Asthma is .a respiratory.,disease.that affects over 300 million people world-wide and is involved in over 250000 deaths annually. Asthma is classically thought of as an allergic disease with variable airflow obstruction and airway hyperresponsiveness (AHR) associated with airway remodeling, although phenotype variations are observed in the population. Due to multiple factors including genes, gender, exposure to pathogens, environmental pollutants, diets, and obesity, a clear picture of the complex interactions between an individual's genes, the environment which they live in, and the development of an asthmatic phenotype remains elusive. Despite the availability of treatment strategies for asthma, varying degrees of airway inflammation, remodeling, and AHR remain present in an asthmatic patient. Our general hypothesis that was the basis for all studies was the following: "Airway remodeling in response to allergen exposure is a major contributing factor to AHR observed in asthmatics. Understanding the mechanisms behind the different components of airway remodeling will provide new avenues for therapeutic development aimed at improving lung function above and beyond current treatment strategies." The currently available therapeutics and management strategies for asthma are unable to prevent or reverse components of airway remodeling. It is possible that with greater understanding of the processes involved in the various indices of airway remodeling new classes of therapeutics could be developed to selectively target this broad, ill-managed aspect of asthma. Collectively the studies contained in this thesis have been linked by the general themes of greater characterization of in vivo mouse models of allergen exposure, the application of these models to mechanistically explore the biological pathways involved in the different components of airway remodeling, and the testing of novel therapeutic strategies targeting these pathways of interest. / Thesis / Doctor of Philosophy (PhD)

This thesis will cover the principle, design, and construction of an automatic esophageal intubation detector. This device uses a giant magneto recitative sensor to and a magnetized stylet to automatically measure the position of an ET tube in a person's throat. This method is less subjective than currently used methods such as end tidal CO2, as it does not rely on user interpretation of data or physiological state of the patient. The device developed during this project was tested on an anatomical mockup, a porcine airway model, and an intubation training dummy. In all three tests, the device performed well, accurately indicating tracheal intubation when the tube was placed in the trachea. Only one instance of a false positive indication of tracheal intubation was recorded and this occurred in an atypical and avoidable situation. As of now, the device functions in non-obese adult male patients, but plans are in place to increase usability for the entire population. / Master of Science

Perfluorinated compounds, non-degradable xenobiotics in many consumer products, can cause developmental toxicity in animals, and human exposure is associated with asthma symptoms. We tested the hypothesis that sustained chronic exposure to perfluorooctanoic acid (PFOA), fluorotelomer alcohol (FTOH) or perfluorooctanesulfonic acid (PFOS) induces lung dysfunction that exacerbates allergen-induced airway hyperresponsiveness (AHR) and inflammation. Mice were exposed to the chemicals from early gestation day to adulthood. Some pups were sensitized and challenged with ovalbumin. Serum PFOA was analyzed by liquid chromatograph-tandem mass spectrometry. Lung function was measured using a small animal ventilator. We assayed inflammatory cells in the lung, performed PCR for lung cytokines, and examined bronchial goblet cell hyperplasia by histology. Here we show that either PFOA or FTOH exposure can induce AHR, but neither one predisposes for exaggerated allergic lung inflammation or AHR. FTOH or PFOS exposure appears to suppress allergic lung inflammation, but does not affect allergic lung dysfunction.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Michigan, 1986.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (M.S.)--University of Michigan, 1986.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

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