Efficacy and safety of combined doxofylline and salbutamol in treatment of acute exacerbation of chronic obstructive pulmonary disease

SUMMARY OBJECTIVE: The aim of this study was to investigate the efficacy and safety of combined doxofylline and salbutamol in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 68 acute exacerbation of chronic obstructive pulmonary disease patients were randomly divided into control group (34 cases) and experimental group (34 cases), who received the doxofylline treatment and combined doxofylline and salbutamol treatment for 1 week, respectively. During the treatment, the remission time of typical respiratory manifestations was recorded, and the adverse reactions were observed. At the end of treatment, the treatment efficacy was evaluated. Before and after treatment, the pulmonary function indexes and serological indicators were detected. RESULTS: After treatment, compared with control group, in experimental group, the effective rate of treatment was significantly increased (p<0.05), the remission time of typical respiratory manifestations was significantly shortened (p<0.05), the pulmonary function indexes were significantly improved (p<0.05), the serum high-sensitivity C-reactive protein and cystatin C levels were significantly decreased, respectively (p<0.05), and the serum prealbumin level was significantly increased (p<0.05). In addition, the adverse reaction rate had no significant difference between two groups (p>0.05). CONCLUSIONS: In the treatment of acute exacerbation of chronic obstructive pulmonary disease, the combined use of doxofylline and salbutamol can quickly relieve the respiratory symptoms, mitigate the pulmonary dysfunction, and reduce the inflammatory response, thus promoting the outcome of patients.

Teofilina como agente capacitante do sêmen bovino / Theophylline as a capacitating agent of bovine semen

Objetivou-se avaliar a teofilina como agente capacitante substituto ou associado à heparina sobre a reação acrossômica dos espermatozoides e o desenvolvimento de embriões produzidos in vitro. O experimento foi realizado com quatro touros e três tratamentos, totalizando 12 grupos experimentais. O sêmen dos touros foi avaliado nos tratamentos descritos a seguir: tratamento 1 (HEP): heparina - 10µg/mL; tratamento 2 (TEO): teofilina - 5mM; tratamento 3 (HEP + TEO): heparina (10µg/mL) + teofilina (5mM), por zero, seis, 12 e 18 horas, corados com trypan blue/Giemsa para avaliação da reação acrossômica. Para a produção dos embriões, os agentes capacitantes foram adicionados aos meios de fertilização. Na análise espermática, a taxa de reação acrossômica verdadeira foi maior (P<0,05) no tempo zero hora, enquanto para espermatozoides mortos, as maiores taxas (P<0,05) foram nos tempos de 12h (84,46±5,82) e 18h (86,75±4,19). A taxa de embriões produzidos (37,97±13) e a taxa de eclosão (33,50±14) foram maiores (P<0,05) para o tratamento HEP. Não foi observada diferença (P>0,05) entre touros na análise de reação acrossômica nem na PIVE. A utilização da teofilina foi tão eficiente quanto a da heparina na indução da reação acrossômica, no entanto resultou em menores taxas de produção embrionária.(AU)

The sperm capacitating process should take special attention during in vitro embryo production (IVEP) once that affects the success of embryo production. The study aimed to evaluate theophylline as substitute capacitating agent or in combination with heparin on the sperm acrosome reaction and development of embryos produced in vitro. The experiment was carried out using 4 bulls and 3 treatments, establishing 12 experimental groups. Each bull was evaluated in the following treatments: Treatment 1 (HEP): Heparin - 10mg/mL; Treatment 2 (THEO): Theophylline - 5mM; Treatment 3 (HEP + THEO), Heparin (10mg/mL) + Theophylline (5mM). The semen of bulls was incubated in each treatment for 0, 6, 12 and 18h, stained with Trypan blue / Giemsa and analyzed by electron microscopy for assessment of acrosome reaction. Using sperm of same bulls, capacitating agents were added to the fertilization media, for IVEP. In sperm analysis, the true acrosome reaction rate was higher (P<0.05) in time 0h, while sperm dead rates were highest (P<0.05) at 12h (84.46±5, 82), and 18h (86.75±4.19). The produced embryos rate (37.97±13) and hatching rate (33.50±14) were larger (P<0.05) for HEP treatment. There was no difference (P>0.05) between bulls in acrosome reaction analysis neither for IVEP. The use of theophylline was as effective as heparin in the induction of the acrosome reaction, although it resulted in lower embryo production rates.(AU)

