The receptor for advanced glycation end-products (RAGE) is a transmembrane cell surface protein of the immunoglobulin superfamily that acts as part of both the innate and adaptive immune system. RAGE is highly expressed in lung tissue and is therefore of interest in the pulmonary immune response. Specifically, RAGE mediates several cell-signaling responses such as inflammation and apoptosis. This work sought to elucidate the role of RAGE in the setting of chronic pulmonary irritation such as that found in long-term exposure to secondhand smoke (SHS). This irritation has several shared characteristics with lung diseases such as chronic obstructive pulmonary disease (COPD) and is therefore of value in discovering potential mechanistic targets for future therapeutic treatments for exacerbations of the disease. We validated the extracellular signal-regulated kinase (ERK) pathway as a downstream RAGE cascade to activate the cellular transcription factor NF-B and excluded the protein kinase B (AKT) pathway in chronic pulmonary inflammation. We also identified several proinflammatory cytokines mediated by RAGE in long-term SHS exposure; these included increased expression of TNF-, MIP-1, IL-13, and IFN, among others. Furthermore, we identified semisynthetic glycosaminoglycan ethers (SAGEs) as effective RAGE inhibitors in acute pulmonary inflammation and the improvement of lung function. RAGE is also implicated in many other diseases such as type II diabetes mellitus, Alzheimer’s disease, atherosclerosis, and obstetric complications. We investigated its postnatal expression in pups that experienced SHS-induced intrauterine growth restriction (IUGR) antenatally. Increased expression of RAGE correlated with concomitant decreased heart and kidney weights at 4 weeks of age. By 12 weeks of age, weights had improved to age-expected measurements, and detected RAGE protein levels had decreased. These results implicate a potential role for RAGE in disease pathologies of adults who experienced antenatal IUGR due to maternal SHS exposure during pregnancy. In addition to the RAGE signaling pathways, we also investigated the Gas6/AXL pathway in the lungs of pregnant preeclamptic rodents. Gas6 is a ligand for the transmembrane AXL receptor and has been found in increased levels in the serum of pregnant women with preeclampsia (PE). Previous studies in our lab demonstrated a rodent Gas6 model of PE. Using this model, we established that the maternal lung from Gas6-induced preeclamptic rats experienced increased AXL mRNA as well as higher total cell counts, protein, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF). These findings established a connection between lung inflammation and the development of preeclampsia that was previously unknown.

Bakgrund Kronisk obstruktiv lungsjukdom (KOL) är en kronisk inflammation i lungorna som förstör lungvävnaden och minskar lungkapaciteten. Sjukdomen går inte att bota. År 2030 beräknas sjukdomen utgöra den tredje största dödsorsaken samt patientgruppen i världen. KOL medför ett stort lidande och försämrad livskvalité för den drabbade. Syfte Syftet med litteraturöversikten är att beskriva personers upplevelser av att leva med kronisk obstruktiv lungsjukdom (KOL). Metod Examensarbetet genomfördes som en strukturerad litteraturöversikt. 13 artiklar från databaserna Cinahl och PsycINFO analyserades och sammanställdes med Fribergs analysmetod. De inkluderade artiklarna var av kvalitativ design. Resultat Resultatet delades in i två huvudkategorier: Förändring av förutsättningar och hantering av förändringarna. De centrala fynden var de fysiska förändringar som upplevdes, att fokus låg på andningen och känslor av att vara begränsad socialt var särskilt framträdande. Känslor av skam och skuld men också kunskapsutbyte och stöd hos andra personer i liknande situation. Att använda fysisk aktivitet som en strategi och ta ansvar för egenvård. Slutsats Resultatet visar att personer med sjukdomen KOL upplever begränsningar i det dagliga livet både gällande den sociala samvaron och fysiska aktiviteter. Hjälpmedel ansågs minska isolering och de dagliga aktiviteterna kunde upprätthållas bättre. Känslor av skuld och skam som har en inverkan på personernas upplevelser av hälsa framträder. Det finns upplevelser om attityder gentemot personer med KOL och att detta kunde leda till att man undvek att söka vård. / Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammation of the lungs that destroys the lung tissue, reduces lung capacity and cannot be cured. In 2023, the disease is estimated to be the third biggest patient group in the world and the third largest cause of death. COPD causes suffering through shortness of breath, limited mobility and are duced quality of life. Aim The purpose of this thesis is to describe people's experiences of living with chronic obstructive pulmonary disease (COPD). Method The thesis was carried out as a structured literature review containing 13 articles from the database CINAHL and PsycINFO. The articles were analyzed and compiled using Friberg´s analysis method. The included articles were of qualitative design. Results The results were divided into two main categories: Change in conditions and management of the changes. The central findings were the physical changes experienced, a focus on breathing and feelings of being socially restricted were particularly prominent. Feelings of shame and guilt but also exchange of knowledge and support from other people in a similar situation. Using physical activity as a strategy and taking responsibility for selfcare. Conclusions The results show that people with the disease COPD experience limitations in daily life both regarding social interaction and physical tasks. The study also reveals feelings of guilt and shame, which are significant for the persons' health. Experiences that there is a certain attitude towards people who suffer from the disease are described.

