A etiologia da síndrome do desconforto respiratório (SDR) é considerada multifatorial e multigênica. A proteína B do surfactante (SP-B) é essencial para a função pulmonar normal. O gene responsável pela produção da SP-B está localizado no braço curto do cromossomo 2 (2p12->p11.2), estendendo-se por aproximadamente por 9.5 Kilobases e contém 11 exons. A presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da SP-B, parece estar associada à SDR. Objetivos: Determinar a freqüência de polimorfismos do gene que codifica a proteína B do surfactante no DNA de recém nascidos pré-termo portadores de SDR e de recémnascidos de termo sadios, comparar as freqüências desses polimorfismos entre os dois grupos e avaliar se existe alguma relação entre sexo, raça e SDR. Casuística e Métodos: Foram incluídos no estudo 150 RN, sendo 50 pré-termo portadores de SDR com idades gestacionais variando entre 28 e 33 semanas e 6 dias, e 100 RN de termo clinicamente sadios com idades gestacionais variando de 37 a 41 semanas e seis dias, no período de junho de 2001 a julho de 2004. Foram analisados quatro polimorfismos: A/C no nucleotídeo - 18; C/T no nucleotídeo 1580; A/G no nucleotídeo 9306 e G/C no nucleotídeo 8714. Os polimorfismos foram determinados através da amplificação dos segmentos de DNA genômico por reação em cadeia da polimerase e posterior genotipagem. Os genótipos foram definidos através da análise dos produtos obtidos a partir de reações com enzimas de S . 22 restrição [PCR-based converted restriction fragment length polymorphism (cRFLP)]. Resultados: O grupo controle foi constituído por 100 RN de termo aparentemente saudáveis; 42(42%) do sexo feminino e 58(58%) do sexo masculino; 39(39%) da raça branca e 61(61%) da raça não branca. O peso variou de 2280g a 4.740g (média de 3.239,9g), e a idade gestacional variou de 37 a 41 semanas e seis dias (média de 39 semanas e 3 dias). O grupo SDR foi composto por 50 RNPT, sendo 21(42%) do sexo feminino e 29(58%) do sexo masculino; 28(56%) eram da raça branca e 22(44%), não brancos. O peso variou de 640g a 2.080g (média de 1273g); a idade gestacional média foi de 31 semanas e dois dias, tendo variado de 28 semanas a 33 semanas e seis dias. Foi encontrada uma diferença estatisticamente significante quando comparados os dois grupos e a variável raça isoladamente no polimorfismo G/C 8714 (p=0,028). Quando a variável sexo foi analisada isoladamente, não houve diferença estatisticamente significante dos polimorfismos entre os dois grupos. As freqüências dos genótipos dos outros três polimorfismos estudados foram muito similares nos dois grupos, não tendo sido encontrada diferença estatisticamente significante quando as variáveis sexo e raça foram avaliadas conjuntamente. Conclusão: A análise do polimorfismo G/C 8714 mostrou que em indivíduos da raça branca, o genótipo GG foi apenas encontrado no grupo SDR, sugerindo que a sua presença possa se constituir em um possível fator de risco para a doença, enquanto que o genótipo GC foi mais prevalente no grupo controle indicando a possibilidade desse genótipo ser um fator protetor / The etiology of respiratory distress syndrome (RDS) is multifactorial and multigenic. Surfactant protein B (SP-B) is essential for normal lung function. The human SP-B gene is located on the short arm of chromosome 2 (2p12->p11.2), encompasses approximately 9.5 kilobases and have 11 exons. Polymorphisms and mutations in the genes that encode the surfactant components, particularly the SP-B gene, have been associated to the pathogenesis of RDS. Aims: To analyze SP-B gene polimorfisms frequencies in preterm babies with RDS and healthy term newborns, to compare the polymorphisms frequencies between both groups and to evaluate if there are differences related to sex, race and RDS. Material and Methods: We included 150 neonates, 50 preterm with RDS and gestational ages ranging from 28 weeks to 33 weeks and 6 days, and 100 healthy term newborns with gestational ages ranging from 37 weeks to 41 weeks and 6 days, during June 2001 to July 2004. Four SP-B gene polymorphisms were analyzed: A/C at - 18, C/T at 1580; A/G at 9306 and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphism (cRFLP). Results: The control group comprised 100 apparently healthy term newborns; 42(42%) were female and 58(58%) male; 39(39%) were Whites and 61(61%) non-Whites. Weight ranged from 2280g to 4.740g (mean 3.239,9g); gestational age ranged from 37 weeks to 41 weeks and six days (mean 39 