The work contained in this thesis was concerned with rebreathing methods of measuring lung volume. In particular, one novel rebreathing technique which uses oxygen as the indicator gas was assessed. This technique appeared methodologically simple and readily applicable in a clinical environment. In essence, it relied on a graphical extrapolation of the time related changes in oxygen concentration to allow for oxygen uptake. This technique has been tested using a mass spectrometer which enabled nitrogen and argon as well as oxygen to be simultaneously used as indicator gases. Although the lung volumes as measured by the different indicator gases should have been the same, these were found to be different. These discrepancies were related to the concentration of the indicator gas which existed in the bag and lung prior to rebreathing. A hypothesis explaining these inconsistancies was formulated. This was based on an initial but non-sustained output of carbon dioxide into the bag-plus-lung system. A numerical model of idealised rebreathing showed that the hypothesis was sufficient to explain the discrepancies observed. A correction procedure was devised which performed successfully in the model. This correction was incorporated into an on-line computing procedure for calculating real lung volume. When tested in normal subjects this gave consistent results for lung volume, irrespective of indicator gas employed. The corrected lung volumes were unaffected by the initial gas compositions in the bag and lung, and were also independent of non-sustained gas exchange, whether this was due to carbon dioxide and/or nitrous oxide. This technique could, therefore, be use under anaesthetic conditions, since the uptake or output of nitrous oxide no longer upsets the calculation of lung volume. The use of more than one indicator gas, within the same manoeuvre, was shown to provide a valuable indication of the presence of errors in the system. When this approach was applied to more conventional rebreathing techniques of lung volume measurement, it also highlighted the presence of inaccuracies.

No description available.

Background: Chronic obstructive pulmonary disease (COPD) is a devastating illness that affects 4.3% of the population of British Columbia over the age of 45 years. Asthma is known to coexist in 10-20% of individuals with obstructive lung disease, and adds to the substantial burden of illness posed by COPD alone. Inhaled corticosteroids (ICS) are currently recommended for the management of COPD among individuals with frequent exacerbations; however, the ability of inhaled corticosteroids to reduce death and hospitalizations among individuals with COPD is controversial. Less is known about the effectiveness of ICS among individuals who are afflicted with both COPD and asthma. Methods: We used a retrospective cohort study design and administrative data to estimate the relative effectiveness of ICS in reducing hospitalizations or death among individuals with concomitant asthma and COPD, compared with individuals with COPD alone. We used an extended Cox model to estimate this association, with a time-varying measure of exposure to ICS. Results: We did not find any association between ICS and hazard of death or hospitalization among individuals with COPD alone (HR = 0.99; 95% CI: 0.94 – 1.05), however the hazard was 18% lower (HR = 0.82; 95% CI: 0.69-0.99) among individuals with concomitant disease. Conclusions: Individuals with combined COPD and asthma show significant benefit from the use of ICS and are more responsive to the effects of ICS than individuals with COPD alone.

