A oxigenoterapia domiciliar é uma terapêutica de extrema importância na faixa etária pediátrica que visa garantir o desenvolvimento pôndero-estatural e cognitivo de crianças hipoxêmicas, bem como prevenir e atenuar o desenvolvimento da hipertensão pulmonar secundária (HPS). OBJETIVO: Descrever a população de crianças e adolescentes em oxigenoterapia domiciliar prolongada (ODP), quanto às suas características demográficas, clínicas, laboratoriais, relativas ao uso do oxigênio (O2) e tempo de sobrevida após início da ODP. Comparar os grupos de pacientes com e sem HPS, em relação às características supracitadas e analisar comparativamente os custos em relação ao uso do concentrador versus cilindro de O2. MÉTODOS: Trata-se de um estudo descritivo retrospectivo de uma coorte de 165 pacientes, cujos dados relativos a um período 2002-2009 foram coletados de prontuários e de questionários aplicados aos pacientes e/ou acompanhantes. Os dados sobre custos foram cedidos pelo Núcleo de Assistência Domiciliar Interdisciplinar do HC-FMUSP. A variável contínua (idade de início do uso de O2) foi descrita através de sua mediana, valores máximo e mínimo. As demais variáveis (nominais), foram descritas através de suas frequências. As análises do tempo de uso do O2 e sobrevida foram feitas através da curva de Kaplan-Meier. Na comparação dos subgrupos com e sem HPS, as frequências (período de uso do O2 e intensidade do fluxo) foram comparadas através do teste do Qui-quadrado; e as curvas de Kaplan-Meier, por meio do teste Logrank. Nas análises, foi usado o software estatístico SPSS 13.0 e adotado um nível de significância de 5%. O custo médio mensal do programa foi calculado a partir das médias mensais de pacientes, segundo o tipo de sistema utilizado (concentrador ou cilindro) no período de um ano. RESULTADOS: A maioria dos pacientes (68%) residia no Município de São Paulo; 53% eram do sexo masculino e a idade de início da ODP variou de 0,1 a 21, 5 anos (mediana: 3,6 anos), sendo que cerca de um terço da casuística iniciou o uso do O2 no primeiro ano de vida. Os principais diagnósticos da doença crônica de base foram: fibrose cística (22%), displasia broncopulmonar (19%), bronquiolite obliterante (15%) e neuropatias crônicas (12%). A ODP foi contínua em 65% dos pacientes, sendo que 87% utilizavam fluxos inferiores a 2 L/min. O dispositivo para administração de O2 mais utilizado foi a cânula nasal (87%), e o sistema provedor foi o concentrador de O2 (58%). A mediana do tempo de uso do O2 foi de 7 anos. A mediana do tempo de sobrevida dos 165 pacientes após início da ODP foi de 13,4 anos. Dos 33 pacientes submetidos aos testes de função pulmonar, 70% apresentaram distúrbio ventilatório obstrutivo grave. O hemograma foi realizado em 150 pacientes. Destes, 37% eram anêmicos e 17%, policitêmicos; os demais apresentaram valores hematimétricos normais. O ecocardiograma foi realizado em 134 pacientes; destes, 51% apresentaram hipertensão pulmonar secundária (HPS). Foi encontrada associação estatisticamente significante entre presença de hipertensão pulmonar e necessidade de maiores fluxos de oxigênio (p = 0,011) bem como presença de hipertensão pulmonar e tempo de uso do O2 mais prolongado (p = 0,0001). O tempo de sobrevida dos grupos com e sem HPS após início da ODP não apresentou diferença estatisticamente significante (p = 0,3445). No tocante aos custos relativos ao tipo de sistema provedor de O2 utilizado, o custo médio mensal do programa utilizando concentradores foi de R$ 4.176,80 e utilizando cilindros foi de R$ 9.396,00. CONCLUSÕES: Nesta casuística a ODP foi empregada em distintas doenças crônicas, com maior frequência de pacientes na faixa etária de lactentes e período pré-escolar. As doenças predominantes foram: fibrose cística, displasia broncopulmonar e bronquiolite obliterante. O tempo de ODP para os pacientes com estas patologias foi relativamente prolongado. A HPS foi frequente nos pacientes em ODP, e a sua presença, comparativamente aos pacientes sem HPS, ocasiona a necessidade de maiores períodos de tratamento e incremento de fluxos de oxigênio, sem interferência na sobrevida. Possivelmente o uso de concentradores de O2, ao invés de cilindros, em programas de ODP para pacientes pediátricos, reduza os custos de maneira significativa / The home oxygen therapy is extremely important in the pediatric age group that aims to ensure the weight, height and cognitive development of hypoxemic children, as well as prevent and mitigate the development of secondary pulmonary hypertension (SPH).OBJECTIVE: This study aimed to describe the population of children and adolescents in prolonged home oxygen therapy (LTOT) as their demographic characteristics, clinical, laboratory, concerning the use of O2, and survival time after onset of ODP. Compare patient groups with and without SPH in relation to the characteristics mentioned above and analyze comparatively the costs in relation to the use of concentrator versus O2 cylinder. Cost data were provided by the Interdisciplinary Center for Home Care. METHODS: This is a retrospective descriptive study of a cohort of 165 patients, whose data covering a period from 2002 to 2009 were collected from medical records and questionnaires applied to patients or caregivers. The continuous variable (age of onset of O2) was described by its median, maximum and minimum values. The other variables (nominal), were described by their frequencies. Analyses of time use of O2 and survival were evaluated by the Kaplan-Meier method. In comparing the groups with and without SPH, the frequency (period of use of O2 and intensity of flow) were compared using the Chi-square and Kaplan-Meier, using log rank test. In the analysis, we used the statistical software SPSS 13.0 and adopted a significance level of 5%. The average monthly cost of the program was calculated from the monthly average of patients, according to the type of system (concentrator or cylinder) during one year. RESULTS: Most patients (68%) resided in Sao Paulo city, 53% were male. The age of onset of LTOT ranged from 0.1 to 21,5 years (median 3.6 years), and about a third of the series initiated the use of O2 in the first year of life. The main diagnoses of chronic illness were: cystic fibrosis (22%), bronchopulmonary dysplasia (19%), bronchiolitis obliterans (15%) and chronic neuropathies (12%). The ODP was continuous in 65% of patients, 87% used flows of less than 2 L/min. The device for administration of O2 consisted