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Although there is a renewed interest in the therapeutic potential of cannabinoids, pharmacological and physiological characterisation of these promising compounds is currently not well documented in the respiratory system. The aim of this study is to increase our understanding of possible roles of cannabinoids in the airways. Apart from CB1 and CB2 receptor-mediated actions, cannabinoid compounds can also target TRPV1 receptors, ion channels or the orphan GPR55. In isolated guinea-pig bronchi, WIN55212-2 probably exerted its inhibitory effect on sensory nerves through CB2-like receptors. VIR did not act prejunctionally but its excitatory action was mediated through TRPV1 receptors. Δ9-THC activated sensory nerves presumably involving CB1 receptors. It was speculated that GPR55 might be activated by VIR and antagonized by CBD. CBD revealed multiple mechanisms of actions: it antagonized effects mediated by TRPV1 and NK2 receptors, modulated mast cell function and showed anti-allergic activity in an in vitro model of bronchial asthma. In a human bronchial epithelial cell line the functional expression of CB1 receptors could not be confirmed. Cannabinoids examined in this study were ineffective to induce signal transduction which would be linked to ion channel activity or to intracellular Ca2+ changes. Only VIR might trigger a CB1 receptor-independent signalling pathway in these cells. In conclusion, the findings presented in this thesis reflect the diversity of cannabinoid pharmacology in the airways. They show for the first time that CBD has the ability to reduce antigen-induced bronchoconstriction, indicating relevance in bronchial asthma.

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Allergen-reactive CD4+ T cells are implicated in the pathogenesis of allergic disease. Peptide immunotherapy (PIT) involves therapeutic administration of short immunodominant peptides from within the protein allergen to which CD4+ T cell responses are directed. This approach can induce tolerance of allergen-reactive CD4+ T cells, while negating the risk of severe allergic reactions associated with whole allergen specific immunotherapy. PIT therefore holds promise as a diseasemodifying treatment for allergic patients. However, further information regarding the mechanisms of action of PIT are required to aid translation to the allergy clinic. Chicken ovalbumin (OVA) is a commonly used model allergen in mouse models of allergic airways inflammation (AAI). Trackable, T cell receptor transgenic T cells recognizing the immunodominant 323-339 peptide of OVA (pOVA) allow mechanistic investigation of PIT in response to pOVA. This thesis investigated the hypothesis that strong, systemic T cell responses induced by intravenous administration of soluble pOVA will induce i) tolerance to pOVA and ii) linked suppression to any additional OVA T cell epitopes, hence improving OVA-induced AAI. Contrary to the hypothesis, intravenous pOVA PIT did not improve disease in a C57BL/6 model of OVA-induced AAI. Models of OVA-induced allergic sensitisation and AAI were therefore developed incorporating trackable CD4+ pOVA-reactive T cells (OT-II cells). pOVA PIT induced tolerance of these cells in an allergic sensitisation setting, but had limited impact on the overall OVA response. Yet, in a model of AAI driven solely by Th2 polarised CD4+ OT-II cells, pOVA PIT did improve disease. It was concluded that, in non-transgenic C57BL/6 mice, CD4+ T cells responding to additional epitope(s) within OVA were important in driving disease and that these T cells were not subject to linked suppression following pOVA PIT. Using a panel of overlapping peptides constituting the sequence of OVA, a novel CD4+ epitope within OVA was characterised. The effects of PIT using pOVA in combination with a peptide containing this additional epitope on OVA-induced AAI were then assessed. Findings from this project therefore hold importance for future mechanistic work surrounding PIT in allergic disease.

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Bibliography: p. 165-171. / South African Airways, the National Airline of the Republic of South Africa, is but one of the five transport services owned by the State, and operated and controlled by the South African Railways and Harbours Administration, a division of the Ministry of Transport. This thesis, traces the administrative and organizational development of the Railways and Harbours Administration, and particularly the establishment of South African Airways, as a departmental undertaking within the Railways and Harbours Administration; examines other airline ownership possibilities, and submits that the government department as an administrative unit is unsuitable for the entrepreneurial activities of an airline organisation; that consequently, South African Airways should extricate itself from the Railways and Harbours Administration, which is primarily concerned with surface modes of transportation within the Republic; and that ownership and control thereof, vest rather in a public corporation, an organizational device of some importance in South Africa, even for major public enterprises, and enjoying significant advantages.

