Pacientes submetidos à cirurgia cardiotorácica com circulação extracorpórea (CEC) apresentam reações inflamatórias, desencadeadas por este procedimento e pela isquemiareperfusão, que acarretam disfunção pulmonar e lesão do endotélio vascular no pósoperatório. Estes processos relativos à cirurgia cardíaca podem afetar a produção e o consumo do óxido nítrico (NO) no pulmão e no endotélio vascular, principalmente na sua participação no processo inflamatório. No pulmão, o NO se difunde com facilidade sendo detectado na via aérea na fase gasosa ou no fluído pulmonar como nitrito e o nitrato. A presença do NO na via aérea pode em algumas situações refletir a sua produção pelo epitélio da via aérea e pelo endotélio microvascular pulmonar. No entanto, os processos que envolvem a produção e o consumo do NO na via aérea ainda não estão totalmente esclarecidos. O condensado do exalado pulmonar (CEP) é um fluido obtido através do resfriamento do ar exalado através de um método totalmente não invasivo e que pode ser utilizado para a investigação do NO nas vias aéreas distais. No desenvolvimento deste estudo foi utilizado um aparato de coleta artesanal e de baixo custo para obtenção do CEP. Assim, foi coletado o CEP de pacientes coronariopatas e valvopatas submetidos à cirurgia cardíaca com CEC nos períodos pré- operatório e pós-operatório (4 horas após a CEC e 12, 24, 48 e 72 horas após a extubação). As concentrações plasmáticas de nitrito/nitrato destes pacientes também foram avaliadas através de amostras de sangue colhidas imediatamente após cada coleta do CEP. O CEP e o plasma foram analisados pela técnica de quimioluminescência para obter as concentrações de nitrito/nitrato. O aparato utilizado obteve utilização reprodutível na rotina clínica da cirurgia cardíaca nesta pesquisa em pacientes sob ventilação espontânea e ventilação mecânica. Não foram encontradas diferenças significativas (p>0,05) nas concentrações de nitrito/nitrato no CEP e plasma entre os pacientes coronariopatas e valvopatas no período pré-operatório. Concentrações significativamente maiores de nitrito/nitrato (p=0,017) foram encontradas no CEP, mas não no plasma, de pacientes que utilizaram nitrato por via oral (dinitrato de isossorbida) no período pré-operatório. Em pacientes que não utilizaram medicação contendo doador de NO (nitroglicerina ou nitroprussiato de sódio) por via endovenosa no pósoperatório ocorreu uma tendência à elevação das concentrações de nitrito/nitrato no CEP que foi numericamente significativa no período de 48 horas do pós-operatório (p=0,008). Em pacientes que receberam ou não doador de NO no pós-operatório as concentrações de nitrito/nitrato foram significativamente maiores nos períodos de 48 horas (p=0,005) e 72 horas (p=0,037) do pós-operatório. A utilização de nitroglicerina (NTG) no período pósoperatório elevou significativamente as concentrações de nitrito/nitrato no CEP nos períodos de 12 horas (p=0,022), 48 horas (p=0,015) e 72 horas (0,048) e no plasma nos períodos de 12 horas (p=0,045). As concentrações de nitrito/nitrato plasmáticos foram significativamente reduzidas (p=0,045) no pós-operatório imediato 4 horas após a CEC em pacientes que receberam ou não doador de NO. A partir destes resultados pode se observar que não houve diferenças significativas nas concentrações de nitrito/nitrato no CEP dos pacientes coronariopatas e valvopatas no período pré-operatório, exceto elevação significativa encontrada em pacientes que utilizaram dinitrato de isossorbida por via oral. As concentrações de nitrito/nitrato no CEP tendem a elevar-se no período pós-operatório principalmente com a utilização de NTG. As concentrações de nitrito/nitrato no plasma foram significativamente reduzidas após 4 horas da CEC no pós-operatório imediato. No entanto foi observado elevação nas concentrações de nitrito/nitrato no plasma de pacientes que usaram NTG. Os achados deste estudo poderão contribuir em futuras pesquisas fornecendo dados comparativos a respeito da