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Background: Chronic obstructive pulmonary disease (COPD) is a long term condition characterised by progressive narrowing of the airways and premature ageing of the lungs. By 2020, it is estimated to be the third biggest cause of death in the UK, after heart disease and stroke. COPD imposes a large financial burden on health services and is among the most costly diseases in the UK. Inhalation therapies are central to the management of COPD; they include pressurised metered dose inhalers (pMDIs), dry powder inhalers (DPIs), and nebulisers. Although, findings from previous studies reveal suboptimal use and a wide range of problems with inhaler handling among COPD patients, very little is known about how and why problems arise. Therefore, the aim of this study was to examine how older patients made decisions regarding the use of inhalers especially when combination of inhalation devices were used at home, how those decision and difficulties contributed to suboptimal outcomes and treatment failures. Method: A cross-sectional study design using semi-structured face to face interviews, observations of inhalation device users, with patients in their own homes, was conducted with 46 patients. Based on previous studies among patients with respiratory diseases, it was anticipated that the sample of 60 patients would enable us to achieve the study objectives and would be able to reach saturation level, additionally, this sample size was achievable within the time and resources of the study. Patients were recruited from Pinn Medical Centre and identified by the staff through patients’ medical notes. All COPD patients, registered at Pinn Medical Centre, and prescribed a combination of at least two different inhalation devices were invited to participate. The practice population includes patients of different ages, duration and experience of inhalation therapies, ethnicity and disease severity. The data were audio recorded for verbatim transcription. Qualitative and quantitative analysis were conducted using Nvivo and SPSS programme, respectively. The study was approved by Newcastle & North Tyneside 2 Research Ethics Proportionate Review Sub-Committee. Results: 46 patients have been interviewed. Male (N=24) and female (N=22), the mean age was 77 years (63-100). Two-thirds of participants (N=31), 67%, used a combination of both pMDIs and DPIs, 10 participants (22%), used a combination of DPIs, three participants (7%) used three different kinds of inhalation devices (pMDIs, DPIs, and nebulisers), whereas the least used group was a combination of pMDIs with just two participants (4%). Differing expectations of treatment (e.g. regarding immediacy and extent of response), and preferences for different type of device were expressed. Treatment failures were of concern to patients who had experienced multiple episodes of exacerbation. The study identified factors which were potential contributors to treatment failures. These included adherence decisions which were influenced by their beliefs about inhalation therapies and concerns of side effects, especially with the long term such as steroids, and willingness to use devices in public. The study findings also revealed practical and technical issues in manipulation and cleaning the inhalation devices especially with the use of DPIs. Discussion and Conclusion: Treatment failures are a major concern for COPD patients. Most patients experienced problems with inhalation devices used at home. To improve treatment, continuous education and follow up needs to be done for COPD patients in order to provide all the necessary assistance in the future tailored to each patient who is at high risk of treatment failures and/or experiencing problems.

In recent years, significant conceptual advances have helped to formulate a broad scheme of the mechanisms which regulate ventricular function. Likewise, methodological advances now enable a wide range of haemodynamic measurements to be made in human subjects, with reasonable precision and relative ease. It has thus become possible to relate changes in several haemodynamic variables recorded simultaneously. Although it is still not feasible to estimate the functional competence of the left ventricle (or the heart as a whole) in absolute terns, the qualitative changes can now be assessed with greater confidence. The studies reported here were designed to investigate the changes in left ventricular performance in man during dynamic exercise and following the administration of two pharmacological agents used in clinical practice. The two pharmacological agents, morphine and propranolol, were selected for different reasons. Morphine was chosen in order to determine the circulatory effects that may be attributable to the drug and thereby provide, if possible, a rational basis for its use in the treatment of acute left ventricular failure. The therapeutic efficacy of morphine in this disorder is widely acknowledged, but to date no attempts, other than the one reported here, seem to have been made, (or at least none reported) to delineate the precise mode of action of this drug in the treatment of acute left ventricular failure. A detailed investigation was, therefore, designed to study the haemodynamic changes, with particular reference to left ventricular function, following an intravenous injection of morphine in therapeutic amounts. The report on this study forms the subject matter of Chapter IV. The other pharmacological agent used was propranolol, which is an adrenergic JS-receptor blocking agent. It is generally agreed that the sympathetic nervous system (and the adrenal medulla) dominates in the regulation of the cardiovascular response during dynamic exercise. Since the sympathetic influence (both chronotropic and inotropic) on the heart is mediated through ^-receptors (Ahlquist, 1948), it was felt that with the help of propranolol it should be possible to assess the importance of the sympatho-adrenal system in the regulation of cardiac performance during dynamic exercise. A study was, therefore, designed to investigate the haemodynamic changes during supine leg exercise before and after ^-adrenergic block with propranolol. The report on this investigation is presented in Chapter V. An assessment of the changes in left ventricular performance rg supine leg exercise, which has been used as the standard physiological stimulus, was also undertaken in the course of the study reported in Chapter V. In Chapter I a summary of the present concepts (and some controversies) regarding the regulation cf left ventricular performance is presented. Also Included in this chapter is additional information relevant to the understanding of left ventricular function and the methods that may be used to assess this. A detailed critique of the methods used is given in Chapter II. Since it was not feasible to measure either end-diastolic fibre length or end-diastolic pressure in the left ventricle, the mean pulmonary wedge pressure has been used as an indirect estimate of left ventricular end-diastolic pressure and hence end-diastolic fibre length. It was felt necessary to determine the confidence with which the mean pulmonary wedge pressure could be used as an estimate of left ventricular end-diastolic pressure. To this end, therefore, another study was designed and the report on this is presented in Chapter III. A brief comment on the statistical methods used is given in the appendix. Since this thesis is being presented In two volumes, it was thought best, for ease of reference, to Include all the tables and references in the companion volume.

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