BACKGROUND: Dampness and mould exposure have been repeatedly associated with respiratory health. However, less is known about the specific agents provoking or arresting health effects in adult populations. We aimed to assess predictors of microbial agents in mattress dust throughout Europe and to investigate associations between microbial exposures, home characteristics and respiratory health. METHODS: Seven different fungal and bacterial parameters were assessed in mattress dust from 956 adult ECRHS II participants in addition to interview based home characteristics. Associations between microbial parameters and the asthma score and lung function were examined using mixed negative binomial regression and linear mixed models, respectively. RESULTS: Indoor dampness and pet keeping were significant predictors for higher microbial agent concentrations in mattress dust. Current mould and condensation in the bedroom were significantly associated with lung function decline and current mould at home was positively associated with the asthma score. Higher concentrations of muramic acid were associated with higher mean ratios of the asthma score (aMR 1.37, 95%CI 1.17-1.61). There was no evidence for any association between fungal and bacterial components and lung function. CONCLUSION: Indoor dampness was associated with microbial levels in mattress dust which in turn was positively associated with asthma symptoms.

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Class of 2007 Abstract / Objectives: Study objective: This study assessed the impact of an Open Airways for Schools Program for children with asthma that is delivered in their school by trained asthma volunteers sponsored by the local American Lung Association. Methods: Design: Retrospective. Setting: Eight elementary schools located throughout Tucson, Arizona. Participants: A total of 77 pre and post questionnaires for children in grades 3 to 5 with asthma, 30 pre and post questionnaires for parents, and 6 demographic questionnaires for school nurses. Measurements and results: Data collection involved obtaining pre and post questionnaires from the sponsoring agency measuring outcomes in knowledge of when and how much medication to take, triggers of asthma, steps to take upon wheezing, and social aspects such as the ability to talk with an adult or teacher when having problems. The dependent variables for the pre and post parent questionnaires include unscheduled visits to providers, and whether the child knows how much medication to take. Paired t test was used to determine whether differences existed between pre and post child and parent questionnaires. Nurse questionnaires were analyzed and reported to see the change in nurse visits. The results are reported as the mean post/pre ± SD. The child questionnaire data for outcomes in knowledge include: when to take medicine (0.14+/-0.35 vs 0.34+/-0.61;p=0.015), how much medicine to take upon wheeze/cough (0.38+/- 0.71 vs 0.67+/-0.80;p=0.003), identifying home triggers (0.36+/-0.68 vs 0.58+/-0.80;p=0.051), identifying school triggers (0.53+/-0.75 vs 0.70+/-0.80;p=0.228), and steps to take upon wheezing (0.21+/-0.48 vs 0.46+/-0.74;p=0.018). Social aspects data include: ability to talk to adult about asthma (0.17+/-0.45 vs 0.29+/-0.58;p=0.159), talk to teacher about asthma (0.28+/-0.57 vs 0.30+/-0.67;p=0.858), and talk to teacher about taking things out of classroom that make them wheeze (0.43+/-0.17 vs 0.77+-0.85;p=0.19). The parent questionnaire data include: unscheduled provider visits (2.83+/- 4.01 vs 3.61+/-7.15;p=0.508) and quantity of medicine to take with incomplete data. The nurse questionnaire showed a mean number of visits at 92.5+/-64.09. Results: See above Conclusions: Conclusion: Providing an asthma education program to children in school can significantly increase outcomes in knowledge of when and how much medicine to take upon wheezing, and the steps to follow when wheezing occurs. Additionally, areas to focus on in the program include identification of triggers at home and school, as well as the ability to talk with an adult or teacher regarding asthma.