weeks and 3 days). The RDS group comprised 50 preterm neonates, 21(42%) female and 29(58%) male; 28(56%) were Whites and 22(44%) non-Whites. Weight ranged from 640g to 2.080g (mean 1273g); mean gestational age was 31 weeks and two days (range, 28-33 weeks and six days). All genotypes frequencies were similar among both groups when sex and race were analyzed together. When race was analyzed separately, there was a statistically significant difference between both groups in the polymorphism G/C at 8714 (p=0,028). There was no difference between both groups in all polymorphisms when sex was analyzed separately. Conclusions: The analysis of the SP-B polymophism G/C 8714 showed that in white neonates the genotype GG was only found in the RDS group and the genotype GC was more frequently found in controls. This suggests that genotype GG could be a risk factor while GC might be a protective genotype for the development of the disease

INTRODUÇÃO: A Síndrome do Desconforto Respiratório (SDR) é uma das principais causas de morbi-mortalidade no período neonatal, acometendo predominantemente os recém-nascidos prematuros, devido a uma está deficiência de surfactante pulmonar. O Instituto Butantan desenvolveu um surfactante de origem porcina com objetivo de torná-lo disponível a todo Sistema Único de Saúde. O objetivo deste estudo foi avaliar, em um modelo experimental de SDR (coelho), a estabilidade do Surfactante Butantan (SB) um ano após sua produção e armazenamento a 2 a 8ºC.. MÉTODOS: 94 coelhos prematuros foram randomizados em dois grupos de tratamento: grupo Butantan e grupo Curosurf (controle), e foram analisados em seis momentos de avaliação: momento zero (imediatamente após a retirada do refrigerador ao final de 1 ano de armazenamento), momento 1 (24 horas após ter sido mantido a 24ºC), momento 2 (após 30 dias de armazenamento a 20º C), momento 3 (após 60 dias de armazenamento a 20º C), momento 4 (após 90 dias de armazenamento a 20º C) e momento 5 (após 180 dias de armazenamento a 20º C). Após receberem o surfactante, os animais foram ventilados por 15 minutos para avaliação da pressão ventilatória e complacência pulmonar dinâmica e curva pressão-volume pulmonar, seguindo-se à avaliação histopatológica dos pulmões. RESULTADOS: A eficácia do SB foi semelhante à do Curosurf, um ano após a sua produção e armazenamento a 2 a 8ºC. Neste momento de avaliação, não houve diferença estatisticamente significante entre os grupos de estudo quanto a: pressão ventilatória, complacência pulmonar dinâmica e curva pressão-volume pulmonar. Ao longo dos seis meses de armazenamento inadequado do SB, demonstrou-se a redução de sua eficácia durante a fase expiratória da curva pressão-volume pulmonar. No entanto, a análise histopatológica, demonstrou não haver diferença significante entre os dois grupos de estudo em nenhum dos momentos de avaliação. CONCLUSÕES: As propriedades bioquímicas do SB foram preservadas após um ano de sua produção e armazenamento em refrigeração de 2 a 8ºC. Condições inadequadas de armazenamento resultam em alterações das propriedades bioquímicas do SB e, conseqüentemente, de sua função, o que foi demonstrado por parâmetros de mecânica ventilatória, mas não pela análise histopatológica dos pulmões / INTRODUCTION: Respiratory Distress Syndrome (RDS) is one of the major causes of death among premature newborns, and its development results from surfactant deficiency. The Butantan Institute has recently produced a porcine-derived surfactant preparation in order to make it available nationwide for RDS treatment in the near future. The aim of this study was to evaluate, in an animal model of surfactant deficiency (premature rabbits), the stability of the Butantan Surfactant (SB) one year after its production and storage in the refrigerator, at 2 to 8ºC. METHODS: 94 premature newborn rabbits were randomized into two treatment groups: SB or Curosurf®(control surfactant), and were assessed in six different time-points: time-point zero (immediately after removal of surfactant from the refrigerator after one year of storage); time-point 1 (after 24h of storage at 24ºC), time-point 2 (after 30 days of storage at 20ºC), time-point 3 (after 60 days of storage at 20ºC), time-point 4 (after 90 days of storage at 20ºC) and time-point 5 (after 180 days of storage at 20ºC). The animals were artificially ventilated for 15 minutes for lung mechanics assessment (ventilatory pressure, dynamic lung compliance and pressure-lung