Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5350. Adviser: Luisa Franzini. Includes bibliographical references (leaves 101-104)

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.

Thesis (M.A.)--Georgia State University, 2005. / Title from title screen. Roger Bakeman, committee chair; Gabriel Kuperminc, John Peterson, Marianne Celano, committee members. Electronic text (57 p.) : digital, PDF file. Description based on contents viewed June 18, 2007. Includes bibliographical references (p. 51-57).

D.Phil. / Asthma exemplifies a major medical concern and is a considerable cause of morbidity and mortality globally and in South Africa. Biokineticists have in the past primarily prescribed aerobic modes of exercise to asthmatics regardless of other modes of exercise that could be used in the management of asthma, each with their own unique benefits. The aim of this investigation was to develop a management model from a biokinetic perspective for the management of asthma in moderate, persistent asthmatics. The present study utilised a quantitative, comparative, research trial making use of a pre-test, eight-week intervention period and a post-test. Eighty-eight sedentary moderate, persistent asthmatics were matched by age and gender and randomly assigned to either a non-exercising control group (NE) (n = 22), an aerobic exercise group (AE) (n = 22), a diaphragmatic inspiratory resistive breathing group (DR) (n = 22) or an aerobic exercise combined with diaphragmatic resistive breathing group (CE) (n = 22). Dependent t-Tests and rank-ordered analyses revealed that five of the 13 pulmonary function parameters assessed were found to be significantly altered following the AE and CE training, with the CE training having a larger impact than AE training. The DR training resulted in improvements in four of the 13 pulmonary function parameters. The CE and AE training were also found to be equally effective at altering physical work capacity, while the DR training proved ineffective at altering physical work capacity. The CE training proved to be the most effective at improving the abdominal and chest wall excursion parameters. The DR training was found to be the least effective mode of exercise training to impact favourably on abdominal and chest wall excursion parameters. The DR and CE training had a similar significant and favourable change in respiratory muscle flexibility followed by the AE training only impacting on nine of the 11 respiratory muscle flexibility parameters. Regarding the respiratory muscle strength, despite AE and CE training altering 18 of the 20 parameters, CE training was found to be more effective. DR training only altered 16 of the 20 respiratory muscle strength parameters. The DR training was the only modality to alter a postural parameter, albeit unfavourably. Even though the DR and AE training significantly altered four of the six anthropometric parameters, the AE training proved to be superior, while CE training proved least effective as it altered v only three of the measured anthropometric parameters. The overall success of the CE training exemplified the fact that an optimal training regime for the management of asthma may require both an aerobic exercise and diaphragmatic inspiratory resistive breathing component. Exercise training, and specifically CE training is a cost-effective, home-based asthma management programme that may reduce the public health burden of this disease and provide the patient with alternative treatment options. CE training should form the cornerstone in the management of asthma to minimise and prevent asthma exacerbations and thus improve health-related quality of life and may even prove to be life-saving.

