Understanding the regenerative capacity and the role of human AT2s in the distal lung is imperative for defining alveolar response to injury and disease. Additionally, due to human AT2 expression of COPD genome wide association study (GWAS) genes, they are an especially relevant cell type to study the disease. Here we apply CRISPR-interference (CRISPRi) to reduce the expression of COPD GWAS gene, ADGRG6, to interrogate its function in induced pluripotent stem cell-derived type 2 alveolar epithelial cells (iAT2s). We find that decreased expression of ADGRG6 in iAT2s caused disruption to iAT2 cell polarity, organization of the actin cytoskeleton, and establishment of tight junctions. In addition, ADGRG6 knockdown (kd) causes a hyperproliferative phenotype. Finally, we find that ADGRG6-kd may contribute to dysregulation of tight junction formation in the presence of cigarette smoke.

This work develops a simple and low-cost microphone-based spirometer with a scalable infrastructure that can be used to monitor COPD and Asthma symptoms. The data acquired from the system is archived in the cloud for further procuring and reporting. To develop this system, we utilize an off-the-shelf ESP32 development board, MEMS microphone, oxygen mask, and 3D printable mounting tube to keep the costs low. The system utilizes the MEMS microphone to measure the audio signal of a user's exhalation, calculates diagnostic estimations and uploads the estimations to the cloud to be remotely monitored. Our results show a practical system that can identify COPD and Asthma symptoms and report the data to both the patient and the physician. The system developed can provide a means of gathering respiratory data to better assist doctors and assess patients to provide remote care.

Introduktion: Kroniskt obstruktiv lungsjukdom (KOL) är en sjukdom som kännetecknas av ihållande luftvägssymtom och begränsningar i luftflöde. Personer med KOL är betydligt mindre aktiva än friska individer. Sänkt fysisk aktivitet är en stark prediktor för mortalitet för personer med KOL.   Syfte: Syftet med denna studie var att undersöka om motiverande samtal om fysisk aktivitet kan användas som intervention för personer med KOL för att påverka self-efficacy (ESES) för fysisk aktivitet samt nivå av ångest och depression. Syftet är även att undersöka om det finns ett samband mellan förändring i self-efficacy samt förändring av fysisk förmåga.   Metod: Studien inkluderar data från 83 deltagare. Under en 6 månader lång interventionsfas har testdeltagarna fått motiverande samtal om fysisk aktivitet. Vår statistiska analys inkluderar hypotesprövning av skillnader på utvalda enkäter. Hypotesprövning av samband har gjorts med Pearsons r.    Resultat: Motiverande samtal ledde till en signifikant ökad self-efficacy gällande fysisk aktivitet efter intervention (m=23.8; sd=7.43) jämfört med före intervention (m=22.3; sd=7.04) med motiverande samtal (p=0.025). Ingen effekt påvisades beträffande ångest och depression. Det finns ett statistiskt signifikant samband (p = <0.001) mellan självskattad self-efficacy gällande fysisk aktivitet och fysisk förmåga mätt med 6-minuters gångtest efter 6 månader. Sambandet var svagt positivt (Pearsons r = 0.410).   Konklusion: Motiverande samtal har visats förbättra self-efficacy, det vill säga tilltro till egen förmåga att utföra fysisk aktivitet. Det finns ett samband mellan tilltro till egen förmåga samt fysisk kapacitet, vilket kan betyda att motiverande samtal är en bra intervention för svårt sjuka personer med KOL.

Many patients are affected by chronic obstructive pulmonary disease (COPD), a progressive lung disease that obstructs air flow, resulting in dyspnea and inability to carry out daily activities. Despite optimal pharmacological management, COPD patients make frequent emergency room visits and are hospitalized due to exacerbations of COPD. Literature has suggested that pulmonary rehabilitation (PR), a nonpharmacological treatment, could help to decrease the symptoms that lead to illness exacerbation, hospital readmissions, and decreased quality of life in patients with COPD. The purpose of the project was to increase the quality of life and reduce admission rates for patients diagnosed with COPD through the development and implementation of patient education material that would increase PR awareness, increase patient motivation, and promote participation. The ACE star model was used to guide the project development, and the theoretical framework of the health belief model was used to enhance patients' perceptions and desires to participate in a PR program. Evaluation of the pretests and posttests revealed significant improvement in various variables, reduction of dyspnea, improved exercise tolerance, and increased knowledge. The evaluation of health-related quality of life using the short form 36 showed significant improvement in some subscales namely: general health, role emotional, with slight significance in bodily pain. There were no readmissions among the participants. The implementation of comprehensive PR has implications for positive social change because it helps patients with COPD to be more knowledgeable about their disease and allows for more independence and a higher quality of life.

