Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke.

Can bronchodilators improve exercise tolerance in COPD patients without dynamic hyperinflation? / Os broncodilatadores podem melhorar a tolerância ao exercício na ausência de hiperinsuflação dinâmica em pacientes com DPOC?

OBJECTIVE: To investigate the modulatory effects that dynamic hyperinflation (DH), defined as a reduction in inspiratory capacity (IC), has on exercise tolerance after bronchodilator in patients with COPD. METHODS: An experimental, randomized study involving 30 COPD patients without severe hypoxemia. At baseline, the patients underwent clinical assessment, spirometry, and incremental cardiopulmonary exercise testing (CPET). On two subsequent visits, the patients were randomized to receive a combination of inhaled fenoterol/ipratropium or placebo. All patients then underwent spirometry and submaximal CPET at constant speed up to the limit of tolerance (Tlim). The patients who showed ΔIC(peak-rest) < 0 were considered to present with DH (DH+). RESULTS: In this sample, 21 patients (70%) had DH. The DH+ patients had higher airflow obstruction and lower Tlim than did the patients without DH (DH-). Despite equivalent improvement in FEV1 after bronchodilator, the DH- group showed higher ΔIC(bronchodilator-placebo) at rest in relation to the DH+ group (p < 0.05). However, this was not found in relation to ΔIC at peak exercise between DH+ and DH- groups (0.19 ± 0.17 L vs. 0.17 ± 0.15 L, p > 0.05). In addition, both groups showed similar improvements in Tlim after bronchodilator (median [interquartile range]: 22% [3-60%] vs. 10% [3-53%]; p > 0.05). CONCLUSIONS: Improvement in TLim was associated with an increase in IC at rest after bronchodilator in HD- patients with COPD. However, even without that improvement, COPD patients can present with greater exercise tolerance after bronchodilator provided that they develop DH during exercise. .

OBJETIVO: Investigar os efeitos moduladores da hiperinsuflação dinâmica (HD), definida pela redução da capacidade inspiratória (CI), na tolerância ao exercício após broncodilatador em pacientes com DPOC. MÉTODOS: Estudo experimental e randomizado com 30 pacientes com DPOC sem hipoxemia grave. Na visita inicial, os pacientes realizaram avaliação clínica, espirometria e teste de exercício cardiopulmonar (TECP) incremental. Em duas visitas subsequentes, os pacientes foram randomizados para receber uma combinação de fenoterol/ipratrópio ou placebo e, em seguida, realizaram espirometria e TECP com velocidade constante até o limite da tolerância (Tlim). Os pacientes com ΔCI(pico-repouso) < 0 foram considerados com HD (HD+). RESULTADOS: Nesta amostra, 21 pacientes (70%) apresentaram HD. Os pacientes HD+ apresentaram maior obstrução ao fluxo aéreo e menor Tlim do que os pacientes sem HD (HD-). Apesar de ganhos equivalentes de VEF1 após broncodilatador, o grupo HD- apresentou maior ΔCI(broncodilatador-placebo) em repouso em relação ao grupo HD+ (p < 0,05). Entretanto, isso não ocorreu com a ΔCI no pico do exercício entre os grupos HD+ e HD- (0,19 ± 0,17 L vs. 0,17 ± 0,15 L; p > 0,05). Similarmente, ambos os grupos apresentaram melhoras equivalentes do Tlim após broncodilatador (mediana [intervalo interquartílico]: 22% [3-60%] e 10% [3-53%]; p > 0,05). CONCLUSÕES: A melhora da CI em repouso após broncodilatador associou-se com ganho de tolerância ao esforço mesmo nos pacientes com DPOC que não apresentem HD. Por outro lado, pacientes sem melhora da CI em repouso ainda podem obter beneficio funcional com o broncodilatador desde que apresentem HD no exercício. .

Doxiciclina em pacientes com linfangioleiomiomatose: biomarcadores e resposta funcional pulmonar / Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response