Background and objective: Asbestos can cause various pulmonary diseases including asbestosis, pleural plaques and pleural thickening. Animal and in vitro studies suggest that the toxicity of asbestos is due to the iron content of the fibres which not only generate oxidants directly, but also activate the inflammatory cells in the lung that contribute to oxidative stress. This study therefore sought to establish data in man to corroborate the animal and in vitro evidence. Exhaled breath condensate (EBC) collection is a novel, non-invasive technique to collect samples from the lung for investigating inflammatory biomarkers of lung diseases. This technique is harmless, rapid and easily repeatable which leads itself to the investigation of lung diseases such as asbestos-related diseases and pulmonary fibrosis (PF) that are otherwise difficult to study. The hypothesis tested was that oxidative and nitrosylative stress markers will be elevated in the EBC of patients with asbestos-related diseases and PF compared to normal control subjects. Methods: The study design was a cross-sectional and observational in vivo study whereby EBC was collected and fractional exhaled nitric oxide (FeNO) and carbon monoxide (eCO) were measured. EBC markers including pH, hydrogen peroxide (H2O2), total nitrogen oxides (NOx), 3-nitrotyrosine (3-NT), 8-isoprostane (8-iso), total protein and transforming growth factor-β1 (TGFβ1) were measured by microelectrode analysis, colorimetric and enzyme immunoassays. 3-NT and 8-iso were further examined by immunohistochemical techniques in samples of lung tissue. Results: Subjects with asbestosis had significantly raised levels of EBC H2O2, 8-iso, total protein and FeNO compared with healthy individuals. The same markers except H2O2, but with 3-NT and eCO were again significantly increased in those with other causes of PF, compared with control subjects. Heavy nitrotyrosine staining was found on the lung sections from patients with asbestosis and PF. Conclusions: This study confirmed that increased production of reactive oxygen and nitrogen species is associated with asbestos exposure and pulmonary fibrosis in vivo confirming animal and in vitro studies. Analysis of EBC may prove a useful non-invasive tool in exploring the basic pathophysiology of lung diseases in clinical research and may in the future be used to monitor progress in asbestosis and pulmonary fibrosis.

Bibliography: leaves 209-254. / viii, 254, [39] leaves, [17] leaves of plates : ill. 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Attempts to construct an evolutionary overview of the regulation of surfactant secretion among the vertebrates. A detailed whole animal and in vitro study of the factors that control surfactant secretion and function in the central Australian agamid lizard Pogona vitticeps was undertaken. Type II pneumocytes were also isolated and cultured from Australian lungfish, North American bullfrogs and fat-tailed dunnarts. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1999

Pulmonary surfactant is a complex mixture of lipids and proteins that lowers surface tension, increases lung compliance, and prevents the adhesion of respiratory surfaces and pulmonary oedema. Pressure can have an enormous impact on respiratory function, by mechanically compressing tissues, increasing gas tension resulting in increased gas absorption and by increasing dissolved gas tensions during diving, resulting in the formation of bubbles in the blood and tissues. The lungs of diving mammals have a huge range of morphological adaptations to enable them to endure the extremely high pressures associated with deep diving. Here, I hypothesise that surfactant will also be modified, to complement the morphological changes and enable more efficient lung function during diving. Molecular adaptations to diving were examined in surfactant protein C (SP-C) using phylogenetic analyses. The composition and function of pulmonary surfactant from several species of diving mammals was examined using biochemical assays, mass spectrometry and captive bubble surfactometry. The development of surfactant in one species of diving mammal (California sea lion), and the control of surfactant secretion using chemical and mechanical stimuli were also determined. Diving mammals showed modifications to SP-C, which are likely to lead to stronger binding to the monolayer, thereby increasing its fluidity. Phospholipid molecular species concentrations were altered to increase the concentration of more fluid species. There was also an increase in the percentage of alkyl molecular species, which may increase the stability of the monolayer during compression and facilitate rapid respreading. Levels of SP-B were much lower in the diving species, and cholesterol was inversely proportional to the maximum dive depth of the three species. Surface activity of surfactant from diving mammals was very poor compared to surfactant from terrestrial mammals. The newborn California sea lion surfactant was similar to terrestrial mammal surfactant, suggesting that these animals develop the diving-type of surfactant after they first enter the water. The isolated cells of California sea lions also showed a similar response to neuro-hormonal stimulation as terrestrial mammals, but were insensitive to pressure. These findings showed diving mammal surfactant to have a primarily anti-adhesive function that develops after the first entry into the water, with a surfactant monolayer, which would be better suited to repeated collapse and respreading. / Thesis (Ph.D.)--School of Earth and Environmental Sciences, 2005.

