Abstract Pulmonary fibrosis, lung cancer and chronic obstructive pulmonary disease (COPD) are severe diseases and common death causes worldwide. Due to the lack of an effective therapy, the investigation of cell biological mechanisms behind these diseases is essential. An activation of stromal cells, including myofibroblasts, is a main feature found in the pathogenesis of lung diseases. Myofibroblasts express alpha-smooth muscle actin (α-SMA), have specific ultrastructure, produce extracellular matrix proteins and possess contractile capacity. Detailed structure and function of myofibroblasts and their roles in healthy and diseased lung are not yet wholly understood. The investigation of the myofibroblasts may further offer novel tools for the acquisition of proper diagnosis, prognosis and medical treatment. The study aimed to characterize the ultrastructural, functional and disease-specific features of stromal cells, particularly myofibroblasts, in interstitial and malignant lung diseases. The functional properties evaluated here were differentiation, invasive and contractile properties. The study material included in vitro stromal cells cultured from bronchoalveolar lavage (BAL) fluids. The appearance and location of myofibroblasts in different lung compartments of non-smokers and the COPD-patients were examined in vivo. The cells were investigated by light and electron microscopy. The α-SMA expression was analysed by gene or protein assays. The study demonstrated that stromal cells could be cultured from diagnostic BAL fluid samples and lung tissues. Cultured cells were a mixture of fibroblasts and myofibroblasts. A small proportion of cells exhibited progenitor-like features. Myofibroblasts revealed differential features in electron microscopy and invasive or contractile assays. When studying tissues from healthy and COPD lungs, myofibroblasts were located both in alveoli and airways. In alveoli myofibroblasts localized in widened alveolar tips which were newly described structures and locations of myofibroblasts in healthy and diseased lung. The amount of myofibroblasts in large airways, but not in peripheral lung, was increased in COPD. We concluded that myofibroblasts have several locations in normal and COPD lung, which suggests a function both in pulmonary regeneration and the pathogenesis of COPD. Smoking altered the phenotype of myofibroblasts regardless of its origin. / Tiivistelmä Keuhkofibroosi, keuhkosyöpä ja keuhkoahtaumatauti (COPD) ovat kansallisesti ja maailmanlaajuisesti yleisiä ja kuolemaan johtavia sairauksia. Taudinmääritys ja hoito ovat vaativia, eikä kaikille potilaille ole parantavaa hoitoa. Keuhkosairauksien kaikkia solubiologisia mekanismeja ei vielä tunneta, mikä on yksi syy lääkekehityksen ongelmiin. Interstitiaaleissa ja pahanlaatuisissa keuhkosairauksissa esiintyy paljon aktiivisia sidekudossoluja, kuten muuntuneita fibroblasteja eli myofibroblasteja. Ne tunnistetaan hienorakenteesta, jota voidaan tutkia elektronimikroskoopilla. Myofibroblastit ilmentävät myös solun sisäistä sileän lihaksen alfa-aktiinia (α-SMA), tuottavat sidekudoksen proteiineja ja kykenevät supistumaan. Myofibroblastien hienorakenteen ja toiminnan selvittäminen voi antaa lisätietoa keuhkosairauksien syntymekanismeista, jolloin diagnostiikkaa, ennustetta sekä hoitoja voidaan arvioida paremmin. Väitöskirjassa selvitettiin myofibroblastien hienorakennetta ja toimintaa eri keuhkosairauksissa. Tutkitut toiminnalliset ominaisuudet olivat erilaistumispotentiaali, invasiivisuus ja supistumiskyky. Sairauksien kliinistä käyttäytymistä ja potilaiden tupakointitottumuksia tarkasteltiin suhteessa solubiologiatason havaintoihin. Tutkimusmateriaali kerättiin taudinmäärityksen yhteydessä interstitiaalisia keuhkosairauksia, keuhkoahtaumatautia tai keuhkosyöpää sairastavilta potilailta. Tulosten mukaan bronkoalveolaarihuuhtelunesteestä (BAL) ja keuhkokudospaloista voidaan soluviljelymenetelmin kasvattaa ja ylläpitää solulinjoja. Viljellyt solut muodostivat sekasolupopulaatiota, joissa esiintyi pääosin fibroblasteja ja vaihteleva osuus myofibroblasteja. Pieni osa soluista ilmensi kantasoluille tyypillisiä piirteitä. Myofibroblastien tyyppipiirteet ja toiminnalliset ominaisuudet vaihtelivat taudeittain. Kudoksessa myofibroblasteja ilmentyi sekä keuhkorakkuloissa että ilmateissä. Keuhkorakkulatasolla myofibroblastit sijoittuivat irrallisten alveoliseinämien laajentuneisiin päihin, joita ei ole aiemmin tutkittu tieteellisessä kirjallisuudessa myofibroblastien yhteydessä. Keuhkoahtaumatauti ja tupakointi vähensivät näiden rakenteiden määrää perifeerisessä keuhkossa, kun taas suurissa ilmateissä keuhkoahtaumatauti lisäsi myofibroblasteja. Päättelimme, että myofibroblastit edistävät keuhkoahtaumataudin syntyä isoissa ilmateissä, mutta saattavat osallistua keuhkojen korjaukseen keuhkorakkuloissa ja pienissä ilmateissä.