OBJETIVO: Avaliar o bloqueio da metaloproteinase da matriz (MMP)-2 e da MMP-9 e a variação do VEF1 em pacientes com linfangioleiomiomatose (LAM) após o uso de doxiciclina, um conhecido inibidor de MMP, durante 12 meses. MÉTODOS: Ensaio clínico aberto de braço único no qual as pacientes com diagnóstico de LAM receberam doxiciclina (100 mg/dia) durante 12 meses. Elas foram submetidas a prova de função pulmonar completa, teste de caminhada de seis minutos, avaliação da qualidade de vida e coleta de amostras séricas e urinárias para dosagem de MMP-2, MMP-9 e VEGF-D antes do início do tratamento com doxiciclina e após 6 e 12 meses de tratamento. RESULTADOS: Trinta e uma pacientes com LAM receberam doxiciclina durante 12 meses. Embora tenha havido um bloqueio efetivo da MMP-9 urinária e da MMP-2 sérica após o tratamento, os níveis séricos de MMP-9 e VEGF-D permaneceram estáveis. Com base na resposta à doxiciclina (determinada pela variação do VEF1), as pacientes foram divididas em dois grupos: respondedoras (doxi-R; n = 13) e não respondedoras (doxi-NR; n = 18). As pacientes com alterações espirométricas leves apresentaram melhor resposta à doxiciclina. Os efeitos colaterais mais comuns foram epigastralgia, náusea e diarreia, todos de leve intensidade. CONCLUSÕES: Em pacientes com LAM, o tratamento com doxiciclina resulta em um bloqueio eficaz das MMP, além de melhorar a função pulmonar e a qualidade de vida daqueles com doença menos grave. No entanto, esses benefícios não parecem estar relacionados ao bloqueio das MMP, o que sugere um mecanismo de ação diferente. (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).

OBJECTIVE: To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months. METHODS: An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline. RESULTS: Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre- and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea. CONCLUSIONS: In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. (Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).

Alterações espirométricas em doenças obstrutivas: afinal, o quanto é relevante? / Spirometric changes in obstructive disease: after all, how much is significant?

OBJETIVO: Estabelecer os limites superiores para mudanças em VEF1, capacidade vital lenta (CVL), CVF e capacidade inspiratória (CI) após o uso de placebo em pacientes com obstrução ao fluxo aéreo. MÉTODOS: Cento e dois adultos com obstrução ao fluxo aéreo (VEF1 = 62 ± 19% do previsto) foram incluídos neste estudo. Todos os participantes realizaram manobras de CVL e CVF antes e depois do uso de spray de placebo. As mudanças em VEF1, CVL, CVF e CI foram expressas em valores absolutos, porcentagem de variação em relação aos valores basais e porcentagem dos valores previstos, e foram calculados os IC95% e os percentis 95. A análise fatorial foi realizada a fim de determinar como essas alterações se agrupavam. RESULTADOS: Considerando os IC95% e percentis 95 e após o arredondamento dos valores, obtivemos os seguintes limites superiores para resposta significante: VEF1 = 0,20 L, CVF = 0,20 L, CVL = 0,25 L e CI = 0,30 L (em valores absolutos); VEF1 = 12%, CVF = 7%, CVL = 10% e CI = 15% (em porcentagem de variação em relação aos valores basais) e VEF1 = 7%, CVF = 6%, CVL = 7% e CI = 12% (em porcentagem dos valores previstos). CONCLUSÕES: Em pacientes com obstrução ao fluxo aéreo, a CI apresenta maior variabilidade do que a CVF e a CVL. Para a CI, valores maiores que 0,30 L e 15% de variação em relação ao valor basal devem ser considerados significantes. Para CVF, valores maiores que 0,20L e 7% de variação em relação ao valor basal são significantes. Alternativamente, alterações de mais de 0,20 L e 7% do previsto no VEF1 e na CVF devem ser consideradas significantes. Na análise fatorial, os parâmetros espirométricos se agruparam em três dimensões, expressando mudanças no fluxo, volume e hiperinsuflação dinâmica.

OBJECTIVE: To establish the upper limits for changes in FEV1, slow vital capacity (SVC), FVC, and inspiratory capacity (IC) after placebo administration in patients with airflow obstruction. METHODS: One hundred and two adults with airflow obstruction (FEV1 = 62 ± 19% of predicted) were included in the study. All of the participants performed SVC and FVC maneuvers before and after the administration of placebo spray. The changes in FEV1, SVC, FVC, and IC were expressed as absolute values, percentage of change from baseline values, and percentage of predicted values, 95% CIs and 95th percentiles being calculated. Factor analysis was performed in order to determine how those changes clustered. RESULTS: Considering the 95% CIs and 95th percentiles and after rounding the values, we found that the upper limits for a significant response were as follows: FEV1 = 0.20 L, FVC = 0.20 L, SVC = 0.25 L, and IC = 0.30 L (expressed as absolute values); FEV1 = 12%, FVC = 7%, SVC = 10%, and IC = 15% (expressed as percentage of change from baseline values); and FEV1 = 7%, FVC = 6%, SVC = 7%, and IC = 12% (expressed as percentage of predicted values). CONCLUSIONS: In patients with airflow obstruction, IC varies more widely than do FVC and SVC. For IC, values greater than 0.30 L and 15% of change from the baseline value can be considered significant. For FVC, values greater than 0.20 L and 7% of change from the baseline value are significant. Alternatively, changes exceeding 0.20 L and 7% of the predicted value can be considered significant for FEV1 and FVC. On factor analysis, spirometric parameters clustered into three dimensions, expressing changes in flows, volumes, and dynamic hyperinflation.

Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.

Evolução da função pulmonar após tratamento com goserelina em pacientes com linfangioleiomiomatose / Evolution of pulmonary function after treatment with goserelin in patients with lymphangioleiomyomatosis

Nas células musculares lisas atípicas características da linfangioleiomiomatose (LAM) encontram-se receptores de estrogênio e progesterona, de modo que o tratamento anti-hormonal pode ser considerado uma opção, mas ainda com resultados controversos. O objetivo deste trabalho foi avaliar retrospectivamente parâmetros hormonais e espirométricos em nove mulheres com LAM após o tratamento com goserelina por um ano. Houve um aumento médio de 80 mL e 130 mL, respectivamente, em VEF1 e CVF, assim como bloqueio hormonal efetivo. Ainda não se pode excluir um potencial efeito favorável da utilização de análogos de hormônio liberador de gonadotrofina em pacientes com LAM, reforçando a necessidade de ensaios randomizados.

In the atypical smooth muscle cells that are characteristic of lymphangioleiomyomatosis (LAM), there are estrogen and progesterone receptors. Therefore, anti-hormonal therapy, despite having produced controversial results, can be considered a treatment option. The objective of this retrospective study was to evaluate hormonal and spirometric data for nine women with LAM after one year of treatment with goserelin. The mean increase in FEV1 and FVC was 80 mL and 130 mL, respectively. There was effective blockage of the hormonal axis. It is still not possible to exclude a potential beneficial effect of the use of gonadotropin-releasing hormone analogues in LAM patients, which underscores the need for randomized trials.

Bloqueio do plexo braquial por via interescalênica: efeitos sobre a função pulmonar / Interscalene brachial plexus block: effects on pulmonary function / Bloqueo del plexo braquial por vía interescalénica: efectos sobre la función pulmonar

JUSTIFICATIVA E OBJETIVOS: A via interescalênica é um dos acessos mais comumente utilizados no bloqueio do plexo braquial. Todavia, tem-se demonstrado associação dessa técnica com o bloqueio do nervo frênico ipsilateral. A disfunção diafragmática daí resultante provoca alterações na mecânica pulmonar, potencialmente deletérias em pacientes com limitação da reserva ventilatória. O objetivo do estudo foi avaliar a repercussão do bloqueio interescalênico sobre a função pulmonar por meio da medida da capacidade vital forçada (CVF). MÉTODO: Estudo duplamente encoberto com 30 pacientes, estado físico I ou II (ASA), distribuídos aleatoriamente em dois grupos de15. Foi administrada solução a 0,5 por cento de ropivacaína (Grupo Ropi) ou bupivacaína a 0,5 por cento com epinefrina (Grupo Bupi). O bloqueio foi realizado utilizando estimulador de nervo periférico e sendo injetados 30 mL de anestésico local. Quatro espirometrias foram realizadas em cada paciente: antes do bloqueio, 30 minutos, 4 e 6 horas após. Os pacientes não receberam sedação. RESULTADOS: Um paciente do Grupo Ropi e três pacientes do Grupo Bupi foram excluídos do estudo por falha de bloqueio. A redução da CVF no Grupo Ropi foi máxima aos 30 minutos (25,1 por cento) e a partir de então houve tendência progressiva à recuperação. Já com bupivacaína, a redução da CVF pareceu ser menos acentuada nos diversos momentos estudados; observou-se redução adicional entre 30 minutos (15,8 por cento) e 4 horas (17,3 por cento), sendo esta sem diferença estatística. A partir de 4 horas, notou-se tendência à recuperação. Em ambos os grupos, após 6 horas de bloqueio a CVF encontra-se ainda abaixo dos valores prévios. CONCLUSÕES: O bloqueio interescalênico reduz a CVF na maioria dos casos; as alterações foram mais acentuadas no Grupo Ropivacaína.

