. Based on the findings from these two projects, this research further undertook a project to develop, implement, and evaluate a school-based asthma education program for primary school teachers in Saudi Arabia. This phase of the research involved a pre- and post-test design with a random sample of teachers recruited from five Saudi primary schools for girls in Riyadh. The educational program was based on the principles of adult learning and supported by well-designed learning objectives; teaching formats matching these objectives; and a mixed-delivery method of hands-on demonstration, didactic lectures, role plays, and games. The knowledge/attitude survey developed above was used as one outcome, while another outcome was the demonstrated competence in asthma first aid provision using a simulated scenario. The data collected were tested for normality and pre- and post-comparisons of knowledge and attitudes. Asthma first aid competence tests were conducted using either parametric analyses methods (such as student’s t-tests) or their non-parametric equivalents (Mann-Whitney U or Wilcoxon signed rank tests). For all statistical analyses, the significance level was set at 0.05. Results The scoping review was first conducted with the aim of identifying evidence for school-based programs (n = 23 articles included). This review indicated that school-based asthma interventions vary in terms of: • Type—educational, non-educational, and mixed • Format—didactic lessons/educational sessions, workshops, structured education activities, extracurricular health activities, interactive digital story and story writing, educational pamphlets, and booklets • The targeted population—children with asthma with/without their peers, parents, school personnel, and school nurses • The method of delivering the intervention—health professionals, peers, school teachers, university students, booklets, pamphlets, and interactive media • The outcomes measured—clinical, humanistic, academic, economic, and system related • The methods/instruments used to measure these outcomes However, in general, these interventions all had positive outcomes, despite their variations. The cross-sectional questionnaire that targeted primary school teachers in Saudi Arabia (n = 1,139 teachers and 82 school managers) highlighted the need for an educational program. The awareness section demonstrated the reliability of the responses (Cronbach’s α = 0.82). Thus, the survey exercise clearly highlighted that Saudi primary school teachers have suboptimal levels of asthma awareness (the sample participants had a score of 9.69 from a range of 0 to 20) and low confidence in managing asthma in children. When asked about school policies, the sample participants alluded to the insignificant policy structure at their school. However, the survey highlighted mostly positive attitudes among participants towards their roles in asthma care and elicited the needs and preferences for school-based educational programs. Importantly, the majority of participants suggested that school-based asthma education would be a worthwhile concept and that they would be willing to participate. The findings of the semi-structured interviews with the parents of children with asthma (n = 20) supported the results of the survey. The parents perceived a lack of asthma-related policy, procedures, care, and support in Saudi primary schools. Their preferences for schoolbased asthma support were directed towards educating teachers and parents about asthma and first aid provision for asthma attacks. Many parents expressed their concerns about the physical and social environment of the school, stating that they preferred to keep their children at home when asthma flare-ups were occurring or were likely. The pilot testing of the asthma educational program (the School Asthma Action Program) with a sample of primary schools in Riyadh (n = 47) indicated improvement in teachers’ awareness of the disease and its management, from a median value of 11 (range: 5–18) pre-program to 15 (range: 7–18) post-program (p < 0.001). The results also demonstrated a small but significant improvement in teachers’ attitudes towards asthma management at schools, from a median value of 74 (range: 15–75) pre-program to 75 (range: 15–75) post-program (p = 0.043). In addition, the pilot testing improved the teachers’ competence and confidence in providing asthma first aid to children at school in case of an emergency. Conclusion The work conducted in this thesis provides vital information to guide the future design of school-based asthma interventions that are sustainable and economically viable. The findings may help health educators and school policy advisors to develop school-based asthma interventions that both school teachers and parents need and are willing to participate in. In general, this research demonstrates the positive effects of a school-based asthma education program on improving primary school teachers’ knowledge, skills, and confidence in assisting children with asthma. The findings also emphasise the need for development and implementation of asthma-related policies and procedures in Saudi Arabian primary schools.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on July 13, 2010). Vita. Thesis advisor: Carol R. Reinero "May 2010" Includes bibliographical references.

