Theses and Dissertations at Montana State University (MSU)
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Item An asthma annual spirometry testing quality improvement project(Montana State University - Bozeman, College of Nursing, 2020) Abraham, Melissa Lynn; Chairperson, Graduate Committee: Laura LarssonAsthma is a chronic inflammatory lung disease that causes coughing, wheezing, shortness of breath and chest tightness. In the United States, 7.6% of adults are living with asthma, and the prevalence of asthma in Montana is 9.1% for adults. The aim for asthma management is to help people living with asthma maintain a better quality of life. In order to bridge the gap in care and provide access to asthma management, more providers need to be well-versed and equipped to meet these needs. Research shows spirometry testing helps a provider diagnose and understand the severity of a patient's asthma symptoms. The purpose of this project is to determine if implementation of a quality improvement (QI) project in clinical practice will improve annual spirometry testing for asthma patients. A 2.5-hour asthma diagnosis and management course was provided for staff implementing spirometry testing and a retrospective chart analysis was conducted, continued support over the course of a twelve-month project period and workflow changes were implemented to facilitate change. The outcome measure focused on was spirometry testing, with a goal of 85% of patients with asthma to receive annual spirometry testing. A survey was given to determine the staff's perspective on implementing the QI project. The QI project increased annual spirometry testing by 37% post intervention. Staff found the education informative and the workflow changes beneficial to improving patient care to meet the national asthma guidelines. Changes to workflow in clinical practice using a QI project could benefit future clinical practice.Item The roles of interleukin-1 and leukotriene-B4 in the innate immune response to pulmonary Aspergillus fumigatus infection(Montana State University - Bozeman, College of Letters & Science, 2017) Caffrey-Carr, Alayna Katherine; Chairperson, Graduate Committee: Mark T. Quinn; Margaret M. Lehmann, Julianne M. Zickovich, Vanessa Espinosa, Kelly M. Shepardson, Christopher P. Watschke, Kimberly M. Hilmer, Arsa Thammahong, Bridget M. Barker, Amariliz Rivera, Robert A. Cramer and Joshua J. Obar were co-authors of the article, 'IL-1A signaling is critical for leukocyte recruitment after pulmonary Aspergillus fumigatus challenge' in the journal 'PLoS pathogens' which is contained within this thesis.; Joshua J. Obar was a co-author of the article, 'Alarmin(G) the innate immune system to invasive fungal infections' in the journal 'Current opinion in microbiology' which is contained within this thesis.; Caitlin H. Kowalski, Sarah R. Beattie, Nate A. Blaseg, Chanell R. Upshaw, Arsa Thammahong, Hannah E. Lust, Yi-Wei Tang, Tobias M. Hohl, Robert A. Cramer, Joshua J. Obar were co-authors of the article, 'IL-1A signaling is critical for resistance against highly virulent Aspergillus fumigatus strains' submitted to the journal 'Infection and Immunity' which is contained within this thesis.; Kimberly M. Hilmer and Joshua J. Obar were co-authors of the article, 'Host-derived leukotriene B4 is critical for resistance against invasive pulmonary Aspergillosis' submitted to the journal 'Microbes and Infection Short Communication' which is contained within this thesis.Aspergillus fumigatus is a ubiquitous environmental mold, and even though most individuals are regularly exposed to fungal spores, clinical invasive disease is a rare manifestation. However, in the growing population of individuals with weakened immune systems, for example due to prolonged corticosteroid treatment or chemotherapeutic interventions, A. fumigatus exposure can cause severe, invasive aspergillosis (IA). Overall, invasive fungal infections are estimated to kill at least 1.5 million people annually (Brown et al. 2012), with IA being the most common and deadly invasive respiratory fungal infection. Thus, it is critical to better understand the host-pathogen interactions after A. fumigatus exposure in order to develop novel treatment options which harness the power of the host's immune response. Defining key immunological events that are needed for the prevention of Aspergillus growth within the pulmonary environment of immune competent individuals is an essential step toward a better understanding of how the immune response is altered within the immune compromised populations that are at risk of developing IA. Utilizing an immune competent murine model of IA, we have shown that signaling through both the Interleukin-1 receptor, type I (IL-1RI) and the Leukotriene B4 receptor (BLT1) are both critical pathways for host resistance against IA through timely neutrophil recruitment which ultimately control fungal germination. More recently, we have found that different environmental and clinical strains of A. fumigatus lead to different inflammatory profiles as well as different disease pathology. Strains that are able to germinate within the lung environment are more virulent, and lead to enhanced lung damage, vascular leakage and inflammation. Furthermore, the more virulent strains induce neutrophil recruitment and subsequent fungal clearance that is dependent on the alarmin IL-1alpha, while clearance of the less