BACKGROUND AND OBJECTIVES: The interscalene is one of the most common approaches used in brachial plexus block. However, the association of this approach with the ipsilateral blockade of the phrenic nerve has been demonstrated. The resulting diaphragmatic dysfunction causes changes in lung mechanics, which can be potentially deleterious in patients with limited respiratory reserve. The objective of the present study was to evaluate the repercussion of interscalene brachial plexus block on pulmonary function by measuring forced vital capacity (FVC). METHODS: This is a double-blind study with 30 patients, physical status ASA I or II, randomly separated into two groups of 15 patients each; 0.5 percent ropivacaine (Ropi Group) or 0.5 percent bupivacaine with epinephrine (Bupi Group) was administered. A peripheral nerve stimulator was used, and 30 mL of the local anesthetic were administered. Four spirometries were done in each patient: before the blockade, 30 minutes, four hours, and six hours after the blockade. Patients were not sedated. RESULTS: One patient in the Ropi Group and three patients in the Bupi Group were excluded from the study due to failure of the blockade. The Ropi Group showed maximal FVC reduction at 30 minutes (25.1 percent), with a tendency for recovery from this point on. With bupivacaine, the reduction in FVC was less important at the different study moments; an additional reduction was observed between 30 (15.8 percent) and four hours (17.3 percent), but it was not statistically significant. A tendency for recovery was observed from four hours on. In both groups, the FVC six hours after the blockade was still below baseline levels. CONCLUSIONS: Interscalene block reduces FVC in most cases. Changes were more pronounced in the Ropivacaine group.

JUSTIFICATIVA Y OBJETIVOS: La vía interescalénica es uno de los accesos más a menudo utilizados en el bloqueo del plexo braquial. Sin embargo, se ha demostrado una asociación de esa técnica con el bloqueo del nervio frénico ipsilateral. La disfunción diafragmática de resultas de esa asociación, provoca alteraciones en la mecánica pulmonar, potencialmente perjudiciales en pacientes con una limitación de la reserva ventilatoria. El objetivo del estudio fue evaluar la repercusión del bloqueo interescalénico sobre la función pulmonar por medio de la medida de la capacidad vital forzada (CVF). MÉTODO: Estudio doble ciego, con 30 pacientes, estado físico I o II (ASA), distribuidos aleatoriamente en dos grupos de 15. Se administró solución a 0,5 por ciento de ropivacaína (Grupo Ropi) o bupivacaína a 0,5 por ciento con epinefrina (Grupo Bupi). El bloqueo fue realizado utilizando estimulador de nervio periférico e inyectando 30 mL de anestésico local. Cuatro espirometrías se hicieron en cada paciente: antes del bloqueo, 30 minutos, 4 y 6 horas después. Los pacientes no recibieron sedación. RESULTADOS: Un paciente del Grupo Ropi y tres pacientes del Grupo Bupi, quedaron excluidos del estudio por fallos de bloqueo. La reducción de la CVF en el Grupo Ropi se hizo máxima a los 30 minutos (25,1 por ciento) y a partir de entonces, hubo una tendencia progresiva a la recuperación. Ya con la bupivacaína, la reducción de la CVF pareció ser menos acentuada en los diversos momentos estudiados; se observó una reducción adicional entre 30 minutos (15,8 por ciento) y 4 horas (17,3 por ciento), siendo esa sin diferencia estadística. A partir de 4 horas, se notó una tendencia a la recuperación. En los dos grupos, después de 6 horas de bloqueo, la CVF todavía estaba por debajo de los valores previos. CONCLUSIONES: El bloqueo interescalénico reduce la CVF en la mayoría de los casos; las alteraciones fueron más acentuadas en el Grupo Ropivacaína.

Repercussão respiratória funcional após colecistectomia com incisão subcostal: efeito analgésico da morfina / Functional respiratory repercussion in opened subcostal cholecystectomy: morphine effect analgesic

OBJETIVO: Avaliar a função pulmonar pós-colecistectomias subcostais abertas de pacientes sob ação da morfina no pós-operatório imediato. MÉTODOS: Tratou-se de um estudo prospectivo, onde se avaliaram espirometrias pós-operatórias de 15 pacientes submetidas à colecistectomias abertas subcostais, que receberam dose única de morfina peridural na anestesia. Os dados pós-operatórios foram comparados aos pré-operatórios pelo teste t-Student emparelhado. Um valor de p < 0,05 foi considerado estatisticamente significativo. RESULTADOS: Existiram diferenças significativas para as variáveis Capacidade Vital Forçada (p = 0,007) e Volume Expiratório Forçado no 1º segundo (p = 0,008) no pré e pós-operatório imediato, indicando distúrbios ventilatórios restritivos. Todas as pacientes apresentaram espirometrias normais no 3º dia de pós-operatório. CONCLUSÃO: Mesmo sob ação analgesia da morfina peridural, no pós-operatória imediato, foram observados distúrbios ventilatórios restritivos leves pós-colecistectomias subcostais abertas. Contudo, observou-se uma rápida recuperação da função pulmonar, o que pode diminuir a morbidade pulmonar pós-operatória.