Title: Kinesiophobia, her predictors and consequences in selected chronic diseases - theoretical review Objectives: To review the issue of the occurrence of kinesophobia in various chronic diseases and to identify its predictors. Methods: The diploma thesis was prepared in the form of a literature search using electronic resources of the National Medical Library, the Central Physical Education Library and professional databases Pubmed, EBSCO, SCORPUS, Medline, Web of Science. The first half of the work summarized all the theoretical background and knowledge of kinesophobia and selected chronic diseases. The second half was focused on the processing of the issue of kinesophobia in selected chronic diseases and on the mapping of their predictors. Results: Based on the processing of available resources dealing with the issue of kinesophobia in selected chronic diseases, a comprehensive overview was created. In patients with chronic low back pain, high levels of kinesophobia were most often associated with chronic pain, functional impairment associated with the disease, obesity, low levels of education, and emotional states (anxiety, depression). In coronary heart disease, high levels of kinesophobia were associated with a lack of understanding of the need for physical activity, social support,...

Lungs transplantation is a solution for the end stage of pulmonary disease after other therapeutic possibilities that the modern medicine has to offer have been exhausted. The main objective of this thesis is to show postoperative patient care after lung transplantation in the department anesthesiology and resuscitation. A highly specialized complex care and cooperation of various fields is needed. Nurses who take care of these patients must be experienced and skillful. They also need to manage well the nursing care for patients in sedation as well as fully conscious patents. It is also needed that the nurses are acquainted with specialized methods of hemodynamics measurements, administration of nitrous oxide and operation of extracorporeal membrane oxygenation machine. They need to know well the drugs that are being administered. The thesis summarizes anatomy and physiology of respiratory system, it deals with lung disease and their symptoms which most often lead to lung transplantation. Finally, the thesis describes the development of lung transplantation from its beginning to the present including the number of cases of lung transplantation per year. The last chapter of the theoretical part also shows indication, contraindication and the main principles of patient care that is given prior to and...

Bakgrund: Kroniskt obstruktiv lungsjukdom (KOL) är ett folkhälsoproblem och den tredje vanligaste dödsorsaken i världen. KOL påverkar andningsvägar och lungor och leder till begränsning av luftflödet in och ut ur lungorna. Den främsta orsaken till sjukdomen är rökning. Sjukdomen påverkar patientens välbefinnande negativt och leder till lidande. Syftet:  Syftet var att beskriva patienters upplevelser av att leva med kroniskt obstruktiv lungsjukdom (KOL).  Metod: En litteraturöversikt med tio vetenskapliga artiklar och kvalitativ innehållsanalys. Resultatet: Tre kategorier och åtta subkategorier identifierades. De tre kategorierna var fysisk påverkan, psykisk påverkan och upplevelser av vård på sjukhus och i hemmet. Subkategorierna var trötthet och andfåddhet, att anpassa sig efter allt, måltidsupplevelse, rädsla, ångestframkallande känslor, isolering, patientupplevelser av sjukhusvistelse och patientupplevelser av att få vård från sina närstående. Slutsats: Patientupplevelser av KOL måste beaktas för att utveckla kunskapen om sjukdomen för denna patientgrupp. Psykiska och fysiska symtom såsom dyspné, ångest, rädsla för kvävning och begränsningar relaterade till trötthet och andningssvårigheter är den gemensamma upplevelsen som patienter med KOL beskrev. Att sjuksköterskan har tillräckligt med kunskap om sjukdomen är viktigt eftersom det skapar förtroende för behandlingen och ger trygghet till patienten. / Background: Chronic obstructive pulmonary disease (COPD) is a public health issue and the third leading cause of death worldwide. COPD affects the airways and lungs and leads to restriction of air flow in and out of the lungs. The main cause of the disease is smoking. The disease affects the patients’ well-being negatively and leads to suffering.  Aim: The aim was to describe the patients' experiences of living with chronic obstructive pulmonary disease (COPD). Method: A literature review with ten scientific articles and qualitative content analysis. Result: Three categories and eight subcategories were identified. The three categories were physical impact, psychological impact, and experiences of care in hospital and at home. Subcategories were fatigue and shortness of breath, adjusting to everything, meal experience, fear, anxiety-provoking emotions, isolation, patient experiences of hospitalization and patient experiences of receiving care from their relatives.  Conclusion: The patient experience of COPD must be taken into account in order to develop knowledge about the disease for this patient group. Mental and physical effects such as dyspnea, anxiety, fear of suffocation and limitations related to fatigue and breathing difficulties are the common experiences described by patients with COPD. That the nurse has sufficient knowledge about the disease is important because it creates confidence in the treatment and gives security to the patient.