Bakgrund: Kronisk obstruktiv lungsjukdom (KOL) är en kronisk inflammation i lungorna och innebär andningssvårigheter som förvärras vid ansträngning. Tidiga symtom är hosta på morgonen och slembildning. Patienter med KOL besväras också av skov, dessa kallas exacerbationer och innebär perioder där symtomen av KOL förvärras och blir mer tydliga. Syfte: Syftet med denna studie är att beskriva individers erfarenheter med diagnosen KOL. Metod: En kvalitativ litteraturstudie har genomförts baserad på 14 artiklar som kritiskt granskats för att få en djupare kunskap av redan publicerad forskning om det valda området. Resultat: Resultatet presenteras i tre huvudteman rädsla för att söka vård på grund av eget vållande, vårdpersonalens påverkan, symtomen begränsar vardagslivet och sju underteman. Konklusion: KOL har en negativ påverkan på den fysiska och psykiska förmågan, sociala relationer, intressen och självbilden. Individer med KOL tvingas ändra hela sitt liv och anpassa sig efter sjukdomens progression. Sjuksköterskan ska bidra med ett motiverande tankesätt och ej vara dömande eller diskriminerande. / Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammation of the lungs and involves breathing difficulties that worsen with exertion. Early symptoms are morning cough and mucus production. Patients with COPD are also troubled by relapses, these are called exacerbations and involve periods where the symptoms of COPD worsen and become more evident. Aim: The purpose of this study is to describe the experiences of individuals diagnosed with COPD. Method: A qualitative literature review has been conducted based on 14 articles that were critically reviewed to gain a deeper knowledge of already published research on the chosen area. Findings: The results are presented in three main themes: fear of seeking care due to one's own fault, the influence of the care staff, the symptoms limit everyday life and seven subthemes. Conclusion: COPD has a negative impact on physical and mental ability, social relationships, interests and self-image. Individuals with COPD are forced to change their entire lives and adapt to the progression of the disease. The nurse must contribute with a motivating way of thinking and not be judgmental or discriminatory.

Bakgrund: ​​Kronisk obstruktiv lungsjukdom (KOL) är en kronisk fortskridande folkhälsosjukdom som mestadels drabbar rökare, men kan även drabba icke rökare. Människor som lever med KOL kan uppleva obehagliga symtom, där andnöd särskilt kan ha en stark påverkan på deras vardag. För sjuksköterskor är det viktigt att förstå hur patienter upplever sjukdomen för att kunna bidra med en personcentrerad vård.​    Syfte: Att beskriva patienters upplevelser av att leva med kronisk obstruktiv lungsjukdom.​       Metod: En litteraturöversikt enligt Fribergs metodbeskrivning genomfördes baserad på tio kvalitativa orginalartiklar som hämtades från databaserna Cinahl Complete och Pubmed. Med sökord som ”leva med”, ”patientupplevelse”, ”kronisk obstruktiv lungsjukdom”, och "kvalitativa studier” hittades 10st orginalartiklar. ​​       Resultat: ​​Analysen resulterade i fyra teman. “Fysiska symtom som medför i svårigheter i det dagliga livet”, som berör hur deltagarna upplever en känsla av färre möjligheter där andningen är ett symtom som påverkar deras vardag. “Emotionella känslor av KOL”, tar upp hur deltagarna känner en identitetsförlust samtidigt som de känner skam, ångest och rädsla i samband med KOL. “Fysisk aktivitet i vardagliga livet”, lyfter hur enkla saker i deltagarnas liv innan sjukdomen har blivit till utmaningar, t.ex. utmaning i träning, korta promenader samt handla. Sista temat “Upplevelse av stöd”, berör deltagarnas upplevelser av stöd som beskrivs som både positiv men även negativt. ​       Slutsats: Resultatet diskuteras med stöd av Katie Eriksson teori om lidande. I resultatet påvisar teorin om lidande en tydlig koppling till upplevelsen av KOL, där deltagarna upplevde KOL som en betungande börda. KOL begränsade deltagarnas liv och ledde till en känsla av isolering där deltagarna behövt anpassa hela deras liv efter sjukdomen. Sjuksköterskan har en viktig i roll i att bemöta patienten på ett professionellt sätt samt anpassa vården efter ett personcentrerat sätt.