virulent strains are independent of IL-1alpha signaling. With this research we will better understand the fungal component(s) that are important in virulence determination, which immune pathways are contributing to the different disease pathologies observed, as well as understand the mechanism through which a healthy immune system can resist A. fumigatus exposure on a daily basis.Item The role of SaeR/S in secondary Staphylococcus aureus Pneumonia(Montana State University - Bozeman, College of Agriculture, 2016) Hisey, Bennett Stephen; Chairperson, Graduate Committee: Jovanka Voyich-Kane; Timothy R Borgogna, Kyler B. Pallister, Eli W. Sward, Fermin E. Guerra and Jovanka M Voyich were co-authors of the article, 'The role of SaeR/S in secondary Staphylococcus aureus pneumonia' submitted to the journal 'Journal of infectious diseases' which is contained within this thesis.Methicillin?resistant Staphylococcus aureus (MRSA) is a Gram?positive pathogen capable of causing diverse disease in humans. MRSA precisely controls virulence factor expression via the SaeR/S two?component gene regulatory system. While much is known about SaeR/S regulation patterns during skin infection, less is understood about the role it plays in the pulmonary environment during secondary staphylococcal pneumonia. Using an isogenic deletion mutant in pulsed field gel electrophoresis type USA300 (strain LAC) of the saeR/S two?component gene regulatory system we examined its role in mouse models of pathogenesis involving primary infection with influenza strain A/WSN/33 followed by USA300 infection. Results demonstrate SaeR/S contributes significantly to mortality during pneumonia following influenza A infection. Reverse transcription PCR and QuantiGene 2.0 assays revealed differences in both transcription of components of SaeR/S as well as virulence factors under SaeR/S control. Primary Influenza infection was seen to up regulate expression of virulence factors under control due to antecedent influenza A infection. These data underscore the importance of pathogen contribution to the pathogenesis of secondary pneumonia.Item Characterization and embellishment of protein cages for nanomedical and nanomaterial applications(Montana State University - Bozeman, College of Letters & Science, 2014) Servid, Amy Eloise; Chairperson, Graduate Committee: Trevor Douglas; Laura E. Richert, Ann L. Harmsen, Agnieszka Rynda-Apple, Soo Han, James A. Wiley, Trevor Douglas and Allen G. Harmsen were co-authors of the article, 'A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose' in the journal 'Vaccine' which is contained within this thesis.; Paul Jordan, Alison O'Neil, Peter Prevelige and Trevor Douglas were co-authors of the article, 'Location of the bacteriophage P22 coat protein C-terminus provides opportunities for the design of capsid-based materials' in the journal 'Biomacromolecules' which is contained within this thesis.In nature, protein cages are found within the structures of viruses, heat shock proteins, and ferritins. They assemble from subunits into spherical oligomeric structures, which serve to encapsulate, protect, and/or deliver cargo. The fundamental understanding of protein cage structure is a key component in the design of novel nanomaterials that best exploit and expand upon the natural functions of protein cage architectures. By mimicking the re-occurring design strategies employed by natural systems, the protein cages produced during virus infection and/or stress responses can be modified to yield particles that fight disease and/or serve as the building blocks for materials design. In particular, the work described here highlights the design and characterization of protein cages in an effort to develop and uncover new strategies for immunization of the lung against a variety of pathogens. A combination of genetic and chemical engineering approaches is described here in order to better understand the structure of protein cage architectures and the relationship between the structure and in vivo function. This work describes the chemical cross-linking of large antigens and immunomodulatory molecules to the surface of a protein cages, and it shows that intensified and accelerated immune responses result from the display of antigens on a protein cage surface. Genetic incorporation of point mutations within the capsid structure provided unique attachment points for chemical functionalization. In addition, genetic modifications revealed information about the location of the C-terminus of the bacteriophage P22 capsid. The knowledge that this position was displayed on the capsid exterior prompted its use to promote inter-capsid interactions and target nanoparticles to melanoma cells. This research emphasizes that both the protein cage structural design and the local in vivo environment can influence the outcomes of protein cages when administered to the lung environment. It also lays the foundation for the logical design of biomaterials that offer enhanced protection against influenza and other respiratory diseases. Finally, regions of protein cages that are amendable to chemical and genetic modifications are described herein, and these have paved the way for the continued development of protein cage platforms for nanomedical and material applications.Item Exercise and chronic obstructive pulmonary disease(Montana State University - Bozeman, College of Nursing, 1995) Lamphier, Jacqueline