of a nasal cannula (87%), and the system provider was the O2 concentrator (58%). The median duration of use of O2 was 7 years. The median survival time of 165 patients after initiation of LTOT was 13.4 years. Of the 33 patients tested for lung function, 70% had severe obstructive respiratory disorder. Blood counts were performed in 150 patients. Of these, 37% were anemic,17% polycythemic, and the others showed normal hematological values. Echocardiography was performed in 134 patients, of which 51% had SPH. Statistically significant association was found between the presence of pulmonary hypertension and need for greater flows of oxygen (p = 0.011) and presence of pulmonary hypertension and longer duration of O2 use (p = 0.0001). The survival time of patients with and without HPS after initiating LTOT was not statistically significant (p = 0.3445).Concerning the costs for the type of O2 system provider used, the average monthly cost of the program using concentrators was R$ 4,176.80 and using cylinder was R$ 9,396.00. CONCLUSIONS: In this sample LTOT has been employed in various chronic diseases with a greater frequency of patients in the age range of infants and preschool period. The predominant diseases were: cystic fibrosis, bronchopulmonary dysplasia, and bronchiolitis obliterans. The period of LTOT for patients with these diseases was relatively prolonged. The SPH was common in patients on LTOT, and their presence compared to patients without SPH, causes the need for greater periods of treatment and increase the flow of oxygen, without interference on survival. Possibly the use of O2 concentrators, instead of cylinders in LTOT programs for pediatric patients, may reduce costs significantly

Existem evidências na literatura de que a administração de medicações, como corticosteróides inalatórios e broncodilatadores, utilizando inaladores pressurizados dosimetrados, é mais eficaz e segura do que com os nebulizadores convencionais. Entretanto, há evidências de que não só pacientes, mas também profissionais de saúde têm dificuldade no manejo dos inaladores pressurizados dosimetrados. A hipótese do presente estudo é que o conhecimento da técnica inalatória entre os profissionais da nossa Instituição é heterogêneo, sendo que não há informações sobre o nível deste conhecimento entre as diversas categorias profissionais. OBJETIVOS: Avaliar o conhecimento prático e teórico de profissionais da área médica, de enfermagem e fisioterapia sobre a utilização do inalador dosimetrado através de testes padronizados. MÉTODOS: Avaliações teóricas e práticas sobre o conhecimento do uso de inaladores pressurizados dosimetrados foram realizadas com médicos, fisioterapeutas, enfermeiras e auxiliares de enfermagem, atribuindo-se uma nota de 0 a 10 para cada avaliação. Calcularam-se as medianas das notas obtidas pelos profissionais de cada categoria, as questões com maiores e menores índices de erros e feita a comparação descritiva do desempenho das diversas categorias profissionais. Após as avaliações, instrução verbal e escrita sobre a utilização correta dos dispositivos foi fornecida a todos os participantes. A análise estatística foi feita através do método de Kruskal-Wallis de comparação de medianas. Também foi realizada a análise através de regressão logística múltipla seqüencial. RESULTADOS: foram avaliados 30 médicos residentes ou estagiários da pediatria, 23 médicos assistentes, 29 fisioterapeutas, 33 enfermeiras e 31 auxiliares de enfermagem, em um total de146 profissionais. Não foram entrevistados residentes ou assistentes do grupo de Pneumologia. Os médicos residentes, fisioterapeutas e os médicos assistentes obtiveram desempenho significativamente superior que os enfermeiros e auxiliares de enfermagem. Apenas os médicos residentes obtiveram mediana superior a seis. As questões práticas com maiores índices de erros foram as relativas à limpeza do espaçador. Questões relativas à agitação do inalador antes do uso e à limpeza da cavidade oral após a sua utilização também obtiveram alto índice de erros. A questão teórica mais errada foi a respeito do tempo necessário entre dois jatos em aplicações sucessivas do inalador pressurizado dosimetrado. CONCLUSÕES: O conhecimento teórico-prático dos profissionais de saúde da Instituição a respeito do uso de inaladores pressurizados dosimetrados é heterogêneo. Os médicos residentes, fisioterapeutas e médicos assistentes obtiveram desempenho significativamente melhor que os enfermeiros e auxiliares de enfermagem sendo que estes últimos estão diretamente envolvidos na aplicação prática destes dispositivos na rotina hospitalar. / There are data in the literature indicating that the administration of medications such as inhaled corticosteroids and bronchodilators, using metered-dose inhalers, is more effective and safer than its dispensation by conventional nebulizers. However, there is evidence that not only patients but also health care professionals have difficulty in dealing with pressurized dose inhalers. The hypothesis of the present study is that the knowledge of inhalation techniques among health professionals of our Institution is heterogeneous, and there is no information about this knowledge among the diverse categories of professionals. OBJECTIVE: To assess the practical and theoretical knowledge of medical professionals, nursing and physiotherapy on the use of metereddose inhalers by standardized testing. METHODS: Practical and written tests on the use of metered-dose inhalers were applied to physicians, physical therapists, nurses and nursing assistants. A score from 0 to 10 was assigned to each evaluation. Median scores were calculated for each professional category. Questions with higher and lower correct values were identified, and a descriptive comparison was made regarding the performance of the diverse professional categories. Following the examination, oral and written instructions on the correct use of the devices were provided for all participants. Statistical analysis was performed using the Kruskal-Wallis method for comparison of medians. A sequential logistic multiple regression analysis was also performed. RESULTS: A total of 146 professionals were assessed, including 30 fellows in pediatrics, 23 attending physicians, 29 physical therapists, 33 nurses and 31 nursing assistants. Fellows or attending physicians of the Pediatric Pulmonology Unit were not included in the study. Fellows, physical therapists and attending physicians performed significantly better than did nurses and nursing assistants. Only fellows had a median score greater than six. On the practical tests for infants and toddlers, the step most often missed was that related to cleaning the spacer. On practical tests, the steps related to shaking the inhaler and cleaning the mouth also presented high error indices. On the written tests, the question most often answered incorrectly was that related to the waiting time between puffs. CONCLUSIONS: The theoretical and practical knowledge of health professionals of our Institution on the use of metered-dose inhalers is heterogeneous. The performance of fellows, physical therapists and attending physicians was significantly better than that of nurses and nursing assistants who are directly involved in the practical application of these devices in the hospital routine.

