Doctor of Nursing Practice, Mount St. Joseph University , 2024, Department of Nursing

Intubation for acute respiratory illness that often leads to acute respiratory distress syndrome (ARDS) is a common threat to the pediatric population worldwide and at the project site pediatric intensive care unit (PICU). The length of mechanical ventilation is a multifactorial determination for each patient circumstance and is strongly associated with the extensiveness of the respiratory illness. Literature supports postural drainage (PD) positioning as a form of treatment for respiratory illness and ARDS, but it is not a common modality utilized in the project site PICU. Using evidence of best positioning practices for lung health, a two-stepped protocol for patient positioning was developed and implemented based on the severity level of ARDS to decrease the length of mechanical ventilation. The application of the positioning protocol for patients that met inclusion criteria demonstrated notable fluid shifting and decreased opacities on chest radiography, a consistent gradual decline in ventilator pressures, oxygen requirement, and ARDS severity levels, and a decrease in the average length of mechanical ventilation. This evidence-based quality improvement initiative provided a strong testimonial to the value of using PD positioning as a treatment method for patients intubated due to respiratory illness and ARDS.

Committee: Kristin Clephane (Advisor) Subjects: Health Care; Nursing

Doctor of Philosophy, The Ohio State University, 2023, Pharmaceutical Sciences

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs suffer from an inflammatory lung injury following insults such as pneumonia, sepsis, trauma, and coronavirus disease 2019 (COVID-19). Patients with ARDS often requires life-support with mechanical ventilation (MV) which can generate injurious physical forces that exacerbate the injury known as ventilator-induced lung injury (VILI). These forces can damage the alveolar-capillary barrier and trigger the release of pro-inflammatory mediators which further damage lung cells including alveolar epithelium, capillary endothelium, and alveolar macrophages (AMs). Although clinicians have tried to minimize lung injury during mechanical ventilation (MV) by using low tidal volume ventilation, it is not possible to completely eliminate it. Clinical trials have failed to identify molecularly targeted pharmacologic therapies for ARDS patients. An incomplete understanding of the role of each lung cell type plays in the development of injury and the mechanosensitive pathways involved in VILI are contributing factors to the unsuccessful outcomes of ARDS clinical trials. Another potential reason is that there has been a relative lack of studies that utilize the pulmonary drug delivery route. In addition, drug delivery during ARDS is challenging due to the heterogeneous nature of lung injury and occlusion of lung units by edema fluid and inflammation. In this dissertation, we demonstrated that AMs respond to mechanical forces by upregulating an anti-inflammatory microRNA, miR-146a, but that this native mechanotransduction response is insufficient to mitigate VILI. Due to various challenges associated with the delivery of miRs, we developed a lipid nanoparticle (LNP) formulation that facilitates the pulmonary delivery of miR-146a. We used an in vitro barotrauma model and an in vivo VILI model to evaluate the therapeutic efficacy of miR-146a loaded LNPs. Our findings indicate that increasing (open full item for complete abstract)

Committee: Joshua Englert MD (Advisor); Mitch Phelps PhD (Committee Member); Alex Sparreboom PhD (Committee Member); Samir Ghadiali PhD (Advisor) Subjects: Pharmaceuticals

Master of Science, The Ohio State University, 2018, Biomedical Engineering

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are lung disorders characterized by increased permeability of the alveolar barrier, resulting in fluid buildup and hypoxia. Patients with ALI or ARDS often require mechanical ventilation to displace occluded fluid and restore blood oxygenation. However, mechanical ventilation exposes alveolar and small airway epithelial cells to abnormal mechanical forces, which can exacerbate lung inflammation and injury, known as ventilator-induced lung injury (VILI). MicroRNAs, short RNAs with post-translational regulatory roles in gene expression, have emerged as promising therapeutic targets to protect against VILI. MicroRNAs 146a and 155 have been implicated in innate immunity, and shown to modulate inflammatory response during simulated lung injury . Delivery of microRNA cargos is critical for clinical translation into future VILI therapy. Endogenous extracellular vesicles (EVs) have emerged as potential drug carriers capable of delivering microRNAs of interest. To study EV-mediated delivery of microRNA-146a, A549 epithelial cell or differentiated THP-1 macrophage monocultures were incubated with either EVs containing pre-miR-146a or scramble gene, or reduced-serum media for 24 hours. MicroRNA expression levels were evaluated via qRT-PCR. EVs delivered pre-miR-146a into A549 and THP-1 cell cocultures, then oscillatory pressure (20 cmH2O, 0.2Hz) was applied for 16 hours. Secretion of interleukin (IL)-1ß, IL-6, and IL-8 was quantified via ELISA. MicroRNA-146a was overexpressed in monocultures of A549 and PMA-differentiated THP-1 cells. In cocultures with applied oscillatory pressure, dampening of IL-1ß and IL-6 secretion was inconclusive. Secretion of IL-8 significantly increased between pressure and no-pressure groups, with EVs potentially increasing pro-inflammatory response. Relative fold-change in cytokine secretion between treatment groups did not change. Overexpression of microRNA-146a (open full item for complete abstract)

Committee: Samir Ghadiali (Advisor); Joshua Englert (Committee Member) Subjects: Biomedical Engineering

MS, University of Cincinnati, 2015, Medicine: Clinical and Translational Research

Background: Hypoxemia following injury contributes significant morbidity and mortality following trauma. The identification of modifiable risk factors for the prevention of acute lung injury in trauma patients remains unclear. We hypothesize that acute crystalloid administration and tidal volume delivery from mechanical ventilation may represent novel modalities to mitigate negative pulmonary outcomes in critically injured patients. Methods: A retrospective, case-control study was undertaken after merging of the institutional trauma registry, trauma ventilator registry and the electronic medical record data from 2/2011 to 8/2014. Patients with survival > 24 hours, at least one PaO2 to FiO2 (P/F) ratio recorded during the first 7 days of hospitalization, and a tidal volume recorded during the first 2 days were included in the final analyses. Multivariate logistic regression models were utilized to investigate the contributions of demographic and injury characteristics, as well as blood products, crystalloid, and tidal volume exposures to negative pulmonary outcomes. The primary outcome of interest was the development of moderate to severe hypoxemia (P/F ratio = 200 mm Hg) during days 1-7. A secondary composite pulmonary outcome was created that included the development of in-hospital pneumonia, tracheostomy, moderate to severe hypoxemia, acute respiratory distress syndrome (ARDS), or early death occurring during days 1-7. Results: Of the 661 patients within the dataset, 531 met inclusion criteria. The median age was 42 years, ISS was 24, 77% were male, 26% suffered a penetrating injury, and 57% experienced a P/F = 200 mm Hg. The median tidal volume was 7.8 (7.0-8.7) mL/kg of predicted body weight and the median crystalloid exposure in the first 24 hours was 2.3 (1.4-3.4) half liters. Those with high tidal volume exposure (>8 ml/kg, n = 224) were significantly older, female, and received less platelets. Those with high crystalloid amounts (> 3 half (open full item for complete abstract)

Committee: Erin Nicole Haynes Dr.P.H. (Committee Chair); Dennis Hanseman Ph.D. (Committee Member); Timothy Pritts M.D. Ph.D. (Committee Member) Subjects: Surgery