Introduction: There is a need for a health-related quality of life questionnaire in COPD that fulfills the advantages of both, generic and disease-specific questionnaires. Objective: To finalize the development of a new, hybrid questionnaire (disease-specific items supplemented with items from the SF-36), the McGill COPD Quality of Life Questionnaire and to evaluate its psychometric properties (reliability, validity, responsiveness) in COPD subjects. [...] / Introduction: Il y a nécessité d'avoir accès à un questionnaire de qualité de vie qui pourrait offrir les avantages d'un questionnaire générique et ceux d'un questionnaire spécifique à la MPOC. Objectif: Finaliser l'élaboration d'un nouveau questionnaire hybride le 'McGill COPD Quality of Life Questionnaire' (éléments spécifiques à la maladie complémentés d'éléments génériques issus du SF-36) et évaluer ses propriétés psychométriques (fiabilité, validité, réponse au changement) chez les sujets atteint d'une MPOC. [...]

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Background: In chronic obstructive pulmonary disease (COPD), understanding the problem of poor patient participation in evidence-based self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as SM support programmes) is critical. This thesis aimed to improve understanding of poor patient participation and retention in these programmes; how participation might be improved; and how might patients be better supported with their SM. Methods: Using the Medical Research Council guidance on complex interventions this thesis (1) quantified the 'actual' patient participation and completion rates; (2) explained, using theory, the factors that influenced participation in studies of SM support including the programmes among chronic disease and COPD patients; and (3) explored patient and expert stakeholders' perspectives on the reasons for non-participation in SM support programmes, how participation might be improved, how might patients be supported with their SM. Results: (1) Among 56 studies, high study participation rates and completion rates were seen however, the incomplete reporting of participant flow confused the problem of participation. (2) Among 31 studies, participation among patients with chronic disease including COPD was shown to be influenced by their 'attitude' and 'perceived social influence/subjective norms'; 'illness' and 'intervention perceptions'. (3) From 38 interviewees, besides patients' beliefs, non-participation was also influenced by resignation and denial of the illness; health systems; and programme organisational factors. Professionals building relationships and supporting patients with their SM alongside programme organisational improvements might encourage patient participation in SM and the programmes. Conclusions Patient participation is a complex behaviour, besides socio-behavioural factors, participation behaviour can by influenced by a mix of several health system and programme organisational factors. Changing the behaviour of health professionals and indeed the wider health system, towards normalising a patient partnership approach, with implementation of SM support in routine care might help more patients to consider participation in their care and improve patient participation in COPD SM support programmes.

Significant cardiovascular morbidity and mortality exists in chronic obstructive pulmonary disease independent of traditional risk factors. A number of different hypotheses exist to explain this association including the contribution arterial stiffness and lung hyperinflation. Non-invasive cardiovascular imaging and assessment are ideal methods through which this relationship can be further studied although a number of the techniques have yet to be validated in COPD. In this thesis we aimed to achieve a number of goals. First, we aimed to assess the reproducibility and level of agreement between different measures of arterial stiffness in stable hyperinflated COPD. Second, we hoped to establish the utility of 3 different measurement techniques for measuring intrinsic cardiac function in stable hyperinflated COPD. Third, in a case-control study we compared surrogates of cardiovascular risk in hyperinflated COPD patients and a group matched for cardiovascular risk with normal lung function. Finally, we sought to understand the impact of pharmacologically reducing lung hyperinflation on cardiovascular structure, function and arterial stiffness. We have firstly demonstrated that non-invasive measures of arterial stiffness are reproducible in stable hyperinflated COPD. Secondly, we have established the level of agreement and reproducibility of three different CMR techniques for measuring intrinsic myocardial function which will provide important information for the powering of future CMR studies in COPD. Thirdly, we have shown that surrogates for cardiovascular outcomes are adversely affected in COPD compared to a group matched for global cardiovascular risk, suggesting that current scoring systems may be suboptimal in risk prediction in COPD. Finally, we have demonstrated that pharmacological lung deflation has consistent and physiologically plausible beneficial effects on cardiac structure, function and the pulmonary vasculature. Whether intrinsic myocardial function can be modulated through prolonged periods of lung deflation is as yet unverified and should be the focus of future clinical trials.

