Biomedical Engineering and Bioengineering Commons^™

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …

Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young

Theses and Dissertations

Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to …

Modeling The Spatiotemporal Dynamics Of Cells In The Lung, Joshua Jeremy Pothen

Graduate College Dissertations and Theses

Multiple research problems related to the lung involve a need to take into account the spatiotemporal dynamics of the underlying component cells. Two such problems involve better understanding the nature of the allergic inflammatory response to explore what might cause chronic inflammatory diseases such as asthma, and determining the rules underlying stem cells used to engraft decellularized lung scaffolds in the hopes of growing new lungs for transplantation. For both problems, we model the systems computationally using agent-based modeling, a tool that enables us to capture these spatiotemporal dynamics by modeling any biological system as a collection of agents (cells) …

The Molecular And Mechanical Mechanisms Of The Age-Associated Increase In The Severity Of Experimental Ventilator Induced Lung Injury, Joseph Ames Herbert

Theses and Dissertations

Abstract

Background

The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and mortality. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood.

Pulmonary edema is a hallmark of VILI and the severity of edema increases with age. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress (ARDS) patients, but has not been investigated in VILI. We hypothesized that age-associated increases in pulmonary edema promote age-related increases in ventilator-associated mortality. Endoplasmic reticulum (ER) …

Optimization Of Spray Droplet Size For Drug Delivery To The Deep Lung, Renee Worden

Electronic Theses and Dissertations

The lower respiratory regions of the lung boast over 900 million alveoli with a combined 85 m2 of surface area of near direct access to the bloodstream. Within the last century the immense potential of the deep lung as a site for the delivery of drugs has begun to be exploited and today pulmonary delivery of aerosolized therapeutic is commonplace. However, the high inter- and intra-patient variability in dosing is almost completely ignored. Currently, no steps are being taken to mitigate the sources of variability beyond injection into the upper airways. This study seeks to prove that a careful selection …

Quantitative Evaluation Of Redox Processes In Intact Rat Lungs And Endothelial Cells And The Effect Of Hyperoxia, Zhuohui Gan

Dissertations (1934 -)

A common initial treatment of hypoxemia in patients with lung failure secondary to acute lung injury (e.g., adult respiratory distress syndrome) is oxygen (O₂) therapy (hyperoxia). However, prolonged O₂ therapy causes lung O₂ toxicity, which can further impair lung functions. The rat model of lung O₂ toxicity replicates key features of human lung O₂ toxicity. In addition, rats develop tolerance or susceptibility to 100% O₂ by pre-exposing them to 85% O₂ (hyper-85) or 60% O₂ (hyper-60) for 7 days, respectively. Therefore, the long-term objectives of this study are to elucidate mechanisms …

Pulmonary Particle Deposition In Relation To Age, Body Weight, And Species, Lisa M. Weber

Electronic Theses and Dissertations

As a result of dissimilarity in lung morphometry and physiological conditions, therapeutic aerosol particles deposit differently in humans of various ages and body weights. These particles also deposit differently in non-human species that are often utilized in inhalation and dosing studies. The focus of this work is to determine the optimal particle size and deposition (traditional efficiency and volume-weighted) of therapeutic particles in humans of both genders ranging in age from 3 months old to 21 years old and three non-human species (B6C3F₁ mouse, Long-Evans hooded rat, and Beagle dog). This study finds that in humans, both optimal …

Development Of A Software Application To Extract The Features Of Normal Respiratory Sounds From The Lungs And The Trachea, Ranjani Sabarinathan

Theses and Dissertations

Auscultation has been widely regarded as one of the most important noninvasive diagnostic tools for clinical diagnosis of the respiratory tract. The purpose of this thesis was to develop a software application capable of extracting the key features of respiratory sound signals from the lungs and trachea of healthy persons. The efficacy of the program was evaluated by the verification of the important features of the sound signals from the left and right lungs and the trachea such as 1) right and left lung symmetry and 2) dissimilarity between the trachea and both lungs. The program was developed in LabView …