Existem evidências na literatura de que a administração de medicações, como corticosteróides inalatórios e broncodilatadores, utilizando inaladores pressurizados dosimetrados, é mais eficaz e segura do que com os nebulizadores convencionais. Entretanto, há evidências de que não só pacientes, mas também profissionais de saúde têm dificuldade no manejo dos inaladores pressurizados dosimetrados. A hipótese do presente estudo é que o conhecimento da técnica inalatória entre os profissionais da nossa Instituição é heterogêneo, sendo que não há informações sobre o nível deste conhecimento entre as diversas categorias profissionais. OBJETIVOS: Avaliar o conhecimento prático e teórico de profissionais da área médica, de enfermagem e fisioterapia sobre a utilização do inalador dosimetrado através de testes padronizados. MÉTODOS: Avaliações teóricas e práticas sobre o conhecimento do uso de inaladores pressurizados dosimetrados foram realizadas com médicos, fisioterapeutas, enfermeiras e auxiliares de enfermagem, atribuindo-se uma nota de 0 a 10 para cada avaliação. Calcularam-se as medianas das notas obtidas pelos profissionais de cada categoria, as questões com maiores e menores índices de erros e feita a comparação descritiva do desempenho das diversas categorias profissionais. Após as avaliações, instrução verbal e escrita sobre a utilização correta dos dispositivos foi fornecida a todos os participantes. A análise estatística foi feita através do método de Kruskal-Wallis de comparação de medianas. Também foi realizada a análise através de regressão logística múltipla seqüencial. RESULTADOS: foram avaliados 30 médicos residentes ou estagiários da pediatria, 23 médicos assistentes, 29 fisioterapeutas, 33 enfermeiras e 31 auxiliares de enfermagem, em um total de146 profissionais. Não foram entrevistados residentes ou assistentes do grupo de Pneumologia. Os médicos residentes, fisioterapeutas e os médicos assistentes obtiveram desempenho significativamente superior que os enfermeiros e auxiliares de enfermagem. Apenas os médicos residentes obtiveram mediana superior a seis. As questões práticas com maiores índices de erros foram as relativas à limpeza do espaçador. Questões relativas à agitação do inalador antes do uso e à limpeza da cavidade oral após a sua utilização também obtiveram alto índice de erros. A questão teórica mais errada foi a respeito do tempo necessário entre dois jatos em aplicações sucessivas do inalador pressurizado dosimetrado. CONCLUSÕES: O conhecimento teórico-prático dos profissionais de saúde da Instituição a respeito do uso de inaladores pressurizados dosimetrados é heterogêneo. Os médicos residentes, fisioterapeutas e médicos assistentes obtiveram desempenho significativamente melhor que os enfermeiros e auxiliares de enfermagem sendo que estes últimos estão diretamente envolvidos na aplicação prática destes dispositivos na rotina hospitalar. / There are data in the literature indicating that the administration of medications such as inhaled corticosteroids and bronchodilators, using metered-dose inhalers, is more effective and safer than its dispensation by conventional nebulizers. However, there is evidence that not only patients but also health care professionals have difficulty in dealing with pressurized dose inhalers. The hypothesis of the present study is that the knowledge of inhalation techniques among health professionals of our Institution is heterogeneous, and there is no information about this knowledge among the diverse categories of professionals. OBJECTIVE: To assess the practical and theoretical knowledge of medical professionals, nursing and physiotherapy on the use of metereddose inhalers by standardized testing. METHODS: Practical and written tests on the use of metered-dose inhalers were applied to physicians, physical therapists, nurses and nursing assistants. A score from 0 to 10 was assigned to each evaluation. Median scores were calculated for each professional category. Questions with higher and lower correct values were identified, and a descriptive comparison was made regarding the performance of the diverse professional categories. Following the examination, oral and written instructions on the correct use of the devices were provided for all participants. Statistical analysis was performed using the Kruskal-Wallis method for comparison of medians. A sequential logistic multiple regression analysis was also performed. RESULTS: A total of 146 professionals were assessed, including 30 fellows in pediatrics, 23 attending physicians, 29 physical therapists, 33 nurses and 31 nursing assistants. Fellows or attending physicians of the Pediatric Pulmonology Unit were not included in the study. Fellows, physical therapists and attending physicians performed significantly better than did nurses and nursing assistants. Only fellows had a median score greater than six. On the practical tests for infants and toddlers, the step most often missed was that related to cleaning the spacer. On practical tests, the steps related to shaking the inhaler and cleaning the mouth also presented high error indices. On the written tests, the question most often answered incorrectly was that related to the waiting time between puffs. CONCLUSIONS: The theoretical and practical knowledge of health professionals of our Institution on the use of metered-dose inhalers is heterogeneous. The performance of fellows, physical therapists and attending physicians was significantly better than that of nurses and nursing assistants who are directly involved in the practical application of these devices in the hospital routine.