Masters of Science in Medicine / The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. Limited research into the relationship between COPD and swallow function suggests that patients with COPD are at increased risk of aspiration. One possible mechanism for this is a reduction in laryngopharyngeal sensitivity (LPS). Reduced laryngopharyngeal sensitivity (LPS) has been associated with an increased risk of aspiration in pathologies such as stroke, however impaired LPS has not been examined with respect to aspiration risk in COPD. The Aims of this study were to investigate the effect of COPD on laryngopharyngeal sensation using Laryngopharyngeal Sensory Discrimination Testing (LPSDT) and to determine whether a relationship between LPS and swallow function in patients with proven COPD exists. Method: 20 patients with proven COPD and 11 control subjects underwent LPSDT utilising an air-pulse stimulator (Pentax AP4000) via a nasendoscope (Pentax FNL10AP). The threshold of laryngopharyngeal sensation was measured by the air pressure required to elicit the laryngeal adductor reflex (LAR). A number of further examinations were also completed for COPD subjects. These included respiratory function testing, self-reporting questionnaire on swallowing ability (SSQ), bedside clinical examination of swallowing (MASA) and endoscopic assessment of swallowing (EAS). Results: subjects with COPD had a significantly higher LAR threshold when compared to their normal healthy counterparts (p<0.001). Positive correlations were identified for the relationships between MASA score and EAS results for presence of laryngeal penetration / aspiration (p<0.04), vallecular residue (p<0.01) and piriform residue (p<0.01). Conclusion: Patients with COPD have significantly reduced mechanosensitivity in the laryngopharynx. Patients with COPD also have impaired swallow function characterised primarily by pharyngeal stasis. These changes may place patients with COPD at increased risk of aspiration.

ABSTRACT Asthma exemplifies a major medical concern and is a considerable cause of morbidity and mortality in Western society. Controversy still exists regarding the most effective mode and intensity of exercise training for asthmatics. Thus, the purpose of the study was to determine whether walking or jogging at 60% of age-predicted heart rate maximum can increase effort-dependent pulmonary function parameters in moderate, persistent asthmatics. Forty-four sedentary asthmatics were randomly assigned to either a non-exercising control (NE) group (n = 22) or an eight-week moderate-intensity aerobic exercise (AE) group (n = 22). Results indicated that the subjects in the AE training group significantly (p = 0.05) increased their forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal voluntary ventilation (MVV) and inspiratory vital capacity (IVC). The NE group did not exhibit any significant changes in any of the measured variables. Therefore, walking or jogging at 60% heart rate maximum for 30 minutes three times a week for eight weeks can effectively improve the effort-dependent pulmonary parameters in moderate, persistent asthmatics. This represents a strong argument to support the inclusion of this mode of aerobic training in the treatment of moderate, persistent asthma due to its effectiveness, inexpensiveness and lowrisk.

Background: Chronic obstructive pulmonary disease (COPD) is a devastating illness that affects 4.3% of the population of British Columbia over the age of 45 years. Asthma is known to coexist in 10-20% of individuals with obstructive lung disease, and adds to the substantial burden of illness posed by COPD alone. Inhaled corticosteroids (ICS) are currently recommended for the management of COPD among individuals with frequent exacerbations; however, the ability of inhaled corticosteroids to reduce death and hospitalizations among individuals with COPD is controversial. Less is known about the effectiveness of ICS among individuals who are afflicted with both COPD and asthma. Methods: We used a retrospective cohort study design and administrative data to estimate the relative effectiveness of ICS in reducing hospitalizations or death among individuals with concomitant asthma and COPD, compared with individuals with COPD alone. We used an extended Cox model to estimate this association, with a time-varying measure of exposure to ICS. Results: We did not find any association between ICS and hazard of death or hospitalization among individuals with COPD alone (HR = 0.99; 95% CI: 0.94 – 1.05), however the hazard was 18% lower (HR = 0.82; 95% CI: 0.69-0.99) among individuals with concomitant disease. Conclusions: Individuals with combined COPD and asthma show significant benefit from the use of ICS and are more responsive to the effects of ICS than individuals with COPD alone.