volume curve), followed by removal of the lungs for histopathologic analysis. RESULTS: After one year of its production and storage at 2 to 8ºC, SB was as efficient as Curosurf. At this time-point, The Butantan Surfactant showed no significant differences with Curosurf® regarding the ventilatory pressure, dynamic lung compliance and pressure-lung volume curve. Throughout the six month period of warming, SB showed a decreasing efficiency, as revealed by the expiratory phase of the pressure-lung volume curve. However, the histopathologic analysis revealed no significant differences between the two groups, in any of the study time-points. CONCLUSIONS: The Butantan Surfactant preserved its biochemical properties one year after its production and storage at 2 to 8ºC. On the other hand, adverse storing conditions can lead to alterations in the SB biochemical properties that result in deterioration of its function, which was demonstrated in this study by changes in lung mechanics, but not in the histopathologic analysis

A síndrome do desconforto respiratório (SDR) é causada pela deficiência transitória de surfactante pulmonar em recém-nascidos (RN) prematuros nos primeiros dias de vida. Estudos sugerem que a etiologia da SDR seja multifatorial e multigênica. A proteína B do surfactante (SP-B) é fundamental para o metabolismo do surfactante e para uma função pulmonar normal. A presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da SP-B, parece estar associada à SDR. Objetivos: Determinar a freqüência de polimorfismos do gene que codifica a proteína B do surfactante no DNA de recém nascidos pré-termo com e sem SDR, comparar as freqüências desses polimorfismos entre os dois grupos e avaliar se existe alguma relação entre sexo, raça e SDR. Casuística e Métodos: Foram incluídos no estudo 151 RNPT, sendo 79 sem SDR com idades gestacionais variando entre 29 semanas e 35 semanas e 6 dias e 72 RN pré-termo com SDR com idades gestacionais variando de 26 a 35 semanas. Foram analisados quatro polimorfismos: A/C no nucleotídeo - 18; C/T no nucleotídeo 1580; A/G no nucleotídeo 9306 e G/C no nucleotídeo 8714. Os polimorfismos foram determinados através da amplificação dos segmentos de DNA genômico por reação em cadeia da polimerase e posterior genotipagem. Os genótipos foram definidos através da análise dos produtos obtidos a partir de reações com enzimas de restrição [PCR-based converted restriction fragment length polymorphism (cRFLP)]. Resultados: O grupo Controle foi constituído por 79 RN pré-termo sem SDR; sendo 42 (53,2%) do sexo feminino e 37 (46,8%) do sexo masculino; 34 (43%) da raça negra, 16(20,3%) da raça branca e 29(36,7) de indivíduos pardos. O peso variou de 1170g a 3260 , e a idade gestacional variou de 29 semanas a 35 semanas e seis dias (média de 33 semanas e 6 dias).O grupo SDR foi composto por 72 RNPT, sendo que 31 (43%) do sexo feminino e 41 (57%) do sexo masculino; 31(43%) da raça negra, 16 (14%) da raça branca e 31(43%) de indivíduos pardos. O peso variou de 614g a 2.410g ; a idade gestacional média foi de 32 semanas , tendo variado de 26 semanas a 35 semanas. O modelo de regressão logística múltipla, utilizado para avaliar a contribuição das diversas variáveis na probabilidade de ocorrer SDR, demonstrou que a idade gestacional foi a variável que mais contribuiu para a ocorrência da patologia, e que o genótipo AG do polimorfismo A/G na posição 9306 foi um fator protetor para a doença nesta população (OR 0.1681; IC 95% 0.0426 - 0.6629). Não foram observadas diferenças entre as freqüências dos demais polimorfismos avaliados entre os 2 grupos de recém-nascidos, bem como diferenças quanto à raça e sexo. Conclusões: A presença do genótipo AG do polimorfismo A/G na posição 9306 do gene que codifica a proteína B do surfactante foi fator protetor para o desenvolvimento da síndrome do desconforto respiratório em recém-nascidos da cidade de Salvador-Bahia. Os polimorfismos A/C no nucleotídeo - 18, C/T no nucleotídeo 1580, e G/C no nucleotídeo 8714 presentes no referido gene não estiveram associados à síndrome do desconforto respiratório em recém-nascidos na amostra estudada. / The respiratory distress syndrome (RDS) is caused by surfactant transient deficiency in preterm babies soon after birht. Studies sugest that RDS etiology is multifactorial and multigenic. Surfactant protein B (SP-B) is essential for surfactant metabolism and fornormal lung function. Polymorphisms and mutations in the genes that encode