A oxigenoterapia domiciliar é uma terapêutica de extrema importância na faixa etária pediátrica que visa garantir o desenvolvimento pôndero-estatural e cognitivo de crianças hipoxêmicas, bem como prevenir e atenuar o desenvolvimento da hipertensão pulmonar secundária (HPS). OBJETIVO: Descrever a população de crianças e adolescentes em oxigenoterapia domiciliar prolongada (ODP), quanto às suas características demográficas, clínicas, laboratoriais, relativas ao uso do oxigênio (O2) e tempo de sobrevida após início da ODP. Comparar os grupos de pacientes com e sem HPS, em relação às características supracitadas e analisar comparativamente os custos em relação ao uso do concentrador versus cilindro de O2. MÉTODOS: Trata-se de um estudo descritivo retrospectivo de uma coorte de 165 pacientes, cujos dados relativos a um período 2002-2009 foram coletados de prontuários e de questionários aplicados aos pacientes e/ou acompanhantes. Os dados sobre custos foram cedidos pelo Núcleo de Assistência Domiciliar Interdisciplinar do HC-FMUSP. A variável contínua (idade de início do uso de O2) foi descrita através de sua mediana, valores máximo e mínimo. As demais variáveis (nominais), foram descritas através de suas frequências. As análises do tempo de uso do O2 e sobrevida foram feitas através da curva de Kaplan-Meier. Na comparação dos subgrupos com e sem HPS, as frequências (período de uso do O2 e intensidade do fluxo) foram comparadas através do teste do Qui-quadrado; e as curvas de Kaplan-Meier, por meio do teste Logrank. Nas análises, foi usado o software estatístico SPSS 13.0 e adotado um nível de significância de 5%. O custo médio mensal do programa foi calculado a partir das médias mensais de pacientes, segundo o tipo de sistema utilizado (concentrador ou cilindro) no período de um ano. RESULTADOS: A maioria dos pacientes (68%) residia no Município de São Paulo; 53% eram do sexo masculino e a idade de início da ODP variou de 0,1 a 21, 5 anos (mediana: 3,6 anos), sendo que cerca de um terço da casuística iniciou o uso do O2 no primeiro ano de vida. Os principais diagnósticos da doença crônica de base foram: fibrose cística (22%), displasia broncopulmonar (19%), bronquiolite obliterante (15%) e neuropatias crônicas (12%). A ODP foi contínua em 65% dos pacientes, sendo que 87% utilizavam fluxos inferiores a 2 L/min. O dispositivo para administração de O2 mais utilizado foi a cânula nasal (87%), e o sistema provedor foi o concentrador de O2 (58%). A mediana do tempo de uso do O2 foi de 7 anos. A mediana do tempo de sobrevida dos 165 pacientes após início da ODP foi de 13,4 anos. Dos 33 pacientes submetidos aos testes de função pulmonar, 70% apresentaram distúrbio ventilatório obstrutivo grave. O hemograma foi realizado em 150 pacientes. Destes, 37% eram anêmicos e 17%, policitêmicos; os demais apresentaram valores hematimétricos normais. O ecocardiograma foi realizado em 134 pacientes; destes, 51% apresentaram hipertensão pulmonar secundária (HPS). Foi encontrada associação estatisticamente significante entre presença de hipertensão pulmonar e necessidade de maiores fluxos de oxigênio (p = 0,011) bem como presença de hipertensão pulmonar e tempo de uso do O2 mais prolongado (p = 0,0001). O tempo de sobrevida dos grupos com e sem HPS após início da ODP não apresentou diferença estatisticamente significante (p = 0,3445). No tocante aos custos relativos ao tipo de sistema provedor de O2 utilizado, o custo médio mensal do programa utilizando concentradores foi de R$ 4.176,80 e utilizando cilindros foi de R$ 9.396,00. CONCLUSÕES: Nesta casuística a ODP foi empregada em distintas doenças crônicas, com maior frequência de pacientes na faixa etária de lactentes e período pré-escolar. As doenças predominantes foram: fibrose cística, displasia broncopulmonar e bronquiolite obliterante. O tempo de ODP para os pacientes com estas patologias foi relativamente prolongado. A HPS foi frequente nos pacientes em ODP, e a sua presença, comparativamente aos pacientes sem HPS, ocasiona a necessidade de maiores períodos de tratamento e incremento de fluxos de oxigênio, sem interferência na sobrevida. Possivelmente o uso de concentradores de O2, ao invés de cilindros, em programas de ODP para pacientes pediátricos, reduza os custos de maneira significativa / The home oxygen therapy is extremely important in the pediatric age group that aims to ensure the weight, height and cognitive development of hypoxemic children, as well as prevent and mitigate the development of secondary pulmonary hypertension (SPH).OBJECTIVE: This study aimed to describe the population of children and adolescents in prolonged home oxygen therapy (LTOT) as their demographic characteristics, clinical, laboratory, concerning the use of O2, and survival time after onset