OBJECTIVE: To evaluate pulmonary function after open subcostal cholecystecomy under action of the morphine in the immediate post-operative. METHODS: This was a prospective study, in which the post-operative spirometries of fifteen patients who underwent open subcostal cholecystectomies which received peridural morphine anesthesia. Post- and pre-operative data were compared using a paired student-t test. A value of p < 0,05 was considered statistically significant. RESULTS: Significant differences existed for the Forced Vital Capacity variable (p = 0,007) and Forced Expiratory Volume in the first second (p = 0,008) between pre- and immediate post-operative, indicating restrictive ventilatory disturbances. All of the patients presented normal espirometries in the third day of post-operative. CONCLUSION: Even under action morphine peridural analgesia, in the immediate post-operative, light restrictive post-cholecystectomy ventilatory disturbances were observed. However, it was observed abbreviated recovery of pulmonary function, which may lower post-operative pulmonary morbidity.

Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration

OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 µg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1 (p=0.085), FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL-1 and morphine group= 4.08 ng.mL-1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not ...

Capacidade inspiratória, limitação ao exercício, e preditores de gravidade e prognóstico, em doença pulmonar obstrutiva crônica / Inspiratory capacity, exercise limitation, markers of severity, and prognostic factors in chronic obstructive pulmonary disease

OBJETIVO: Correlacionar a capacidade inspiratória (CI), por cento do previsto, pós-broncodilatador (pós-BD), com outras variáveis indicativas de gravidade e prognóstico, na doença pulmonar obstrutiva crônica (DPOC). MÉTODOS: Oitenta pacientes estáveis com DPOC realizaram manobras de capacidade vital forçada, capacidade vital lenta, e teste de caminhada de 6 min, antes e após salbutamol spray (400 µg). Foram divididos em quatro grupos, segundo o volume expiratório forçado no primeiro segundo pós-BD. Diversas variáveis foram testadas, por análise univariada e multivariada, com a distância caminhada pós-BD, por cento do previsto. A CI pós-BD foi correlacionada com o estadiamento Global Initiative for Chronic Obstructive Lung Disease (GOLD) e o índice Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE). RESULTADOS: Por análise de regressão multivariada, a CI pós BD, por cento do previsto, (p = 0,001), o uso de oxigênio a longo prazo (p = 0,014), e o número de medicamentos usados (p = 0,044), mantiveram associação significativa com a distância caminhada, por cento do previsto. A CI < 70 por cento foi observada em 56 por cento dos pacientes em estágios GOLD 3 ou 4 comparado a 20 por cento em estágios GOLD 1 ou 2 ( p < 0,001). A CI < 70 por cento foi observada em 60 por cento dos pacientes com escore BODE 3 ou 4 vs. 33 por cento com BODE 1 ou 2 (p = 0,02). CONCLUSÃO: A CI, por cento do previsto, pós-BD é o melhor preditor funcional da distância caminhada, associando-se significativamente com o escore GOLD e o índice BODE. Por isso, propomos que a CI seja incluída na rotina de avaliação dos portadores de DPOC.

OBJECTIVE: To correlate the postbronchodilator (post-BD) inspiratory capacity (IC), percent of predicted, with other markers of severity and prognostic factors in chronic obstructive pulmonary disease (COPD). METHODS: Eighty stable patients with COPD performed forced vital capacity and slow vital capacity maneuvers, as well as the 6-min walk test, prior to and after receiving albuterol spray (400 µg). Patients were divided into four groups, based on post-BD forced expiratory volume in one second. Several variables were tested to establish correlations with the post-BD distance walked, using univariate and multivariate analysis. Post-BD IC was found to correlated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging and with the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index. RESULTS: Multivariate regression analysis revealed that the distance walked, percent predicted, correlated significantly with the IC post-BD, percent predicted (p = 0.001), long-term oxygen use (p = 0.014), and number of medications used in the treatment (p = 0.044). IC < 70 percent was observed in 56 percent patients in GOLD stages 3 or 4 vs. 20 percent in GOLD 1 or 2 (p < 0.001). IC < 70 percent was observed in (60 percent) patients with BODE score 3 or 4 vs. (33 percent) BODE score 1 or 2 (p = 0.02). CONCLUSION: Post-BD IC percent predicted is the best functional predictor of distance walked and is significantly associated with GOLD staging and BODE index. Therefore, We propose that the inspiratory capacity should be added to the routine evaluation of the COPD patients.