the surfactant components, particularly the SP-B gene, have been associated to the pathogenesis of RDS. Aims: To analyze SP-B gene polimorfisms frequencies in preterm babies with RDS and healthy term newborns, to compare the polymorphisms frequencies between both groups and to evaluate if there are differences related to sex, race and RDS. Material and Methods: We included 151 neonates, 79 preterm babies without RDS and gestational ages ranging from 26 weeks to 35 weeks , and 72 preterm newborns with RDS, gestational ages ranging from 29 weeks to 35 weeks and 6 days. Four SP-B gene polymorphisms were analyzed: A/C at - 18, C/T at 1580; A/G at 9306 and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphism (cRFLP). Results: The control group comprised 79 preterm babies without RDS; 42(53,2%) were female and 37(46,8%) male; 34(43%) were black, 16(20,3) were Whites and 29(36.7%) non- Whites/non black. Weight ranged from 1.170g to 3.260g ; gestational age ranged from 29 weeks to 35 weeks and six days (mean 33 weeks and 6 days). The RDS group comprised 72 preterm neonates, 31(43%) female and 41(57%) male; 31(43%) were black, 16(14%) were Whites and 31(43%) non-Whites/non black. Weight ranged from 614g to 2.410g ; mean gestational age was 32 weeks (range, 26-35 weeks). The logistic regression model showed that gestational age was the variable that most contributed to the ocurrence of the respiratory distress syndrome and the AG genotype of the polymorphism A/G at 9306 was a protector factor for the disease in the studied population (OR 0.1681; CI 95% 0.0426 - 0.6629). We did not detect differences between the frequencies of the other evaluated polymorphisms between both groups of newborns. Conclusions: The presence of AG genotype at 9306 of the surfactant protein B (SP-B) gene was a protector factor for the development of the respiratory distress syndrome in newborns from the city of Salvador-Bahia. The polymorphisms A/C at nucleotide - 18, C/T at 1580, and G/C at nucleotide 8714 from the SP-B gene were not associated with respiratory distress syndrome in the studied population.

INTRODUÇÃO: Existem muitas controvérsias, nos estudos epidemiológicos existentes, a respeito da incidência e desfechos da síndrome de lesão pulmonar aguda. A incidência e as características clínicas da síndrome dependem principalmente da definição utilizada e da metodologia empregada no estudo, bem como da disponibilização e utilização dos leitos nas unidades de terapia intensiva da região estudada. Pela ausência de dados epidemiológicos existentes de lesão pulmonar aguda na Grande Vitória, no Espírito Santo, realizamos este estudo para analisar a incidência, características, sobrevida aos 28 dias e mortalidade hospitalar. MÉTODOS: Os pacientes internados nas 14 unidades de terapia intensiva da Grande Vitória, durante o período de 15 meses, submetidos à ventilação mecânica e que preencheram os critérios de lesão pulmonar aguda da Conferência de Consenso Européia-Americana de 1994 foram selecionados prospectivamente para o estudo. Os pacientes também foram classificados de acordo com a nova definição de Berlim. Avaliamos as características clínicas e funcionais no primeiro dia de internação, durante a primeira semana, no 14º dia e no 28º dia de evolução. Foram calculadas a incidência da síndrome acumulada/ano, a sobrevida aos 28 dias e a mortalidade hospitalar. RESULTADOS: Foram avaliados 7.133 pacientes admitidos nas unidades de terapia intensiva, dos quais 130 (1,8%) foram selecionados. A mediana de tempo para o diagnóstico de lesão pulmonar aguda foi de 2 dias (IQ: 0-3 dias), sendo 25,4% dos diagnósticos realizados no momento da internação na unidade de terapia intensiva. Os fatores de risco foram principalmente pneumonia (35,3%), sepse não pulmonar (31,5%) e trauma (16,9%). A média de idade dos pacientes foi de 44,2 ± 15,9 anos, sendo 61,5% do sexo masculino. A média do APACHE II foi de 20,7 ± 7,9 e a média da PaO2/FiO2, de 206,7 ± 61,6. O tempo médio em ventilação mecânica foi de 21 ± 15 dias e o tempo médio de permanência na unidade de terapia intensiva foi de 26,4 ± 18,7 dias. De acordo com a nova definição de Berlim, os pacientes com a síndrome de desconforto respiratório agudo foram classificados em: leve, com 49 casos (37,7%); moderada, com 68(52,3%); e grave, com 13(10%). A incidência acumulada de LPA foi de 10,1 casos/100.000 habitantes/ano, sendo 3,8 casos/100.000 habitantes/ano para LPA sem SDRA e 6,3 casos/100.000 