Asthma management places significant financial demands on health services. With increased understanding of the mediators involved in asthma pathophysiology more specific agents could be developed for treatment. We studied the effects of oxidant injury- on adult asthmatic cells in vitro and showed asthmatic epithelium more susceptible to oxidative stress at high concentrations of hydrogen peroxide. Cell death occurred via caspase independent apoptosis. However, at lower doses of hydrogen peroxide proliferation was observed suggesting a biphasic response. We investigated levels of Matrix Metalloproteinase-9 (MMP-9) and its inhibitor Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) in the induced sputum, bronchial wash and bronchoalveolar lavage fluid (BALF) of adult asthmatics and their correlation to- their respective immunostaining in bronchial biopsies. Bronchoalveolar lavage fluid in asthmatics demonstrates significantly raised TIMP-1 levels suggesting derangement in extracellular matrix turnover. Involvement of TIMP-1 in asthma pathophysiology is further supported by the finding that TIMP-1 immunostaining correlated with markers of asthma severity. In contrast no such relationship was observed with MMP-9, suggesting an imbalance between MMP-9 and TIMP-1 may be important in remodelling 'of the airway in asthma. Increased Epithelial Growth Factor (EGF) staining was observed within the basal • controls. However, no difference in EGF levels between asthmatics and controls in epithelial layer and in submucosal macrophages of asthmatics compared to either BALF or bronchial wash was found. In the 'asthmatic subjects studied response. In conclusion, this data suggests the epithelial response to increased Epithelial Growth Factor Receptor (EGFR) correlated positively with PC20 suggesting that in mild asthma increased EGFR represents an appropriate repair EGFR expression in mild asthma appears appropriate. In summary, asthmatic bronchial epithelium demonstrates an altered response to oxidative stress. This thesis further supports the evidence for abnormal epithelial cell response in asthma to oxidative stress and an imbalance in matrix turnover in the asthmatic airway.

Asthma is a heterogeneity disease that is mostly managed successfully using bronchodilators and anti-inflammatory drugs. Around 10%-15% of asthmatics however have difficult or severe asthma which is less responsive to treatments. Asthma and in particular severe asthma are now thought of a description of symptoms which may contain possible sub-groups with possible different pathologies which could be useful for targeting different drugs for different sub-groups. However little statistical work has been carried out to determine these sub-phenotypes. Studies have been carried out to partition severe asthma variables in to a number of sub-groups but the algorithms used in these studies are not based on statistical inference and it is difficult to select the number of best fitting sub-groups using such methods. It is also unclear where the clusters or sub-groups returned are actual sub-groups or reflect a bigger non-normal distribution. In the thesis we have developed a statistical model that combines factor analysis, a method used to obtain independent factors to describe processes allowing for variation over variables, and infinite mixture modelling, a process that involves determining the most probable number of mixtures or clusters thus allowing for variation over individuals. This model created is a Dirichlet process normal mixture latent variable model DPNMLVN and it is capable of determining the correct number of mixtures over each factor. The model was tested with simulations and used to analysis two severe asthma datasets and a cancer clinical trial. Sub-groups were found that reflect a high Eosinophilic group and an average eosinophilic group, a late onset older non atopic group and a highly atopic younger early onset group. In the clinical trial data 3 distinct mixtures were found relating to existing biomarkers not used in the mixture analysis.

