Chronic obstructive pulmonary disease (COPD) is characterized by periodic episodes of worsening symptom (e.g., shortness of breath, irregular breathing, and worse coughing with increased phlegm production), also called pulmonary exacerbations. Inflammation is an important cause of reduced lung function as inflammation contributes to airflow obstruction in the small airways and lung parenchyma. Even in individuals with mild COPD, inflammation reduces lung function, accelerates decline in lung function overtime, and increases the risk for respiratory exacerbations. Agents that reduce systemic inflammation are hypothesized to decrease the inflammation in the lungs, resulting in improvements in lung function and a decrease in exacerbation frequency. We hypothesize that antidepressants have a beneficial effect on lung function. In addition to having anti-inflammatory properties, antidepressants act upon serotonin, which is integral in central breathing control. The combination of the anti-inflammatory and serotonergic effects may provide users of selective serotonin reuptake inhibitors with a lung function benefit while avoiding the side effects of steroids. This dissertation assesses whether selective serotonin reuptake inhibitors increase concurrent lung function and reduce the risk for respiratory exacerbations. It consists of three parts: a systematic literature review and two analytic papers using large prospective databases. The systematic review of the literature identified limitations concerning the effect of selective serotonin reuptake inhibitors on lung function. Overall, the analytic papers found no support for a beneficial association between selective serotonin reuptake inhibitors and spirometry, dyspnea or pulmonary exacerbations; indeed the association was in the opposite direction as hypothesized. In addition, there was no support for meaningful mediation by inflammatory markers. Further research is needed to determine if selective serotonin reuptake inhibitors have a harmful effect on lung function and pulmonary exacerbations.

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

Thesis (M.Sc. (Hons.))--University of Western Sydney, Nepean. / Bibliography: leaves 104-108.

Thesis (Ph. D.)--University of Sydney, 2007. / Title from title screen (viewed 10 June 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Medicine, Faculty of Medicine. Degree awarded 2007; thesis submitted 2006. Includes bibliographical references. Also available in print form.

Thesis (M.S.)--University of Michigan, 1975.

Thesis (M.S.)--University of Michigan, 1975.