participação do NO na via aérea e no plasma nos processos que envolvem a cirurgia cardíaca nos períodos pré e pós-operatório. / Patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB) have inflammatory reactions triggered by this procedure and by ischemia-reperfusion, which cause lung dysfunction and injury of vascular endothelium in the postoperative period. These processes related to cardiac surgery may affect the production and consumption of nitric oxide (NO) in the lung and vascular endothelium, especially in their participation in the inflammatory process. In the lung, NO diffuses easily and can be detected in the airway in the gas phase or in the lung fluid as nitrite and nitrate. The presence of NO in exhaled air may reflect the airway epithelium and lung microvascular endothelium in some situations. However, processes involving the production and consumption of NO in the airway are not totally understood. The exhaled breath condensate (EBC) is a fluid obtained by cooling exhaled air wich can be used for the investigation of NO in the distal airways. For this study we used an apparatus homemade and with low cost for collecting and obtain the EBC. The EBC was collected from patients with coronary artery disease and heart valve disease undergoing cardiac surgery with CPB in the preoperative and postoperative period (4 hours after CPB and 12, 24, 48 and 72 hours after extubation). Plasma concentrations of nitrite/nitrate in these patients were also evaluated using blood samples taken immediately after each collection of the EBC. The EBC and plasma were analyzed by chemiluminescence method to obtain the concentrations of nitrite/nitrate. The apparatus used was reproducible in clinical routine of cardiac surgery in patients under spontaneous ventilation or mechanical ventilation. There were no significant differences (p> 0.05) in concentrations of nitrite/nitrate in EBC and plasma in patients with coronary artery disease and heart valve disease in the preoperative period. Significantly higher concentrations of nitrite/nitrate (p=0.017) were found in EBC, but not in plasma of patients who used oral nitrate (isosorbide dinitrate) in the preoperative period. In patients who did not use medication containing NO donor (nitroglycerin or sodium nitroprusside) intravenously in the postoperative period there was a tendency to high concentrations of nitrite/nitrate in EBC that was numerically significant in the period of 48 hours postoperative (p=0.008). In patients who received or not NO donor in postoperative period the concentrations of nitrite/nitrate were significantly higher in periods of 48 hours (p=0.005) and 72 hours (p=0.037) after surgery. The use of nitroglycerin (GTN) in the postoperative period significantly elevated concentrations of nitrite/nitrate in the EBC in periods of 12 hours (p=0.022), 48 hours (p=0.015) and 72 hours (0.048) and plasma in period of 12 hours (p=0.045). The concentrations of nitrite/nitrate were significantly reduced (p=0.045) in the immediate postoperative period 4 hours after CPB in patients who received or not NO donor. From these results we could observe that there were no significant differences in concentrations of nitrite/nitrate in the EBC of patients with heart valve disease and coronary artery disease in the preoperative period, but we found a significant increase in these concentrations in patients who used isosorbide dinitrate orally. The concentrations of nitrite/nitrate in EBC presented a tendency to increase in postoperative period especially in patients who used GTN. The concentrations of nitrite/nitrate in plasma were significantly reduced after 4 hours of CPB in the immediate postoperative period. However, was observed that GTN tended to increase the concentration of nitrite/nitrate in plasma. These findings could help in future research providing comparative data about the role of NO in the airway and plasma in processes involving cardiac surgery in the pre and postoperative periods.

