There is evidence to suggest that inspiratory muscle training (IMT) may influence the functional properties of the muscles of the upper (UA) and lower (LA) airway. However, the nature and functional relevance of this influence is currently unclear. This thesis examined the effect of acute and chronic IMT in the context of UA and LA function. The ability of IMT to activate the UA dilator muscles, genioglossus (GG) and geniohyoid (GH), was examined using magnetic resonance imaging (MRI), as was the effect of chronic training on these muscles. In addition, the effect of acute and chronic IMT upon LA resistance (Rrs) and function was investigated in people with asthma using the Forced Oscillation Technique and conventional spirometry. For the UA, an acute bout of IMT at 60% maximal inspiratory mouth pressure (MIP) resulted in significant GG and GH activation (P < 0.001) as demonstrated by increases in the transverse relaxation time of muscle water (T2). Despite this, MRI was unable to detect any effect of chronic IMT upon UA function. For the LA, the usual increase in Rrs, following deep inhalation (DI) in people with asthma was attenuated with both single and multiple breaths against a pressure-threshold load equal to 50% MIP. However, six weeks IMT had no effect on baseline airway function or response to DI. In conclusion, an acute effect of pressure-threshold IMT upon UA and LA function was demonstrated. A strong rationale for a beneficial influence of chronic pressure-threshold IMT was therefore demonstrated. However, the data were insufficient to either reject, or accept the hypothesis that IMT exerts more than a transient influence upon UA and LA function, but insights are presented that support the need for further investigations.

INTRODUCTION: Recent epidemiological studies have shown that Diesel Engine Exhaust (DEE) exposure is associated with lung cancer. Well recognized exposures, such as smoking, have long been known to cause lung cancer, and the mechanisms by which the disease occurs have been closely investigated. However, there is very little information regarding the mechanisms by which chronic DEE exposure leads to a disease outcome. It has also been shown that transcriptomic changes in the deeper portions of the airway may be detectable in the more proximal parts. The goal of this study was to assess transcriptomic alterations in the nasal epithelium of DEE exposed factory workers to better understand the physiologic effects of DEE and how chronic exposure may lead to disease. METHODS: Nasal epithelium brushings were obtained from 41 subjects who work in a factory with DEE exposure, and 38 comparable control subjects who work in factories without DEE exposure. The median Elemental Carbon (EC) levels of exposed individuals was 60.7g/m3, with a range of 17.2-105.4 g/m3, while the median of EC levels of unexposed controls was 10.87g/m3, with a range of 9.89-12.55g/m3. RNA was isolated from nasal epithelial cells, and profiled for gene expression using Affymetrix Human Gene 1.0ST microarray chips. Linear modeling was used to detect differential expression between DEE exposure and controls. Pathway enrichment in differentially expressed genes was assessed using EnrichR. GSEA provided comparisons between the genes known to be differentially expressed due to smoking, and the genes that were found in our data to be differentially expressed due to smoking or DEE. A linear modeling approach was further used to investigate the effects of the interaction between smoking status and DEE exposure, and boxplot analysis was used to explore the interaction effect. RESULTS: We found 225 genes whose expression is associated with DEE exposure at FDR q < 0.25, after adjusting for smoking status. Within this set of genes, we observed increased expression of genes involved in the oxidative stress response, cell cycle, and protein modification, as well as genes associated with the AhR pathway and the Nrf2-mediated xenobiotic metabolism response. Additionally, decreased expression of genes involved in transmembrane transport, such as CFTR and the solute carrier family genes was also found. Furthermore, we discovered 8 genes at FDR q < 0.25 that have altered expression due to the interaction of DEE and smoking status, suggesting a synergistic relationship between the effects of these exposures on some aspects of the physiological response. For these genes, the effects of DEE were generally more dramatic in never smokers. CONCLUSIONS: The transcriptomic alterations we identified may help provide insight into the underlying mechanisms of DEE carcinogenicity. The relationship between cigarette smoke exposure and DEE exposure may provide more information about how chronic DEE exposure leads to lung cancer and other respiratory diseases.

Acute respiratory distress syndrome (ARDS) and infant respiratory distress syndrome (IRDS) are severe pulmonary syndromes affecting approximately 190,000 in the United States with a mortality rate of 40%. During ARDS, hypoxemia can follow, which requires mechanical ventilation. This assisted ventilation can injure the lung by inducing large mechanical stresses from an air-liquid interface propagating through occlusion, and exposing the vessel wall to large mechanical stress gradients. In this study we investigate airway reopening scenarios by creating a model of terminal pulmonary airways using flexible tubing with monolayer coverage of lung epithelial cells. Specifically, we attempt to find a relationship between the state of collapse of a channel and the stress the cells undergo during the reopening event. This study is the first demonstration of an experimental tube with a tube law approximately physiological range. Our results indicated that in collapsed channels, as the velocity of reopening increases, the amount of damage to cells increases. This indicates flexibility causes an increase in cell damage which agrees with the stimulus-response behavior from prior studies. However, in fully-inflated channels, we see transitional behavior between flexible and rigid models. This research is a good starting point to investigate recruitment-derecruitment events in flexible channels, which could give a better representation of the mechanisms that cause cell damage in cases of ARDS and VILI. / 1 / Michael C Harrison

No description available.

