京都大学 / 新制・論文博士 / 博士(医学) / 乙第13555号 / 論医博第2284号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森信 暁雄, 教授 中本 裕士, 教授 永井 純正 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Problém: Obstrukce dýchacích cest a průtoková limitace, způsobená chronickou obstrukční plicní nemocí (CHOPN) nebo astma bronchiale (AB), může způsobit změny tvaru, pozice a pohybů bránice v důsledku zvýšení plicních objemů. Hypotézy: U pacientů s obstrukčním respiračním onemocněním se bude funkce bránice lišit oproti kontrolní skupině zdravých jedinců, což se projeví na jejím postavení a rozsahu pohybu. Existuje vztah mezi plicními funkcemi a polohou a pohyby bránice. Cíl: Cílem práce bylo zjistit, zda pozice, tvar a pohyby bránice u ležících pacientů s průtokovou limitací během maximálních dechových a posturálních manévrů se liší od tvaru, pozice a pohybů bránice za stejné situace u jedinců bez patologie respiračního systému. Zkoumali jsme rozdíly mezi pacienty s CHOPN, pacienty s AB a zdravými jedinci. Cílem bylo také stanovit tyto vztahy v kontextu vážnosti průtokové limitace, resp. obstrukce dechových cest. Metodika: Soubor tvořily 3 skupiny probandů, celkem 31 dospělých: 10 jedinců s klinicky stabilním AB (5 žen a 5 můžů), 11 jedinců s klinicky stabilním, středně těžkým CHOPN (7 mužu a 4 ženy) a kontrolní skupinu tvořilo 10 zdravých jedinců (5 mužů a 5 žen). Všichni probandi podstoupili komplexní měření plicních funkcí a kardiopulmonální zátežové vyšetření. Bránici jsme vyšetřovali pomocí...

Lung cancer remains the leading cause of cancer deaths in the United States despite public health campaigns aimed at reducing its rate of mortality. Kentucky is the state with the highest lung cancer incidence and mortality. This study aims to assess the impact of misclassification of cause of death from Lung Cancer in Kentucky for the period 1979 to 2002. We will examine the potential competing classification of death for two other smoking-related diseases, Chronic Obstructive Pulmonary Disease (COPD) and Emphysema. Age-adjusted mortality rates for these diseases for white males were obtained from the National Center for Health Statistics. There was little evidence that any misclassification between COPD or Emphysema mortality rates was in agreement with the rising lung cancer rates in Kentucky. The long-term increase in lung cancer mortality in Kentucky is likely because of a combination of risk effects between smoking and other risk-factors for this disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder and the third leading cause of mortality. In this thesis we performed a clustering analysis of four specific immune cells in the GSE136831 dataset, using the default recommended parameters of the Seurat package in R, and obtained 16 subclasses with various COPD and cell-type proportions. Clusters 3, 7 and 9 had more pronounced independence and were all composed of macrophage-dominated control samples. The results of the pseudo-time analysis based on Monocle 3 package in R showed three different patterns of cell evolution. All started with a high percentage of COPD states, one ended with a high rate of Control states, and the other two still finished with a high percentage of COPD states. The results of differentially expressed gene analysis corroborated the existence of finer clusters and provided support for their rational categorization based on the similar marker genes. The gene ontology (GO) enrichment analysis for cluster 0 and cluster 6 provided feedback on enriched biological process terms with significant and unique characteristics, which could help explore latent novel COPD treatment directions. Finally, some top-ranked potential pharmaceutical molecules were searched via the connectivity map (cMAP) database. / Graduate / 2023-08-12