Técnica de oscilações forçadas na análise da resposta broncodilatadora em voluntários sadios e indivíduos portadores de asma brônquica com resposta positiva / Using the forced oscillation technique to evaluate bronchodilator response in healthy volunteers and in asthma patients presenting a verified positive response

OBJETIVO: Analisar, através da técnica de oscilações forçadas, pacientes asmáticos com resposta broncodilatadora positiva pelo laudo espirométrico e comparar esses resultados com os obtidos em indivíduos sadios. MÉTODOS: Foram analisados 53 indivíduos não tabagistas, sendo 24 sadios sem história de doença pulmonar e 29 asmáticos com resposta broncodilatadora positiva segundo o laudo espirométrico. Todos foram submetidos à técnica de oscilações forçadas e a espirometria antes e após vinte minutos da administração de salbutamol spray (300 g). Os parâmetros derivados da técnica de oscilações forçadas foram: resistência total, reatância total, resistência extrapolada para o eixo y, coeficiente angular da reta de resistência e complacência dinâmica. Na espirometria, os parâmetros utilizados foram o volume expiratório forçado no primeiro segundo e a capacidade vital forçada. RESULTADOS: No grupo controle, a utilização do broncodilatador produziu alteração significativa na resistência extrapolada para o eixo y (p < 0,001), embora o coeficiente angular da reta de resistência e a complacência dinâmica não tenham apresentado diferenças estatisticamente significativas. A análise dos asmáticos mostrou que a diferença entre as medidas pré e pós-broncodilatador foi significativa, tanto para os parâmetros espirométricos quanto para os de técnica de oscilações forçadas. Valores de p < 0,001 foram obtidos em todas as comparações relacionadas aos asmáticos. CONCLUSÃO: As alterações nos parâmetros obtidos a partir da técnica de oscilações forçadas mostraram-se em estreita concordância com a fisiopatologia da resposta broncodilatadora em asmáticos, indicando que a técnica de oscilações forçadas pode ser útil como análise complementar à espirometria nesses pacientes.

Effect of oral contraceptives on respiratory function.

The present study was carried out to assess the lung functions in oral contraceptive administered women. Lung function tests were carried out with Spirometer (Vitallograph Compact II). A significant increase in vital capacity (VC) was observed in these women as compared to normal control. There was also a significant decrease in forced expiratory volume in 1 sec./vital capacity (FEV1/VC%) and forced expiratory volume in 1 sec./forced vital capacity (FEV1/FVC%) among oral contraceptive administered women as compared to controls. Further, a significant increase in peak expiratory flow rate (PEF), reduction in forced expiratory flow rate (FEF75-85%) and FEF75% were observed among oral contraceptive administered women as compared to controls. The increase in VC and PEF might be due to the synthetic form of progesterone (progestins) present in oral contraceptive pills which causes hyperventilatory changes. Synthetic progesterone during luteal phase of menstrual cycle might increase the static and dynamic volumes of lung i.e. VC and PEF. But FEF75% showed a decrease which might be due to the lower neuromuscular coordination during breathing.

Impact of particulate air pollutants on allergic diseases, allergic skin reactivity and lung function.

Elevated levels of particulate matter can exacerbate existing asthma and atopy, while evidence that it can promote the induction of atopy and asthma is limited. A cross sectional study was taken to compare the prevalence of eye, nose, ear and airway allergic symptoms, allergic skin sensitivity and lung function in 290 high school students with a history of high 24 hour average exposure to particulate matter less than 10 microm in diameter (PM10) = 170 microg/m3 versus low PM10 of 36 microg/m3 in central Bangkok. Multivariate analysis revealed an increased risk of eye and airway symptoms in groups exposed to higher PM10 levels (p = 0.003, and 0.05, respectively). Positive skin prick tests and a history of having a lawn at home were associated with nasal symptoms (p = 0.008 and 0.04, respectively). Mean FEF(25-75%) (forced expiratory flow that occurs during the middle 50% of the forced expiratory effort) was significantly lower in those who were exposed to higher PM10 levels (3.89 +/- 1 vs 4.42 +/- 0.9 l/sec, p < 0.001). A significant increase in days of school absence and medical expenses was associated with high PM10 exposure. It is concluded that chronic exposure to high PM 10 levels was significantly associated with increased prevalence of eye and airway symptoms and a decrement of FEF(25-75%) resulting in increase of school absence and medical expense.

Comparison of bronchodilator responsiveness in asthma and chronic obstructive pulmonary disease.