Asma grave / Severe asthma

Heterogeneidade é um traço marcante da asma. Síndrome complexa, resulta da interligação de uma rede genética com fatores ambientais, o que gera um comportamento alterado das células estruturais e funcionais do trato respiratório que desemboca em diferentes processos inflamatórios. Como resultado final, distingue-se uma ampla gama de apresentações clínicas e desfechos terapêuticos. Estima-se que 5%-10% dos asmáticos sejam portadores de uma forma grave, caracterizada pelo controle insuficiente da disfunção, apesar do uso de doses elevadas de múltiplos medicamentos. Asmáticos graves têm taxas mais elevadas de idas a serviços de emergência, hospitalizações, absenteísmo e letalidade. Mesmo comprometendo uma parcela menor de pessoas, essa categoria responde pela maior parte dos gastos envolvidos com a asma. Com a identificação progressiva de novos alvos terapêuticos e consequente desenvolvimento de novos medicamentos, é possível que, num futuro próximo, possamos oferecer tratamento efetivo e maior qualidade de vida a essa parcela mais comprometida dos asmáticos.

Heterogeneity is a striking feature of asthma. Asthma is a complex syndrome, in which a link between a genetic network and environmental factors generates altered behavior of structural and functional cells of the respiratory tract that ends in different inflammatory processes. The result is a wide range of clinical presentations and therapeutic outcomes. It is estimated that 5%-10% of those with asthma suffer from a severe form characterized by insufficient control of the dysfunction, despite the use of high doses of multiple drugs. Those with severe asthma have higher rates of visits to the emergency services, hospitalizations, absenteeism and mortality. Despite those with severe asthma representing only a small percentage of the total, this group accounts for most of the expense associated with asthma. With the progressive identification of new therapeutic targets and the consequent development of new drugs, it is possible that in the near future, we can provide more effective treatment and improved quality of life for those with the more severe disease.

Addition of Theophylline or Increasing the Dose of Inhaled Corticosteroid in Symptomatic Asthma: A Meta-Analysis of Randomized Controlled Trials

PURPOSE: Low-dose theophylline has anti-inflammatory effects. The aim of this study was to evaluate the effects of adding theophylline compared with increasing the dose of inhaled corticosteroid (ICS) on symptomatic asthma. MATERIALS AND METHODS: The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. The extracted data were further analyzed by a meta-analysis RESULTS: Four randomized, controlled, parallel studies were selected. Addition of theophylline produced a greater increase of forced expiratory volume in one second as %predicted (FEV1pred) by 2.49% [95% confidence interval (CI) 1.99-3.00; z = 9.70; p < 0.001], compared with increasing the dose of ICS. There was no difference between the two treatments in terms of peak expiratory flow (PEF). CONCLUSION: Addition of theophylline to ICS has similar therapeutic effects on improving lung function as increasing the dose of ICS in the treatment of symptomatic asthma.

Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma

Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung inflammation partly induced by Th1 immune response. ASA attenuated the beneficial effects of theophylline. However, co-administration of the ASA metabolite salicylic acid (SA) showed no attenuating effect on theophylline treatment. The therapeutic effect of theophylline was associated with increase in cAMP levels, which was blocked by co-treatment of theophylline and ASA. ASA co-treatment also attenuated the anti-inflammatory effects of a specific phosphodiesterase 4 inhibitor. These results demonstrate that ASA reverses anti-inflammatory effects of theophylline, and that ASA exerts its adverse effects through the inhibition of cAMP production. Our data suggest that ASA reverses lung inflammation in patients taking theophylline, although clinical evidence will be needed.

