Ensaio clínico randomizado duplo-cego do perfil inflamatório e do nível de estresse oxidativo em indivíduos com diagnóstico polissonográfico de SAOS antes e após o uso de CPAP
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2016-03-02
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Universidade Estadual Paulista (Unesp)
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Introdução: A Síndrome da Apneia Obstrutiva do Sono (SAOS) é uma desordem com alta incidência na população, associada a risco elevado de doença cardiovascular. O tratamento ouro é a pressão positiva contínua nas vias aéreas, proporcionada pelo uso do Continuous Positive Airway Pressure (CPAP). A SAOS está associada a produção de resposta inflamatória no indivíduo assim como ao aumento do estresse oxidativo provocado pelos fenômenos hipóxia/reoxigenação. O tratamento com CPAP normaliza os eventos respiratórios e a estrutura do sono, porém existem muitos estudos controversos em relação ao tratamento com o CPAP e a redução dos marcadores inflamatórios e de estresse oxidativo. Também não há consenso quanto ao tempo mínimo de uso de CPAP para observar uma resposta à repercussão nociva da SAOS. Objetivo: Avaliar os níveis séricos de citocinas pró e anti-inflamatórias e de marcadores de estresse oxidativo em pacientes com SAOS tratados com CPAP pelo período de sete dias. Pacientes e Métodos: Trata-se de um ensaio clínico randomizado duplo-cego, com aprovação pelo Comitê de Ética em Pesquisa local (CAAE: 20839713.3.0000.5411). Foram convidados a participar do estudo 60 pacientes adultos (acima de 18 anos), de ambos os gêneros, com diagnóstico polissonográfico de SAOS, atendidos no Ambulatório de Ventilação Domiciliar, da Faculdade de Medicina de Botucatu, Unesp. Os grupos foram constituídos por seleção aleatória da amostra, a qual viabilizou a distribuição dos sujeitos em dois grupos, sendo o Grupo I constituído por pacientes em uso do CPAP na pressão mínima de 4 cmH2O (n=30) e o Grupo II por pacientes em uso do CPAP na pressão terapêutica ideal (n=30). Todos os pacientes receberam o aparelho de CPAP, com visor vedado, e fizeram uso de uma semana. Foram coletados 20mL de sangue por punção venosa, antes e após o tratamento. A dosagem das citocinas interleucina-6 (IL-6), interleucina-10 (IL-10) e fator de necrose tumoral-α (TNF- α) foi realizada por Ensaio Imunoenzimático (ELISA), além da dosagem de Capacidade Antioxidante Hidrofílica (CAH) e Malonildialdeído (MDA) por técnicas fluorométricas e cromatográficas, respectivamente. Os pacientes foram avaliados antes da intervenção (uso do CPAP), sendo apresentada média e desvio padrão para gênero, idade, IMC, IAH, IL-6, IL-10, TNF-α, CAH e MDA, e correlação dos níveis de todos os marcadores com IMC e IAH pelo teste de correlação de Pearson. Foi também realizada a avaliação nos dois grupos antes e após a intervenção (uso do CPAP), sendo apresentada média e desvio padrão para gênero, idade, IMC, IAH, IL-6, IL-10, TNF-α, CAH e MDA, com verificação da homogeneidade entre os grupos, utilizando o teste t-student para gênero, idade, IMC e IAH, e modelo linear generalizado com distribuição gamma para IL-6, IL-10, TNF-α, CAH e MDA. Os resultados dos níveis de IL-6, IL-10, TNF-α, CAH e MDA foram comparados entre os dois grupos, antes e após o uso do CPAP, pelo modelo linear generalizado com distribuição gamma. Resultados: A avaliação antes do uso do CPAP teve a participação de 53 pacientes (32 homens) com idade média de 52,62±12,70, IMC de 32,78±5,37, IAH de 33,41±18,71, IL-6 de 8,86±26,97, IL-10 de 12,01±42,04, TNF-α de 76,28±169,29, CAH de 30,99±10,17 e MDA de 1,03±0,35. Não foi encontrada correlação entre os marcadores dosados com IMC e IAH, antes da intervenção (uso do CPAP), sendo observada uma tendência de correlação entre os níveis de CAH e gravidade de SAOS (p=0,0690). A análise nos dois grupos, antes e após o uso do CPAP, teve a participação de 38 pacientes (24 homens), e mostrou homogeneidade entre os dois grupos para gênero, idade, IMC, IAH, IL-6, IL-10, TNF-α, CAH e MDA. Quando comparados os dois grupos, tanto antes quanto após o uso do CPAP, não foi observada nenhuma diferença significativa para IL-6, IL-10, TNF-α e MDA. Foi observado aumento significativo de CAH após o uso do CPAP na pressão mínima de 4cmH2O e tendência ao aumento de CAH em pacientes com uso de CPAP terapêutico. Conclusão: O perfil inflamatório e o nível de estresse oxidativo não sofreram variação com o uso do CPAP pelo período de uma semana, contudo foi observada tendência de correlação de CAH com a gravidade de SAOS antes do uso de CPAP, aumento significativo de CAH após o uso do CPAP na pressão mínima de 4cmH2O e tendência ao aumento de CAH em pacientes com uso de CPAP terapêutico.