habitantes/ano para SDRA, representando 1,7% das admissões no ano. A relação PaO2/FiO2 nos dias 6 e 7 de evolução após o diagnóstico da síndrome foi um fator preditor independente para a mortalidade aos 28 dias, que foi de 38,5% (95% IC, 30,1-46,8). A mortalidade intrahospitalar foi de 49,2% (95% IC, 40,6-57,8), não diferindo entre os pacientes com LPA sem SDRA e SDRA. CONCLUSÕES: A incidência de LPA nos pacientes submetidos à ventilação mecânica invasiva na região da Grande Vitória, Espírito Santo, foi baixa, sendo a maioria dos casos diagnosticada 2 dias após a admissão nas unidades de terapia intensiva. A mortalidade aos 28 dias e a hospitalar dos pacientes com LPA sem SDRA e com SDRA não foram estatisticamente diferentes neste estudo. As mudanças nas práticas assistenciais nas unidades de terapia intensiva poderão contribuir para a redução da incidência da SDRA intrahospitalar / INTRODUCTION: There are many controversies in the existing epidemiological studies regarding the incidence and outcomes in acute lung injury. The incidence and clinical features of the syndrome mainly depend on the definition adopted and on the methodology employed in the study, as well as on the availability and use of beds in intensive therapy units in the regions studied. Due to the absence of existing epidemiological data concerning acute lung injury in Vitória, Espírito Santo, we conducted this study to analyze the incidence, clinical characteristics, survival rate at 28 days, and mortality rate. METHODS: The patients hospitalized in the 14 units of intensive therapy in the region of Grande Vitória for the period of 15 months submitted to mechanical ventilation, who fulfilled the criteria of acute lung injury as defined by the Conference of European-American Consensus of 1994, were prospectively selected for the study. These patients were also classified according to the new Berlin definition. We evaluated the clinical and functional characteristics on the first day of hospitalization, during the first week, on day 14 and on day 28 of clinical evolution. We calculated the cumulative incidence/year for the syndrome, the survival rate at 28 days, and hospital mortality. RESULTS: A total of 7,133 patients admitted to the intensive care units was evaluated, of whom 130 (1.8%) were selected. The median time to diagnosis of acute lung injury was 2 days (IQR: 0-3 days), 25.4% of diagnoses being made at admission to the intensive care unit. The risk factors were mainly pneumonia (35.3%), nonpulmonary sepsis (31.5%) and trauma (16.9%). The patients\' mean age was 44.2 ± 15.9 years, 61.5% being male. The APACHE II prognostic score averaged 20.7 ± 7.9, mean arterial oxygenation variable PaO2/FiO2 206 ± 61.6 and time on mechanical ventilation with a mean of 21 ± 15 days. The average length of stay in intensive care unit was 26.4 ± 18.7 days. Based on the new Berlin definition, patients with acute respiratory distress syndrome were classified as mild: 49 (37.7%); moderate: 68 (52.3%); and severe: 13 (10%). The cumulative incidence was 10.1 cases per 100,000 inhabitants /year for ALI, of which 3.8 cases per 100,000 inhabitants / year were for non-ARDS ALI and 6.3 cases per 100,000 inhabitants / year were for ARDS, representing 1.7% of admissions in the year. The variable arterial oxygenation on days 6 and 7 of evolution after the diagnosis of the syndrome was an independent factor for mortality at 28 days, which was 38.5% (95% CI, 30.1 to 46.8). In-hospital mortality was 49.2% (95% CI, 40.6 to 57.8), and did not differ between patients with ALI non-ARDS and acute respiratory distress syndrome Summary (ARDS). CONCLUSIONS: The incidence of acute lung injury in patients undergoing invasive mechanical ventilation in the region of Grande Vitória, Espírito Santo was low, most of them being diagnosed 2 days after admission to intensive care units. Mortality at 28 days and hospital mortality of patients with ALI non-ARDS were not statistically different in this study. Changes in care practices in intensive therapy units can contribute to reduce the incidence of in-hospital ARDS