O objetivo deste estudo foi de comparar a eficácia clínica de enxaguatórios bucais a higienizadores linguais e à escovação com dentifrício para higiene convencional, medidos por um monitor portátil de sulfetos BreathAlert&trade;. Vinte voluntários saudáveis, com idade entre 18 e 50 anos (média de 35,9 anos), de ambos os gêneros, foram aleatoriamente alocados em um ensaio cruzado de cinco períodos. Foram testados: um higienizador de língua convencional (Kolbe®), um higienizador integrado à escova dental (Johnson´s Professional Extreme®), dois enxaguatórios bucais: 0,05% de cloreto de cetilpiridínio (Oral-B®) e 0,12% de digluconato de clorexidina (Periotherapy®- Bitufo) e uma escova dental (Johnson´s Professional Extreme®) com dentifrício fluoretado (Contente®) como controle positivo. Todos os voluntários foram orientados a permanecer por 20 horas sem qualquer tipo de higiene bucal, para registro dos índices iniciais de halitose. Cada produto foi utilizado uma vez seguido por uma semana de washout. O hálito foi mensurado antes (00), imediatamente após (0) e após 1, 2 e 3 horas do procedimento. Os produtos e os tempos foram comparados entre si pelo teste de Friedman (p<0,05) e, havendo diferenças significantes, foram analisados aos pares pelo teste de Wilcoxon, com ajuste de Bonferroni. Imediatamente após o uso dos produtos, somente o higienizador lingual acoplado à escova foi capaz de reduzir significantemente o hálito (p=0.0031) e seu efeito perdurou por até 2 horas. A clorexidina reduziu o hálito somente no final da segunda hora (p=0.004) e durou até três horas, enquanto que a higienização bucal com escova e dentifrício foi eficaz em reduzir o hálito já na primeira hora (p=0.002), perdurando por até 3 horas. Conclui-se que a higiene mecânica da língua foi capaz de reduzir imediatamente o hálito, porém com duração relativamente curta de seu efeito, enquanto que a clorexidina e a higienização da boca conseguiram reduzir o hálito por períodos maiores do que os observados na literatura que trabalha com halitose persistente. / The aim of this study was to compare the chemical effect of antimicrobial agents in mouthrinses and mechanical effect of tongue scrapers along with toothbrushing and dentifrice for conventional oral hygiene, measured by a handheld sulphide monitor BreathAlert&trade;. Twenty healthy volunteers, from 18 to 50 years-old (the mean age was 35,9 years-old), of either gender, were randomly allocated into a five period cross-over trial. They were tested a conventional tongue scraper (Kolbe®), a tongue scraper coupled at the back of a toothbrushs head (Johnson&prime;s Professional Extreme®), two mouthwashes: 0,05% cetylpyridinium chloride (Oral-B®) and 0,12% chlorhexidine digluconate (PerioTherapy®); and a soft-bristle toothbrush (Johnson&prime;s Professional Extreme®) with fluoride toothpaste (Contente®) as a positive control. All the volunteers were asked to refrain from any kind of oral hygiene for a 20-hours period for baseline scores. Each product was used at once, followed by a one-week washout period. The breath was measured before (00), immediately after (0) and after 1, 2 and 3 hours after the procedure. A Friedman&prime;s test (p <0.05) was used to compare the products and the times and, when significant differences were detected, a Wilcoxon&prime;s test with Bonferroni correction was used (group to group). Immediately after the products use, only the toothbrush&prime;s tongue scraper was able to significantly reduce the breath (p=0.0031) and its effect lasted for up to two hours. Chlorhexidine reduced the breath only at the final of the second hour (p=0.004) and lasted for three hours, while oral hygiene with toothbrush and toothpaste was effective in reducing the breath at the first hour (p=0.002) and lasted for up to three hours. It can be concluded that the mechanical cleaning of the tongue was able to immediately reduce the breath, but with relatively short duration of its effect, while chlorhexidine and the association of mechanical with chemical agents in oral hygiene can reduce the breath for longer periods than those observed in the literature which deals with chronic halitosis.

O objetivo deste estudo foi de comparar a eficácia clínica de enxaguatórios bucais a higienizadores linguais e à escovação com dentifrício para higiene convencional, medidos por um monitor portátil de sulfetos BreathAlert&trade;. Vinte voluntários saudáveis, com idade entre 18 e 50 anos (média de 35,9 anos), de ambos os gêneros, foram aleatoriamente alocados em um ensaio cruzado de cinco períodos. Foram testados: um higienizador de língua convencional (Kolbe®), um higienizador integrado à escova dental (Johnson´s Professional Extreme®), dois enxaguatórios bucais: 0,05% de cloreto de cetilpiridínio (Oral-B®) e 0,12% de digluconato de clorexidina (Periotherapy®- Bitufo) e uma escova dental (Johnson´s Professional Extreme®) com dentifrício fluoretado (Contente®) como controle positivo. Todos os voluntários foram orientados a permanecer por 20 horas sem qualquer tipo