L’objectif principal de la thèse était de comprendre le rôle complexe des facteurs nutritionnels dans l’asthme, avec une première partie portant sur l’alimentation et une seconde sur l’obésité. Alimentation – L’objectif était de comparer les typologies alimentaires obtenues par une analyse en composantes principales (ACP) à celles identifiées par une analyse factorielle confirmatoire (AFC) grâce aux données de l’étude E3N (étude épidémiologique auprès des femmes de la MGEN, 30589 femmes). En utilisant les ACP et les AFC, 3 typologies alimentaires ont été identifiées. Selon la méthode, des corrélations différentes étaient observées entre les typologies alimentaires et les groupes d’aliments, conduisant à des associations différentes avec les caractéristiques socio-économiques et l’incidence de l’asthme chez l’adulte. Obésité – Le premier objectif était de comprendre les rôles conjoints et indépendants, dépendants du temps, de l’activité physique et l’obésité sur l’asthme en utilisant des modèles marginaux structuraux chez 15352 femmes d’E3N. L’obésité était liée de façon causale à l’asthme actuel avec symptômes, indépendamment de l’activité physique. Le second objectif était de considérer le rôle modificateur du surpoids dans l’association entre l’exposition domestique aux sprays de nettoyage et l’asthme chez 304 femmes d’E3N. Parmi les femmes sans traitement anti-inflammatoire, le rôle délétère de l’utilisation de sprays sur l’asthme était plus fort chez les femmes en surpoids. L’AFC devrait être utilisée pour l’identification des typologies alimentaires en épidémiologie nutritionnelle. L’obésité pourrait causer de l’asthme indépendamment de l’activité physique, et pourrait augmenter l’effet délétère d’autres facteurs environnementaux de l’asthme
The general aim of the thesis was to assess the complex role of nutritional factors in asthma, with a first part focused on diet, and a second part focused on obesity. Diet – The objective was to compare dietary patterns based on principal component analysis (PCA) to patterns based on confirmatory factor analysis (CFA). The analysis was performed among 30,589 women from the E3N study (epidemiological cohort study among women of the Mutuelle Générale de l’Education Nationale). Whether PCA or CFA was used, 3 patterns were derived. For each pattern, we reported different correlations between food groups and dietary patterns when using PCA or CFA, leading to different associations between dietary patterns with socio-economic characteristics and adult-onset asthma. Obesity – The first objective was to assess the joint and independent, time-dependent, roles of physical activity and obesity on asthma using marginal structural models. Among 15,352 women from E3N, analyses showed that obesity was related causally to current asthma with symptoms independently of physical activity, whereas no association was reported for physical activity. The second objective was to assess the modifying role of overweight in the association between domestic exposure to cleaning sprays and current asthma. Among 304 women from E3N, analysis showed that among women without anti-inflammatory therapy, the effect of spray use on asthma was higher in overweight women. CFA should be considered for the assessment of dietary patterns in nutritional epidemiology. Obesity may lead to asthma independently of physical activity, and may increase the deleterious effect of other environmental factors of asthma

Our knowledge and understanding of asthma have evolved over time, leading to new and improved treatments for this disease. Despite existing treatments however, there remains to date a significant proportion of asthmatics who remain poorly controlled, with unmet needs. Most existing treatments are based on the Th2-driven inflammation model of asthma, however there is increasing recognition of the importance of the epithelium in asthma pathogenesis. It has been proposed that the asthmatic epithelium is chronically damaged and unable to repair, with increased permeability as a result. Existing treatments do not address the epithelial damage directly, however there are now available recombinant growth factors that have been shown to have beneficial effects on epithelial healing. Our hypothesis was that modification of the epithelium, in effect boosting its repair using recombinant human keratinocyte growth factor (rhKGF), would lead to improvement in clinical parameters. This was explored in several fashions. Firstly a randomised, double-blind, placebo-controlled clinical trial was performed using 20 poorly controlled, moderate asthmatics, with the active treatment group receiving parenteral rhKGF. Assessments before and after drug administration included objective, clinically relevant, measures of asthma such as airway hyperresponsiveness (AHR) measurements, spirometric measures, exhaled nitric oxide measurements and peak flow recording. Subjective, patient-centred assessments were also made using questionnaires to assess asthma control and quality of life, and bronchoscopy was performed to obtain samples to measure biological effects of the drug. KGF treatment resulted in a significantly greater improvement in the primary outcome of mannitol AHR, together with greater improvements in quality of life in the active treatment group compared to placebo. Other features (such as methacholine AHR, asthma control questionnaire scores, spirometric values, exhaled nitric oxide and peak flow variability) did not differ significantly between the groups, although this may be due to a greater than expected placebo response. Biological outcomes also did not differ significantly between the groups, although this may have been due to the sampling time-point used. Concurrently to the clinical trial above, in vitro experiments were performed on cell cultures of epithelial cells from asthmatic and healthy donors, to verify and further explore the effects of KGF on an asthmatic epithelium. Specifically mechanical wounds were inflicted on the cultures, with assessment of the repair process using wound imaging, measurement of trans-epithelial electrical resistance (TER) and permeability to FITC-labelled dextran, in the presence and absence of KGF. As a subset of these experiments, some cultures were exposed to mechanical compression using air pressure, as a mimic for bronchoconstriction, to see if KGF was effective in these circumstances. Results confirm a biological effect for KGF on wound repair in the asthmatic epithelium, which can also partially overcome the deleterious effect of compression on wound healing. An intrinsic difference in wound healing between asthmatic and healthy cohorts, as previously reported, was not apparent. Lastly the potential of nuclear medicine imaging, to assess epithelial permeability, was explored, for its potential use in future studies of asthma treatments addressing the epithelium directly. Unfortunately this was halted after a pilot study suggested potential methodological flaws – the results and conclusions from this pilot study are presented here, with suggestions for future studies in this area.

