CT is a powerful method for noninvasive assessment of the lung. Advancements to CT technology have guided the high-resolution structural and functional assessment of lung diseases. This has helped make the transition from characterizing the severity of lung disease to novel phenotyping of disease subtypes. Chronic obstructive pulmonary disease (COPD) is a spectrum of inflammatory lung disease affecting lung parenchyma, airways, and the pulmonary and systemic vasculature. Quantitative CT-based measures have largely focused on quantifying the extent of airway and parenchymal damage with disease. Recently perfusion CT method has been used to assess the pulmonary vascular bed. This technique was used to demonstrate a vascular etiology of smoking-associated centriacinar emphysema (CAE), a subtype of the COPD spectrum. However, technical challenges have limited the transition of this CT method to clinical studies to assess pulmonary vascular physiology. In this thesis, we introduce dual energy CT-perfused blood volume (DECT-PBV) as a novel image-based biomarker to assess peripheral pulmonary vascular dysfunction. Using this technique, we show that smoking-associated pulmonary perfusion heterogeneity, a marker of abnormal blood flow is a reversible process, in the midst of smoking-associated lung inflammation, and not a product of advanced lung disease. We demonstrate, via regional PBV measures and structural measures of the central pulmonary vessels, that the reversibility of pulmonary perfusion heterogeneity is a direct result of increased peripheral (downstream) parenchymal perfusion. We validate our quantitative imaging approach in a unique cohort of early CAE-susceptible smokers using a pharmaceutical intervention to dilate the pulmonary parenchymal vascular bed. The validated DECT approach and our novel DECT imaging findings extend our characterization of the vascular phenotype in inflammatory lung disease and provide a framework for future quantitative imaging studies of the lung to assess early intervention targeted to pulmonary vessels.

Chronic pulmonary diseases include a wide range of illnesses that differ in etiology, prevalence, symptomatology and available therapy. A common link among these illnesses is their impact on patients’ vital function of breathing, high symptom burden and significantly impaired quality of life. This dissertation research evaluates disease severity, symptom burden and health behaviors of patients with three different chronic pulmonary conditions. First, alpha-1 antitrypsin deficiency (AATD) is an inherited condition that typically is associated with an increased risk of early onset pulmonary emphysema. This study examines differences in demographic, health, and behavioral characteristics and compares clinical outcomes and health related behaviors and attitudes between two severe genotypes of AATD - ZZ and SZ. The findings of the study suggest that patients with SZ genotype and less severe form of deficiency report higher number of exacerbations, comorbidities, as well as unhealthy behaviors such as lack of exercise and current smoking. In addition, individuals with the more severely deficient ZZ genotype are more adherent to disease management and prevention program recommendations and maintain a healthier lifestyle than individuals with SZ genotype. Second chronic lung disease examined in this research was chronic obstructive pulmonary disease (COPD), the fourth leading cause of death and second leading cause of disability in the United States. Prevalence and burden of cough and phlegm, two of the most common symptoms of the COPD, were assessed among participants of the COPD Foundation’s Patient-Powered Research Network (COPD PPRN). In addition, association between patient-reported levels of phlegm and cough, clinical outcomes and patients’ quality of life were evaluated. Participants’ quality of life was assessed using Patient Reported Outcome Measurement Information System instrument PROMIS-29. Association between changes in symptom severity over time and patient-reported quality of life were examined. Findings of this study indicated that severity of cough and phlegm were associated with higher number of exacerbations, greater dyspnea, and worsened patient-reported quality of life including physical and social functioning. Improvement in cough and phlegm severity over time was associated with better patient-reported quality of life. Third pulmonary illness described in this dissertation is non-cystic fibrosis bronchiectasis (NCFB), a rare and etiologically diverse condition characterized by dilated bronchi, poor mucus clearance and susceptibility to bacterial infection. Association between presence of Pseudomonas aeruginosa (PA), one of the most frequently isolated pathogens in patients with NCFFB, and disease severity was assessed utilizing enrollment data from the Bronchiectasis and NTM Research Registry (BRR). NCFB disease severity was evaluated using modified versions of validated in large international cohorts instruments, the Bronchiectasis Severity Index (BSI) and FACED. The findings of this study indicate that PA infection is common in NCFB patients, and presence of PA in patients’ sputum is associated with having moderate and high severity of bronchiectasis. In addition, the results of this study suggest that the two severity assessment instruments classify patients with NCFB differently which may be attributed to a greater number of severity markers utilized in the calculation of the BSI compared to FACED. In conclusion, the proposed dissertation aims to enhance understanding of differences in health outcomes between genotypes of AATD within AlphaNet registry, and to guide future health-promoting behaviors. It highlights the burden of common symptoms such as cough and phlegm in patients with COPD within COPD PPRN and their association with patients’ quality of life. In addition, it introduces modified indices of NCFB severity and emphasizes high burden of the disease in patients with presence of PA within the US BRR.