of ODP. Compare patient groups with and without SPH in relation to the characteristics mentioned above and analyze comparatively the costs in relation to the use of concentrator versus O2 cylinder. Cost data were provided by the Interdisciplinary Center for Home Care. METHODS: This is a retrospective descriptive study of a cohort of 165 patients, whose data covering a period from 2002 to 2009 were collected from medical records and questionnaires applied to patients or caregivers. The continuous variable (age of onset of O2) was described by its median, maximum and minimum values. The other variables (nominal), were described by their frequencies. Analyses of time use of O2 and survival were evaluated by the Kaplan-Meier method. In comparing the groups with and without SPH, the frequency (period of use of O2 and intensity of flow) were compared using the Chi-square and Kaplan-Meier, using log rank test. In the analysis, we used the statistical software SPSS 13.0 and adopted a significance level of 5%. The average monthly cost of the program was calculated from the monthly average of patients, according to the type of system (concentrator or cylinder) during one year. RESULTS: Most patients (68%) resided in Sao Paulo city, 53% were male. The age of onset of LTOT ranged from 0.1 to 21,5 years (median 3.6 years), and about a third of the series initiated the use of O2 in the first year of life. The main diagnoses of chronic illness were: cystic fibrosis (22%), bronchopulmonary dysplasia (19%), bronchiolitis obliterans (15%) and chronic neuropathies (12%). The ODP was continuous in 65% of patients, 87% used flows of less than 2 L/min. The device for administration of O2 consisted of a nasal cannula (87%), and the system provider was the O2 concentrator (58%). The median duration of use of O2 was 7 years. The median survival time of 165 patients after initiation of LTOT was 13.4 years. Of the 33 patients tested for lung function, 70% had severe obstructive respiratory disorder. Blood counts were performed in 150 patients. Of these, 37% were anemic,17% polycythemic, and the others showed normal hematological values. Echocardiography was performed in 134 patients, of which 51% had SPH. Statistically significant association was found between the presence of pulmonary hypertension and need for greater flows of oxygen (p = 0.011) and presence of pulmonary hypertension and longer duration of O2 use (p = 0.0001). The survival time of patients with and without HPS after initiating LTOT was not statistically significant (p = 0.3445).Concerning the costs for the type of O2 system provider used, the average monthly cost of the program using concentrators was R$ 4,176.80 and using cylinder was R$ 9,396.00. CONCLUSIONS: In this sample LTOT has been employed in various chronic diseases with a greater frequency of patients in the age range of infants and preschool period. The predominant diseases were: cystic fibrosis, bronchopulmonary dysplasia, and bronchiolitis obliterans. The period of LTOT for patients with these diseases was relatively prolonged. The SPH was common in patients on LTOT, and their presence compared to patients without SPH, causes the need for greater periods of treatment and increase the flow of oxygen, without interference on survival. Possibly the use of O2 concentrators, instead of cylinders in LTOT programs for pediatric patients, may reduce costs significantly

Foram utilizados vinte ovinos, machos com idade entre um e três anos, com peso médio de 33,1 ± 3,1 kg. Os animais foram distribuídos de forma aleatória em três grupos, designados como GH (halotano), GI (isofluorano) e GS (sevofluorano) em experimento do tipo cruzado com intervalo mínimo de 1 semana entre os tratamentos. Numa primeira etapa, os animais foram anestesiados com auxílio de máscara facial, intubados e mantidos sob anestesia com agente segundo a determinação de cada grupo e obtida a concentração alveolar mínima (CAM) dos agentes por meio de estímulo nociceptivo com eletroestimulação. Em uma segunda etapa, os animais foram mantidos com a CAM previamente compreendendo os momentos de M0 a M8 com intervalo de 15 minutos entre os mesmo. Foram avaliadas as funções hemodinâmicas, respiratórias, hemogasométricas, endócrinas e o índice biespectral. Os valores médios de CAM foram de 0,71 ± 0,09%, 1,31 ± 0,33% e 2,69 ± 0,29% para o halotano, isofluorano e sevofluorano respectivamente. Houve redução dos valores do índice cardíaco no GI em todos os momentos comparativamente ao basal (p<0,001); na comparação entre os grupos os valores do M0 no GI foram superiores aos verificados em GH e GS (p<0,01). O valores do volume e índice sistólico foram inferiores ao basal a partir de M6 no grupo GH (p<0,05) e no GI todos os momentos foram inferiores ao