de higiene bucal, para registro dos índices iniciais de halitose. Cada produto foi utilizado uma vez seguido por uma semana de washout. O hálito foi mensurado antes (00), imediatamente após (0) e após 1, 2 e 3 horas do procedimento. Os produtos e os tempos foram comparados entre si pelo teste de Friedman (p<0,05) e, havendo diferenças significantes, foram analisados aos pares pelo teste de Wilcoxon, com ajuste de Bonferroni. Imediatamente após o uso dos produtos, somente o higienizador lingual acoplado à escova foi capaz de reduzir significantemente o hálito (p=0.0031) e seu efeito perdurou por até 2 horas. A clorexidina reduziu o hálito somente no final da segunda hora (p=0.004) e durou até três horas, enquanto que a higienização bucal com escova e dentifrício foi eficaz em reduzir o hálito já na primeira hora (p=0.002), perdurando por até 3 horas. Conclui-se que a higiene mecânica da língua foi capaz de reduzir imediatamente o hálito, porém com duração relativamente curta de seu efeito, enquanto que a clorexidina e a higienização da boca conseguiram reduzir o hálito por períodos maiores do que os observados na literatura que trabalha com halitose persistente. / The aim of this study was to compare the chemical effect of antimicrobial agents in mouthrinses and mechanical effect of tongue scrapers along with toothbrushing and dentifrice for conventional oral hygiene, measured by a handheld sulphide monitor BreathAlert&trade;. Twenty healthy volunteers, from 18 to 50 years-old (the mean age was 35,9 years-old), of either gender, were randomly allocated into a five period cross-over trial. They were tested a conventional tongue scraper (Kolbe®), a tongue scraper coupled at the back of a toothbrushs head (Johnson&prime;s Professional Extreme®), two mouthwashes: 0,05% cetylpyridinium chloride (Oral-B®) and 0,12% chlorhexidine digluconate (PerioTherapy®); and a soft-bristle toothbrush (Johnson&prime;s Professional Extreme®) with fluoride toothpaste (Contente®) as a positive control. All the volunteers were asked to refrain from any kind of oral hygiene for a 20-hours period for baseline scores. Each product was used at once, followed by a one-week washout period. The breath was measured before (00), immediately after (0) and after 1, 2 and 3 hours after the procedure. A Friedman&prime;s test (p <0.05) was used to compare the products and the times and, when significant differences were detected, a Wilcoxon&prime;s test with Bonferroni correction was used (group to group). Immediately after the products use, only the toothbrush&prime;s tongue scraper was able to significantly reduce the breath (p=0.0031) and its effect lasted for up to two hours. Chlorhexidine reduced the breath only at the final of the second hour (p=0.004) and lasted for three hours, while oral hygiene with toothbrush and toothpaste was effective in reducing the breath at the first hour (p=0.002) and lasted for up to three hours. It can be concluded that the mechanical cleaning of the tongue was able to immediately reduce the breath, but with relatively short duration of its effect, while chlorhexidine and the association of mechanical with chemical agents in oral hygiene can reduce the breath for longer periods than those observed in the literature which deals with chronic halitosis.

Pacientes submetidos à cirurgia cardiotorácica com circulação extracorpórea (CEC) apresentam reações inflamatórias, desencadeadas por este procedimento e pela isquemiareperfusão, que acarretam disfunção pulmonar e lesão do endotélio vascular no pósoperatório. Estes processos relativos à cirurgia cardíaca podem afetar a produção e o consumo do óxido nítrico (NO) no pulmão e no endotélio vascular, principalmente na sua participação no processo inflamatório. No pulmão, o NO se difunde com facilidade sendo detectado na via aérea na fase gasosa ou no fluído pulmonar como nitrito e o nitrato. A presença do NO na via aérea pode em algumas situações refletir a sua produção pelo epitélio da via aérea e pelo endotélio microvascular pulmonar. No entanto, os processos que envolvem a produção e o consumo do NO na via aérea ainda não estão totalmente esclarecidos. O condensado do exalado pulmonar (CEP) é um fluido obtido através do resfriamento do ar exalado através de um método totalmente não invasivo e que pode ser utilizado para a investigação do NO nas vias aéreas distais. No desenvolvimento deste estudo foi utilizado um aparato de coleta artesanal e de baixo custo para obtenção do CEP. Assim, foi coletado o CEP de pacientes coronariopatas e valvopatas submetidos à cirurgia cardíaca com CEC nos períodos pré- operatório e pós-operatório (4 horas após a CEC e 12, 24, 48 e 72 horas após a extubação). As concentrações plasmáticas de nitrito/nitrato destes pacientes também foram avaliadas através de amostras de sangue colhidas imediatamente após cada coleta do CEP. O CEP e o plasma foram analisados pela técnica de quimioluminescência para obter as concentrações de nitrito/nitrato. O aparato utilizado obteve utilização reprodutível na rotina