This thesis follows the paper based format in that Papers One and Two are stand-alone papers prepared for submission for Clinical Child and Family Psychology Review and the Journal of Clinical Child and Adolescent Psychology respectively. The relevant submission guidelines are included in the appendix (Appendix 1). Asthma is the most common childhood chronic illness affecting an estimated 1.1 million children in the UK. A substantial body of research has shown that asthma prevalence and morbidity rates are associated not only with physiological factors but also with environmental and psychosocial factors. Identifying modifiable psychosocial variables involved in the expression and outcome of asthma in children enables identification of how and where interventions could be targeted. Two papers are presented in this thesis, which aims at contribute to research in this area followed by a critical evaluation of the research process, relevance and implications of the presented papers.Paper One is a review of the literature highlighting the biopsychosocial variables involved in the onset and development of childhood asthma. A model is proposed which aims at demonstrate the bidirectional influence of many variables thought to be involved in paediatric asthma expression. One significant area within the literature highlights the extent to which behaviour problems are elevated in asthmatic children. The prognosis for children who develop significant behaviour difficulties is poor.Research has shown that the quality of parenting a child receives has a significant impact on both the child's well-being and development. Literature included in Paper One highlights the relationship between asthma and parenting. Caregivers of asthmatic children have been shown to be more hostile and critical compared with caregivers of non-asthmatic children.Intervening early with families to promote warm, consistent and positive parenting is considered one of the most effective ways to treat behaviour difficulties. Parent training programmes have emerged as the most efficacious method of intervening with and treating child behaviour difficulties and enhancing parenting skills. In spite of their demonstrated effectiveness, engagement with programmes is often poor. As a result researchers have developed self-directed and web-based interventions. Despite their apparent benefits, uptake and continued engagement remains low.Paper Two aimed at examine whether providing asthma specific information enhanced engagement with a Triple P web-based intervention and identify any pre-treatment variables that predicted engagement. The final section, the Critical Evaluation, aimed at place the research in the wider context, consider the findings from both papers, highlight additional and unexpected outcomes and discuss the implications for future studies and limitations of the thesis.

The aims of this thesis were to determine if there is an association between damp housing and asthma and to investigate whether damp housing adversely influences asthma severity. Asthmatic subjects reported more damp in both their current (Odds Ratio 4.1, 95%CL 2.3 to 7.6) and previous (Odds Ratio 1.9, 95%CI 1.1 to 3.2) dwellings than control subjects. The surveyor confirmed 112 (51%) dwellings to have evidence of damp and 57 (26%) evidence of visible mould growth. Dampness was detected in 58/90 (64%) dwellings of asthmatic subjects compared with 54/132 (41%) dwellings of control subjects (Odds Ratio 2.62, 95%CI 1.50 to 4.55). There was an increasing prevalence of damp in the dwelling with increasing severity of asthma. This association could not be explained by potential bias in study design and persisted after controlling for socio-economic and other confounding variables (adjusted odds ratio 3.03, 95% CI 1.65 to 5.57). Asthma severity scores correlated statistically with measures of total damp (r=0.30, p=0.006) and visible mould growth (r=0.23, p=0.035) in the dwelling. Patients living in homes with evidence of damp had a lower FEV₁ (mean difference 10%, 95% CI 1.0 to 20) and a lower FEV₁/FVC ratio (mean difference 5.4%, 95% CI -0.1 to 10.9) than patients living in dry dwellings. These associations persisted after controlling for unemployment, household income and cigarette smoking. Asthma is significantly associated with living in damp housing. Measures of asthma severity, disability and airflow obstruction are higher in patients living in damp, mouldy dwellings. Effective measures to reduce the risk of damp and condensation occurring in dwellings are required to be incorporated into future housing design.