This research focuses on investigating the vibration characteristics of branched circular cylindrical shells with applications to airway passages. Analytical modelling is carried out based on Donnell-Mushtari equations of thin elastic membrane type of shells while numerical validation is conducted using the Finite Element Method (COSMOS/Works). Further validation of the results is performed using experimental investigation of tracheobronchial tissues dissected from pigs. The analytical, numerical and experimental results are in acceptable agreement. Further investigation of the vibration characteristics of the airways for cases which cannot be dealt with analytically is carried out using COSMOS/Works. Results show a strong trend relationship which suggests that the natural frequency of the trachea and the primary tracheobronchi is approximately 10 Hz. Radial resonances of lower bronchi are predictable through trends found in this work that the resonant frequency is a linear function in certain region of generations.

Thesis (M.D.S.)--University of Hong Kong, 1997. / Includes bibliographical references (leaves 244-306) Also available in print.

Objective: To determine the upper airway morphometry of Chinese adults by computed tomography. Study Design: This anatomical study consisted of radiological examination of Chinese adults’ upper airway and trachea using computed tomography and image analysis with the help of post-data capture processing software. Materials and Methods: A retrospective review of sixty-five Chinese adults who underwent computed tomography of head and neck region at a regional hospital in Hong Kong was conducted. Computed tomography performed by a Philips Gemini 16? PET/CTPhilips Gemini GXL 16 PET/CT Scanner. Post-data capture processing was performed on GE Advantage Window 4.3 workstation. Measurements were made on standard or oblique reformatted orthogonal planes. Results: 65 consecutive computed tomography scans of the head and neck region of Chinese adults werereviewed. The distance between lower incisor and vocal cords was 144.0mm (±12.1 SD) in men and 124.8mm (±10.4 SD) in women. The distance between the vocal cord and cricoid ring was 21.5mm (±5.8SD) in men and 16.1mm (±6.3SD) in women. The distance between the lower incisor and cricoid ring was 165.5mm (±10.7SD) in men and 140.9 mm (±11.1SD) in women. The distance between the vocal cord and carina was 142.4mm (±12.1SD) in men and 130.4mm (±12.6SD) in women. The distance between the cricoid ring and carina was 121.0mm (±12.7SD) in men and 114.3mm (±10.2SD) in women. All these measurements showed statistically significant gender difference. In men, the anteroposterior diameter of cricoid ring was 21.8mm (±1.4SD) and the transverse diameter was 17.0mm (±1.7SD). In women the anteroposterior diameter of cricoid ring was 17.4mm (±1.9SD) and the transverse diameter was 13.4mm (±1.8SD). Both were statistically different among men and women. The anteroposterior diameter of trachea of men was 21.1mm (±2.9 SD) and the transverse diameter was 17.8mm (±2.7 SD). While the corresponding anteroposterior diameter was 16.1mm (±2.2 SD) and the transverse diameter was 15.9mm (±1.6 SD) in women with statistically significant difference. Using the Pearson correlation, body height but not age of subjects was statistically correlated with all the airway measurements Conclusion: This study reports the tracheal morphometry and dimensions in a Chinese population and their correlation with body height. Details of these measurements will aid airway management and other upper airway procedures in this population. Conclusion: This study reports the tracheal morphometry and dimensions in a Chinese population and their correlation with body height. Details of these measurements will aid airway management and other upper airway procedures in this population. Conclusion: This study reports the tracheal morphometry and dimensions in a Chinese population and their correlation with body height. Details of these measurements will aid airway management and other upper airway procedures in this population. / published_or_final_version / Anatomy / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Doctor of Medicine

No description available.

Oscillatory velocity profiles and the pressure-flow relationship were measured in a 3:1 scale rigid model of the human central airways. A reciprocating pump provided flows with frequencies of 0.25, 1, 2 and 4 Hz and tidal volumes of 300, 500 and 1500 mL giving tracheal Womersley numbers up to 31 and peak tracheal Reynolds numbers up to 17000. A hot wire anemometer was used to measure velocities along two perpendicular diameters (one in the plane of the model and the other in the plane perpendicular to the model) at 10 stations distributed through the model. Velocities were also measured with and without a model larynx and with tracheal intubation in steady inspiratory flows. The flow distribution to the five lobar bronchi was identical in all experiments. / Oscillatory velocity profiles were compared with the steady velocity profiles at nearly identical Reynolds numbers. The flow in a branch was quasi-steady below a critical Strouhal number in agreement with an order of magnitude analysis. For quasi-steady oscillatory flows the velocity profile developed from an initially flat shape to the profiles characteristic of steady flow in branching tubes. Flows that were not quasi-steady exhibited relatively flat profiles over the entire respiratory cycle. The effects of tidal volume, frequency and the geometry of the airways on the velocity profiles were determined. / While the larynx produced a significant jet within the trachea it had no effect on the velocity profiles beyond the carina. The presence of a concentric endotracheal tube located halfway between the glottis and the carina had little effect on the velocity profiles in the main stem and the lobar bronchi. Inserting the tube further into the trachea altered the velocity profiles in the right upper lobar bronchus. / In oscillating flow the pressure was essentially uniform around the periphery of a branch in strong contrast to the results for steady flow. The pressure drop in oscillating flow was much larger than the pressure drop in steady flow at an equivalent flow rate. The functional form of the relationship between the pressure drop across the different branches of the model and the tracheal Reynolds number was similar to that suggested by earlier researchers, however the coefficients were very sensitive to the geometry of the model.