basal (p<0,001); na comparação entre os grupos verificou-se que os valores dessas variáveis no momento M0 no GI foram superiores a GH (p<0,05) e GS (p<0,001). As médias da pressão venosa central foram inferiores no grupo GH em todos os momentos comparativamente a M0 (p<0,001), e neste mesmo momento, as médias foram superioriores comparativamente aos outros grupos (p<0,05). Quanto ao índice de resistência vascular sistêmica, os valores foram superiores nos momentos M6, M3 e M7 nos grupos GH (p<0,05), GI (p<0,001) e GS (p<0,01), respectivamente; houve incremento do índice de resistência vascular periférica no momento M7 (p<0,01) no grupo GH a partir de M3 (p<0,001), em GI e em M7 e M8 (p<0,05) comparativamente ao basal. Os valores de tensão de dióxido de carbono no final da expiração foram superiores no grupo GH a partir de M4 (p<0,05) e no GI a partir de M3 (p<0,01) comparativamente ao basal. Os valores do índice biespectral no GI, foram superiores a partir de M5 em relação ao valor basal (p<0,01); na comparação entre os grupos, os momentos M2 e M3 foram inferiores no GI comparativamente ao GH e GS (p<0,05). Houve redução da temperatura retal em todos os grupos e momentos comparativamente ao valor basal (p<0,001). O período de recuperação foi superior no grupo GH (p<0,05). Nas condições do presente estudo a CAM em ovinos é de 0,71%, 1,31% e 2,69% para o halotano, isofluorano e sevofluorano respectivamente; os três agentes promovem redução do débito cardíaco e do volume sistólico; os valores do índice biespectral são semelhantes entre os fármacos, com valores inferiores quando tratados com isofluorano; há indução de estresse neuroendócrino avaliado por meio da dosagem de cortisol; os agentes promovem hipotermia tempo dependente; o halotano promove recuperação anestésica mais prolongada. / Twenty sheep, all males, were used in this experiment. Age ranged from one to three years and mean weight was 33.1 ± 3.1 kg. In a crossover design, animals were randomly treated with halothane (GH), isoflurane (GI) and sevoflurane (GS), with interval of 1 week between treatments. In a first phase, anesthesia was induced by facemask, animals were then intubated and anesthesia maintained with one of the three treatments. Minimum alveolar concentration (MAC) was obtained by nociceptive stimulation for each animal. In phase 2, the animals were anesthetized again by facemask and maintained at the predetermined MAC (Phase 1) for two hours. Data was collected at moments (M0-M8) with intervals of 15 minutes. Cardiovascular, respiratory and bispectral index parameters were recorded. Blood gas analysis, CBC and cortisol levels were also measured and recorded. MAC of each group were 0.71± 0.09%, 1.31 ± 0.33% e 2.69 ± 0.29% for GH, GI and GS respectively. There was a reduction in cardiac index in GI at all times compared to baseline (p<0.001). Among groups the values of M0 in GI were higher than those in GH and GS (p<0.01). In GH, the end systolic volume and stroke index were lower than baseline from M6 until the end of the experiment (p<0.05). In GI, ESV and SI were below the baseline at all times (p<0.001). Among groups it was found that the GI baseline values of these variables were higher than GH (p<0.05) and GS (p<0.001). The mean central venous pressure were lower in the GH group at all times compared to M0 (p<0.001), which was higher than the baseline of the other groups (p<0.05). When compared to baseline, systemic vascular resistance index was higher in the moments M6, M3 and M7 in GH (p<0.05), GI (p<0.001) and GS (p<0.01), respectively. There was an increase in peripheral vascular resistance index (PVRI) at the time M7 (p<0.01) in GH from M3 to the end of the study (p<0.001). In GI, PVRI was increased at M7 and M8 (p<0.05) in comparison to baseline. The values of end-tidal of carbon dioxide were higher than baseline in the GH group from M4 (p<0.05) until the end of study. The same occurred in GI starting at M3 (p<0.01). In GI, the bispectral index values were higher starting at M5 to the end when compared to baseline (p<0.01). Among groups, BIS was lower at M2 and M3 in GI when compared to GH and GS (p< 0.05). Rectal temperature decreased in all groups at all moments in comparison to baseline (p<0.001). The recovery period was longer in GH (p<0.05). Under this study conditions MAC in sheep were 0.71%, 1.31% and 2.69% for halothane, isoflurane and sevoflurane, respectively. All treatments further reduced cardiac output and stroke volume; bispectral index values were similar among drugs, with lower values when treated with isoflurane. A stress response was believed to be induced due to elevation of serum cortisol in all groups. These inhalants promote time-dependent hypothermia. Halothane anesthesia promotes prolonged recovery.

