Association between beta-2 adrenergic receptor variants and clinical outcomes in children and adolescents with acute asthma

ABSTRACT Objective To investigate whether different genotypes of p.Arg16Gly, p.Gln27Glu, p.Arg19Cys and p.Thr164Ile variants interfere in response to treatment in children and adolescents with moderate to severe acute asthma. Methods This sample comprised patients aged 2 to 17 years with a history of at least two wheezing episodes and current moderate to severe asthma exacerbation. All patients received multiple doses of albuterol and ipratropium bromide delivered via pressurized metered-dose inhaler with holding chamber and systemic corticosteroids. Hospital admission was defined as the primary outcome. Secondary outcomes were changes in forced expiratory volume in the first second after 1 hour of treatment, and for outpatients, length of stay in the emergency room. Variants were genotyped by sequencing. Results A total of 60 patients were evaluated. Hospital admission rates were significantly higher in carriers of the genotype AA relative to those with genotype AG or GG, within the p.Arg16Gly variant (p=0.03, test χ2, alpha=0.05). Secondary outcomes did not differ between genotypes. Conclusion Hospital admission rates were significantly higher among carriers of the genotype AA within the p.Arg16Gly variant. Trial registration: ClinicalTrials.gov: NCT01323010

Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.@*METHODS@#A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.@*RESULTS@#Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.@*CONCLUSIONS@#SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.@*PROSPERO REGISTRATION NUMBER@#CRD42019133156.

Exercise-Induced bronchoconstriction and therapeutic modulation in Iraqi Girls Intermediate School Students

EIB (Exercise-Induced Bronchoconstriction) describes the narrowing that accurs in the airway follow a short period of exercise. EIB is found in 8-10% of normal children population as occult bronchospasm during or after physical activities. The mecanisms of EIB are related to rapid ventilation and mouth brathing which cause beat and water loss during breathing leading to bronchoconstriction. Peak Expiratory Flow Rate (PEFR) measured pre and post-exercise in students aged 12-16 years in girl intrmediate school. Any female shows PEFR values reduction 15% after 6 minutes continuous free running considered as asthmatic patient, this give an incidence rate of asthmatic patient of 9% in female students in this age. Treatment of EIB, Zafirlukast treatment gives (85.7%) protection rate. While salbutamol inhalation gives a protection rate 88%. Only 66.6% of girls with EIB give an improvement in PEFR values after sodium cromoglycate treatment. A regular measurement of PEFR in school students appears to be a good indicator of EIB, while inhalation of salbutaol 15 minutes before exercise give a good protection against EIB attacks at least for 4 hours (AU)

Broncodilatadores en pacientes con bronquiolitis / Bronchodilators for bronchiolitis

La bronquiolitis es una infección respiratoria aguda baja de causa viral, de aparición invernal, que es común en bebés de 0a 12 meses de edad. Conduce a que las vías respiratorias pequeñas se inflamen y se llenen de desechos, obstruyéndose.El bebé tiene una tos fuerte, secreción nasal, generalmente fiebre y puede presentar sibilancias dificultad respiratoria ydesaturación de oxígeno. Tras la presentación de un caso en la guardia se generó una controversia científica sobre lautilidad de los broncodilatadores en pacientes con bronquiolitis. Luego de realizar una búsqueda bibliográfica y seleccionarla evidencia más reciente y de mejor calidad, se concluye que la evidencia no apoya el uso de broncodilatadores enpacientes con bronquiolitis.(AU)

Bronchiolitis is a low acute respiratory lower respiratory tract infection of viral origin, winter appearance, which is commonin babies from 0 to 12 months of age. It causes the small airways in the lungs to become inflamed and fill with debris. Theinfant has a harsh cough, runny nose, usually fever and may have wheezing, respiratory distress and oxygen desaturation.After the presentation of a case in the emergency department, a scientific controversy was generated about the usefulnessof bronchodilators in patients with bronchiolitis. After conducting a literature search and selecting the most recent and bestquality evidence, it is concluded that evidence does not support the use of bronchodilators in patients with bronchioliTIS.(AU)

Mioclonías inducidas por salbutamol / Myoclonus induced by salbutamol: A case report

Resumen El salbutamol es un agonista adrenérgico β2 ampliamente empleado en pacientes con enfermedades pulmonares obstructivas y restrictivas. Sus principales efectos secundarios son la taquicardia y el temblor. Las mioclonías son contracciones musculares involuntarias, irregulares, bruscas, breves y repentinas, y pueden ser generalizadas, focales o multifocales. Se presenta el caso de un paciente de 61 años con mioclonías de difícil manejo que solo presentó mejoría tras la suspensión definitiva del agonista adrenérgico β2. Se describen los hallazgos clínicos, las intervenciones y el resultado en las mioclonías asociadas con el uso de salbutamol y se discuten la posible génesis y la importancia de este efecto adverso. Para documentar el caso, se siguieron las recomendaciones de las guías para el reporte de casos (CAse REport, CARE). Aunque en diversos estudios se han descrito mioclonías secundarias al uso de diferentes fármacos, hasta donde se sabe, este sería el cuarto reporte de un caso asociado específicamente con el uso del salbutamol.

Abstract Salbutamol is a β2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the β2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.

