Background: Accurate and appropriate spirometry reference values allow for early detection of respiratory illness and perform an important role in monitoring lung health. There is, in general, a scarcity of data from Africa, and the Global Lung Initiative (GLI) has published global reference equations but models did not include data from African studies. The aim of this study was to investigate lung function in a group of healthy South African females and the applicability of the GLI reference equations. Methodology: Maternal lung function testing was undertaken at 6 to 10 weeks post-partum as part of a birth cohort study, the Drakenstein Child Health Study. Pre- and post-bronchodilator spirometry was performed according to a standardised protocol and correlated with clinical information. Bronchodilator response was assessed by repeating spirometry 15 minutes after administration of inhaled 400mcg salbutamol. Results: A total of 462 women were included, mean age 17 years (range 18- 42 years). The GLI reference equations fitted the observed lung function results well for the group of mothers who did not self-report smoking or asthma. There were 64 (14%) mothers with an abnormal Forced Expiratory Volume in 1 Second (FEV 1) result, 60 (13%) mothers with an abnormal Forced Vital Capacity (FVC), and 35 (8%) mothers with an abnormal FEV 1 /FVC ratio. There were 22 (5%) mothers who had reversible FEV 1; the rate of undiagnosed reversibility was 4% of the cohort. High body mass index was associated with a higher risk for poor FVC and FEV 1 /FVC lung function, OR 1.40 (CI: 1.01, 1.65) and OR 1.25 (CI 1.10, 1.95) respectively. Mothers with a higher socio-economic status had better FEV 1 with the adjusted SES OR 0.65 (CI 0.36, 1.08). Conclusions: There was a high prevalence of abnormal lung function in this cohort of South African adult females and a number of cases of undiagnosed reversibility. Spirometry testing is important to diagnose lung disease in South African communities. The GLI's reference equations were appropriate and applicable for a cohort of South African adult women.

The increasing rate of Acute Respiratory Distress Syndrome (ARDS) reinforces the need for additional resources to assist clinical staff with an individual's care and recovery. Pronation therapy involves physically rotating an individual from the posterior position to the prone position. Pronation therapy has successfully been used for individuals diagnosed with ARDS in Intensive Care Units for decades. However, manual pronation maneuvers by staff members poses risks for those who are critically ill and risk of physical injury to caregivers. Mechanical pronation beds have revolutionized the art of pronation therapy, minimizing risks, and decreasing possibility of kinking or pulling out life supporting lines. The methodology for this thesis included searching electronic database of research and clinical peer reviewed journals. Search terms included the keywords: Rotopron* OR "Rotoprone therapy" OR "rotation* bed" AND ARDS or "acute respiratory distress syndrome" OR "acute respiratory failure". Inclusion criteria included articles published in English between 2005– present. A table of evidence was being developed to summarize key points from each reviewed article. The articles were individually critiqued. Synthesis of the findings were discussed to identify consistent and inconsistent findings, along with gaps in the literature. Preliminary literature analysis suggests research is needed regarding standardization of mechanical pronation procedures along with staff education

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Respiratory syncytial virus (RSV) is a pathogen associated with lower respiratory tract infection, and is a common cause of infant hospitalization worldwide. Despite efforts to create safe and cost-effective RSV therapeutics, there remains no vaccine, and antiviral drugs have been developed with limited success. Among the 11 proteins coded by the negative-sense single-stranded RNA genome of RSV, the phosphoprotein (P) and nucleoprotein (N) aid in the formation of an RNA-dependent RNA polymerase (RdRp) complex, which is essential for RSV virulence. The specificities of the N-P binding interaction have been researched extensively, which has provided researchers with a novel target for an RSV therapeutic. In this study, a recombinant peptide mimetic (P220-241) containing the final 21 C-terminal amino acids of RSV P fused to Maltose-Binding Protein (MBP), and a cell-penetrating peptide (CPP), was purified for the purpose of targeting this interaction. In addition to successfully entering cells, the peptide was shown to inhibit both RSV subtype A and subtype B infection in vitro, with a percent inhibition (PI) of infection as high as 95% at 20 μM. Additionally, P220-241 did not inhibit infection of parainfluenza virus type 2 (PIV-2), indicating this inhibition was not an artifact of the peptide acting as a pathogen-associated molecular pattern (PAMP). A series of three different assays demonstrated that P220-241 does not appear to have any cytotoxic effects in vitro. Finally, using both glutathione S-transferase (GST) pull-downs and in vitro immunoprecipitations, we demonstrated that P220-241 is able to bind the N protein, while also preventing binding of full-length P protein. Taken together, this study provides the framework for a novel method of targeting RSV protein-protein interactions using chimeric cell-penetrating peptide mimetics. / Thesis / Master of Science (MSc)

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published_or_final_version / abstract / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Background: Cotton workers are highly exposed to organic dust. Inhalation of cotton based particulate has been associated with various respiratory symptoms and impaired lung function. This study investigates the respiratory health profile of textile mill workers in Nepal in relation to dust and endotoxin exposure. Methods: This study was conducted in four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal. A total of 938 individuals completed a health questionnaire and performed spirometry. A subset of 384 workers performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full-shift for a 114 workers. Results: Geometric mean concentrations of personal exposure to cotton dust and endotoxin were 0.81 mg/m3 and 2160 EU/m3 respectively. Overall prevalence of persistent cough, persistent phlegm, wheeze, breathlessness and chest tightness were 8.5%, 12.5%, 3.2%, 6.5%and 3.6% respectively. Symptoms were most common among the recyclers and less in the garment sector. Exposure to inhalable dust significantly predicted the symptoms of persistent cough and chest tightness. Significant cross-shift reduction in FEV1, FVC, and FEF25_75 were measured in the textile workers (p<0.001 for all); reductions being greater in the recyclers (-143 ml) and smallest in the garment workers (-38 ml) (p=0.012). Cross-shift reduction in FEV1 was significantly predicated by exposure to inhalable dust. Exposure to endotoxin did not correlate with any of the respiratory symptoms nor to lung function. Conclusion: The measured association between exposure to inhalable dust and reporting of respiratory symptoms and lung function suggests that despite high levels of endotoxin exposures, inhalable dust is the driver for these effects and attention should turn to what might be the toxic component in this dust other than endotoxin.