Background: Chronic obstructive pulmonary disease (COPD) is a devastating illness that affects 4.3% of the population of British Columbia over the age of 45 years. Asthma is known to coexist in 10-20% of individuals with obstructive lung disease, and adds to the substantial burden of illness posed by COPD alone. Inhaled corticosteroids (ICS) are currently recommended for the management of COPD among individuals with frequent exacerbations; however, the ability of inhaled corticosteroids to reduce death and hospitalizations among individuals with COPD is controversial. Less is known about the effectiveness of ICS among individuals who are afflicted with both COPD and asthma. Methods: We used a retrospective cohort study design and administrative data to estimate the relative effectiveness of ICS in reducing hospitalizations or death among individuals with concomitant asthma and COPD, compared with individuals with COPD alone. We used an extended Cox model to estimate this association, with a time-varying measure of exposure to ICS. Results: We did not find any association between ICS and hazard of death or hospitalization among individuals with COPD alone (HR = 0.99; 95% CI: 0.94 – 1.05), however the hazard was 18% lower (HR = 0.82; 95% CI: 0.69-0.99) among individuals with concomitant disease. Conclusions: Individuals with combined COPD and asthma show significant benefit from the use of ICS and are more responsive to the effects of ICS than individuals with COPD alone.

Masters of Science in Medicine / The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. Limited research into the relationship between COPD and swallow function suggests that patients with COPD are at increased risk of aspiration. One possible mechanism for this is a reduction in laryngopharyngeal sensitivity (LPS). Reduced laryngopharyngeal sensitivity (LPS) has been associated with an increased risk of aspiration in pathologies such as stroke, however impaired LPS has not been examined with respect to aspiration risk in COPD. The Aims of this study were to investigate the effect of COPD on laryngopharyngeal sensation using Laryngopharyngeal Sensory Discrimination Testing (LPSDT) and to determine whether a relationship between LPS and swallow function in patients with proven COPD exists. Method: 20 patients with proven COPD and 11 control subjects underwent LPSDT utilising an air-pulse stimulator (Pentax AP4000) via a nasendoscope (Pentax FNL10AP). The threshold of laryngopharyngeal sensation was measured by the air pressure required to elicit the laryngeal adductor reflex (LAR). A number of further examinations were also completed for COPD subjects. These included respiratory function testing, self-reporting questionnaire on swallowing ability (SSQ), bedside clinical examination of swallowing (MASA) and endoscopic assessment of swallowing (EAS). Results: subjects with COPD had a significantly higher LAR threshold when compared to their normal healthy counterparts (p<0.001). Positive correlations were identified for the relationships between MASA score and EAS results for presence of laryngeal penetration / aspiration (p<0.04), vallecular residue (p<0.01) and piriform residue (p<0.01). Conclusion: Patients with COPD have significantly reduced mechanosensitivity in the laryngopharynx. Patients with COPD also have impaired swallow function characterised primarily by pharyngeal stasis. These changes may place patients with COPD at increased risk of aspiration.