Records of all neurosurgical inpatients admitted to Royal North Shore Hospital since 1976 have been prospectively kept in a relational database. Demographic details, diagnoses, operations and complications have been entered continuously since 1982 by the author of this study. Complications are monitored at monthly review meetings attended by medical staff. The recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) at these meetings, despite continual improvements in patient care, prompted this study. It aims to use the database to study changes in the incidence of DVT and PE over the previous twenty years; to find what database variables predict these complications; and whether use of mechanical and pharmacological agents has had an impact on DVT and PE rate. Univariate analysis of the incidence of DVT and PE by age, sex, length of stay (LOS), admission month, diagnosis, operation and surgeon over time was run. Any significant variables were then analysed by multivariate logistic regression. The DVT rate was low by world standards, but rose from 0.6% in 1979-83 to 1.2% in 1984-88, then rose exponentially to 3.60% in 1994-98 with a significantly increasing trend over the twenty years (c2 MH =114.20, with IDF, P<0.001). PE rate doubled significantly over the twenty years from 0.6% to 1.2% (c2 MH =17.94 with 1DF, P<0.001). Age, LOS, diagnosis, operation and surgeon were significant predictors of DVT and PE. After adjustment for LOS, time period and age, vascular surgery was found to be the strongest predictor of DVT (OR=2.82, 95% CI: 2.08-3.82, c2 =43.91, P<0.01). Vascular diagnosis was the strongest diagnosis predictor. No effect of sex or month of admission was shown. After adjustment for LOS, time period and age, spinal fusion was the strongest predictor of PE (OR=4.04, 95% CI: 1.81-9.03). Anterior communicating artery aneurysm was the diagnosis most highly associated with PE. The rise in DVT rate may be due to increased complexity of surgical and nursing management, and some screening of patients with the introduction of duplex scanning. The doubling of PE rate is unexplained. The risk of brain or spinal cord haemorrhage makes prophylactic anticoagulation a difficult choice. This study reveals groupings which can be used to determine appropriate prophylaxis. Use of mechanical and pharmaceutical agents is not recorded consistently in the database, but it is known approximately when they were introduced. No impact on the rate of DVT and PE can be demonstrated by these agents. More vigilant and widespread use of mechanical prophylaxis might be just as effective in controlling DVT and PE.

Masters of Science in Medicine / The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. Limited research into the relationship between COPD and swallow function suggests that patients with COPD are at increased risk of aspiration. One possible mechanism for this is a reduction in laryngopharyngeal sensitivity (LPS). Reduced laryngopharyngeal sensitivity (LPS) has been associated with an increased risk of aspiration in pathologies such as stroke, however impaired LPS has not been examined with respect to aspiration risk in COPD. The Aims of this study were to investigate the effect of COPD on laryngopharyngeal sensation using Laryngopharyngeal Sensory Discrimination Testing (LPSDT) and to determine whether a relationship between LPS and swallow function in patients with proven COPD exists. Method: 20 patients with proven COPD and 11 control subjects underwent LPSDT utilising an air-pulse stimulator (Pentax AP4000) via a nasendoscope (Pentax FNL10AP). The threshold of laryngopharyngeal sensation was measured by the air pressure required to elicit the laryngeal adductor reflex (LAR). A number of further examinations were also completed for COPD subjects. These included respiratory function testing, self-reporting questionnaire on swallowing ability (SSQ), bedside clinical examination of swallowing (MASA) and endoscopic assessment of swallowing (EAS). Results: subjects with COPD had a significantly higher LAR threshold when compared to their normal healthy counterparts (p<0.001). Positive correlations were identified for the relationships between MASA score and EAS results for presence of laryngeal penetration / aspiration (p<0.04), vallecular residue (p<0.01) and piriform residue (p<0.01). Conclusion: Patients with COPD have significantly reduced mechanosensitivity in the laryngopharynx. Patients with COPD also have impaired swallow function characterised primarily by pharyngeal stasis. These changes may place patients with COPD at increased risk of aspiration.

Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: School of Nursing. Bibliography: leaves 117-143. Also available online via the Internet.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 6 uppsatser.