The present project investigated the use of oscillometry as a mean for the diagnosis of equine asthma, evaluating two different Techniques: the impulse oscillometry system (IOS) and the Forced Oscillation Technique (FOT). The aim of the first study was to evaluate whether the IOS could be sensitive enough to discriminate amongst healthy and asthmatic horses in different clinical conditions. Seven severely asthmatic (SEA) horses in disease exacerbation, 7 asthmatic horses in clinical remission and 7 control horses from a cohort of experimental age-matched animals underwent IOS testing. Only data at 3, 5 and 7Hz with coherence >0.85 at 3Hz and >0.9 at 5 and 7Hz were considered in the study. Mean, inspiratory and expiratory resistance (R) and reactance (X) and the difference between inspiratory and expiratory X (ΔX) were calculated at each frequency. The three groups were compared using one-way ANOVA and Dunnett’s multiple comparison test or Kruskal-Wallis test and Dunn’s multiple comparison test. Significant differences were found between SEA horses in exacerbation and control horses for all R parameters at 3Hz. For X, significant differences were present between exacerbation horses and control horses at each frequency for mean, inspiratory and expiratory parameters. Between controls and remission horses differences were present for X7 and for inspiratory X3, X5 and X7. Regarding Delta X, values in exacerbation horses were significantly higher than remission or control horses. Results indicate that, as reported in humans during tidal expiratory flow limitation (EFL), X during the expiratory phase is more negative than during inspiration in exacerbated horses. Difference in inspiratory X appears to be promising to discriminate between healthy horse and SEA horses in clinical remission. The aim of the second study was to evaluate the application of a FOT device specially designed for horses and his ability in discriminate between healthy subjects, SEA horses in exacerbation and moderate asthmatic horses (MEA). 4 SEA horses, 4 MEA horses and 4 controls from a clinical population were selected, age-matched. Data of FOT measurement at 2, 3, 4, 5 and 6 Hz were considered in the study. Mean, inspiratory and expiratory resistance (R) and reactance (X) and the difference between inspiratory and expiratory X (ΔX) were calculated at each frequency. The three groups were compared using Kruskal-Wallis test and Dunn’s multiple comparison test. Statistical comparison showed significant differences between SEA and control group for R at 3Hz and for R at 2 Hz in expiration phase. Regarding X, several differences were found between controls and SEA horse at frequencies ranging from 2 to 6 Hz in all the phases of the breath. Finally, comparison for ΔX showed that values in SEA horses were significantly higher than MEA or control horses, indicating that in SEA horses in exacerbation the reactance during expiratory phase is worse than during inspiration. No differences were found between controls and MEA horses. Results showed that the new FOT device was able to discriminate between healthy and SEA horses. EFL in SEA horses was identified also by this system. Further studies are required in order to increase the sensitivity in discriminate between healthy and MEA horses.

