Doctor of Philosophy (PhD) / Exercise and physical activity have many benefits for adults with cystic fibrosis (CF), including the potential to aid mucus clearance, improve lung function, exercise capacity and quality of life. Despite the recommendations from consensus documents for CF adults to engage in regular physical activity, exercise participation amongst this population is often very low. No in-depth study has been undertaken to explore the determinants of exercise participation for this group and no studies have examined the benefits of habitual physical activity on the health status and quality of life of CF adults. As well, the current methods to quantify physical activity are problematic. The series of studies, involving CF adults, in this thesis was therefore undertaken in order to examine the physiological rationale for the use of exercise as an airway clearance technique, to understand the decision making process to engage in exercise, to determine if health status and quality of life were affected by exercise participation, and to establish the accuracy of a recently-developed objective measure of physical activity. The study in Chapter 2 provided some physiological rationale for choosing treadmill exercise to aid airway clearance in CF. The main findings were that a single bout of moderate intensity exercise increased the subjective ease of expectoration, most likely due to the increased ventilation with exercise, and that sputum viscoelasticity was favourably decreased immediately following treadmill exercise compared to cycle exercise and control. The studies in Chapters 3 and 4 identified the main beliefs regarding exercise for CF adults and highlighted that the main predictors of exercise intention and participation for this group were aspects of perceived and actual control to exercise, namely self-efficacy or confidence to exercise, feeling healthy, receiving encouragement to exercise, and rating exercise as a high priority treatment. Positive ratings of these aspects of control either increased exercise participation directly, indirectly by increasing intention, or strengthened the conversion of exercise intention to participation. Strategies aimed at targeting these aspects of control are therefore likely to be effective in increasing exercise participation for CF adults. The study in Chapter 5 demonstrated that CF adults, who reportedly performed at least 90 minutes of moderate to strenuous exercise per week, had significantly higher quality of life and fewer days in hospital over the following year than their peers, who exercised less. The difference in hospitalisation between the CF adults, who reportedly exercised more than 90 minutes per week and those who did not, was independent of baseline lung function, and the females who reportedly performed less than 90 minutes of exercise per week had three times as many days in hospital than their high-activity peers. The study in Chapter 6 showed that the SenseWear Pro3 Armband activity monitor provided a reasonable estimate of energy expenditure and step count. Also, its accuracy was not affected by diagnosis with CF, despite the potential for the high salt content in the sweat to interfere with the device’s physiological sensors placed on the skin. Overall, this series of studies adds to the growing evidence of the physical and psychological benefits from exercise participation for CF adults, as well as providing some empirical evidence upon which to base strategies to improve exercise participation for this group and support for an objective measure of physical activity.

