Browsing by Subject "Pulmonary"

Now showing 1 - 5 of 5
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    Hospital-associated functional status decline in pulmonary patients
    (2017-06-26) Shay, Amy Cornett; Fulton, Janet; Von Ah, Diane; Otte, Julie Elam; Warden, Stuart J.; O'Malley, Patricia
    Chronic obstructive pulmonary disease (COPD) is a significant worldwide cause of chronic illness and mortality and one of the most common admitting diagnoses in the United States. Persons with COPD are at increased risk for deconditioning during hospitalization, which can lead to decreased functional status at discharge. Disease-related factors and elements of the hospital environment make older adults with COPD vulnerable to hospital-associated functional status decline. The purpose of this dissertation was to identify activity factors that contribute to hospital-associated functional status decline in older adults with COPD by promoting functioning during hospitalization. This predictive correlational study is a secondary analysis of a pre-existing dataset. Patients with COPD were pulled from the larger parent study sample for comparison with patients without COPD. The convenience sample consisted of 111 patients with COPD and 190 patients without COPD. Subjects were 46.5% male, 53.5% female, and a mean age of 66 years. All subjects were patients admitted to a pulmonary unit and received an intervention protocol designed to address mobility barriers related to COPD and hospitalization. Statistical analysis explored the number, type, and timing of activity events in relation to the selected functional status outcomes of discharge disposition, length of hospital stay, and 30-day readmission rates for hospitalized older adults with COPD. Multivariate and bivariate analyses results indicated ambulation to the bathroom, ambulation outside the patient room, and number of days to first out-of-bed activity were significant predictors (p < 0.05) of patient discharge to home; days to first activity and ambulation were significant predictors (p < 0.05) of reduced length of stay; none of the variables were predictive of 30-day readmission. Patients with COPD experienced longer lengths of stay and more non-weight bearing activity than patients without COPD in this sample. These findings provide a foundation for future research to explore hospital environmental factors influencing mobility, determine optimal modes of activity during hospitalization, and examine potential cost savings associated with promotion of early mobility. Findings help explain the effects of physical activity during hospitalization and may aid development of nursing interventions to prevent or alleviate functional status decline in this vulnerable population.
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    Mechanisms of HIV-Nef Induced Endothelial Cell Stress: Implications of HIV-Nef Protein Persistence in Aviremic HIV Patients
    (2019-05) Chelvanambi, Sarvesh; Clauss, Matthias; Basile, David; Day, Richard; Yu, Andy
    HIV-associated cardio-pulmonary vascular pathologies such as coronary artery disease, pulmonary hypertension and emphysema remain a major issue in the HIVinfected population even in the era of antiretroviral therapy (ART). The continued production of HIV encoded pro-apoptotic protein, such as Nef in latently HIV-infected cells is a possible mechanism for vascular dysfunction underlying these diseases. HIVNef persists in two compartments in these patients: (i) extracellular vesicles (EV) of plasma and bronchoalveolar lavage (BAL) fluid and (ii) PBMC and BAL derived cells. Here I demonstrate that the presence of HIV-Nef protein in cells and EV is capable of stressing endothelial cells by inducing ROS production leading to endothelial cell apoptosis. HIV-Nef protein hijacks host cell signaling by interacting with small GTP binding protein Rac1 which activates PAK2 to promote the release of pro-apoptotic cargo containing EV and surface expression of pro-apoptotic protein Endothelial Monocyte Activating Polypeptide II (EMAPII). Using this mechanism, Nef protein robustly induces apoptosis in Human Coronary Artery Endothelial Cells and Human Lung microvascular endothelial cells. Endothelial specific expression of HIV-Nef protein in transgenic mice was sufficient to induce vascular pathologies as evidenced by impaired endothelium mediated vasodilation of the aorta and vascular remodeling and emphysema like alveolar rarefaction in the lung. Furthermore, EV isolated from HIV patients on ART was capable of inducing endothelial apoptosis in a Nef dependent fashion. Of therapeutic interest, EMAPII neutralizing antibodies to block EMAPII mediated apoptosis and statin treatment to ameliorate Nef induced Rac1 signaling was capable of blocking Nef induced endothelial stress in both in vivo and in vitro. In conclusion, HIV-Nef protein uses a Rac1-Pak2 signaling axis to promote its dissemination in EV, which in turn induces endothelial cell stress after its uptake.