In June 2008, the Cedar River crested flooding more than 5,000 Cedar Rapids homes. Residents whose homes were flooded were invited to participate in this study. We characterized exposures and symptoms experienced by individuals inhabiting 73 flood-damaged homes. Exposures and questionnaire-based health assessments were compared at two levels of remediation, in-progress and completed. Homes with remediation in-progress (n=24), as compared to the completed homes (n=49), had significantly higher airborne concentrations of mold, bacteria, iPM, endotoxin and glucan. Residents of in-progress homes had a significantly higher prevalence of doctor diagnosed allergies (adjusted OR=3.08; 95%CI: 1.05-9.02) and all residents had elevated prevalence of self-reported wheeze (adjusted OR=3.77; 95%CI: 2.06-6.92) and prescription medication use for breathing problems (adjusted OR=1.38; 95%CI: 1.01-1.88) after the flood as compared to before. Proper post-flood remediation led to improved air quality and lower exposures among residents living in flooded homes. Recognition of endotoxin as a proinflammatory ligand for pattern recognition receptors has increased the demand for endotoxin assessment in studies of environmental lung disease. Measurements using the Limulus amebocyte lysate (LAL) assay of air and reservoir dust samples are routinely incorporated into epidemiologic studies. However, it is unknown if endotoxin reactivity in the LAL assay varies by its physical presentation as aggregates, as membrane components of whole bacteria or as shed membrane blebs or if this parallels differences in the inflammatory potency of endotoxin in vivo. Endotoxins as14C-labeled-lipooligosaccharide (14C-LOS) and 14C- labeled-lipopolysaccharide (14C-LPS) were produced from Neisseria meningitidis and Escherichia coli. The reactivity of the endotoxin presentations was assessed in the LAL assay and in vivo using a murine model. The LAL assay significantly underestimated the quantity of endotoxin in the whole bacteria form whereas there was no significant difference in detecting endotoxin in aggregate and bleb forms. The failure of the LAL assay to equally quantify endotoxin was not mirrored in vivo where all three presentations of endotoxin were equally inflammatory. The inability of the LAL assay to detect the full quantity of endotoxin presented in the whole bacteria form has troubling implications for exposure assessment studies. Various extraction methods were applied to samples of known endotoxin quantity to improve the detection ability of the LAL assay. Extraction using EDTA and Tris/EDTA significantly improved the detection of endotoxin compared to the reference method of extracting in pyrogen-free water. These extraction methods also significantly increased the quantity of endotoxin measured in house and barn dust samples. A higher quantity of endotoxin measured in the LAL assay corresponded to a higher neutrophilic response in vivo. A standardized methodology for endotoxin detection that mimics the in vivo response is necessary for accurate and consistent endotoxin analysis.

Background : Atrazine is an agricultural herbicide used extensively in corn production worldwide. Atrazine is an endocrine disruptor and has been linked to many other deleterious health outcomes. Exposure assessment studies have been carried out in Iowa among farm and non-farm populations. However, commercial pesticide applicators have been left out of those studies. Atrazine is also used in developing countries in grain production. In developing countries there is great concern about acute pesticide poisonings, but chronic exposure to less acutely toxic pesticides has not been studied extensively. This study assessed the in-home contamination of atrazine among commercial pesticide applicators in Iowa and then quantitatively analyzed these results with results from similar studies. Occupational inhalation exposure to atrazine was also assessed in Honduras. Methods : Dust samples were taken from 29 commercial pesticide applicator households in four different locations. This sampling was done once during the atrazine application season and again six months later during winter months to assess atrazine persistence. Occupational and household characteristics were analyzed for associations with atrazine dust levels. Data from two previous studies that analyzed farm and non-farm household dust samples for atrazine were combined with data from the commercial applicator's homes. This new and larger dataset was analyzed to identify which population has the greatest risk for take-home atrazine exposure and what determinants were associated with in-home atrazine dust levels. Lastly, corn production practices in Honduras were evaluated and personal air samples were taken from pesticide applicators during atrazine application to assess inhalation exposure. Results : The first study found that atrazine levels persist into the winter months in the homes of commercial applicators. Atrazine handling (days, pounds, and acres sprayed) were all positively associated with in-home atrazine levels. Commercial applicators that change their shoes inside had higher atrazine levels. More frequent floor cleaning was associated with lower atrazine levels. The second study identified commercial applicators' homes as the most contaminated compared with farmers who apply atrazine to their own land, farmers who hire out atrazine application, and non-farm homes. Farmers that apply their own atrazine also had significantly higher atrazine levels in their homes. The association between atrazine handling and household atrazine levels was highly significant in this study (p < 0.001). In Honduras, atrazine is applied to corn fields with tractor/boom equipment and manual backpack sprayers. Despite applying about one-fifteenth the amount of atrazine, backpack sprayers are exposed to nearly equal amounts of atrazine via inhalation exposure and likely have greater exposure via the dermal route. Among backpack sprayers, which type of spray nozzle used is associated with inhalation exposure. Among tractor/boom applicators, tractor drivers have much lower inhalation exposure than workers who operate and observe the boom. Conclusions : The amount of atrazine handled is the most important determinant for predicting in-home atrazine levels in Iowa. Ubiquitous atrazine contamination and its distribution within homes and among household type provide strong evidence for the take-home pathway. While some improvements have been made in Honduras regarding pesticide application, poor farm workers and small farmers still use antiquated pesticide application techniques which leads to a higher risk of inhalation and dermal exposure.

Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological and respiratory toxicities are expansive and growing. Existing inhalation estimates demonstrate ubiquitous exposure to World Health Organization (WHO) indicator PCBs and limited other PCB congeners in North America and Europe. However, inhalation exposure estimates of most lower-chlorinated congeners are lacking, and continuing release of PCBs from urban areas demands location-specific assessments of PCB exposure in ambient air and contaminated environments. Using paired indoor and outdoor airborne PCB measurements and activity questionnaires from the AESOP Study, we assess congener-specific exposure rates for adolescent children and their mothers in East Chicago, Indiana and Columbus Junction, Iowa. Our cohorts of 129 (EC) and 135 (CJ) and our detection of 202 individual congeners and coelutions allows unprecedented quantification of congener-specific inhalation exposure, which we compare to dietary exposure using Total Diet Survey PCB concentrations. ∑PCB inhalation is greater for children than for their mothers in both locations, and is greater for East Chicago mothers and children than for Columbus Junction mothers and children, respectively. Schools attended by AESOP Study children have higher indoor PCB concentrations than do homes, and contribute to more than half of children's inhalation PCB exposure. Inhalation of the potentially neurotoxic congeners PCB 11, 40/41/71, and 51 was apparent among individuals at each location. Additional, congener-specific and biological inferences are possible via comparison with sera-based PCB concentrations for these cohorts.