INTRODUÇÃO: A insuficiência respiratória acomete grande parte dos pacientes oncológicos levando a altos índices de mortalidade. A ventilação não invasiva (VNI) pode auxiliar seu manejo, mas seus efeitos ainda são pouco conhecidos sobre os mecanismos de defesa pulmonar. OBJETIVOS: Observar o efeito da VNI com máscara facial usando-se geradores de fluxo com pressão positiva contínua (CPAP) e ventilador microprocessado no modo pressão de suporte + pressão positiva ao final da expiração (PSV + PEEP), a fim de verificar impacto nas propriedades viscoelásticas do muco respiratório e o conforto proporcionado ao paciente. MÉTODOS: A VNI foi instalada após diagnóstico de insuficiência respiratória em dezenove pacientes, admitidos nas unidades de tratamento intensivo do Hospital A. C. Camargo, sendo nove submetidos ao CPAP e dez com PSV + PEEP. Foram colhidos antes e após uma hora de VNI: os dados clínicos, secreção nasal, gasometria, e o grau de conforto através de uma escala visual. As propriedades físicas do muco (transportabilidade in vitro, adesividade e wettabilidade ou hidrofobicidade) foram avaliadas respectivamente no palato de rã, máquina da tosse e ângulo de contato. RESULTADOS: Os grupos eram homogêneos entre si em relação à idade, sexo, tipo e estadiamento do tumor e SAPS II. Em relação às propriedades físicas do muco, houve um aumento da transportabilidade in vitro do muco nasal com o sistema PSV + PEEP (p = 0,04) e um aumento na wettabilidade no grupo CPAP (p = 0,06). Os dois sistemas foram eficazes em melhorar significativamente os sinais vitais, a PaO2/FiO2, o padrão e o conforto respiratório e em evitar a intubação traqueal nas primeiras 24 horas (p < 0,05). Entretanto, independentemente do tipo de sistema de VNI usado, foram encontrados altos índices de intubação endotraqueal e mortalidade no seguimento destes pacientes. CONCLUSÃO: As propriedades físicas do muco (transportabilidade in vitro e wettabilidade) se alteraram após uma hora de uso da VNI e parecem ser dependentes da temperatura e umidificação dentro da máscara. A VNI mostrou-se útil em reverter a insuficiência respiratória em pacientes selecionados, ou pelo menos em trazer conforto para pacientes hipoxêmicos que a princípio recusam a intubação endotraqueal / INTRODUCTION: Respiratory failure is a common situation among cancer patients leading to high rates of mortality. Noninvasive ventilation (NIV) can help its management, but its effects are still unknown regarding the pulmonary defense mechanisms. OBJECTIVES: Observe the effect of NIV with facial mask using a flow generator with continuous positive pressure (CPAP) and standard intensive care unit ventilator using pressure support ventilation + positive end expiratory pressure (PSV + PEEP), to verify impact on the physical properties of respiratory mucus and the comfort provided to the patient. METHODS: NIV was started after diagnosis of respiratory failure in nineteen patients, admitted in the intensive care unit of the A. C. Camargo Hospital. Nine patients were submitted to CPAP and ten to PSV + PEEP. Nasal mucus, blood gases, and the degree of comfort through a visual scale were accessed before and after one hour. The physical properties of nasal mucus (transportabilility in vitro, adhesivity and wettability or hydrofobicity) were evaluated respectively by frog palate, cough machine and contact angle. RESULTS: Groups had similar characteristics about age, sex, tumor and SAPS II score. Regarding the physical properties of the mucus, there was an increase in mucus transportability (by the frog palate model) with the system PSV + PEEP (p = 0.04) and an increase in the contact angle in the CPAP groupo (p = 0.06). The two systems were effective in improving the vital signs, the PaO2/FiO2, the respiratory pattern and comfort and avoiding endotracheal intubation in the first 24 hours (p < 0.05). However, regardless of the type of NIV system used, high rates of endotracheal intubation and mortality were found. CONCLUSION: The physical properties of the mucus (transportability in vitro and wettability) changed after an hour of use of the NIV as a result of temperature and humidification into the mask. NIV was useful in reversing the respiratory failure in selected patients, or at least in bringing comfort for those who refuse endotracheal intubation