Bakgrund KOL är en global folksjukdom, och patienterna tillhör en patientgrupp som är frekvent inom hälso- och sjukvården. Dyspné, ångest och/eller depression tillhör de mest frekventa symtomen på KOL och kan ha en påverkan på livskvalitén. Då sjukdomen är kronisk innebär det att vårdfokus ligger i att underlätta symtom och förebygga snabb progression. En av de mer vanliga omvårdnadsåtgärderna vid KOL är fysisk aktivitet. Då detta är en egenvårdsåtgärd ställer det både vissa krav på patienten men även på sjuksköterskans förmåga att främja dessa åtaganden och vara behjälplig patienten med sin expertis. Syfte Syftet var att belysa sambandet mellan fysisk aktivitet och livskvalité hos patienter med KOL.​ Metod En systematisk litteraturöversikt baserad på resultatet av 10 artiklar med kvantitativ metod, vars innehåll analyserades och kvalitetsgranskades. Artiklarnas resultat jämfördes och resulterade i tre övergripande teman för vilket resultatet baserades på. Resultat I resultatet framkom tre utmärkande huvudteman gällande fysisk aktivitet och dess samband med livskvalitén hos personer med KOL. Dessa tre belyste olika träningsformers påverkan på livskvalitén, träningsintensiteten betydelse för livskvalitén och dem positiva bieffekterna som träningen innebar och deras samband med en högre livskvalité. Slutsats Slutsatsen av litteraturöversikten visar att fysisk aktivitet hade ett positivt samband med livskvalitet hos KOL-patienter. Sambandet är oberoende av intensitet och träningsmetod. Främjande av fysisk aktivitet kan förbättra inte bara livskvaliteten, utan även andra KOL-relaterade symtom som depression, ångest och dyspné. KOL anses fortfarande som en lågstatussjukdom och patienterna upplever stigmatisering och skam. Detta talar för att kontinuerliga utbildningar för sjuksköterskor och vårdpersonal är avgörande för att kunna erbjuda personcentrerad vård och stödja patienterna mot en mer aktiv livsstil, vilket kan mildra negativa konsekvenser i patienternas vardag. / Background COPD is a global public health issue, and the patients belong to a group that frequently seeks healthcare services. Dyspnea, anxiety, and/or depression are among the most common symptoms of COPD and can impact the quality of life. As the disease is chronic, the focus of care is on alleviating symptoms and preventing rapid progression. One of the more common nursing interventions for COPD is physical activity. As this is a self-care measure, it places certain demands on the patient as well as on the nurse's ability to promote these commitments and assist the patient with their expertise. Aim The aim of this study was to illustrate the relationship between excersise and quality of life in patients living with COPD. Method A systematic literature review based on the findings of 10 articles using a quantitative approach, whose content was analyzed and quality-reviewed. The results of the articles were compared, resulting in three overarching themes upon which the findings were based. Results In the results, three distinctive main themes emerged, regarding physical activity and its correlation with the quality of life in individuals with COPD. These three highlighted the impact of different forms of exercise on the quality of life, the significance of exercise intensity for the quality of life, and the positive side effects that exercise entailed and their connection to higher quality of life. Conclusions The conclusion of the literature review indicates that physical activity has a positive correlation with the quality of life in COPD patients. This association is independent of intensity and training method. The study emphasizes that promoting physical activity can improve not only the quality of life, but also other COPD-related symptoms such as depression, anxiety, and dyspnea. COPD is still considered a low-status disease, and patients experience stigma and shame. This emphasizes the need for continuous education for nurses and healthcare professionals to provide person-centered care and support patients toward a more active lifestyle, which can alleviate negative consequences in their daily lives.