The purpose of the project was to increase awareness about alpha-1 antitrypsin deficiency (AATD) in chronic obstructive pulmonary disease (COPD), particularly among those with a familial history of genetic factor AATD; an additional goal was to understand its relationship to COPD. COPD is the third leading cause of death in the United States, with more than half of COPD patients experiencing significant disabilities. Major causes for COPD include smoking, air pollution, secondary smoke, upper respiratory infections, hereditary factors, occupational factors, environmental factors, and socioeconomic factors. Genetic factors, however, also play a significant role in early onset COPD and in those who smoke and have the genetic factor related to COPD (AATD), symptoms are more severe and exacerbations more frequent. Undiagnosed AATD can result in under treatment and lack of planning for preventing COPD onset and exacerbation in these patients. COPD clients of a local pharmacy (n =31) were invited to complete a Likert survey and given materials on COPD exacerbation prevention and information on AATD. Results indicated that 38.7% of respondents had early onset symptoms, positive family history, and no improvement in symptoms with smoking cessation. The results support that targeting those family members with COPD and providing information on genetic factors for this condition could decrease the frequency and severity of exacerbations. This is in keeping with the health belief model that guided this study in that a perceived risk for harm has the potential to improve the use of preventative health measures in individuals.

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease almost exclusively related to tobacco smoke. COPD symptoms are typical of numerous other ailments making it difficult to diagnose and track. Technological advancements in CT imaging have allowed clinicians and researchers to expand simple structural information to functional information. These advancements have helped to increase the use of CT imaging in the study of smoking related lung disease. In this thesis, we investigate observations from a previous study which suggested pulmonary artery constriction in inflamed lung regions promotes emphysema progression in smokers susceptible to emphysema. We use CT data from a 1 year longitudinal study to evaluate the pulmonary artery dimensions in rapid and non-progressing emphysema subjects. We show that the enlargement of arteries predicts emphysema progression and can be used to identify subjects showing signs of rapid emphysema progression. We attempt to further our ability to use dual energy computed tomography (DECT) for longitudinal and multi-center studies by developing a DECT perfusion blood volume (PBV) imaging protocol with low radiation dose and diluted contrast. We demonstrate that we can reduce radiation dose by up to 34% with the advanced technology of Siemens SOMATOM Force scanner. Finally, we use DECT PBV imaging to compare perfusion heterogeneity in a multi-center study with both GE and Siemens scanners. We show that perfusion heterogeneity is increased in lung regions showing signs of emphysema, but scanner model/manufacturer appears to be the most important factor as data from the GE scanner had greater noise and thus increased perfusion heterogeneity.