Work-related asthma surveillance is needed to improve management of occupational exposures, clinical recognition/diagnosis, and worker compensation policies. This work investigated asthma in relation to work by evaluating the utility of existing Canadian surveillance data in providing useful information about the burden of work-related asthma; estimating the burden of work-related asthma among Canada's adult population; and evaluating the effect of job risk on asthma after considering other potential risk factors for asthma. The working population formed samples from two Statistics Canada surveillance programs: Canadian Community Health Survey (CCHS), 2002/03 Cycle 2.1 and National Population Health Survey (NPHS), Longitudinal Component (1994/95-2002/03). Both surveys enquired about health professional-diagnosed asthma; NPHS additionally asked age at time of diagnosis, so adult-onset versus childhood-onset asthma was determined. Both surveys enquired about current job held; corresponding job codes were linked to an asthma-specific job exposure matrix to judge job risk for occupational asthma. CCHS only provided current job information, in contrast, NPHS longitudinal data was used to determine job held at time of asthma-onset. Statistical measures for asthma in relation to job risk were estimated. CCHS results were likely biased by the healthy worker effect, as it showed the opposite effect of job risk on asthma than the NPHS; higher asthma prevalence was shown for NPHS men and women in high risk jobs. NPHS results indicated a large burden of adult-onset asthma among men (19,000) and childhood-onset asthma among women (17,000) attributed to working in high risk jobs for occupational asthma. Using NPHS, adjusted and crude prevalence odds ratio estimates were compared to further assess effect of job risk on asthma. For adult-onset asthma, there was no difference between estimates (men: 1.8, women: 1.1); for childhood-onset asthma, adjusted estimates were larger than crude, respectively (men: 1.3 v 1.2, women: 2.0 v 1.7). Age of asthma-onset and job held at time of asthma-onset is necessary surveillance information for estimating work-related asthma. There may be increased risk of work" caused" asthma among men and work "exacerbated" asthma among women in high risk jobs. Considering other risk factors for asthma did not reduce effect of job risk on asthma. / Medicine, Faculty of / Population and Public Health (SPPH), School of / Graduate

Introduction: Mepolizumab is a humanized monoclonal antibody that binds to and inactivates IL-5. It is available as a subcutaneous preparation. The practical application of mepolizumab is as an add-on therapy in the treatment of severe eosinophilic asthma. Areas covered: This article was created from a comprehensive literature search with information taken from meta-analyses, systematic reviews, and clinical trials of adults. The articles that have been selected evaluate the use of mepolizumab and its role in eosinophilic asthma. Expert opinion: Mepolizumab is significantly more effective than placebo in reducing exacerbations and need for systemic corticosteroids in severe eosinophilic asthma. There is a lack of head to head studies comparing mepolizumab to other monoclonal anti-IL-5 inhibitors in severe eosinophilic asthma. Post marketing surveillance revealed risk of anaphylaxis that is below 1%.

Traditional animal models of severe asthma do not recapitulate defining asthma characteristics, including persistent airway hyper-responsiveness, and chronic neutrophilic inflammation. This is problematic because moderating airway hyper-responsiveness decreases asthma frequency and severity, making it a paramount pharmacological goal in asthma research. Employing a spontaneous equine asthma model (equine pasture asthma, EPA), we first confirmed reversible airway obstruction in eight diseased horses during asthma exacerbations in response to ß2renergic agonist stimulation. Next, non-specific airway hyper-responsiveness was confirmed using methacholine bronchoprovocation to identify the provocative concentration causing a 40% increase in baseline lung resistance (PC40RL)- a threshold similarly employed in evaluating human asthmatics unable to mount forced expiration. The PC40RL of ten EPA horses was consistently <1mg/ml of methacholine, which is a cutoff that has been used to diagnose severe human asthma. Like non-asthmatic humans, ten control horses did not respond to methacholine doses up to 16 mg/ml. Finally, persistence of AHR was documented during absence of seasonal aeroallergen triggers in five horses that were evaluated between 3 and 31 months following the initial methacholine bronchoprovocation. This unique ability of EPA horses to model AHR attributes that are not addressed by other animal models points to the suitability of EPA horses to decipher the mechanistic basis of airway hyper-responsiveness. Building on knowledge that 2renergic receptor (AR) signaling is required to develop the asthma phenotype in a murine model, differentially expressed genes from serial lung biopsies of two EPA affected and two controls were filtered to identify genes that interact with the 2-AR. Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 4 (HCN4) was prioritized because of its interactions with the 2-AR. Relative to control horses, HCN4 was constitutively expressed in airway smooth muscle of EPA horses during remission and increased during seasonal disease exacerbation. Agonism of airway contraction by HCN4 was proven using the specific HCN4 antagonist, ivabradine, which caused dose dependent decreases in carbachol induced contractile responses in both EPA and control bronchi in vitro. These findings highlight utility of EPA as a model of severe asthma and HCN4 as a mediator of airway contraction that warrants further investigation in severe human asthma.

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