<p>The breathing pattern of preterm infants is immature and is associated with a variety of reflexes. In a patient on the ventilator these reflexes interfere with spontaneous breathing. A better understanding of the immature control of breathing could lead to further improvements in ventilatory techniques. This thesis concerns studies of pulmonary stretch receptor (PSR) and phrenic nerve activity as part of the regulation of breathing in an animal model. </p><p>During assist/control ventilation with three different inspiratory pressure waveforms in animals with healthy lungs, squarewave pressure waveform<b> </b>strongly inhibits spontaneous inspiratory activity.</p><p>During partial liquid ventilation (PLV) in animals with healthy lungs, all PSRs studied maintained their phasic character, with increased impulse frequency during inspiration. PSR activity was not higher during PLV than during gas ventilation (GV), indicating that there was no extensive stretching of the lung during PLV.</p><p>During proportional assist ventilation (PAV) the applied airway pressure is servo-controlled proportionally to the ongoing breathing effort, thereby interacting with the activity of PSRs. Peak PSR activity was higher and occurred earlier during PAV than during CPAP. The regulation of breathing is maintained during PAV in surfactant-depleted animals before and early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP in both conditions.</p><p>Both lung mechanics and gas exchange influence the regulation of breathing. Inhibition of inspiratory activity occurred at a lower arterial pH and a higher PaCO₂ during PLV than during GV in animals with surfactant-depleted lungs, which might be related to recruitment of a larger number of pulmonary stretch receptors during PLV.</p><p>In summary, selected aspects of the regulation of breathing were studied in an animal model with different ventilatory techniques under different lung conditions similar to those that can occur in infants.</p>

Introduction: The use of high frequency oscillatory ventilation is increasing in treatment ofacute respiratory distress syndrome over the past decade. The technique of HFOV of ventilatingthe lungs at volumes less than the anatomical dead space calms the clinical concerns surroundingventilating stiff ARDS lungs with high pressures and volumes. This largely reduces theprobability of barotraumas and/or atelectrauma. Purpose: The study was on an in vitro bench model that answered the following researchquestions: 1. The effect of three inline closed suction adapters on delivered tidal volume duringHFOV with varying lung compliance 2. The effect of varying compliance on the amplitudedelivered by HFOV; and 3. The effect of compliance on tidal volume delivered by HFOV. Method: An in vitro bench model using high fidelity breathing simulator (ASL 5000, IngMarMedical) simulating an adult patient with ARDS was set up with 3100B SensorMedic highfrequency ventilator. The simulation included varying the compliance for each lung at 50, 40, 30and 20cmH2O while maintaining fixed resistance of 15 cmH2O/L/sec. The ventilator was set tothe following parameters: power of 6, frequency (f) of 5, inspiratory time (Ti) of 33%, bias flow(BF) of 30 LPM and oxygen concentration of 50%. The breathing simulator was connected withthe high frequency ventilator using a standard HFOV circuit and a size 8.0mm of endotrachealtube. Fourteen French Kimberly Clark suction catheters (with T and Elbow adapters) and Air-Life suction catheters (Y adapter) were placed in-line with the circuit successively to carry outthe study. Each run lasted for 1 minute after achieving stable state conditions. Thisapproximated to 300 breaths. The data was collected from the stimulator and stored by the hostcomputer. Data Analysis: The data was analyzed using SPSS v.11 to determine the statistical significance.A probability value (P value) of ≤ 0.001 was considered to be statistically significant. Results: The data analysis showed that Air-Life Y-adapter suction catheters caused the least lostin tidal volume when placed in line with HFOV and hence proved to be the most efficient. Thestudy also showed a direct relationship between amplitude and lung compliance i.e. an increasein lung compliance caused an associated increase in amplitude (power setting remainingunaltered). Lastly, the study did not show a statistically significant change in tidal volume withchanges in lung compliance. Future studies may be required to further evaluate the clinicalsignificance of the same. Conclusion:1. Many factors affect delivery of tidal volume during high frequency ventilation and thus it isnot constant. Choice of in-line suction system to be placed in line is one of the determinants ofthe same.2. Lung compliance changes lead to associated changes in amplitude delivery by HFOV. Thisshould be adjusted as patient condition improves by altering the power settings to ensure optimalventilation and to avoid trauma to the lungs.