clínica da cirurgia cardíaca nesta pesquisa em pacientes sob ventilação espontânea e ventilação mecânica. Não foram encontradas diferenças significativas (p>0,05) nas concentrações de nitrito/nitrato no CEP e plasma entre os pacientes coronariopatas e valvopatas no período pré-operatório. Concentrações significativamente maiores de nitrito/nitrato (p=0,017) foram encontradas no CEP, mas não no plasma, de pacientes que utilizaram nitrato por via oral (dinitrato de isossorbida) no período pré-operatório. Em pacientes que não utilizaram medicação contendo doador de NO (nitroglicerina ou nitroprussiato de sódio) por via endovenosa no pósoperatório ocorreu uma tendência à elevação das concentrações de nitrito/nitrato no CEP que foi numericamente significativa no período de 48 horas do pós-operatório (p=0,008). Em pacientes que receberam ou não doador de NO no pós-operatório as concentrações de nitrito/nitrato foram significativamente maiores nos períodos de 48 horas (p=0,005) e 72 horas (p=0,037) do pós-operatório. A utilização de nitroglicerina (NTG) no período pósoperatório elevou significativamente as concentrações de nitrito/nitrato no CEP nos períodos de 12 horas (p=0,022), 48 horas (p=0,015) e 72 horas (0,048) e no plasma nos períodos de 12 horas (p=0,045). As concentrações de nitrito/nitrato plasmáticos foram significativamente reduzidas (p=0,045) no pós-operatório imediato 4 horas após a CEC em pacientes que receberam ou não doador de NO. A partir destes resultados pode se observar que não houve diferenças significativas nas concentrações de nitrito/nitrato no CEP dos pacientes coronariopatas e valvopatas no período pré-operatório, exceto elevação significativa encontrada em pacientes que utilizaram dinitrato de isossorbida por via oral. As concentrações de nitrito/nitrato no CEP tendem a elevar-se no período pós-operatório principalmente com a utilização de NTG. As concentrações de nitrito/nitrato no plasma foram significativamente reduzidas após 4 horas da CEC no pós-operatório imediato. No entanto foi observado elevação nas concentrações de nitrito/nitrato no plasma de pacientes que usaram NTG. Os achados deste estudo poderão contribuir em futuras pesquisas fornecendo dados comparativos a respeito da participação do NO na via aérea e no plasma nos processos que envolvem a cirurgia cardíaca nos períodos pré e pós-operatório. / Patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB) have inflammatory reactions triggered by this procedure and by ischemia-reperfusion, which cause lung dysfunction and injury of vascular endothelium in the postoperative period. These processes related to cardiac surgery may affect the production and consumption of nitric oxide (NO) in the lung and vascular endothelium, especially in their participation in the inflammatory process. In the lung, NO diffuses easily and can be detected in the airway in the gas phase or in the lung fluid as nitrite and nitrate. The presence of NO in exhaled air may reflect the airway epithelium and lung microvascular endothelium in some situations. However, processes involving the production and consumption of NO in the airway are not totally understood. The exhaled breath condensate (EBC) is a fluid obtained by cooling exhaled air wich can be used for the investigation of NO in the distal airways. For this study we used an apparatus homemade and with low cost for collecting and obtain the EBC. The EBC was collected from patients with coronary artery disease and heart valve disease undergoing cardiac surgery with CPB in the preoperative and postoperative period (4 hours after CPB and 12, 24, 48 and 72 hours after extubation). Plasma concentrations of nitrite/nitrate in these patients were also evaluated using blood samples taken immediately after each collection of the EBC. The EBC and plasma were analyzed by chemiluminescence method to obtain the concentrations of nitrite/nitrate. The apparatus used was reproducible in clinical routine of cardiac surgery in patients under spontaneous ventilation or mechanical ventilation. There were no significant differences (p> 0.05) in concentrations of nitrite/nitrate in EBC and plasma in patients with coronary artery disease and heart valve disease in the preoperative period. Significantly higher concentrations of nitrite/nitrate (p=0.017) were found in EBC, but not in plasma of patients who used oral nitrate (isosorbide dinitrate) in the preoperative period. In patients who did not use medication containing NO donor (nitroglycerin or sodium nitroprusside) intravenously in the postoperative period there was a tendency to high concentrations of nitrite/nitrate in EBC that was numerically significant in the period of 48 hours postoperative (p=0.008). In patients who received or not NO donor in postoperative period the concentrations of nitrite/nitrate were significantly higher in periods of 48 hours (p=0.005) and 72 hours (p=0.037) after surgery. The use of nitroglycerin (GTN) in the postoperative period significantly elevated concentrations of nitrite/nitrate in