Complicaciones respiratorias de la tetraplejia: una mirada a las alternativas terapéuticas actuales / Respiratory complications in tetraplegia: overview to current therapeutic alternatives

Respiratory complications are the first cause of death in patients with tetraplegia, including both the acute and chronic stage of the disease. They include a wide variety of respiratory problems, such as repeated pneumonias, atelectasis, unsatisfactory secretions manage, respiratory failure, hypoventilation, and other complex pathologies such as pulmonary embolism and sleep apnea syndrome. It has been postulated that the main cause of all these respiratory complications is weakness of inter costais and abdominal muscles, and partial or complete dysfunction of the diaphragm. Today we have multiple therapeutic alternatives to prevent, manage and specifically treat the multiple types of complications. The main objective of this article is to review the different therapeutical alternatives and encourage the study of this important topic.

Las complicaciones respiratorias son la principal causa de muerte en los pacientes con tetraplejia, tanto en el período agudo como crónico. En esta categoría se incluyen diversas alteraciones como neumonías recurrentes, atelectasias, mal manejo de las secreciones, insuficiencia respiratoria e hipoventilación. Además, son frecuentes patologías más complejas como el tromboembolismo pulmonar y la apnea obstructiva del sueño. Se postula que las causas principales de los problemas respiratorios son la debilidad de los músculos intercostales y abdominales, y la disfunción parcial o total del diafragma. Hoy en día existen múltiples alternativas terapéuticas para prevenir, manejar y tratar en forma específica las diversas complicaciones. El propósito de este artículo es revisar las opciones terapéuticas actualmente vigentes y despertar el interés entre los clínicos para profundizar más en este importante tema.

Efeito da teofilina associada ao beta2-agonista inalatório de curta ou longa duração, em pacientes com doença pulmonar obstrutiva crônica estável: revisão sistemática / Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review

OBJETIVOS: Avaliar se o tratamento com teofilina associada ao beta2-agonista inalatório de curta ou longa duração é mais eficaz que o placebo e que o uso isolado de cada um dos fármacos, para os pacientes com doença pulmonar obstrutiva crônica estável. MÉTODOS: Realizou-se uma revisão sistemática com metanálise, sendo selecionados todos os ensaios clínicos aleatórios e duplo-cegos encontrados na literatura. RESULTADOS: Foram incluídos oito estudos. Teofilina associada ao beta2-agonista vs. placebo: houve melhora estatisticamente significante para o VEF1 (L), com média 0,27 (IC95 por cento 0,11 a 0,43); e para a dispnéia, com média -0,78 (IC95 por cento -1,26 a -0,29). Teofilina associada ao beta2-agonista vs. beta2-agonista isolado: nenhuma das metanálises realizadas detectou diferença entre os grupos. Teofilina associada ao beta2-agonista vs. teofilina isolada: houve melhora estatisticamente significante para a dispnéia, com média -0,19 (IC95 por cento -0,34 a -0,04). CONCLUSÕES: Em pacientes com doença pulmonar obstrutiva crônica estável: 1) teofilina associada ao beta2-agonista é mais eficaz que o placebo, em relação ao VEF1 e dispnéia; 2a) teofilina associada ao beta2-agonista é mais eficaz que a teofilina isolada, em relação à dispnéia; e 2b) teofilina associada ao beta2-agonista não é mais eficaz que o beta2-agonista isolado, para quaisquer das variáveis estudadas.