Introduction Chronic obstructive pulmonary disease (COPD) has emerged as a major policy focus for health systems throughout Western Europe. This reflects the increased prevalence, associated healthcare utilisation and costs of COPD, and the potential to substantially improve outcomes through achieving reductions in smoking. The aim of this PhD was to develop projections for the prevalence, healthcare costs and number of deaths in people with COPD in England and Scotland over a 20-year horizon (i.e. from 2011 to 2030). Methods I undertook a phased programme of work, which began with a systematic review of the published and unpublished literature to identify models that were suitable for estimating and/or projecting the prevalence and disease and economic burden from COPD. This involved searching Medline, Embase, CAB Abstracts, World Health Organization (WHO) Library and Information Services and WHO Regional Indexes, and Google over the time period 1980-2013. The models were then critically appraised for their quality of reporting. From these, I selected the Dutch Model developed by Erasmus University for generating projections. Suitable data sources from both England and Scotland were identified, sourced and carefully processed in order to run the modelling exercises. Rates of incidence and prevalence were calculated using English and Scottish healthcare datasets and population data were obtained from the Office for National Statistics (ONS) and the General Register Office for Scotland (GROS). Relative risks for all-cause mortality among people with COPD were calculated from the Clinical Practice Research Datalink and mortality data were obtained from the ONS and GROS. The Model was thus adjusted to apply to England and Scotland. I then travelled to the Netherlands to work with the developers of the Dutch Model and ran a baseline model and an array of sensitivity analyses with modified inputs to the Model. Finally, my Rotterdam colleagues calculated uncertainty intervals for some of the estimates using probabilistic analysis. Results Using the probabilistic means and uncertainty intervals, in England, the modelled prevalence of diagnosed COPD among males of all ages in 2011 was 1.8% (95% uncertainty interval 1.8-1.9) increasing to 2.0% (1.7-2.1) by 2030. In females, in England, the baseline estimate was 1.8% (1.7-1.8) in 2011 increasing to 2.4% (2.0-2.6) in 2030. In Scotland, the modelled prevalence among males was 1.9% (1.8-1.9) in 2011 and this was projected to stay the same at 1.9% (1.7-2.2) by 2030. In females in Scotland, the estimated prevalence was 2.2% (2.1- 2.3) in 2011 and was projected to increase to 2.5% (2.1-2.7) in 2030.Using the Model I estimated that overall in 2011 there were a total of 952,000 (941,000-966,000) people with diagnosed COPD in England and 106,000 (103,000-110,000) in Scotland and that these numbers would increase to 1,325,000 (1,117,000-1,408,000) in England in 2030 and 125,000 (113,000-136,000) in Scotland in 2030, respectively. The greatest increase in COPD was projected to be in females over 65 years of age in both countries. The total annual direct healthcare costs of COPD in England were projected to increase from £1.60 (95% uncertainty interval 1.18-2.5) billion in 2011 to £2.35 (1.85-3.08) billion in 2030. In Scotland, costs were projected to increase from £170 (128-268) million in 2011 to £210 (165-274) million in 2030. These costs were calculated in terms of 2011 costs without the application of any economic trends (i.e. no annual increase applied for inflation). The number of deaths among people with COPD in England was estimated to be 99,000 (93,000-129,000) in 2011, increasing to 129,000 (126,000-133,000) in 2030. In Scotland there were estimated to be 10,000 (9,000-12,000) deaths in 2011, increasing to 14,000 (13,000-15,000) in 2030. The Dutch Model demonstrated a 39% increase in the number of people with COPD in England and a 17% increase in Scotland between 2011 and 2030. It provided an estimate of a 30% increase in deaths among people with COPD in England and of a 43% increase in Scotland. Overall, there was a projected 46% increase in the direct healthcare costs required to care for people with COPD in England and a 23% increase in Scotland between 2011 and 2030. The reasons for these differences are largely due to higher COPD-related excess mortality in Scotland and to differences in the data used for populating the model in both countries. Conclusions There are likely to be substantial increases in the number of people with COPD, associated morbidity, direct healthcare costs and mortality in both England and Scotland over the next two decades. These increases in numbers will predominantly occur in females over 65 years of age and are likely to have substantial societal impact in terms of organising the health and social care for this frail population.