the EBC in periods of 12 hours (p=0.022), 48 hours (p=0.015) and 72 hours (0.048) and plasma in period of 12 hours (p=0.045). The concentrations of nitrite/nitrate were significantly reduced (p=0.045) in the immediate postoperative period 4 hours after CPB in patients who received or not NO donor. From these results we could observe that there were no significant differences in concentrations of nitrite/nitrate in the EBC of patients with heart valve disease and coronary artery disease in the preoperative period, but we found a significant increase in these concentrations in patients who used isosorbide dinitrate orally. The concentrations of nitrite/nitrate in EBC presented a tendency to increase in postoperative period especially in patients who used GTN. The concentrations of nitrite/nitrate in plasma were significantly reduced after 4 hours of CPB in the immediate postoperative period. However, was observed that GTN tended to increase the concentration of nitrite/nitrate in plasma. These findings could help in future research providing comparative data about the role of NO in the airway and plasma in processes involving cardiac surgery in the pre and postoperative periods.

Multiple breath washout (MBW) of inert gas for assessment of airway disease in children is an emerging technique. In many studies Lung Clearance Index (LCI), derived from multiple breath washout of SF6, is more able to detect early or mild lung disease than standard lung function measurements. It is also able to detect very early lung disease in progressive conditions such as Cystic Fibrosis (CF). Where infants born with this condition were thought to have minimal lung disease activity, LCI is higher in these children than healthy controls. Lack of available commercial devices has hampered expansion of this technique to centres other than specialist research teams. Innocor (Innovision, Dk), a photoacoustic mass spectrometer capable of performing multiple breath washout, was adapted within this research group for use in adults. This thesis describes the setup, adaptation and validation of Innocor for use in children. In 4 studies, healthy controls, children with asthma and children with CF were recruited to perform MBW. In one study, 29 healthy controls and 31 children with asthma were recruited. Healthy controls performed 1 set of washouts, establishing a normative range. Children with asthma performed measurements before and after bronchodilator. Results showed increased LCI in children with asthma even though they were clinically stable as defined by symptoms. LCI stayed high even following bronchodilator suggesting evidence of residual airway disease in well controlled asthmatics despite adequate symptom control. To investigate short term variability of MBW measurements, two other studies recruited 18 children with CF in each. They performed measurements before and after standard physiotherapy manoeuvres and during sitting and lying posture. LCI did not change significantly after airway clearance physiotherapy, compared with children who did no intervention. Variability was high in both groups however suggesting CF lung disease is a complex interaction of changing ventilation in adjacent lung units. Lying posture induced greater changes in lung function in children with CF than controls. LCI appears to be more sensitive to this change than standard lung function measurements (spirometry). In another study 32 children with CF were recruited to perform serial lung function measurements over 18 months. These were data collected as part of the UK Cystic Fibrosis Gene Therapy Consortium (CFGTC) clinical studies in preparation for planned gene therapy trials. LCI appears comparable to FEV1 and may be able to detect another aspect of airway disease. All initial studies were performed in older children (>5yrs). The basic Innocor device is unsuitable for testing of younger patients with low breath volume and high respiratory rate. In-house adaptations following detailed lung model experimentation led to a faster analyser response, potentially capable of MBW in younger children. The second part of this thesis concerns lab experiments and an in-vivo comparison with the current gold-standard MBW device, a respiratory mass spectrometer. 16 healthy volunteers and 9 children with CF were recruited. Ages ranged from 0.4 yrs to 49 yrs. Innocor values for lung volume estimation compared favourably with the mass spectrometer. No evidence of bias caused by Innocor error was seen, however intra-test variability was rather high, reducing the precision of the results. These studies indicate Innocor is a robust, simple to use device with potential as a commercial lung function system. Modifications were made to make it suitable for use in all ages. Further development will need to focus on the patient interface and software, which is the domain of the manufacturers. The experiments contained in this thesis are therefore of interest to the wider respiratory research community as well as manufacturers of MBW devices.