Semi-volatile lower chlorinated PCBs (LC-PCBs), comprised of mostly tetra or lower chlorinated congeners, are detected in old buildings and outdoors in high concentrations. PCBs cause endocrine disruption, neurotoxicity and many other adverse effects, and are human carcinogens. Epidemiological studies so far have relied upon serum concentrations of PCBs or OH-PCBs as markers of exposure. Despite the detection of LC-PCBs in high levels in buildings and other environments, only a few studies have reported LC-PCBs in human serum. One of the reasons for low serum detection of LC-PCBs could be the further biotransformation and excretion of OH-PCBs from the body. Therefore, the objective of this dissertation research was to study the metabolism of one of the LC-PCBs in rats and to identify a suitable metabolite marker of inhalation exposure for a future epidemiological study in humans. We chose PCB3 (4-chlorobiphenyl), a mono chlorinated PCB found in high concentrations in many buildings, as a model to study the metabolism. The first aim was to identify final metabolites of PCB3 in vivo. Male Sprague-Dawley rats were held in metabolism cages following exposure to PCB3 via i.p. injection. Blood, urine and feces were collected, and an analytical method for extraction of PCB3 metabolites was developed. By identifying the metabolites by LC/MS, a complete biotransformation pathway for PCB3 was elucidated. Major urinary metabolites of PCB3 were sulfates and mercapturates, while glucuronides and free phenolic forms were minor. The second aim was to study the disposition and toxicity of phenolic and sulfate metabolites after inhalation exposure to PCB3 in female Sprague-Dawley rats. Airborne PCB3 vapor was generated in a flask and passed through an inhalation exposure system, where rats were exposed via nose-only inhalation. Both hydroxylated and sulfated metabolites were detected in serum, liver, lungs, and brain. The serum clearance half-lives of these metabolites were less than two hours. Serum chemistry parameters were similar in PCB3 exposed and control rats. As a marker of bioactivation of PCB3 to electrophilic species, 8-oxo-dG was quantified in urine, but the difference was not statistically significant between control and exposed rats. The third aim was to study the routes of excretion of metabolites after inhalation to airborne PCB3. Bile cannulated and intact rats were exposed to PCB3 via nose only inhalation. Metabolites detected in bile were mostly sulfates and some glucuronide. Fecal metabolites were exclusively phenols despite very low concentration of free phenolic forms in bile. Peak excretion of metabolites in feces and urine occurred within 24 h, and over sixty percent of the dose was recovered within 24 h. The major route of excretion of PCB3 was urine in the form of sulfated metabolites. Sulfated metabolites were stable in urine for a month without aid of any preservatives. This dissertation shows that PCB3 is rapidly metabolized to phenols and conjugated mostly to sulfates. Conjugated metabolites, elaborated into bile, are either reabsorbed or hydrolyzed in the gut and excreted in feces as phenolic forms. Serum concentrations of sulfates are higher than free phenolic forms at any time after exposure, and are also detected in lungs and brain. PCB3 sulfates are stable metabolites and can serve as a metabolite marker of inhalation exposure to PCB3.

Regulatory agencies have recently focused on assessing the potential for soil vapor intrusion (SVI) and risk posed to occupants of residential and commercial properties overlying and surrounding former Manufactured Gas Plants (MGPs). This study evaluated the potential for SVI at 10 commercial buildings and 26 single family and multi-family residential properties overlying and/or adjacent to three former MGPs. The potential for SVI exposure was categorized into three groupings according to thickness of the vadose zones: no vadose zone; 0 - 6 feet thick, and 6 to 25 feet thick. Indoor and outdoor air and soil vapor samples were collected and analyzed for VOCs by the USEPA Method TO-15. These findings were compared to federal and state regulatory background data sets. The results did not identify evidence of MGP-related soil vapor intrusion from any of the 36 sites regardless of depth to water table or proximity to MGP source tar or dissolved phase plumes. In addition, comparative risks were calculated based on maximum and mean concentrations for benzene, toluene, ethylbenzene, and xylenes measured in ambient air samples, soil vapor, and indoor air. These chemicals were selected based on frequency of detection within the data sets. Hazard Indexes were calculated using the study results and the mean, maximum and 95th percentile concentrations from regulatory data bases. Carcinogenic risks associated with benzene were calculated using both the measured mean and maximum study results and the mean, maximum and 95th percentile concentrations from state and federal data bases. The calculated Hazard Indexes were less than 1 or were comparable to the regulatory mean and maximum background levels. Calculated cancer risks for residential and occupational exposures ranged from 9.75x10-6 to 4.52x10-4. However background benzene exposure not related to former MGP sites ranged from 9.9x10-6 to 3.59x10-3. Cancer risk and exposures to indoor air, soil vapor or ambient air concentrations were equivalent or less than a normal resident in the northeast United States. No increased public health risks were associated with occupied residential or commercial properties overlying or surrounding MGPs.