Background: Asthma is a common chronic disease that causes substantial morbidity and reduced quality of life when poorly controlled. Identifying clinical and psychosocial characteristics that influence long-term asthma control can help to match asthma management programs to the individuals' needs. Objective: Study1: To estimate the extent to which symptom status, beliefs about medications, self-efficacy, emotional function, and health care utilization predict perceived asthma control perceived asthma control over a 16 months period of time among a primary care population. Study2: To estimate the extent to which symptom status, physical, mental, and social function, and healthcare utilization predict perceived asthma control over a 6 month period of time among individuals receiving care at a respiratory specialty clinic. Methods: Study 1 and 2 are secondary analysis of data from two longitudinal studies that examined health outcomes of asthma. The first study recruited the participants from primary clinics, while the second one recruited the participants from a specialty clinic at a Montreal territory hospital. Evaluations on measures of symptom status, beliefs about medications, self-efficacy, physical, mental, and social function, and healthcare utilization were evaluated over 2 time points. Path analysis models were used to estimate the predictors of perceived asthma control in both studies, which were modeled based on the Wilson & Cleary and ICF models. The first study's path model hypothesized that symptoms, self-efficacy, beliefs about medications, emotional function, physical activity, and healthcare utilization are predictors of perceived asthma control. The second study's path model hypothesized that FEV1, symptom, mental health, physical and social function, role emotional, and healthcare utilization are predictors of perceived asthma control. Results: Study1: the path model indicated asthma symptom (B= 0.35, p= 0.00) and physical activity (B= 0.24, p= 0.01) had a significant positive total effect on perceived asthma control, while emotional function (B= 0.08, p= 0.05) and self-efficacy (B= 0.07, p= 0.02) were significant predictors indirectly through physical activity. The model explained 24% of perceived asthma control. Overall, the model fit the data well (Χ2 = 15.98, df = 10, P-value = 0.1, RMSEA = 0.045, and CFI = 0.98). Study 2: the path model indicated that FEV (B= 0.12, p= 0.01), asthma symptom (B= 0.42, p= 0.001), and social function (B= 0.37, p= 0.02) had a significant positive total effect on perceived asthma control. The model explained 34% of perceived asthma control. Overall, the model fit the data well (Χ2= 39.83, df = 27, P-value = 0.053, RMSEA = 0.065, and CFI = 0.95). Conclusion: FEV1, asthma symptom, physical activity, emotional function, social function, and self-efficacy can be used to identify patients likely to have poor perceived asthma control in the future, and should be considered when planning patient management. Identifying these predictors is important to help the care team tailor interventions that will allow individuals to optimally manage their asthma, to prevent exacerbations, to prevent other respiratory-related chronic disease, and to maximise quality of life.
Contexte: L'asthme entraîne une morbidité importante et réduit la qualité de vie lorsqu'elle est mal contrôlée. L'identification des caractéristiques cliniques et psychosociales qui influent sur contrôle de l'asthme à long terme peut aider à faire concorder les programmes de gestion de l'asthme aux besoins des individus. Objectif: Étude 1: Estimer la mesure dans laquelle le statut des symptômes, les croyances concernant les médicaments, l'auto-efficacité, l'émotion, et l'utilisation des soins de santé permettent de prédire le contrôle de l'asthme perçu sur une période de 16 mois dans une population des soins primaires. Étude 2: Estimer la mesure dans laquelle le statut des symptômes physiques et mentaux, les fonctions sociales, et l'utilisation des soins de santé permettent de prédire le contrôle de l'asthme perçu sur une période de 6 mois chez les personnes recevant des soins dans une clinique spécialisée en pneumologie.Méthodes: Les études 1 et 2 sont des analyses secondaires des données provenant de deux études longitudinales qui ont examiné les effets de l'asthme sur la santé. La première étude a recruté les participants de cliniques de soins primaires, tandis que la seconde a recruté les participants à partir d'une clinique spécialisée dans un hôpital à Montréal. Les évaluations sur les mesures de l'état de symptôme, les croyances concernant les médicaments, l'auto-efficacité, physique, mental, et les fonctions sociales, et l'utilisation des soins de santé ont été évaluées à 2 points dans le temps. Des modèles d'analyse de pistes causales ont été utilisés pour estimer les facteurs prédictifs de le contrôle de l'asthme perçu dans les deux études. Les modèles utilisés se basent sur les modèles Wilson & Cleary et modèles ICF. Le modèle de piste pour la première étude a émis l'hypothèse que les symptômes, les auto-efficacités, les croyances au sujet des médicaments, l'émotion, l'activité physique, et l'utilisation des soins de santé sont des facteurs prédictifs du contrôle de l'asthme perçu. Le modèle de piste pour la deuxième étude a émis l'hypothèse que le VEMS, les symptômes, la santé mentale, les fonctions physiques et sociales, le rôle émotionnel, et l'utilisation des soins de santé sont des facteurs prédictifs du contrôle de l'asthme perçu. Résultats: Étude 1: le modèle de piste causale a indiqué que les symptômes de l'asthme (B = 0,35, p = 0,00) et l'activité physique (B = 0,24, p = 0,01) ont eu un effet positif important sur la le contrôle de l'asthme perçu totale, tandis que la fonction émotive (B = 0,08, p = 0,05) et l'auto-efficacité (B = 0,07, p = 0,02) étaient des prédicteurs significatifs indirectement au moyen de l'activité physique. Le modèle explique 24% de la le contrôle de l'asthme perçu. Les statistiques d'ajustement indiquent un bon ajustement du modèle (= 15,98 Χ2, df = 10, P-value = 0,1, RMSEA = 0,045, et la FCI = 0,98). Étude 2: le modèle de piste causale a indiqué que le VEMS (B = 0,12, p = 0,01), les symptômes d'asthme (B = 0,42, p = 0,001), et la fonction sociale (B = 0,37, p = 0,02) a eu un effet positif important sur la le contrôle de l'asthme perçu totale. Le modèle explique 34% de la le contrôle de l'asthme perçu. Les statistiques d'ajustement indiquent un bon ajustement du modèle (= 39,83 Χ2, df = 27, P-value = 0,053, RMSEA = 0,065, et la FCI = 0,95). Conclusion: Le VEMS, les symptômes de l'asthme, l'activité physique, la fonction émotive, la fonction sociale, et l'auto-efficacité peuvent être utilisés pour identifier les patients susceptibles d'avoir une mauvaise le contrôle de l'asthme perçu dans l'avenir, et devrait être considéré lors de la planification de gestion des patients. L'identification de ces prédicteurs est une étape importante pour aider les équipes d'interventions à administrer des soins sur mesure afin de contrôler l'asthme et les exacerbations des patients de façon optimale, mais également de prévenir les maladies chroniques associées, et de maximiser la qualité de vie.