Kroniskt Obstruktiv Lungsjukdom (KOL) är en sjukdom som mellan 500 000 och 700 000 människor beräknas lida av i Sverige idag och det är en sjukdom som blir allt vanligare. Enligt nya riktlinjer ifrån Socialstyrelsen kan daglig träning i form av styrka och kondition ge en ökad livskvalité för personer som är sjuka i KOL. Det är dock svårt att få patienterna till daglig fysisk träning, en av anledningarna är att patienterna har svårt att andas vilket leder till ångest vid till exempel pulshöjning. Vi ställer oss därmed frågan om patienterna med hjälp av en applikation till smartphones som har inslag av spelifiering skulle kunna öka sin motivation till daglig träning.Arbetet inleds med en förundersökning där det utförs en litteraturstudie, en analys av fyra olika motivations-applikationer samt intervjuer med fem stycken sjuksköterskor och sjukgymnaster som arbetar med KOL-patienter inom primärvården. Detta görs för att få ett underlag om vad för funktionalitet och vilken design applikationen bör ha för att tilltala sin målgrupp. Utifrån det underlaget utarbetas en applikation som testas på sex personer genom användartester med efterföljande intervjuer.Resultat visar på att det framtagna konceptet är intressant och de tillfrågade anser att applikationen kan öka deras motivationen till daglig träning. Graden av spelifiering i applikationen upplevs motiverande och kul och att det finns utrymme för vidareutveckling av detta. / Chronic Obstructive Pulmonary Disease (COPD) is a disease that is estimated to affect 500 000 to 700 000 people in Sweden today and it is a disease that keeps becoming more common. According to new guidelines from The National Board of Health and Welfare daily exercise give increased quality of life to a person ill from COPD. It is however difficult to get these people to exercise daily due to the fact that their breathing difficulties increase during training. So we want to examine the possibilities to increase these peoples motivation to enhance their daily exercise with a mobile application containing elements of gamification.With that in mind we start of by performing a literature study, an analysis of four motivational applications and interviewing five people who works with COPD in the primary care units. The goal of this is to get a feel of what functionality this kind of application should contain. We then develop an application and test it on six people to get an indication whether the design works or not. The tests are followed by an interview of each of the testers. What we find is that the application as a concept works very well. The interviewed people think it is an interesting solution to increase their daily exercise. The degree of gamification that the application contains is perceived to be motivational and fun.

Background Chronic Obstructive Pulmonary Disease (COPD) is a common disease affecting people worldwide, with smoking being the most common cause. COPD affects the airways and presents symptoms such as breathlessness and coughing. The nurse's role is to identify and understand the patient's unique needs to provide adequate help and support.   Aim The aim was to describe patients’ experiences of living with COPD.  Method A litterature review was conducted based on eleven qualitative scientific articles. Articles searches were obtained from the databases Cinahl Complete and PubMed. The articles were analysed according to Friberg’s (2017) method. Results The results are presented within three main themes: physical limitations, emotional distress, and support in daily life. Regarding physical limitations, breathlessness, fatigue, and reduced mobility were common symptoms that restricted daily activities. In the theme of emotional distress, anxiety, fear, guilt, and shame were symptoms that negatively impacted patients with COPD. In the final theme support in daily life, patients reported that family members and healthcare professionals played crucial roles in providing support. Conclusions Patients with COPD experienced significant physical, psychological, and social challenges in their daily lives. These challenges negatively impact the quality of life and well-being of these patients and can lead to social isolation and loneliness. Person-centered care is crucial for meeting the needs of these patients and involving both the patient and relatives in care can be very helpful. / Bakgrund Kronisk obstruktiv lungsjukdom (KOL) är en folksjukdom som påverkar människor över hela världen, och den vanligaste orsaken till sjukdomen är rökning. KOL karaktäriseras av luftvägsobstruktion och ger symtom såsom andnöd och hosta. Det är av stor vikt att sjuksköterskan identifierar och förstår varje patientens unika behov för att kunna erbjuda ett optimaltstöd och vård. Syfte Syftet var att beskriva patienters erfarenheter av att leva med KOL. Metod En litteraturöversikt baserad på elva kvalitativa vetenskapliga artiklar. Artikelsökningar hämtades från databaserna Cinahl Complete och PubMed. Artiklarna analyserades enligt Fribergs (2017) metod. Resultat Resultatet presenteras i tre huvudteman; fysiska begränsningar, emotionella påfrestningar och stöd i vardagen. I temat fysiska begränsningar var andfåddhet, trötthet och nedsatt rörlighet vanliga symtom som begränsade patienters vardag. I temat emotionella påfrestningar var ångest, rädsla, skuld och skam, symtom som påverkade patienterna negativt. I det sista temat stöd i vardagen rapporterade patienterna att anhöriga och vårdpersonal var viktiga i stödarbetet. Slutsats Patienter med KOL upplevde betydande fysiska, psykiska och sociala utmaningar i sitt dagliga liv. Dessa utmaningar påverkade patienters livskvalitet och välbefinnande på ett negativt sätt och kan leda till social isolering och ensamhet. Personcentrerad vård är avgörande för att möta behov hos patienter med KOL och att involvera både patienter och närstående i vården kan vara till stor hjälp.

No / Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide nanoparticles in consumer products. This has increased the likelihood of human exposure to this engineered nanoparticle (ENPs) through different routes. At present, the majority of the studies concerning ZnO ENPs toxicity have been conducted using in vitro and in vivo systems. In this study, for the first time we assessed the effect of ZnO ENPs on the major cellular pathways in the lymphocytes of healthy individuals as well as in susceptible patients suffering from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using the differential expression analysis, we observed a significant (P < 0.05) dose-dependent (10, 20 and 40 microg/ml for 6h) increase in the expression of tumour suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N-terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD patient samples where a significant (P < 0.05) dose-dependent increase in the expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and 77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the aforesaid concentrations. However, the increase in the expression profile of tested protein was not significant in the asthma patients as compared to controls. Our results reiterate the concern about the safety of ZnO ENPs in consumer products and suggest the need for a complete risk assessment of any new ENPs before its use.

Cystic fibrosis (CF) is the most common genetic disease affecting Canadian newborns (1 in 3,850) and is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. This gene encodes for CFTR, a phosphorylation-dependent ion channel localized at the apical membrane. Phosphorylation of CFTR by the cyclic adenosine monophosphate (cAMP)-dependent enzyme protein kinase A activates its activity, facilitating the transport of chloride and bicarbonate ions across the epithelial membrane. CFTR contributes to ion and airway surface liquid regulation, crucial for maintaining host defenses. The inheritance of CFTR mutations leads to a variety of respiratory complications, including impaired mucociliary clearance, excessive mucus production, persistent airway infections, and heightened inflammation, ultimately causing lung damage. While there is currently no cure for CF, the development of CFTR modulators, targeting the defective CFTR protein directly, has significantly improved the quality of life for many CF patients. Despite these advancements, many patients remain unresponsive to current treatment options. It has been well-established that combination therapies outperform monotherapies, emphasizing the need for alternative or complementary therapeutic strategies for CF management. Furthermore, CFTR dysfunction extends beyond CF and has been implicated in other respiratory diseases, such as chronic obstructive pulmonary disease, which is primarily linked to tobacco smoke exposure. This Ph.D. thesis explores a complementary therapeutic approach, targeting proteins within the CFTR-containing macromolecular signaling complex to elevate intracellular cAMP levels, thereby enhancing CFTR function. We hypothesized that synergistic use of cAMP modulators, alongside CFTR modulators, will serve as an effective therapeutic strategy for CF and other respiratory diseases. Collectively, our studies highlight the potential of cAMP and CFTR modulation as a therapeutic strategy for improving the treatment of CF and other respiratory diseases, warranting further investigation, offering insights for future studies, and contributes to the ongoing pursuit of improved combination treatments. / Dissertation / Doctor of Philosophy (PhD) / Cystic fibrosis (CF) is the most common genetic condition affecting Canadian newborns, caused by inheritance of mutations in the CF transmembrane conductance regulator (CFTR) gene. These mutations result in respiratory issues, including breathlessness, excess mucus, and susceptibility to infections, causing lung damage and premature death. Despite progress in CF drug development, some patients remain unresponsive to existing drug combinations, highlighting the need for new combinations to improve the quality of life for all CF patients. CFTR function is also compromised in other respiratory diseases like chronic obstructive pulmonary disease, a lung disease that shares many characteristics with CF and is mainly caused by tobacco smoke exposure. This Ph.D. thesis explores the effectiveness of a new drug strategy targeting proteins interacting with CFTR. By investigating drugs to complement existing treatments, we aim to improve CFTR function. This research offers a promising strategy to improve treatment for CF and other respiratory diseases.

Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had 6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan–Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.