<p>SAMMANFATTNING</p><p>Syftet var att undersöka hur personer med Kronisk Obstruktiv Lungsjukdom (KOL) upplever ambulanssjukvårdens omhändertagande och bemötande vid akuta besvär i hemmet och under pågående ambulanstransport. Studien genomfördes som en kvalitativ intervjustudie. Hjärt och lungsjukas förening i Dalarna kontaktades för att förmedla respondenter till studien. Totalt intervjuades fem kvinnor och tre män utifrån de kriterier att de skulle ha diagnosen KOL samt att under de senaste tre åren varit i kontakt med sjuksköterska inom ambulanssjukvården i Landstinget Dalarna. Intervjuerna var semistrukturerade med öppna frågor. Deltagarna i studien fick berätta om sina erfarenheter, upplevelser samt ambulanspersonalens bemötande i omvårdnadssituationer i hemmet och under pågående ambulanstransport. Data analyserades utifrån en kvalitativ innehållsanalys. Resultatet redovisas med fem övergripande kategorier och tretton subkategorier som beskriver deras upplevelse av bemötandet och omhändertagandet. Det framkom i studien att deltagarna upplevt ett lugnt och trevligt bemötande från sjuksköterskan inom Ambulanssjukvården Dalarna. Personerna i studien upplevde även trygghet under vårdsituationen i det akuta sjukdomstillståndet som KOL förorsakat.</p><p>Nyckelord: Bemötande, Omhändertagande, Upplevelse, KOL</p> / <p>ABSTRACT</p><p>The aim was to investigate how Chronic Obstructive Pulmonary Disease (COPD) patients experience the approach and medical care provided by ambulance workers during transportations and domestic emergencies. The investigation was carried out as a qualitative interview study. The heart and lung-disease association in Dalarna was contacted in order to supply respondents to the study. Overall five women and three men were interviewed, based on the criteria that they would all be diagnosed with COPD and that they had, during the past three years, been in contact with a nurse within the ambulance health care in the county council of Dalarna. The interviews were semi structured with open questions. All participants got to tell about their experiences and how they were received, approached and treated by ambulance workers when having domestic emergencies or during ambulance transportations. Data were parsed on the basis of a qualitative analysis. The result is presented in five main categories and thirteen subcategories which describes the participant’s experiences with approaches and treatments. The people investigated felt very secure during treatments given to them in their urgent state of illness caused by COPD. It came to light that participants experienced a composed and pleasant approach from the nurse within the ambulance healthcare in Dalarna.</p><p>Keywords: Attitude, take care of, experience, COPD</p>

<p>Chronic obstructive pulmonary disease (COPD) is in up to 90 % of all cases caused by</p><p>smoking. COPD often has negative effects on circulation, effects that first and foremost can be</p><p>observed as respiratory insufficiency. Reduced function of the right ventricle of the heart is</p><p>common in patients suffering from chronic obstructive pulmonary disease, especially if they</p><p>also have hypoxemi; insufficient levels of oxygen in blood or tissue. The incidence of this</p><p>cardiac complication reduces the survival time. It is possible in chronic obstructive pulmonary</p><p>disease that the pressure in the pulmonary circulation gradually increases resulting in</p><p>pulmonary hypertension followed by a slow adaptation of the right ventricle by hypertrophy of</p><p>the myocardium.</p><p>To investigate a correlation between COPD and pulmonary hypertension COPD patients</p><p>were subjected to spirometry and ultrasound on heart.</p><p>Of 14 examined patients 5 had developed pulmonary hypertension. A correlation between</p><p>obstruction in the COPD- patients and an increase in left ventricular diameter was found.</p><p>DLCO (diffusion capacity) of the lungs is directly connected to PA (pulmonary arterial</p><p>pressure). The lower DLCO, the higher risk to develop pulmonary hypertension. However, we</p><p>could not find a significant correlation between COPD and pulmonary hypertension in this</p><p>study even if most patients had a decreased DLCO.</p>