​ / Background: Chronic obstructive pulmonary disease (COPD) is a chronic progressive public health disease that mostly affects smokers but can also affect non-smokers. People living with COPD can experience unpleasant symptoms, where shortness of breath in particular can have a strong impact on their everyday life. For nurses, it is important to understand how patients experiences the disease in order to contribute with person-centered care.      Aim: To describe patients' experiences of living with chronic obstructive pulmonary disease.       Method: A literature review according to Friberg's method description was carried out based on ten qualitative original articles that were retrieved from the databases Cinahl Complete and Pubmed. With keywords such as "living with", "patientexperience", "chronic obstructive pulmonary disease", "qualitative studies" were 10 original articles found.       Results: The analysis resulted in four themes. "Physical symptoms that lead to difficulties in daily life", which concerns how the participants experience a feeling of fewer opportunities where breathing is a symptom that affects their everyday life. “Emotional feelings of COPD”, addresses how the participants feel a loss of identity while also feeling shame, anxiety, and fear associated with COPD. "Physical activity in everyday life", highlights how simple things in the participants' lives before the disease have become challenges, e.g. challenge in training, short walks and shopping. The last theme, "Experience of support", concerns the participants' experiences of support which they describe as both positive but also negative.        Conclusions: The result is discussed with the support of Katie Eriksson's theory of suffering. In the results, the theory of suffering shows a connection to COPD, the participants experience COPD as an onerous burden. COPD limits participants' lives and has led to a sense of isolation where participants have had to adapt their entire lives to the disease. The nurse has an important role in treating the patient in a professional manner and adapting care in a person-centered manner.

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<p><strong>Abstract:</strong><strong> </strong></p> <p><em>Introduction:</em></p> <p>Because the relationship between pulmonary function and exercise tolerance is highly variable in COPD, other contributing factors were investigated. Physiological factors that contribute to exercise tolerance must contribute to the symptoms limiting exercise, thus the symptoms limiting exercise in COPD and their contributing factors were explored, including an investigation of novel mechanisms to explore the reported tiotropium bromide-mediated improvement in exercise tolerance in COPD.</p> <p><em>Methods:</em></p> <p>We conducted a retrospective, cross-sectional analysis of 4,424 COPD patients and 4,221 healthy subjects; referred to McMaster University Medical Center for exercise testing. Multiple linear regression, ridge regression, and MANOVA were utilized to determine the factors contributing to exercise tolerance, important symptoms limiting exercise, and factors contributing to dyspnea.</p> <p>A randomized, double-blind, placebo-controlled, crossover study of 20 COPD subjects was performed. Repeated measures ANOVA was utilized to determine effects of 3 weeks tiotropium bromide vs. 3 weeks placebo on cardiac output and efficiency of gas exchange during exercise.</p> <p><em> </em></p> <p><em>Results:</em></p> <p>MBC, DL_CO, and quadriceps strength were the three major, independent, contributors to exercise capacity (MPO = -206.3 + 5.1*Quadriceps Strength + 1.8*MBC + 10.0*DL_CO, r² = 0.677). MANOVA further illustrated this.</p> <p>Dyspnea, alone or in equal combination with leg effort, was the most important symptom limiting exercise in COPD. V_E and MBC were the two major, independent, contributors to dyspnea (Dyspnea = 0.95 + 0.08*V_E + -0.01*MBC, r² = 0.457). The increase in dyspnea with V_E was much greater than the decrease with MBC.</p> <p>Tiotropium bromide did not significantly (p = 0.72) improve the efficiency of gas exchange for oxygen, significantly worsened (p = 0.005) the efficiency of gas exchange for carbon dioxide, and did not improve cardiac output.</p> <p><em>Conclusion:</em></p> <p>We concluded the reported tiotropium bromide-mediated improvement in exercise tolerance in COPD is not mediated through improvements in gas exchange efficiency and/or cardiac output.</p> <p><strong><br /></strong></p> / Doctor of Philosophy (Medical Science)