OBJECTIVES: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS: A total of eight studies were included. In comparing the effect of theophylline combined with beta2-agonists to that of a placebo, we found a statistically significant improvement in mean FEV1 (0.27 L; 95 percentCI: 0.11 to 0.43) and mean dyspnea (-0.78; 95 percentCI: -1.26 to -0.29). None of the meta-analyses performed detected any difference between the results obtained using theophylline combined with beta2-agonists and those obtained using beta2-agonists alone. When the administration of theophylline combined with beta2-agonists was compared to that of theophylline alone, there was a statistically significant improvement in mean dyspnea (-0.19; 95 percentCI: -0.34 to 0.04). CONCLUSION: In patients with stable chronic obstructive pulmonary disease, theophylline combined with beta2 agonists is more efficacious than is a placebo in terms of improving FEV1 and dyspnea. In addition, theophylline combined with beta2 agonists is more efficacious than is theophylline in improving dyspnea. Furthermore, administration of theophylline combined with beta2 agonists is no more efficacious, for any of the variables studied, than is the use of beta2-agonists in isolation.

Investigation and treatment of asthma.

Asthma is one of the most common chronic respiratory diseases presenting with a variety of symptoms from cough, chest tightness, wheeze, difficulty breathing and in many cases persistent dyspnea. The individual has been effected usually spends a significant amount of time and financial resources in order to control the symptoms. Even though asthma has been known for more than several decades, the medications for the condition are relatively limited. This article has reviewed currently available guidelines, classifications, investigations for the diagnosis and treatment recommendations of asthma for both the general practitioners and the specialists who mainly taking care of patients with this chronic airway condition.

Clinical Characteristics of Hypervagotonic Sinus Node Dysfunction

BACKGROUND: Sinus node dysfunction (SND) is caused not only by intrinsic sinus node disease, but also by the extrinsic factors. Among the extrinsic factors, autonomic imbalance is most common. Symptomatic SND usually requires permanent pacemaker therapy. However, the clinical characteristics and patient response to medical therapy for hypervagotonic SND have not been properly clarified. MATERIALS AND METHODS: Thirty two patients (14 men, 18 women, 51 +/- 14 years) with hypervagotonic SND were included in this study, but those patients who had taken calcium antagonists, beta-blockers or other antiarrhythmic drugs were excluded. Hypervagotonic SND was diagnosed if the abnormal electrophysiologic properties of the sinus node were normalized after the administration of atropine (0.04 mg/kg). RESULTS: The presenting arrhythmias were 16 cases of sinus bradycardia (50.0%), 12 of sinus pause (37.5%), 3 of sinoatrial block (9.4%) and 1 of tachy-bradycardia (3.1%). Nine (28.1%) patients had hypertension, 7 (21.9%) smoked, 2 (6.3%) had diabetes mellitus, and 1 (3.1%) had hypercholesterolemia. Among the patients, 3 had no remarkable symptoms, 13 had dizziness, 7 had syncope, 3 had weakness and 6 had shortness of breath. Twenty five (78.1%) patients were treated with theophylline, 1 patient with tachy-bradycardia syndrome was treated with digoxin and propafenone, and 6 (18.8%) were treated with no medication. During the 43 +/- 28 month follow-up, 25 patients remained asymptomatic, but 6 who took no medication developed mild dizziness. One patient needed permanent pacemaker implantation owing to recurrent syncope despite of theophylline treatment. CONCLUSION: These results show that hypervagotonic SND has a benign course and most of the patients can be managed safely without implanting a pacemaker. (Ed note: I like the abstract. It is short and direct, as it should be.)

Efecto clínico de una formulación de teofilina de liberación sostenida en pacientes asmáticos moderados o severos con intercrisis / Clinic effect of a theophylline of sustained action in asthmatic patients with moderate o severe asthma

Se evaluó el efecto clínico de la formulación de teofilina de acción sostenida (Aristegui 300 mg, cápsulas) a la dosis de 9 mg/kg de peso/día (cada 12 horas) en la consulta de asma bronquial del Hospital Docente Provincial Clínico Quirúrgico de Santa Clara, en el periodo comprendido de febrero a septiembre de 1997. El tiempo de tratamiento fue de un mes y se realizaron cinco consultas. La muestra estuvo constituida por 30 pacientes asmáticos, moderados o severos. Se analizaron las variables: asistencia a cuerpo de guardia, uso de salbutamol en aerosol y se realizaron mediciones objetivas de la función pulmonar a todos los pacientes en las diferentes consultas. Con la utilización de la formulación disminuyeron significativamente el flujo espiratorio pico, el volumen espiratorio forzado en un segundo y el flujo medio espiratorio máximo y existió baja incidencia de efectos adversos.