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    miR‐145 transgenic mice develop cardiopulmonary complications leading to postnatal death
    (Wiley, 2021-09) Thomas, Shelby; Manivannan, Sathiyanarayanan; Sawant, Dwitiya; Kodigepalli, Karthik M.; Garg, Vidu; Conway, Simon J.; Lilly, Brenda; Pediatrics, School of Medicine
    Background: Both downregulation and elevation of microRNA miR-145 has been linked to an array of cardiopulmonary phenotypes, and a host of studies suggest that it is an important contributor in governing the differentiation of cardiac and vascular smooth muscle cell types. Methods and results: To better understand the role of elevated miR-145 in utero within the cardiopulmonary system, we utilized a transgene to overexpress miR-145 embryonically in mice and examined the consequences of this lineage-restricted enhanced expression. Overexpression of miR-145 has detrimental effects that manifest after birth as overexpressor mice are unable to survive beyond postnatal day 18. The miR-145 expressing mice exhibit respiratory distress and fail to thrive. Gross analysis revealed an enlarged right ventricle, and pulmonary dysplasia with vascular hypertrophy. Single cell sequencing of RNA derived from lungs of control and miR-145 transgenic mice demonstrated that miR-145 overexpression had global effects on the lung with an increase in immune cells and evidence of leukocyte extravasation associated with vascular inflammation. Conclusions: These data provide novel findings that demonstrate a pathological role for miR-145 in the cardiopulmonary system that extends beyond its normal function in governing smooth muscle differentiation.
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    Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction
    (Wolters Kluwer, 2024) Jheng, Jia-Rong; DesJardin, Jacqueline T.; Chen, Yi-Yun; Huot, Joshua R.; Bai, Yang; Cook, Todd; Hibbard, Lainey M.; Rupp, Jennifer M.; Fisher, Amanda; Zhang, Yingze; Duarte, Julio D.; Desai, Ankit A.; Machado, Roberto F.; Simon, Marc A.; Lai, Yen-Chun; Medicine, School of Medicine
    Background: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear. Methods: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples. Results: Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, B2m deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF. Conclusions: Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.
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    A Post-Mortem Examination of COVID-19 Pulmonary Pathology in 9 Cases
    (Peertechz Publications, 2020-06-10) Bloom, Alexis; Colter, Austyn; Jacobsen, Max; Battles, Domnique; Albertson, Tamara; Sandusky, George; Pathology and Laboratory Medicine, School of Medicine
    A new novel virus called SARS-CoV-2 has expanded into a pandemic in the past several months. The virus is an acute respiratory RNA virus that has symptoms in three clinical groups: asymptomatic, suspicious, and COVID-19 positive. The clinical lab tests used for diagnosis are Nasalpharyngeal swabs, with further testing done with sputum or BAL samples. Serological samples are collected for diagnosis in deceased patients using RT-PCR. The clinical symptoms usually occur 2 to 14 days after exposure and include fever, dry cough, and fatigue. In some cases, symptoms can progress and cause multiple organ failure due to adult respiratory distress syndrome (ARDS). The virus is in the family of coronaviruses and has also been identified in lung tissue using transmission electron microscopy. Gross and microscopic lung pathology was examined in five positive cases and four negative cases by hematoxylin and eosin (H&E) and Masson’s Trichrome stains. Of the collected, the age range was 28 to 76. The ethnicities were six Caucasians and three minorities, with a male to female ratio of 7:2. The salient histology features seen in the study were multifocal to diffuse alveolar necrosis, bronchiolar epithelial necrosis, and interstitial mononuclear lymphocytic infiltrates. Other features were perivascular and peribronchiolar lymphoid infiltrates and marked congestion. Scattered fibroplasia was found in the damaged alveoli and the alveolar septae in the more severe cases. These pathologic features are similar to other coronaviruses.