Asthma can be a chronic disorder requiring regular medications if the symptoms are persistent. The regimen is often complex, involving a number of drugs and a variety or routes of administration. Although drug therapy may not alter the natural history of asthma it can improve lung function enabling those with asthma to lead as near a normal life as possible. Thus medication compliance is an important factor in the managemnt of asthma. (Note : Special enclosures (Publication reprints) at end of thesis have been removed for digital submission, with permission of author)

Doctor of Philosophy
Asthma can be a chronic disorder requiring regular medications if the symptoms are persistent. The regimen is often complex, involving a number of drugs and a variety or routes of administration. Although drug therapy may not alter the natural history of asthma it can improve lung function enabling those with asthma to lead as near a normal life as possible. Thus medication compliance is an important factor in the managemnt of asthma. (Note : Special enclosures (Publication reprints) at end of thesis have been removed for digital submission, with permission of author)

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.

The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
Medicine, Faculty of
Experimental Medicine, Division of
Medicine, Department of
Graduate

In this thesis the long term stability of eosinophilic bronchitis has been investigated in a longitudinal study. Induced sputum has been used to investigate a possible difference in expression of IL-13 in asthma and eosinophilic bronchitis. Bronchoscopy has been used to compare the airway immunopathology of eosinophilic and non eosinophilic asthma and the long term stability and response to inhaled corticosteroids in non eosinophilic asthma was studied in a prospective randomised controlled trial. Alveolar nitric oxide concentration has been validated as a measure of distal lung inflammation. Finally the role of TNF-alpha and response to etanercept has been investigated in patients with refractory asthma. Evolution from eosinophilic bronchitis into asthma was rare, decline in lung function was not increased, although female gender, smoking and prolonged eosinophilic airway inflammation were independent risk factors for an accelerated decline. IL-13 concentrations were elevated in asthma compared to eosinophilic bronchitis, suggesting a role for this cytokine in the development of airway hyperresponsiveness. Non eosinophilic asthma remained stable over the period of investigation and was associated with reduced response to inhaled corticosteroids. Mast cells were present in airway smooth muscle in eosinophilic and non eosinophilic asthma but not normal controls. Subepithelial layer thickening was a feature of eosinophilic but not non eosinophilic asthma. Alveolar nitric oxide was increased in refractory asthma and reduced by oral but not inhaled corticosteroids.