<p>Most patients are non-adherent with their medication sometimes, i.e. that they do not always use their medicines as prescribed. This might result in both under- and overuse and can lead to therapy failure, resulting in both unnecessary suffering and high costs. Therefore, medication adherence should be as high as possible. </p><p>The aims of this thesis were to investigate the refill adherence to long-term drug treatment, especially for patients with asthma and chronic obstructive pulmonary disease (COPD), and to study treatment gaps for patients with undersupply and drug costs for patients with oversupply. Further aims were to compare different methods for assessing refill adherence and analyse whether the same patient has the same refill adherence pattern to two different chronic drug treatments, i.e. diabetes and asthma/COPD. </p><p>The thesis shows that satisfactory refill adherence (80-120% of the prescribed dose) was 57% for repeat prescriptions with long-term drug treatment; undersupply was 21% and oversupply 22%. Patients with undersupply were without drugs more than half of the prescribed treatment time and the median oversupply for 90-100 days dispensation interval was 28 days. Patients who were exempt from charges had significantly higher oversupply than non-exempt patients and that leads to unnecessary cost for society. The level of satisfactory refill adherence for repeat prescriptions dispensed for asthma/COPD was on average 30%. The same low level was displayed for the elderly, where undersupply was more common than oversupply. </p><p>Assessments of refill adherence during a one-year period gave the same results irrespective of whether the repeat prescriptions were from an individual pharmacy record database or were manually collected at a pharmacy.</p><p>Patients with concomitant use of diabetes and asthma/COPD drugs do not have the same dispensation pattern for both drug types. </p><p>The introduction of patient profiles as a new approach to complement the calculated refill adherence needs to be further studied in larger and more divergent populations. In the future, the new national pharmacy record database in Sweden has opened up for larger studies and will be valuable when studying patterns of drug utilization.</p>

Most patients are non-adherent with their medication sometimes, i.e. that they do not always use their medicines as prescribed. This might result in both under- and overuse and can lead to therapy failure, resulting in both unnecessary suffering and high costs. Therefore, medication adherence should be as high as possible. The aims of this thesis were to investigate the refill adherence to long-term drug treatment, especially for patients with asthma and chronic obstructive pulmonary disease (COPD), and to study treatment gaps for patients with undersupply and drug costs for patients with oversupply. Further aims were to compare different methods for assessing refill adherence and analyse whether the same patient has the same refill adherence pattern to two different chronic drug treatments, i.e. diabetes and asthma/COPD. The thesis shows that satisfactory refill adherence (80-120% of the prescribed dose) was 57% for repeat prescriptions with long-term drug treatment; undersupply was 21% and oversupply 22%. Patients with undersupply were without drugs more than half of the prescribed treatment time and the median oversupply for 90-100 days dispensation interval was 28 days. Patients who were exempt from charges had significantly higher oversupply than non-exempt patients and that leads to unnecessary cost for society. The level of satisfactory refill adherence for repeat prescriptions dispensed for asthma/COPD was on average 30%. The same low level was displayed for the elderly, where undersupply was more common than oversupply. Assessments of refill adherence during a one-year period gave the same results irrespective of whether the repeat prescriptions were from an individual pharmacy record database or were manually collected at a pharmacy. Patients with concomitant use of diabetes and asthma/COPD drugs do not have the same dispensation pattern for both drug types. The introduction of patient profiles as a new approach to complement the calculated refill adherence needs to be further studied in larger and more divergent populations. In the future, the new national pharmacy record database in Sweden has opened up for larger studies and will be valuable when studying patterns of drug utilization.