This thesis uses the International Classification of Functioning, Disability and Health (ICF) model (World Health Organisation, 2001) to explore the multidimensional presentation of strengths and problems in young people with cystic fibrosis (CF), firstly examining its theoretical “fit” to the health condition, and secondly using it to characterise the performance of those with CF. Few studies in the literature demonstrate such an holistic approach to the physiotherapy assessment and management of this population. It was expected that this description of performance would provide a framework for identifying key areas for physiotherapy exercise intervention. This then formed the basis for further studies to examine the effect of a targeted exercise program (compared to current exercise practice) on inpatient outcomes, as well as on outcomes of outpatient management. The position paper included provides theoretical support for the ICF model as an appropriate tool in the management of young people with CF. Building on this, Study 1 explored the practical utility of the ICF model for describing the presentation of young inpatients and outpatients with CF. Eighty-four participants with CF were recruited as a consecutive series who satisfied selection criteria to provide a cross-sectional view at younger (7-12 years, n=51) and older (13-17 years, n=33) ages. Musculoskeletal, respiratory and physiological measures represented the body structures and functions domain, the six-minute walk test and jump tests were included in the activities domain, and participation was described by the Cystic Fibrosis Questionnaire–Revised Version and Fels Physical Activity Questionnaire. Contextual factors were also considered (age, gender, inpatient/outpatient status). In this exploratory study, performance of this population was compared to normative data where available. Also, correlations between measures within and between ICF domains were examined as suggested by the model itself. Finally, effects of contextual factors on performance were investigated using univariate analysis of variance. This first study and the position paper support the ICF model as an effective tool for describing performance of young people with CF, and for investigating functional relationships within and between domains. Results showed significant differences in this population compared to normative data, and interrelationships were identified within and between ICF domains. Between inpatients and outpatients in the specified age groups, there was a statistically significant difference in means for a number of measures, whereby inpatients displayed consistently poorer mean scores than outpatients, with this effect significantly stronger in the older age group. The application of the ICF model was useful for highlighting areas to target in physiotherapy exercise intervention, and for substantiating selected measures to assess the program’s effectiveness across domains. Study 2 was a randomised controlled trial with blinded assessor, which investigated the effectiveness of a 10-14 day inpatient-based exercise program (the Cystic Fibrosis: Fitness Challenge) (CF:FC) tailored for young people with CF (7-17 years). The CF:FC program (n=15) included exercise strategies based on recommendations from previous work in the field, and from findings from Study 1. This program included a portable exercise package (FitKitTM) designed to be adaptable to limited space environments such as at the hospital bedside, important when inpatients with CF are isolated according to infection control procedures. Participants in the control program (n=16) received the current exercise practice provided for young people with CF at a tertiary hospital, which included mainly aerobic-type activities to affect airway clearance. Performance on study measures (scoped within the framework of the ICF model, presented in Study 1) were compared pre- and post-intervention (admission and completion of the inpatient exercise program) between the groups. This trial showed significant improvements for participants in both groups from admission to discharge for a range of measures, including respiratory function, muscle strength and quality of life measures. Participants in the intervention group showed significantly greater improvements for some measures, for example: ankle dorsiflexor strength, six-minute walk distance and perception of their respiratory status. The continuation of the intervention and control programs into the outpatient setting was the focus of Study 3. The FitKitTM was provided for the intervention group, incorporating strategies to enhance adherence including a physical activity log (PAL) and internet-based follow-up. The control home exercise program consisted of the current practice provided on discharge. Interestingly, the control group improved significantly in hip abductor strength and six-minute walk distance during the outpatient period, whereas the intervention group sustained the improvements gained in the inpatient period but generally showed no further significant improvement. When the change from inpatient admission to outpatient follow-up was considered, it was apparent that greater improvements during the inpatient period provided a ‘buffer’ to accommodate for possible deteriorations in function in the outpatient phase. Issues regarding adherence to exercise programs during the outpatient period are discussed. This thesis confirms the usefulness of the ICF model for describing young people with CF, guiding assessment and review processes to achieve comprehensive management, and strengthening the evidence-base for targeted physiotherapy exercise intervention. A novel, tailored exercise program is introduced which is effective during inpatient periods, and provides a maintenance effect during outpatient periods, but strategies to enhance adherence during outpatient periods require further investigation.

[Truncated abstract] Urinary desmosines have been proposed as a biomarker for inflammatory lung damage. Desmosine, a breakdown product of elastin, is an effective marker of the degradation of elastin and has been studied in many disease scenarios where there is acute and chronic lung inflammation. Lung matrix degradation has been proven in vitro and in vivo with many experiments showing that the excess proteases degrades lung matrix. The secretion of proteases by neutrophils is an innate response of the body to the invasion by micro organisms and when secreted in excess, the protective anti-protease mechanism is swamped. Chronic inflammation and persistent infection eventually leads to bronchiectasis and respiratory failure. Urinary desmosine has been shown to be elevated in respiratory conditions with acute and chronic inflammation . . . Urinary desmosine levels in a large cohort of healthy children have been established using this method and predictive Z-score formulae have been developed to use in children with lung disease. Exploration of these scores in children with CF have shown that the levels of urinary desmosine appear to be sensitive to the clinical setting, where high urinary desmosine levels were present during exacerbation and significantly reduced when treated for infection with antibiotic therapy and physiotherapy. The study of young children under the age of seven was undertaken to determine if the urinary desmosine levels could indicate when lung damage was occurring and to determine what mechanisms might be involved. Since there appeared to be no apparent relationship between elevated desmosines and proteases in the lung in young children with CF, further studies are required to define the mechanisms behind increased elastin metabolism in those children.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Feb. 6, 2008). Includes bibliographical references.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Cornell University, May, 1997. / Includes bibliographical references (leaves 170-181).

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 131-132). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / "December 1998" Typescript. Vita. Includes bibliographical references (l. 140-148). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 131-132). Also available on the Internet.