Introduction: Obstructive Sleep Apnea Syndrome (OSAS) is a disorder with high incidence in population, associated to high cardiovascular risk factor. Its main treatment uses Continuous Positive Airway Pressure (CPAP). OSAS is associated to the production of inflammatory response in the individual as well as to the increase of oxidative stress caused by hypoxia/ re-oxygenation phenomena. Treatment with CPAP normalizes respiratory events and sleep structure, but there are many controversial studies regarding treatment with CPAP and reduction of inflammatory markers and oxidative stress. There is not a consensus in relation to the minimum time of CPAP utilization to observe a response to the harmful outcome of OSAS. Objective: To evaluate the serum levels of pro- and anti-inflammatory cytokines and markers of oxidative stress in OSAS patients treated with CPAP for seven days. Patients and Methods: It was a randomized double-blind clinical trial approved by the local Committee of Ethics in Research (CAAE: 20839713.3.0000.5411). 60 male and female adult patients (over 18 years old) with polysomnographic diagnosis of OSAS, attended at the Homecare Ventilation Clinic of Botucatu Medical School, UNESP, were invited to participate in the study. The groups were distributed by random sampling selection which allowed the distribution into two groups where Group I consisted of patients using CPAP at minimum pressure of 4 cmH2O (n=30) and Group II was formed by patients utilizing CPAP at the ideal therapeutic pressure (n=30). All patients received a CPAP device with a total face mask and used it for one week. 20mL of blood was collected by venous puncture before and after the treatment. The dose of interleukin-6 (IL-6), interleukin-10 (IL-10) cytokines and tumor necrosis factor-α (TNF- α) was verified by Enzyme-Linked Immunosorbent Assay (ELISA), besides measuring Hydrophilic Antioxidant Capacity (HAC) and Malonildialdehid (MDA) by fluorometric and chromatographic techniques, respectively. The patients were evaluated before the intervention (CPAP utilization), and average and standard deviation were calculated for sex, age, BMI, HAI, IL-6, IL-10, TNF-α, HAC and MDA, and the correlation among the levels of all markers with BMI and HAI by Pearson’s correlation. Both groups were also evaluated before and after the intervention (CPAP utilization), and average and standard deviation for sex, age, BMI, HAI, IL-6, IL-10, TNF-α, HAC and MDA were calculated with verification of homogeneity between the groups utilizing t-student’s test for sex, age, BMI and HAI, and generalized linear model with gamma distribution for IL-6, IL-10, TNF-α, HAC and MDA. The results for IL-6, IL-10, TNF-α, HAC and MDA levels were compared between both groups before and after CPAP use by generalized linear model with gamma distribution. Results: The evaluation before CPAP utilization had 53 patients (32 males) with average age of 52.62±12.70, BMI of 32.78±5.37, HAI of 33.41±18.71, IL-6 of 8.86±26.97, IL-10 of 12.01±42.04, TNF-α of 76.28±169.29, HAC of 30.99±10.17 and MDA of 1.03±0.35. There was no correlation between the markers calculated by BMI and HAI before the intervention (CPAP utilization), and a correlation tendency between the levels of HAC and OSAS severity was observed (p=0.0690). The analysis of both groups, before and after CPAP utilization, had 38 patients (24 males) and showed homogeneity between both groups for sex, age, BMI, HAI, IL-6, IL-10, TNF-α, HAC and MDA. When both groups were compared, before and after CPAP use, no significant difference was observed for IL-6, IL-10, TNF-α and MDA. A significant increase was verified for HAC after the use of CPAP at minimum pressure of 4 cmH2O and there was an increase tendency for HAC patients with the utilization of therapeutic CPAP. Conclusion: The inflammatory profile and oxidative stress level did not vary with CPAP utilization for one week; however, the following were observed: a tendency of HAC correlation with OSAS severity before CPAP use, significant increase in HAC after utilizing CPAP at minimum pressure of 4cmH2O, and tendency to increase HAC in patients using therapeutic CPAP.