acase@tulane.edu

The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 µm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected pores facilitates cell infiltration and tissue remodelling in vitro, suggesting its high potential in regenerative medicine and tissue engineering applications. In the second part of the dissertation, the versatility of breath figure polymers was explored as a reverse template to create micropatterned soft materials. Unlike traditional lithographic masters, the breath figure assembly is a simple and cost-effective approach to create micro/nano sized “bead†like uniform patterns on the surface of hydrogels and biopolymers. By incorporating iron nanoparticles into the pores, this technique was extended to form hydrogels decorated with nanoparticles specifically in the pattern. The morphology features and the functional characteristics were demonstrated through scanning electron microscopy. The potential applications of these micro-fabricated materials in biosensors and cell culture substrates are outlined. / acase@tulane.edu

Background: Respiratory conditions are prevalent and cause an enormous burden on society. In recent decades, there has been a global increase in asthma in children and adults, yet the diagnosis of asthma must be made on clinical grounds as the diagnostic use of pharmacological reversibility of airway obstruction remains controversial. It is possible however that tools exist from different medical paradigms that may assist in the clinical diagnosis of asthma. Tools such as Traditional Chinese Medicine (TCM) enquiry, Breath Holding Time (BHT) or Electro-Dermal Screening Test (EDST) may provide useful clinical information, yet their use has not been widely explored or validated. Integrative medicine may be considered to represent a new frontier in medicine where each therapy and diagnostic method is seen to have its own advantages and limitations and where an integration of both diagnostic and therapeutic techniques from conventional and complementary medicine is seen to produce the best results. However, while there is a high community use of complementary therapies for conditions such as asthma, there is also a need to maintain accepted standards of medical and scientific principles and foster high quality research into complementary therapies. Objectives: The current study sought to determine: • If there is a correlation between conventional measures of lung function such as Forced Expiratory Volume in one second (FEV1) and less conventional measures such as airways expired NO level (eNO), electrodermal measures, TCM enquiry and BHT. • If any of the lung function measures are able to distinguish between asthmatic and healthy subjects. • If the use of a rye grass extract is better than placebo in improving requirements for bronchodilator medication, peak flow, forced expiratory volume in one second or quality of life in mild to moderate childhood asthma. Rational for carrying out two separate studies as one study; The author was interested on both the integration of diagnostic techniques as well as the effect of the herbal extract on asthma so it was decided to use the opportunity and put both in one study. Method: A range of conventional and non-conventional measures were conducted in healthy and asthmatic children including demographic details, quality of life data, spirometry measures, airway nitric oxide levels, electro-dermal measures, TCM history enquiries, breath holding time, and skin prick tests. The data were analysed to determine any significant correlations between these measures. A double blind randomized controlled pilot clinical trial was also performed to assess the effect of using rye grass extract in asthmatic children aged 8 to 16 years. Results: There were significant correlations between forced expiratory volume in one second and active quality of life, TCM spleen score and fraction of exhaled nitric oxide measurements. There were also statistically significant differences between asthmatic and healthy subjects in TCM history, breath holding time and exhaled nitric oxide. The use of rye grass extract did not produce any significant improvement over placebo in any of the asthma outcome measures. Conclusions: The use of inexpensive measures such as BHT and TCM enquiry may provide useful clinical information when assessing respiratory conditions such as asthma. However, further research is required in larger populations to confirm their use. The use of the rye grass extract at the dose given in this study did not provide any clinical benefit for the asthmatic children in this study.

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The goal of this research project was to characterize the physical and electrochemical properties of a commercially available fuel cell-based breath alcohol sensor. Characteristics of the existing sensor were compared with state of the art power generating fuel cells with the goal of understanding the factors that limit performance, lifetime and cost effectiveness of the sensors. This will guide the development of the next generation of breath alcohol sensors. The average lifetime of the current sensor falls short of the industry standards. In particular, sensors operating in dry conditions experience more rapid loss of sensitivity and failure. Two primary causes of degradation were investigated in this study. Loss of proton conductivity as a result of membrane dehydration was shown to be reversible by rehydrating the membrane in humid conditions. Loss of electrochemically active surface area of Pt is irreversible and seems to be caused by a change in sensor morphology after long-term exposure to dry conditions. / UOIT