Síncope neurocardiogénico cardio-inhibitorio en niños y adolescentes: características clínicas, tratamiento y evolución / Neurocardiogenic syncope in children and adolescents: clinical course and treatment

Los síndromes de hipotensión arterial ortostáticos constituyen las principales causas que explican muchos de los síncopes de etiología no precisada. En la mayoría de los pacientes pediátricos se documenta síncope neurocardiogénico mixto y vasodepresor t, en menor proporción, síncope cardioinhibitorio. El pronóstico de este último subgrupo no está del todo dilucidado. El objetivo del presente trabajo fue evaluar las características clínicas, tratamiento y evolución de los síncopes cardio-inhibitorios, definidos como IIA y IIB según clasificación del grupo VASIS, en un grupo de niños y adolescentes. Se estudió prospectivamente a 100 niños y adolescentes de 8 a 16 años de edad, con síncope o pre-síncope de etiología no precisada, desde 1/1/98 hasta 1/7/99. Se practicó test de Tilt a todos según recomendaciones del ACC Expert Consensus Document. 52 por ciento no presentó alteraciones. 10 por ciento presentó síncope neurocardiogénico cardioinhibitorio, 34 por ciento síncope neurocardiogénico mixto y vasodepresor, 4 por ciento pooling venoso patológico, 3 por ciento síndrome de taquicardia postural ortostática, 1 por ciento prolongación del QT. En el grupo de pacientes con síncope cardio-inhibitorio, la edad promedio fue de 12 ñ 2 años (4 mujeres y 6 hombres). Ninguno requirió isoprotenol para reproducir el síncope cardio-inhibitorio. 5/10 presentaron mioclonías y no hubo traumatismos secundarios. Casi todos presentaron más de 5 episodios sincopales (8/10) e historia de más de 1 año de evolución (9/10). 9/10 fueron síncopes cardio-inhibitorios tipo IIA y 1/10 de tipo IIB. El tipo de tratamiento fue individual y dependió del médico tratante. Un paciente requirió marcapaso (tipo IIB). El seguimiento promedio fue de 6 meses (3 a 13 meses), con excelente respuesta clínica. Conclusiones: En población pediátrica, 10 por ciento de los síncopes de etiología no precisada correspondió a síncope cardioinhibitorio. La mayoría recibió tratamiento farmacológico por períodos relativamente breves (2-3 meses) o no recibió tratamiento, con excelente respuesta clínica a los 6 meses de seguimiento (3-13 meses)

Preparação e estabilidade de suspensões e elixires à base de teofilina / Preparation and stability of theophylline suspension and elixirs

Foram preparadas quatro suspensões e três elixires à base de teofilina anidra. As suspensões foram obtidas modificando-se a concentração do agente suspensor e substituindo-se o xarope simples por sorbitol 70 por cento, sacarina e sacarose ou eliminando-se o Tween. Para a obtenção das suspensões, o agente suspensor foi dissolvido separadamente. Posteriormente, os outros componentes foram adicionados e homogeneizados. Os elixires foram preparados modificando-se o teor alcoólico, a conventração do sorbitol 70 por cento e a presença ou não de Nipagin e benzoato de sódio. Os diversos constituintes dos elixires foram adicionados à solução de sacarose previamente preparada. Todas as preparações obtidas foram submetidas à determinação dos caracteres físico-químicos e organolépticos...