Introduction: Obstructive Sleep Apnea Syndrome (OSAS) is a disorder with high incidence in population, associated to high cardiovascular risk factor. Its main treatment uses Continuous Positive Airway Pressure (CPAP). OSAS is associated to the production of inflammatory response in the individual as well as to the increase of oxidative stress caused by hypoxia/ re-oxygenation phenomena. Treatment with CPAP normalizes respiratory events and sleep structure, but there are many controversial studies regarding treatment with CPAP and reduction of inflammatory markers and oxidative stress. There is not a consensus in relation to the minimum time of CPAP utilization to observe a response to the harmful outcome of OSAS. Objective: To evaluate the serum levels of pro- and anti-inflammatory cytokines and markers of oxidative stress in OSAS patients treated with CPAP for seven days. Patients and Methods: It was a randomized double-blind clinical trial approved by the local Committee of Ethics in Research (CAAE: 20839713.3.0000.5411). 60 male and female adult patients (over 18 years old) with polysomnographic diagnosis of OSAS, attended at the Homecare Ventilation Clinic of Botucatu Medical School, UNESP, were invited to participate in the study. The groups were distributed by random sampling selection which allowed the distribution into two groups where Group I consisted of patients using CPAP at minimum pressure of 4 cmH2O (n=30) and Group II was formed by patients utilizing CPAP at the ideal therapeutic pressure (n=30). All patients received a CPAP device with a total face mask and used it for one week. 20mL of blood was collected by venous puncture before and after the treatment. The dose of interleukin-6 (IL-6), interleukin-10 (IL-10) cytokines and tumor necrosis factor-α (TNF- α) was verified by Enzyme-Linked Immunosorbent Assay (ELISA), besides measuring Hydrophilic Antioxidant Capacity (HAC) and Malonildialdehid (MDA) by fluorometric and chromatographic techniques, respectively. The patients were evaluated before the intervention (CPAP utilization), and average and standard deviation were calculated for sex, age, BMI, HAI, IL-6, IL-10, TNF-α, HAC and MDA, and the correlation among the levels of all markers with BMI and HAI by Pearson’s correlation. Both groups were also evaluated before and after the intervention (CPAP utilization), and average and standard deviation for sex, age, BMI, HAI, IL-6, IL-10, TNF-α, HAC and MDA were calculated with verification of homogeneity between the groups utilizing t-student’s test for sex, age, BMI and HAI, and generalized linear model with gamma distribution for IL-6, IL-10, TNF-α, HAC and MDA. The results for IL-6, IL-10, TNF-α, HAC and MDA levels were compared between both groups before and after CPAP use by generalized linear model with gamma distribution. Results: The evaluation before CPAP utilization had 53 patients (32 males) with average age of 52.62±12.70, BMI of 32.78±5.37, HAI of 33.41±18.71, IL-6 of 8.86±26.97, IL-10 of 12.01±42.04, TNF-α of 76.28±169.29, HAC of 30.99±10.17 and MDA of 1.03±0.35. There was no correlation between the markers calculated by BMI and HAI before the intervention (CPAP utilization), and a correlation tendency between the levels of HAC and OSAS severity was observed (p=0.0690). The analysis of both groups, before and after CPAP utilization, had 38 patients (24 males) and showed homogeneity between both groups for sex, age, BMI, HAI, IL-6, IL-10, TNF-α, HAC and MDA. When both groups were compared, before and after CPAP use, no significant difference was observed for IL-6, IL-10, TNF-α and MDA. A significant increase was verified for HAC after the use of CPAP at minimum pressure of 4 cmH2O and there was an increase tendency for HAC patients with the utilization of therapeutic CPAP. Conclusion: The inflammatory profile and oxidative stress level did not vary with CPAP utilization for one week; however, the following were observed: a tendency of HAC correlation with OSAS severity before CPAP use, significant increase in HAC after utilizing CPAP at minimum pressure of 4cmH2O, and tendency to increase HAC in patients using therapeutic CPAP.
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Palavras-chave
Apnéia obstrutiva no sono, CPAP, Perfil inflamatório, Estresse oxidativo, Obstructive sleep apnea, CPAP, Inflammatory profile, Oxidative stress