Thesis (MMed)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Background: The LODOX Statscan is a whole-body digital X-ray scanning device which was adapted for medical usage. The LODOX has an established role in the field of Forensic Pathology where it shows high sensitivity and specificity for the detection of skeletal pathology and foreign bodies. The role of the scanner in the detection of soft tissue pathology in the lungs of adults has not been reported and this study aims to review the radio-pathological correlation and the applicability of LODOX as a viable screening tool in the detection of lung pathology in post mortem cases. Methods: We prospectively reviewed cases which were referred for medico-legal autopsy between November 2012 and March 2013 to the Tygerberg Forensic Pathology Service mortuary, Cape Town, South Africa. All cases meeting the prescribed inclusion criteria underwent LODOX scanning as well as macroscopic and microscopic evaluation of the lungs as permitted by the Inquests Act 58 of 1959. The macroscopic and microscopic variables were considered the “gold standard” when compared with the results of the LODOX. The sensitivity, specificity, positive and negative predictive values were assessed. Results: One hundred and fifty nine cases (159) were included in the study. The most common radiographic patterns reported were the presence of ground glass opacities and consolidation. Overall, low to moderate sensitivity of these LODOX patterns in the prediction of pneumonic microscopic pathology (oedema, acute and chronic inflammation and features of diffuse alveolar damage) was noted. These values were lower than that reported for pneumonia using conventional X-rays. Additionally, these LODOX patterns have a high probability of representing oedema or autolytic/decomposition change. Pneumothorax was the most common pleural pathology detected on LODOX, but autopsy correlation could not be performed. Poor to no correlation was noted with the variables of cavity, malignant tumour, and bronchiectasis, but the prevalence of these conditions in our cohort was low. In general, LODOX predictions were better at excluding pathology which was not present rather than confirming pathology which was present. Conclusions: The LODOX offers excellent evidentiary value in the demonstration of a pneumothorax but currently has limited value as a “stand alone” test in the field of Forensic Pathology. However the continued use of the LODOX as an adjunct examination, as well as prospective study of its applicability, is advised. / AFRIKAANSE OPSOMMING: Agtergrond: Die LODOX Statscan is ‘n heel-liggaam digitale X-straal skandeer apparaat wat aangepas is vir mediese gebruik. Die LODOX het ‘n gevestigde rol in Geregtelike Patologie, waar dit ‘n hoë sensitiwiteit en spesifisiteit het in die opsporing van skeletale patologie en vreemde voorwerpe. Die rol van die skandeerder in die opspoor van sagte weefsel patologie in die longe van volwassenes is nog nie gerapporteer nie, en hierdie studie ondersoek die radio-patologiese korrelasie en toepaslikheid van LODOX as ‘n doeltreffende siftingsmeganisme om long patologie op te spoor in post-mortale gevalle. Metode: Gevalle wat verwys is na die Tygerberg Geregtelike Patologie Diens lykshuis in Kaapstad, Suid-Afrika vir medies-geregtelike outopsies tussen November 2012 en Maart 2013, is prospektief geëvalueer. Alle gevalle wat die voorgeskrewe insluitingskriteria nagekom het, het LODOX skandering asook makroskopiese en mikroskopiese ondersoek van die longe ondergaan, soos toegelaat deur die Wet op Geregtelike Doodsondersoeke Nr 58 van 1959. Die makroskopiese en mikroskopiese veranderlikes is beskou as die “goud standaard” in vergelyking met die resultate van die LODOX. Die sensitiwiteit, spesifisiteit, positiewe en negatiewe voorspellingswaardes is beoordeel. Resultate: Eenhonderd-nege-en-vyftig gevalle (159) is ingesluit in die studie. Die algemeenste radiografiese pattroon wat gerapporteer is, was die teenwoordigheid van gemaalde glas opasiteit en konsolidasie. In geheel is lae to matige sensitiwiteit van hierdie LODOX beelde waargeneem in die voorspelling van pneumoniese mikroskopiese patologie (edeem, akute en chroniese ontsteking, en eienskappe van diffuse alveolêre skade). Hierdie waardes was laer as die wat gerapporteer is vir pneumonie met konvensionele X-strale. Verder het hierdie LODOX beelde ‘n hoë waarskynlikheid om edeem en/of outolise/ontbinding uit te beeld. Pneumotoraks was die algemeenste pleurale patologie wat waargeneem is met die LODOX, maar outopsie korrelasie kon nie gedoen word nie. Swak tot geen korrelasie is gemerk vir die veranderlikes kaviteit, maligne tumor en brongi-ektase, maar die prevalensie van hierdie toestande in ons kohort was laag. Oor die algemeen was LODOX voorspellings beter om patologie wat nie teenwoordig is nie, uit te skakel, eerder as om patologie wat teenwoordig is, te bevestig. Gevolgtrekking: The LODOX is ‘n uitstekende bewysstuk in die aantoon van ‘n pneumotoraks, maar huidiglik het dit beperkte waarde as onafhanklike toets in die veld van Geregtelike Patologie. Desnieteenstaande word die verdere gebruik van LODOX as bydraende ondersoek, sowel as die prospektiewe studie van sy toepaslikheid aanbeveel.

No description available.

Lung disease is the third leading cause of death worldwide. The only curative intervention for end-stage lung disease is lung transplantation, which remains limited by the shortage of viable donor organs. Strategies to improve outcomes for patients with end-stage lung disease include: (i) ex vivo recovery of initially unusable donor lungs to a level suitable for transplantation, and (ii) repair of damaged lungs in situ to avoid the need for transplantation. Recovery of damaged lungs both ex vivo and in situ necessitates precise regulation of the lung extracellular environment, which includes biochemical, physical, and mechanical stimuli across scales. This thesis describes the development of bioengineering tools, including bioreactors and biomaterials, that leverage the lung extracellular environment across cellular, tissue, and organ scales to: (i) recover whole injured donor lungs ex vivo, (ii) assess and repair regional lung tissue injury in situ, and (iii) study the pathological cellular microenvironment in cystic fibrosis. In Chapter 1, regulation of the organ macroenvironment (ventilation, perfusion, systemic metabolism) with a homeostatic cross-circulation bioreactor enabled up to 100 hours of ex vivo lung support and recovery of injured human donor lungs. In Chapter 2, quantitative analysis of localized lung tissue properties, including lung sounds, enabled detection and assessment of pulmonary air leak, and recapitulation of lung microenvironmental features (structure, mechanics, composition) in a therapeutic biomaterial sealant enabled rapid treatment of air leaks. In Chapter 3, the first quantitative characterization of the cystic fibrosis matrisome (matrix proteome) identified pathological alterations to the microenvironment, and investigated implications for inflammation and immunity in cystic fibrosis. Collectively, these studies demonstrate that macro- and microenvironmental signals, including ventilation and perfusion mechanics, homeostatic metabolic regulation, and extracellular matrix structure and composition, can be leveraged to reveal previously unknown drivers of disease and promote recovery and repair of damaged lungs.

published_or_final_version / Pathology / Master / Master of Philosophy