Prior to the coronavirus disease-2019 (COVID-19) pandemic people with chronic obstructive pulmonary disease (COPD) were already experiencing social isolation due to the complex intersection of symptoms, and perceptions towards the illness. COPD is a chronic lung illness characterized by progressive shortness of breath, and decreasing lung function, with influenza and other respiratory illnesses more likely to have fatal consequences for this population. Societal beliefs and assumptions around behavioural risk factors, and in particular smoking, contribute to perceptions that COPD diagnosis, outcomes and experiences are self-inflicted and an individual responsibility. This is a perspective that fails to take into the account the complex contextual factors of the social determinants of health, where structural inequities result in higher smoking rates among populations with lower socioeconomic status. Further, these underlying societal values may compound the isolation experienced with COPD in which ongoing stigma towards the illness discourages people from identifying with a COPD diagnosis. The lack of identity may discourage developing a community where people can share experiences and strategies in living with COPD, and form a collective group that can advocate for change. Digital technologies (DTs), such as Facebook and Zoom offer new avenues to support social connectedness. However, little focus has been given on how people with COPD may (or may not) be using DTs to support their illness. This study explored the role DTs could serve in addressing social connectedness and experiences and outcomes for the COPD community. The study was informed by Mertens (2003, 2007) transformative approach where the knowledge of people living with COPD was prioritized in finding out what DTs they may be using to maintain social connectedness and to support their illness. The three stage mixed methods research design consisted of interviews, patient-reported outcome measures, patient-reported experience measures and a DT survey. Bazeley's (2018) approach was used to guide the integrative mixed analysis on data collected across the three stages. The overall findings were: 1) Participants’ experiences in living with COPD had uniquely prepared them for the COVID-19 pandemic, and it was the community that lacked capacity; 2) Dominant discourse around technology may be creating further harms to the COPD population that extend beyond the digital world; 3) Current digital health monitoring strategies for other chronic illnesses do not fully translate to the interests and needs for people living with COPD; 4) People living with COPD are using DTs, but prefer to keep their virtual world separate from their illness world; and 5) Considerations for DTs for COPD should move beyond managing outcomes, and include supporting experiences of living. Conducted between December 2018 and July 2020, and concurrent with the COVID-19 pandemic, the study demonstrated even greater importance with the onset of the pandemic in understanding how DTs may support social connectedness for people living with life-limiting chronic lung conditions. / Graduate / 2022-02-07