SAMMANFATTNING Syftet var att undersöka hur personer med Kronisk Obstruktiv Lungsjukdom (KOL) upplever ambulanssjukvårdens omhändertagande och bemötande vid akuta besvär i hemmet och under pågående ambulanstransport. Studien genomfördes som en kvalitativ intervjustudie. Hjärt och lungsjukas förening i Dalarna kontaktades för att förmedla respondenter till studien. Totalt intervjuades fem kvinnor och tre män utifrån de kriterier att de skulle ha diagnosen KOL samt att under de senaste tre åren varit i kontakt med sjuksköterska inom ambulanssjukvården i Landstinget Dalarna. Intervjuerna var semistrukturerade med öppna frågor. Deltagarna i studien fick berätta om sina erfarenheter, upplevelser samt ambulanspersonalens bemötande i omvårdnadssituationer i hemmet och under pågående ambulanstransport. Data analyserades utifrån en kvalitativ innehållsanalys. Resultatet redovisas med fem övergripande kategorier och tretton subkategorier som beskriver deras upplevelse av bemötandet och omhändertagandet. Det framkom i studien att deltagarna upplevt ett lugnt och trevligt bemötande från sjuksköterskan inom Ambulanssjukvården Dalarna. Personerna i studien upplevde även trygghet under vårdsituationen i det akuta sjukdomstillståndet som KOL förorsakat. Nyckelord: Bemötande, Omhändertagande, Upplevelse, KOL / ABSTRACT The aim was to investigate how Chronic Obstructive Pulmonary Disease (COPD) patients experience the approach and medical care provided by ambulance workers during transportations and domestic emergencies. The investigation was carried out as a qualitative interview study. The heart and lung-disease association in Dalarna was contacted in order to supply respondents to the study. Overall five women and three men were interviewed, based on the criteria that they would all be diagnosed with COPD and that they had, during the past three years, been in contact with a nurse within the ambulance health care in the county council of Dalarna. The interviews were semi structured with open questions. All participants got to tell about their experiences and how they were received, approached and treated by ambulance workers when having domestic emergencies or during ambulance transportations. Data were parsed on the basis of a qualitative analysis. The result is presented in five main categories and thirteen subcategories which describes the participant’s experiences with approaches and treatments. The people investigated felt very secure during treatments given to them in their urgent state of illness caused by COPD. It came to light that participants experienced a composed and pleasant approach from the nurse within the ambulance healthcare in Dalarna. Keywords: Attitude, take care of, experience, COPD

The goal of this thesis is to analyze and understand the risks of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer with respect to the provinces of Turkey according to the results of spatial analysis. The insurance sector of the country needs that kind of analysis to make more precise pricing in insurance products. Especially in health and life insurance products, morbidities like COPD and lung cancer may aect the life expectancy as much as the premiums. COPD and lung cancer prevalence may exhibit spatial autocorrelation due to spatial similarity of provinces. Hence understanding of spatial pattern of COPD and lung cancer prevalence may provide better actuarial decisions. In this research, common risk factors of COPD and lung cancer are considered to be tobacco sales, air pollution, urbanization, gross schooling rate, life expectancy, median age and GDP per capita of the provinces. The spatial patterns of these factors in Turkey as well as their correlations to COPD and lung cancer prevalence are explored in this study. The raw data of the morbidities (COPD and lung cancer) are collected from the Social Seiv curity Institution (SGK) and the useful data are selected in these raw data. The data of the independent variables are collected and derived from the Turkish Statistical Institute (TUIK) and Tobacco and Alcohol Market Regulatory Authority (TAPDK). First of all, COPD prevalence ratios and lung cancer prevalence ratios are grouped by 81 provinces of Turkey and every morbidity is separated by gender. Then, it needs to be decided the variables which define prevalence of COPD and that of lung cancer. Age, gender, socio-economic status, urbanization, schooling rate, life expectancy, tobacco sales and air quality may be some of the random variables which are categorized by provinces for both morbidities. After data collection spatial analysis is applied with visualization, explanatory analysis and modeling by using Geographic Information Systems (GIS). In visualization, general spatial patterns are identified for morbidities and variables. In explanatory analysis part, proximity matrices are used to evaluate Moran&rsquo / s I values for understanding the spatial autocorrelation. Then, these Moran&rsquo / s I values are used for plotting correlograms in order to follow the spatial dependence better. After identifying spatial dependence of the variables, Ordinary Linear Regression and Spatial Regression models are established and compared. Finally, as a result of those findings in the analysis, actuarial risk assessments are found for both two morbidities with respect to provinces and gender. The risk assessments are mapped and compared with the explanatory variables in the models which are found in the previous part and the relations between risks and variables are observed. As a result, the parameters show spatial autocorrelation which means that / financial risk assessments of COPD and lung cancer should be taken into account when deciding the pricing of some actuarial products such as health insurance. Generally, spatial correlation is ignored in this kind of calculations, but due to the high autocorrelation the results may indicate serious change. From the actuarial perspective, the results of the analysis are suggested to be used in health insurance premium pricing. Since the analysis could not have been made on the basis of individuals, and financial burden of morbidities for insurance companies are not given clearly, it is not possible to calculate any health insurance product premium, but it is more appropriate to consider the importance of these risk results in the calculations of health insurance products.