While asthmatics are known to have a greater response to bronchodilators than patients of chronic obstructive pulmonary disease (COPD), whether the pattern of response also differs has not been explored. Forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1) were measured before and 20 minutes after inhalation of 200 microg salbutamol in patients of bronchial asthma (n=133) and (COPD) (n=116). Three types of responses (defined as > or = 12% and 200 ml increase in FEV1 or FVC) were identified: increase in (i) only FVC (FVC response), (ii) only FEV1 (FEV1 response), and, (iii) both FVC and FEV1 (double response). The mean +/- SEM absolute increase in FEV1 was significantly greater in asthmatics (307+/-17ml) as compared to 120+/-12 ml in COPD patients (p<0.0001). On the other hand, the increase in FVC was not different in the two groups (296+/-22 ml and 230+/-24 ml, respectively, p>0.05). The proportion of subjects showing a > or = 200 ml increase in FEV1 was greater among asthmatics as compared to COPD (p<0.0001) but the proportions showing a > or = 200 ml in FVC were similar (p>0.05). All the three types of responses were observed in asthmatics with a double response being the commonest. In COPD, an FVC response was the predominant response while the FEV1 response was rare. Multinomial logistic regression revealed that younger subjects (below 45 years) were more likely to have a double or exclusive FEV1 response. Greater severity of obstruction was associated with higher odds for each of the three responses, the odds being especially very high for an exclusive FEV1 response. The odds for a double response and an exclusive FEV1 response were significantly increased in asthmatics as compared to COPD. For FVC response, age category and disease were not significant determinants. It was concluded that bronchodilator responsiveness in asthma and COPD differs not only quantitatively but also in the pattern.

Comparación entre el porcentaje de respuesta del VEF al broncodilatador con respecto a otros índices espirométricos en pacientes pediátricos / Bronchodilator response in pediatrics patients: changes in FEV in comparison to other spirometric indices

El porcentaje significativo de cambio en el volumen espiratorio forzado al primer segundo (VEF) posterior a broncodilatador, oscila entré el 10 y 15 por ciento en la literatura. El objetivo de este trabajo fue comparar la magnitud del cambio de VEF y su correlación con el cambio de otros índices de la espirometría habitualmente utilizados como respuesta broncodilatadora, tales como flujo espiratorio forzado al 25 y 75 por ciento de la capacidad vital (FEM50) y forma de la curva flujo/volumen. Se revisaron 734 espirometrías clasificándolas según la magnitud del cambio del VEF1 posterior a broncodilatador en normales (< 10 por ciento) y patológicas (> 10 por ciento), a su vez las espirometrías con respuesta mayor al 10 por ciento se subdividieron en 3 rangos: 10 - 12 por ciento, 12 - 15 por ciento y > 15 por ciento. En cada uno de los intervalos anteriormente descritos se estudió si hubo cambios asociados significativos en FEF25-75' FEM50, morfología de la curva flujo/volumen, la combinación entre estos índices (todos) o la ausencia de ellos (ninguno). Los resultados fueron analizados estadística por X², encontrándose un 77 por ciento (564) de las espirometrías con cambios menores a 10 por ciento del VEF1 (normales) y un 23 por ciento (170) con cambios mayores a 10 por ciento, (patológicas). Se observo un cambio significativo postbroncodilatador en todos los índices evaluados (FEF 25-75' FEM50, curva flujo/volumen), en la mitad de las espirometrías patológicas, y en solo el 6 por ciento de las espirometrías clasificadas como normales. En base a estos resultados se propone considerar como aumento significativo del VEF1 en niños a partir de un cambio post broncodilatador de un 10 por ciento si se acompaña en una mejoría en los otros índices descritos. Se sugiere considerar en la interpretación de la espirometría no sólo la respuesta broncodilatadores al cambio de VEF1 sino también correlacionarlo con los cambios producidos en los flujos espiratorios y forma de la curva flujo/volumen

Tratamiento de la fibrosis pulmonar idiopática con colchicina / Treatment of idiopathic pulmonary fibrosis with colchicine