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Overall, the work presented in this thesis explored the impact of cigarette smoke on the immunopathogenesis of respiratory disease. This thesis highlighted the determinantal impact of cigarette smoke on (auto)antibody levels and pulmonary macrophage composition. Work completed by Steven P Cass 2016-2021. / Cigarette smoke is an insidious insult that is associated with a spectrum of respiratory diseases that range from cancer to obstructive diseases such as chronic obstructive pulmonary disease (COPD), to restrictive diseases such as idiopathic pulmonary fibrosis (IPF). In this thesis, we explore how cigarette smoke impacts immune components that contribute to respiratory disease. To begin, we assessed the impact of cigarette smoke on airway antibody and autoantibody levels. We assessed sputum, a non-invasive method to sample the lower airways, to directly assess the presence of antibodies and autoantibodies in COPD. Total immunoglobulin M (IgM), IgG and IgA were detectable in the sputum of subjects. Notably, in patients with mild to moderate COPD, current smoking status was associated with decreased IgM and IgG. Next, using a comprehensive autoantigen array, we measured matched sputum and serum autoantibodies in 224 individuals. Serum autoantibodies were more abundant than sputum autoantibodies and correlated strongly between two independent COPD cohorts. Overall, the autoantibody profile of a patient with COPD was the same as a control subject. A proportion of autoantibody specificities were differentially expressed in patients with COPD with anti-tissue autoantibodies weakly associated with measures of emphysema. Taken together, these data suggested chronic cigarette smoke exposure was associated with limited differential expression of autoantibodies, but these changes were not a reliable method to identify COPD status. In our third study, we assessed the impact of cigarette smoke exposure on the composition and function of pulmonary macrophage subpopulations. Macrophages perform a central role in respiratory host defence and are implicated in the pathobiology of several respiratory diseases. Using a mouse model of cigarette smoke exposure, we reported cigarette smoke-induced expansion of CD11b+ macrophage subpopulations including monocyte-derived alveolar macrophages and interstitial macrophages. The altered pulmonary macrophage composition following cigarette smoke exposure contributed to attenuated fibrogenesis in a model of bleomycin-induced lung injury. This study offered insight to pulmonary macrophage composition and function following cigarette smoke exposure. This thesis summarises the original contributions and work completed during the course of this Ph.D., aimed at understanding the impact of cigarette smoke exposure on immune components central to respiratory disease. In conclusion, these findings shed light on the presence of (auto)antibodies in patients with COPD and the composition of macrophage subpopulations following cigarette smoke exposure. / Thesis / Doctor of Philosophy (PhD) / Currently there are 1.3 billion people who use tobacco across the world. The most common method to consume tobacco is by smoking cigarettes. Cigarette smoking is well-known to cause disease; however, smoking rates are still increasing with more daily cigarette smokers in 2012 than there were in 1980. In this thesis, we explore the impact of cigarette smoke upon the immune system. We first assessed whether cigarette smoking impacts the levels of antibodies, proteins that are produced by the immune system to protect against foreign bodies, in healthy individuals, cigarette smokers without disease and patients with chronic obstructive pulmonary disease (COPD). We found that current smokers had decreased antibodies in the airways, thus predisposing cigarette smokers to increased damage. In our second study, we measured the presence of airway and blood autoantibodies. These are antibodies that target self and have the potential to inflict damage. We discovered that patients with COPD had minor changes in autoantibodies and these changes were weakly associated with emphysema. In our third study, we evaluated the impact of cigarette smoke on lung macrophages, cells that eat and destroy foreign bodies, in a mouse model of cigarette smoke exposure. Cigarette smoke increased the number of bone marrow-derived macrophages and this change in macrophage populations was associated with a reduced wound healing ability. Overall, these studies offer insight into how cigarette smoke impairs the function of the immune system and contributes to lung disease.

Kronisk obstruktiv lungsjukdom (KOL) är en av våra största folksjukdomar och den fjärde vanligaste dödsorsaken i världen. KOL är en progressiv sjukdom med symtom som påverkar livskvalitén. Rökning kombinerat med hög ålder är dominerande riskfaktor. Behandlingsmål för KOL är att minska symtom, förebygga exacerbationer och förbättra livskvalitén. Patientutbildningens syfte är att stödja och stärka patientens kontroll över sjukdom och behandling. I Sverige förekommer ingen standardiserad patientutbildning för KOL-patienter. Syftet med denna litteraturstudie var att identifiera kritiska aspekter i en utbildning för patienter med diagnosen KOL. Litteratursökning gjordes i PubMed och Cinahl. Åtta kvantitativa och två kvalitativa studier som överensstämde med problemformuleringen kvalitetsgranskades och inkluderades. I denna litteraturstudie har vi sett att patientut-bildning kan innefatta många olika moment och de kan inte utvärderas enskilt. Dock tycks faktorer som individuellt anpassad utbildning utifrån patientens tidigare erfarenheter och regelbunden uppföljning vara grundläggande för en utbildning som påverkar patientens följsamhet och därigenom en positiv effekt på patientens behandlingsmål. / Chronic Obstructive Pulmonary Disease (COPD) is a common disease, the 4th cause of global mortality. COPD is progressive and its symptoms influence the daily life. Smoking and ageing are risk factors. The treatment goals are to decrease the symptoms, prevent exacerbation and increase the quality of life. The aim of patient education are supporting and encouraging the patient to take control over the disease and the treatment. Sweden does not have any standard education concerning patients with COPD. The aim of this review was to identify critical aspects in an education for patients with COPD. The literature was searched in PubMed and Cinahl. Eight quantitative and two qualitative studies were selected as they were according to the aim of the study. The quality of the studies was evaluated. In this review we found patient education contenting different factors which could not be evaluated separately. Tailor made education based on the patient previous experience and regular follow-up seems to influence patient adher-ence and thereby give a positive effect on the treatment goals.