Severe asthmatic patients continue to have poorly controlled disease despite the use of anti-inflammatory medication such as corticosteroids. The aims of this thesis were to determine whether severe asthma is associated with corticosteroid insensitivity, and to begin an exploration of the cellular mechanisms involved. In this study, severe asthmatics had more severe airway obstruction and greater airway inflammation despite the use of high dose inhaled or oral corticosteroids. In peripheral blood mononuclear cells, relative corticosteroid insensitivity was present, evidenced by impaired steroid-regulated suppression of lipopolysaccharide-induced cytokine release. These cells also had diminished histone deacetylase activity, and this was linked with the degree of asthma severity, airway inflammation and corticosteroid insensitivity. Conversely, an associated reduction in histone acetyltransferase activity was related to the use of corticosteroid therapy rather than disease severity. Relative corticosteroid insensitivity was also detected in alveolar macrophages of severe asthmatic patients. This was seen in conjunction with impaired MAP kinase phosphatase-l (MKP-l) induction by dexamethasone in the presence of lipopolysaccharide, and exaggerated p38 mitogen activated protein (MAP) kinase activation by lipopolysacharide. This suggests that dysregulation of the p38 MAP kinase pathway may be an important determinant of corticosteroid insensitivity in alveolar macrophages of these severe asthmatic patients. In summary, this study has demonstrated the presence of relative corticosteroid insensitivity in both circulating peripheral blood mononuclear cells as well as alveolar macrophages from the airways of severe asthmatic patients. This corticosteroid insensitivity is linked to diminished histone deacetylase activity, and also to dysregulation of p38 MAK kinase activation. Overcoming corticosteroid insensitivity by targeting these pathways may offer a new strategy in the treatment of severe asthma.

Rationale Cough is an important symptom in asthma. In addition, cough is both troublesome to patients and may be important in the development of more severe disease. Moreover, it is a key symptom in the diagnosis of asthma, according to international guidelines. Little is known regarding the mechanism of cough in asthma. Until now, subjective measures of cough have been used in mechanistic and therapeutic studies relating to both cough in asthma and chronic cough. There is no published literature documenting cough rates in asthma or the relationship between cough rates and both subjective measures of cough and asthma control. In addition, the relationship between objective cough rates and airway inflammation, and the effects of cough on airway function and inflammation is unknown. Methods A series of studies was designed and carried out to answer the above questions. Firstly, a cross sectional study examining the relationships between objective and subjective measures of cough in classical asthma (CA), secondly a longitudinal study examining the relationship between cough rates and CA control and thirdly a cross-sectional study examining the effects of voluntary cough on airway function and inflammation. Results There was a poor correlation between objective and subjective measures of cough in CA. Cough-related quality of life correlated most closely with cough rates. Traditional measures of CA (e.g. spirometry) poorly reflected cough rates. Objective cough rates and sputum eosinophils were predictive of CA control as defined by ACO. Objective cough rates did not reflect sputum inflammatory cell count or mediators. Voluntary cough induced small changes in peak flow in mildmoderate CA and small changes in sputum ECP that were not reflected by changes in sputum eosinophils. Conclusions Subjective measures of cough in asthma are poor substitutes for objective cough rates. When designing studies for cough in asthma, both objective cough rates and cough-related quality of life should be incorporated. Objective cough rates reflect asthma control (independent of airway inflammation) more closely than traditional measures of asthma. Airway inflammation does not appear to directly reflect cough rates. In addition, short bouts of coughing in mildmoderate asthma induce neither significant changes in airway function nor airway inflammation.