Background: Experimental and clinical evidences suggest that colchicine can be effective in the treatment of patients with idiopathic pulmonary fibrosis. Aim: To assess the effect of colchicine in the treatment of idiopathic pulmonary fibrosis. Patients and methods: Patients with clinically diagnosed idiopathic pulmonary fibrosis were treated with colchicine in doses of 0.5 to 1 mg/day, according to tolerance and followed for periods ranging from 7 to 40 months. The clinical and radiological score reported by Watters et al was used for the longitudinal assessment of patients. Maintenance or improvement in forced vital capacity and maintenance or decrease in alveolar arterial O2 gradient during follow up, were considered as positive therapeutic responses. Results: Seventeen patients (10 male, aged 61 to 81 years old) were studied. Their basal score for dyspnea was 5.8 (over 20), for the chest X ray examination was 2.4 (over 3) and for CT scan was 2.8 (over 3). Basal FVC was 77 percent of predicted value (range 51-108 percent), basal FEV, was 82 percent (range 59-117 percent) and FEV1/FVC was 0.82 (range 0.68-0.95). PaO2 at rest was 78 mm Hg (ranges 63-97). Alveolar-arterial PO2 gradient was 16 mm Hg (range 5-31.6) at rest and 31 mm Hg (range 5.7-51.4) after exercise. Six patients (35 percent) had a positive response to therapy. Conclusions: The response rates of these patients to colchicine are at least similar to those obtained with steroids, but with less side effects

A study of pulmonary profile of hypertensive patients--comparison of atenolol vs amlodipine.

Two groups of drugs commonly used for the treatment of hypertension are atenolol and amlodipine. These drugs are reported to have conflicting changes on pulmonary responses. In order to study the effect of hypertension and antihypertensive treatment on pulmonary responses, 40 patients with essential hypertension having diastolic blood pressure between 90-114 mmHg on three consecutive weekly visits were taken. Pulmonary responses were tested at the end of 2 weeks of placebo washout period and then at the end of 6 weeks of treatment with either atenolol or amodipine. Using a computerized autospiror along with the weekly recordings of heart rate and blood pressure, the various pulmonary and cardiac parameters were taken. Analysis of the result showed that atenolol treatment resulted in significant decline of forced vital capacity (FVC), % forced vital capacity (%FVC), and forced expiratory volume in first second (FEV1) whereas amlodipine did not show any significant change on pulmonary parameters.

Efecto broncodilatador de salbutamol más bromuro de ipratropio en niños asmáticos: relación dosis respuesta / Bronchodilator effect of ipratropium bromide plus salbutamol in asthmatic children: dose response relationship

El bromuro de ipratropio (BI) asociado con un agente beta 2 agonista en aerosol producido por inhalador de dosis medida (IDM) es frecuentemente empleado en lactantes y niños con obstrucción bronquial. En este estudio se evaluó el efecto broncodilatador de dos dosis diferentes (2 y 4 puffs) de una mezcla de BI más salbutamol (S) en IDM (Combivent) en 28 niños con asma leve a moderada. El estudio fue aleatorio, cruzado, controlado con placebo y simple ciego. La CVF, VEF1 y FEF25-75 se midieron en condiciones basales, antes y después de placebo y de cada una de las dosis empleadas. El análisis estadístico se realizó mediante pruebas no paramétricas para muestras pareadas. No hubo diferencias significativas en ninguno de los índices espirométricos descritos al usar 2 o 4 "puffs" de BI+S. Sin embargo, en los pacientes que tuvieron un aumento del VEF1 > o igual 15 por ciento con cualquiera de las 2 dosis de BI+S, el aumento del FEF25-75 fue significativamente mayor al usar 4 "puffs". Lo anterior sugiere que 2 "puffs" de BI+S serían igualmente efectivos para producir broncodilatación en niños asmáticos. Sin embargo, en aquellos pacientes que presentan un mayor grado de obstrucción bronquial, o como en este estudio, una reversibilidad bronquial más alta al broncodilatador, el empleo de 4 "puffs" de BI+S podría ser más eficiente para obtener una mejor broncodilatación

Evaluacion funcional de broncodilatadores beta 2 agonistas en pacientes asmaticos / Functional evaluation of Beta 2 agonists bronchodilators in asthmatic patients

Se estudio la funcion pulmonar de 80 pacientes asmaticos tratados con salmeterol, fenoterol, bitolterol y metaproterenol, indistintamente, por via inhalatoria. Se compararon los valores de algunos parametros funcionales respiratorios como FVC, FEV1 y FEF25-75 antes y a los 10 y 30 minutos de aplicado cada medicamento. Los resultaron evidenciaron la accion broncodilatadora de los 4 farmacos, demostrado por las variaciones de los valores espirometricos medidos antes y despues de la aplicacion del medicamento. No hubo diferencias enlas acciones entre los 4 farmacos; la cardioestimulacion fue mas notoria entre el fenoterol y el metaproterenol a los 10 minutos. A los 10 minutos no se encontraron diferencias significativas entre los 4 en cuanto a la cardioestimulacion. Concluimos que no existen diferencias en las acciones broncodilatadoras entre estos mediamentos. La cardioestimulacion detectada fue de corta duracion