Eine Schwäche der Atemmuskulatur tritt als häufige „Klinik“ bei Herz-Lungenerkrankungen, Kritisch-Kranken und Maschinell-Beatmeten auf. Als Hauptatemmuskel ist vornehmlich das Zwerchfell - die Luftpumpe des Lebens – betroffen und Belastungsintoleranz, pulmonale Komplikationen sowie eine verschlechterte Gesamtprognose die mögliche Folgen. Typisches Charakteristikum einer Diaphragmalen Dysfunktion ist die abnorme mikrovaskuläre Blut- und Sauerstoffversorgung. Hier ent- und besteht ein Milieu aus Gewebshypoxie, vermehrten Sauerstoffradikalen, Inflammation (Zytokinerhöhung) und gestörter Proteinhomöostase. Dieses wird verdächtigt, einen Prozess von Atrophie und kontraktiler Dysfunktion in Gang zu setzen. Der Vascular Endothelial Growth Factor A spielt als Protein der Gefäßhomöostase eine entscheidende Rolle in der skelettmuskulären Kapillaritätsregulation und ermöglicht den Myofibrillen die Anpassung an (Trainings-)Aktivität oder Inaktivität. Für das Zwerchfell sind Inaktivität unter Beatmung und erhöhte Beanspruchung unter CHI, COPD und bei Kritisch-Kranken bekannt. Einendes Element dieser Krankheitsbilder auf skelettmuskulärer Ebene scheint die abnorme Sauerstoffversorgung. Das Diaphragma wurde bisher wenig untersucht - bekannt ist die hohe Empfindlichkeit des Zwerchfells auf eine veränderte, skelettmuskuläre Homöostase aus Tiermodellen zu CHI, Bluthochdruck, COPD und VIDD. Es ist unklar, ob eine niedrigere VEGF-Expression zur Dysfunktion beiträgt. An gängigen Tiermodellen mit konditioniertem skelettmuskulärem VEGF-Knockout wurde bisher für das Diaphragma weder eine reduzierte kontraktile Funktion in vitro beschrieben noch eine direkte Verbindung zwischen Zwerchfelldysfunktion und reduzierter VEGF-Expression untersucht. In unserer Arbeit gelang es uns nach konditioniertem VEGF-Mangel in diaphragmalen Muskelproben eine reduzierte Kraft (-15%) nachzuweisen. Hinzu kamen spezifische Faserveränderungen der Knockoutgruppe: Ein reduzierter Typ I-Faserquerschnitt und ein reduziertes Kapillar-Faser-Verhältnis. Zudem zeigt die Knockoutgruppe eine reduzierte Expression des kontraktilen Hauptproteins Aktin. Weitere Signaltransduktionsproteine für Muskelatrophie und oxidativen Stress wurden charakterisiert. Letztlich weist diese Arbeit den Kontraktilitätsverlust im Diaphragma bei skelettmuskulärem VEGF-Mangel am Mausmodell nach. Als Ursache dafür sind eingeschränkte Kapillarität, Faseratrophie und sarkolemmales Aktindefizit zu sehen. Vermehrte postulierte Sauerstoffradikale konnten nicht aufgezeigt werden. Möglicherweise aufgrund einer mitochondrialen Kompensation. Der diaphragmale VEGF-Mangel könnte den Schlüsselfaktor für den Beginn der Zwerchfelldysfunktion darstellen und ein möglicher therapeutischer Ansatzpunkt für betroffene Patienten sein.

COPD is the third leading cause of death in the United States and is the sixth leading cause of death for low-to middle income countries (Downs & Appel, 2006; GOLD, 2011). COPD is a largely preventable disease due to the lifestyle factors that heavily contribute to disease onset and severity. Although traditionally COPD research has focused on health outcomes related to risk factors, compliance, comorbid psychological and physical conditions, and treatment interventions, a growing body of research suggests religious and spiritual factors may play an equally important role in health outcomes for several medical conditions, including pulmonary disease. However, studies of this kind have not specifically examined COPD nor have they examined the role of religious and spiritual beliefs in COPD management among ethnic minority patients. As such, the current study aimed to examine whether spiritual ethnic minority patients with COPD hold religious fatalistic attitudes and less active religious problem solving . A sample of 35 ethnic minority patients from the Louis. B. Stokes Cleveland VA Medical Center (LSCVAMC) Outpatient Pulmonary Clinic in Cleveland, OH. were recruited to participate in the study. Due to the acknowledgeable limitations of the present study, results are preliminary but convey associations between religious health fatalistic beliefs and religious problem solving approaches. Implications and areas of future study are discussed.