Bakgrund: Kronisk obstruktiv lungsjukdom (KOL) är en folksjukdom, sompåverkar kroppen både fysiskt och emotionellt. Enligt världshälsoorganisationenberäknas sjukdomen öka och bli den tredje största dödsorsaken år 2030. Syfte:Syftet med litteraturstudien var att belysa patienters upplevelser av att leva medKOL genom frågeställningen; hur upplevs det emotionellt av att leva med KOL.Metod: En litteraturstudie bestående av tio kvalitativa artiklar genomdatabassökning i CINAHL, Medline och PubMed. Resultat: Det framkom en radolika känslor i relation till olika upplevelser. Fyra huvudkategorier identifieradestill: upplevelser av fysiska begränsningar, upplevelser av att leva med syrgas,upplevelser av minskad självständighet och betydelsen av sociala relationer. Denförsta kategorin delades in i en underkategori som var upplevelser av att leva meddyspné. Slutsats: Att leva med KOL kan upplevas med varierande emotioner. Detär viktigt vid omvårdnad av dessa patienter att ha en förståelse för derasupplevelser. / Background: Chronic obstructive pulmonary disease (COPD) is a common disease that affects the body both physically and emotionally. According to the World Health Organization it is estimated that the disease will increase in number and become the third largest cause of death in 2030. Aim: The aim of this literature review was to elucidate patients' experiences of living with COPD through the question of issue; how it is perceived emotionally by living with COPD. Method: A literature review consisting of ten qualitative articles through database search in CINAHL, Medline and PubMed. Results: There emerged a range of emotions in relation to different experiences. Four main categories were identified: experiences of physical limitations, experiences of living with oxygen therapy, experiences of reduced independence and significance of social relationships. The first category was divided into a subcategory that was experiences of living with dyspnoea. Conclusion: Living with COPD can be experienced with varying emotions. It is important when caring for these patients to have an understanding of their experiences.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and asthma constitute the majority of the pulmonary disease burden in the United States. Various kinds of inhalers are used for treating both these conditions, and Medicare is the biggest payer for them. We analyze the trend in prescriptions and associated expenses of various inhaler prescriptions from 2014 to 2018 using the Medicare part D database. METHODS: Medicare part D data is analyzed for the years 2014-2018. Inhalers are grouped based on their drug class. The number of beneficiaries and the associated expenses for each inhaler and the groups were calculated separately and analyzed using statistical software. RESULTS AND CONCLUSION: Some 85 million beneficiaries received inhalers through Medicare part D over the four years. Medicare spent 50.5 billion US dollars on these prescriptions, which showed an increase of 130% users and 128% expenditure over the four years. Medicare's expense for inhaler prescriptions is growing and is expected to increase even more in the near future.

Chronic cardiovascular and pulmonary diseases are prevalent in the US home health population. Heart failure and chronic obstructive pulmonary disease are both chronic and terminal, but they are not always perceived as serious illnesses with imminent death. Therefore, they provide a context for advance care planning that is distinct from the diagnostic contexts of cancer, end-stage renal disease, or dementia. Advance care planning is defined as a process that supports adults at any age or stage of health in understanding and sharing their goals, values, and preferences about future medical care, including the designation of a surrogate decision-maker. This study tests the hypothesis that US home health agencies with higher percentages of patients with chronic cardiovascular and pulmonary conditions have less robust advance care planning protocols. The Spearman correlation coefficient was r = 0.22 (S = 74684, P =.025, 1-tailed), which was statistically significant and an unexpected finding. The greater percentage of patients with chronic cardiac and pulmonary diagnoses in an agency, the more robust the advance care planning protocol was. This supports our previous findings and existing literature indicating that agencies may be using exacerbation events marked by acute care use as opportunities to initiate or repeat advance care planning.

Background: Blood flow restriction training (BFRT) is an effective way of training that enables training with low external load while receiving similar effects to high load training. The lack of knowledge of BFRT for people with chronic obstructive pulmonary disease (COPD) or heart failure (HF) led to the making of this scoping review.  Objective: This scoping review aims to map the existing knowledge, effects, safety, and feasibility of BFRT for people with COPD or heart failure HF. Method: The review followed PRISMAs structure for scoping review. Selection involved title and abstract screening, followed by full text analysis and peer-review by both authors.  Results: A wide variety of study designs was included in this scoping review. Of 11 included studies all were original intervention studies-, whereof 8/11 studies were focused on HF. A large majority of participants were male. Training methods used in intervention studies varied from exercises like leg extensions, leg press and cycling, all while using vascular blood flow restriction. All studies followed different training protocols. The reported outcomes indicated promising improvements like increased functional exercise capacity, muscle strength, reduced symptom burden, and several positive physiological changes for both people with COPD and HF. Some concerns remain regarding the safety of BFRT, but no serious adverse events were reported directly linked to BFRT.  Conclusion: With many reported improvements, BFRT could be a safe and feasible alternative rehabilitation method for people with COPD or HF. Furthermore, with minimal reported adverse events, the method appears safe for both groups. Despite this, the included studies all had small sample sizes, so more high-quality studies with larger sample sizes are needed to give a better understanding on BFRTs effects on both short- and long term. Better studies including females are also needed.