Cette thèse porte sur la mise en place, sur un imageur clinique, de nouveaux protocoles adaptés à l'IRM de l'hélium3 hyperpolarisé et sur leur validation au cours d'études précliniques et cliniques. L’IRM de l’hélium3 hyperpolarisé étant non invasive et non ionisante, elle est bien adaptée à l'utilisation chez l'enfant, dès le plus jeune âge, et aux suivis longitudinaux. Pourtant, les protocoles d’imagerie sont le plus souvent réalisés pendant l’apnée, rendant la technique difficilement applicable chez de jeunes enfants. La première contribution de cette thèse porte sur un protocole de respiration spontanée, sa modélisation et sa validation préclinique, préalables à une application chez des patients non coopératifs. La deuxième étude traite de l'application conjointe de l'IRM proton et hélium3 hyperpolarisé à un modèle de pathologie aiguë chez le lapin, maladie jusqu’à présent non étudiée en IRM de l’hélium3 hyperpolarisé. Enfin, la troisième étude s’intéresse à l’évaluation de la sensibilité de la technique et de l'influence d'une séance de drainage bronchique, chez des enfants atteints de mucoviscidose dont la fonction pulmonaire est asymptomatique. / This work deals with the design, on a clinical scanner, of new protocols for helium3 MRI and with their application to preclinical and clinical studies. Allowing for a virtually unlimited number of acquisitions, helium3 MRI is well adapted for longitudinal or pediatric studies. Acquisitions, however, are mostly performed under breath-hold, precluding the application to non cooperative patients. The first part of this thesis addresses the use of a free-breathing protocol, validated in vivo on rabbit and optimized using a model of gas exchange. A second study tackles the joint use of helium3 and proton MRI to study acute diseases, using a rabbit model of Acute Respiratory Distress Syndrome. Finally, the third study demonstrates the sensitivity of helium3 MRI and evaluates the influence of chest physical therapy on cystic fibrosis children with normal respiratory function.

The breathing pattern of preterm infants is immature and is associated with a variety of reflexes. In a patient on the ventilator these reflexes interfere with spontaneous breathing. A better understanding of the immature control of breathing could lead to further improvements in ventilatory techniques. This thesis concerns studies of pulmonary stretch receptor (PSR) and phrenic nerve activity as part of the regulation of breathing in an animal model. During assist/control ventilation with three different inspiratory pressure waveforms in animals with healthy lungs, squarewave pressure waveform strongly inhibits spontaneous inspiratory activity. During partial liquid ventilation (PLV) in animals with healthy lungs, all PSRs studied maintained their phasic character, with increased impulse frequency during inspiration. PSR activity was not higher during PLV than during gas ventilation (GV), indicating that there was no extensive stretching of the lung during PLV. During proportional assist ventilation (PAV) the applied airway pressure is servo-controlled proportionally to the ongoing breathing effort, thereby interacting with the activity of PSRs. Peak PSR activity was higher and occurred earlier during PAV than during CPAP. The regulation of breathing is maintained during PAV in surfactant-depleted animals before and early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP in both conditions. Both lung mechanics and gas exchange influence the regulation of breathing. Inhibition of inspiratory activity occurred at a lower arterial pH and a higher PaCO2 during PLV than during GV in animals with surfactant-depleted lungs, which might be related to recruitment of a larger number of pulmonary stretch receptors during PLV. In summary, selected aspects of the regulation of breathing were studied in an animal model with different ventilatory techniques under different lung conditions similar to those that can occur in infants.

The acute respiratory distress syndrome (ARDS) and its less severe form, acute lung injury (ALI), are among the leading causes of morbidity and mortality in critically ill patients. Commonly induced by conditions associated with severe pulmonary inflammation, ALI results in disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Sepsis is another frequent and often fatal clinical condition for patients in the intensive care unit. It is characterized by a combination of infection and systemic inflammatory response syndrome (SIRS). Current effective treatment strategies for both ALI/ARDS and sepsis are lacking. We first examined the potential therapeutic role of mesenchymal stromal cells (MSCs) alone or together with the vasculoprotective factor, angiopoietin-1 (ANGPT1), for treatment of experimental ALI in mice. MSCs significantly reduced LPS (lipopolysaccharide)-induced pulmonary inflammation, as reflected by cell counts in bronchoalveolar lavage (BAL) fluid and pro-inflammatory cytokine levels in both BAL fluid and lung parenchymal homogenates. More importantly, administration of MSCs transfected with human ANGPT1 plasmid (MSCs-pANGPT1) completely reversed LPS-induced permeability in the lung (i.e., ALI). A follow-up study showed that MSCs remained effective in rescuing mice with LPS-induced ALI; however, the additional benefit from ANGPT1 was no longer observed. To further evaluate MSC-based therapy in a more clinically relevant model of acute injury, the cecal-ligation-and-puncture (CLP) model for sepsis was employed. Our results demonstrated that MSCs can reduce both systemic and pulmonary inflammation, as well as renal and liver dysfunction/injury, as reflected by plasma urea and bilirubin levels, in septic mice. Most notably, MSCs reduced sepsis-associated mortality from 45% to 24%. Our data demonstrate the feasibility and effectiveness of MSC- and MSC-based gene therapy for experimental ALI and sepsis, and provide the basis for the development of an innovative approach for the prevention and treatment of clinical ALI/ARDS and sepsis.