Manejo ambulatorio de la EPOC: informe de una Reunión de Consenso / Ambulatory management of chronic obstructive pulmonary disease COPD: a consensus report

Based on the Consensus of the Chilean Respiratory Society, this article summarizes the main topics of the ambulatory management of patients with COPD. The Consensus proposes operative definitions in order to prevent the most frequent conceptual errors, specially those related to the confusion between patients with chronic bronchitis without chronic obstruction and those with COPD. Among the diagnostic criteria, the consensus emphasizes the importance of demonstrating irreversible airway obstruction through spirometry, as well as strategies to the differential diagnosis between COPD and asthma. The Consensus summarizes the therapeutic interventions used in the ambulatory setting, including smoking cessation, bronchodilators, corticosteroids, antibiotics, vaccination, oxygen therapy, respiratory rehabilitation and environmental management. The Consensus emphasizes the importance of patient education in order to involve them in their own management. Some criteria for referral of patients are given and the role of exceptional therapeutical interventions, such as non invasive mechanical ventilation and lung reduction surgery are mentioned. The Consensus states that a significative improvement of the quality of life can be achieved with a proper combination of therapeutic interventions

Aspectos farmacológicos de la terapéutica del paciente asmático / Pharmacological aspects of the therapautics of the asthmatic patient

Elasma bronquial es un importante problema de salud en la atención primaria. Se sabe que un tratamiento correcto de la enfermedad contribuye a mejorar la calidad de vida de estos pacientes. Se revisan los principales aspectos farmacológicos (acciones, indicaciones, efectos adversos, vía de administración y dosis de los 2 grupos de medicamentos más empleados en la terapéutica de la enfermedad que son: los broncodilatadores (salbutamol, teofilina, bromuro de ipratropio) y los antiinflamatorios (cromoglicato de sodio y glucocorticoides)

Apneias no período neonatal: fisiopatologia e prognóstico / Neonatal apnea: physiopatology and prognosis

Apneias neonatais säo frequêntes e decorrem de inúmeras causas, dentre elas, a prematuridade e uma das mais importantes. Recém-nascidos saudaveis, tanto de termo como pré-termo, com idade gestacional pós-conceptual superior a 40 semanas, normalmente näo apresentam apnéia. Caso estes episódios ocorram, deve-se proceder a uma investigaçäo minuciosa, inclusive com registros polissonográficos, pois eles ja podem ser considerados como "episódios agudos ameacadores da vida", que apresentam uma relaçäo importante com a sindrome da morte subita do lactente

Encuesta sobre conocimiento del tratamiento del asma aguda en un grupo de médicos pediatras de la Ciudad de Mérica, Yucatán, México / Survey on the knowledge of acute asthma treatment among a group of pediatricians in the city of Merida, Yucatan

Introducción. Objetivo. determinar el nivel de conocimiento sobre el tratamiento del asma aguda en un grupo de médicos pediatras por medio de un cuestionario de la American Academy of Pediatrics denominado:"Tratamiento del asma aguda infantil en el consultorio". Material y métodos. Diseño. estudio descriptivo, observacional y transversal. Lugar de la investigación: consultorios pediátricos privados de la Ciudad de Mérida, Yucatán, México. Unidades de estudio. se estudió una muestra probabilística formada por 48 pediatras seleccionados de los miembros activos del "Colegio de Pediatras de Yucatán" por muestreo aleatorio simple. Mediciones: el cuestionario incluyó preguntas sobre: equipo disponible en el consultorio para el tratamiento del asma aguda, clasificación de la intensidad de un episodio de la enfermedad, dosis de los medicamentos utilizados, dependiendo de la intensidad de la crisis y efectos adversos de los mismos. Resultados. Con relación al equipo disponible, 94 por ciento contaba con un inhalador de dosis medida o con un nebulizador, pero sólo 25 por ciento tenía flujómetro y 39 por ciento equipo para administrar oxígeno. El promedio de aciertos respecto de las otras preguntas fue de 49 por ciento. Conclusiones. Se encontraron deficiencias en el equipamiento y en el conocimiento necesarios para una adecuada atención de los niños asmáticos