Many respiratory patients misuse their inhaler. Although training improves their inhaler technique, patients do forget the correct inhaler use with time. In the current work, three clinical studies investigated novel tools designed with feedback mechanisms to ensure patients use the correct inhalation method when using their inhaler. Research Ethics Committee approval was obtained and all the participants signed an informed consent form. In the first study, the recruited asthmatic children (n=17) and adults (n=39) had their metered dose inhaler (MDI) technique assessed. Those who attained the recommended inhalation flow rate (IFR) of < 90 l/min through their MDI formed the control group. Whilst those who had a poor MDI technique with an IFR ¿ 90 l/min were randomized into either the verbal counselling (VC) group; or the 2ToneTrainer (2TT) group that, in addition to the verbal training, received the 2ToneTrainer MDI technique training device equipped with an audible feedback mechanism of correct inhalation flow. All the participants were assessed on two occasions (6 weeks apart) for their inhalation flow rate, asthma control and quality of life. The study showed that the 2ToneTrainer tool was as efficient as verbal training in improving and maintaining the asthmatic patients¿ MDI technique, particularly using the recommended slow inhalation flow through the MDI. Although statistically insignificant, potential improvement in quality of life was demonstrated. The 2ToneTrainer tool has the advantage of being available to the patients all the time to use when they are in doubt of their MDI technique. In the second research study, the inhalation profiles of asthmatic children (n=58) and adults (n=63), and of COPD patients (n=63) were obtained when they inhaled through the novel Spiromax dry powder inhaler (DPI) which was connected to an electronic pressure change recorder. From these inspiratory profiles; the peak inhalation flow, inhalation volume and inhalation acceleration rate were determined. The variability (23% - 58%) found in these inhalation profile parameters among various patient groups would be expected in all DPIs. The effect of the inhalation acceleration rates and volumes on dose emission characteristics from DPIs should be investigated. Attention, though, should be paid to the patients¿ realistic inhalation profile parameters, rather than the recommended Pharmacopoeial optimal inhalation standard condition, when evaluating the in-vitro performance of DPIs. Finally, in preschool asthmatic children, the routine use of the current AeroChamber Plus spacer (n=9) was compared with that of a novel version; the AeroChamber Plus with Flow-Vu spacer (n=10) over a 12-week period. The Flow-Vu spacer has a visual feedback indicator confirming inhalation and tight mask-face seal. The study showed that the new AeroChamber Plus with Flow-Vu spacer provided the same asthma control as the AeroChamber Plus in preschool children and maintained the same asthma-related quality of life of their parents. However, the parents preferred the new Flow-Vu spacer because its visual feedback indicator of inhalation reassured them that their asthmatic children did take their inhaled medication sufficiently.

Due to the safety concerns surrounding viral vectors, non-viral alternatives are desirable for fulfilling the aim of gene therapy. In this project gel mobility shift assays demonstrated how cross-linked PVA nanoparticles successfully form complexes with plasmid DNA and are of a size and charge that should, theoretically, permit endocytosis by eukaryotic cells. However, during in vitro transfection studies no reporter (GFP) gene expression was noted. The collective evidence from electroporation, fluorescent-DNA-tagging, Lipofectin® or calcium phosphate chimeric and chloroquine experiments suggest that a lack of cell uptake is responsible. Nevertheless, the same cross-linked PVA nanoparticles have been shown to exhibit much promise in the field of drug delivery during in vitro experiments, even when used to target the same cell types as those used during transfection studies. Nanagel®, a cross-linked PVA nanoparticle containing budesonide, achieved higher levels of drug delivery than a commercially available form of the same drug (Pulmicort®) after 1 or 24 hours drug exposure. Furthermore, by measuring superoxide production during a stimulated respiratory burst, the budesonide delivered to cells appears fully functional and significantly more effective than Pulmicort® in preventing the formation of reactive oxygen species, following a 24-hour pre-treatment period with the formulation. These findings have exciting possibilities for the use of hard-to-dissolve corticosteroids in the treatment of respiratory disease. / AGT Sciences Ltd