TeleCondutas: asma / TeleGuides: asthma

Asma é uma doença respiratória crônica frequente no atendimento da Atenção Primária à Saúde (APS) com prevalência nacional de 4,4% em adultos e cerca de 20% em crianças e adolescentes. Conforme a gravidade da doença, apresenta diversos graus de incapacidade e piora na qualidade de vida. A doença tem características heterogêneas, usualmente com inflamação crônica das vias aéreas, sendo definida pela história de sintomas respiratórios (sibilância, dispneia, desconforto torácico e tosse), que variam no tempo e em intensidade, associados a limitação variável de fluxo aéreo expiratório. O diagnóstico é baseado nas características clínicas da doença e testes de função pulmonar que identificam limitação variável do fluxo aéreo. Esta guia apresenta informação que orienta a conduta para casos de asma no contexto da Atenção Primária à Saúde, incluindo: Avaliação clínica Teste de função pulmonar Controle dos sintomas Riscos para desfechos desfavoráveis Tratamento Farmacológico Medidas complementares Técnica inalatória Plano de ação Manejo da exacerbação Encaminhamento para serviço especializado.

Do we really ponder about necessity of intravenous hydration in acute bronchiolitis? / Debemos reflexionar sobre la necesidad de una hidratación intravenosa en la bronquiolitis aguda?

Objective: The goal was to establish the role of intravenous hydration therapy on mild bronchiolitis. Methods: This was a retrospective case control study. Infants between 1 month and 2 years of age admitted to our general pediatrics ward between June 2012 and June 2013 with a diagnosis of uncomplicated acute bronchiolitis were enrolled to the study. Hospital medical files were reviewed to get information about children personal history, symptoms of the disease, disease severity scores and their management. Patients were classified into 4 groups according to the management; nebulized short-acting β2-agonist (salbutamol) +hydration; nebulized short-acting β2-agonist (salbutamol); hydration and neither bronchodilator nor hydration. We examined length of stay in the hospital as an outcome measure. Results: A total of 94 infants were studied. There was no significant difference between groups in terms of length of stay in hospital. Conclusions:IV hydration is not effective on length of stay in hospital in mild acute bronchiolitis patients.

Objetivo: Establecer la función de la terapia de hidratación intravenosa leve. Métodos: Estudio descriptivo retrospectivo. En el estudio fueron reclutados niños entre 1 mes y 2 años de edad atendidos en la sala de pediatría general entre junio 2012 y junio 2013, con diagnóstico de bronquiolitis aguda no complicada. Se revisaron historias médicas de los niños para obtener datos personales, síntomas de la enfermedad, grado de severidad y el manejo instaurado. Los pacientes fueron clasificados en cuatro grupos de cuerdo al manejo: hidratación + nebulización de corta acción con β2-agonista (salbutamol); nebulización de corta acción con β2agonista (salbutamol); hidratación; o sin hidratación y broncodilatador. Se determinó la duración de la estancia hospitalaria como medida resultado. Resultados: Un total de 94 niños fueron estudiados. No hubo diferencia significativa entre los grupos en términos de duración de la estancia en el hospital. Conclusiones: La hidratación IV no es efectiva en la duración de la estancia hospitalaria en pacientes con bronquiolitis aguda leve.

Comparative Efficacy of Generic Salmeterol Xinafoate/Fluticasone Propionate MDI Fixed Dose Combination and Seretide ® MDI in Asthmatic Patients: An Open Label, Randomized, Phase III Study.

The addition of an inhaled long-acting β2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients. The long-acting β2-agonist (LABA) Salmeterol xinafoate (Salmeterol) and inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) are being made available as a combination product Seretide® pMDI (Salmeterol/ Fluticasone) in a single aerosol inhaler. This randomized, open label, non-inferior, multicentric, 12-week, phase III study compared the efficacy and safety of generic Salmeterol/Fluticasone with commercially available product Seretide®. Materials and methods:Patients aged > 12 years inclusive of either sex (N = 372) with persistent asthma as defined by NHLBI for > 6 months prior to screening were included in the study. After a screening phase (1 week), eligible patients were enrolled in the trial with 2 weeks run in period. Eligible patients were randomized to receive either of the two treatment groups [HFA-Propelled pMDI Salmeterol/Fluticasone (25/250mcg) or HFA-Propelled Seretide® (25/250mcg) pMDI] in a ratio of 1:1 for the 12- week treatment period. The primary objective was to demonstrate non-inferiority of Salmeterol/Fluticasone versus Seretide®, measured by mean pre-dose forced expiratory volume in the first second (FEV1), at week 12. Results: This study provides evidence for the primary efficacy endpoint that Salmeterol/Fluticasone was statistically as well as clinically non-inferior to Seretide® in the treatment of patients with persistent asthma. This was supported by secondary endpoints which demonstrate that Salmeterol/Fluticasone appeared to be comparable to Seretide® in terms of efficacy for the secondary efficacy endpoints (morning PEFR, evening PEFR, diurnal variability of PEFR, daytime and night-time asthma symptoms score, average need for short acting-β2-agonists, proportion of patients that required rescue medication, patients with nocturnal asthma, patients without asthma symptoms of score 0 and average number of days without asthma symptoms of score 0). Salmeterol/Fluticasone was safe and well tolerated; and safety profile is comparable to comparator Seretide®. Conclusion: The results of study demonstrate that generic and innovator HFA formulations of Salmeterol/Fluticasone are clinically interchangeable. Overall, the study indicates that HFA-Propelled Salmeterol/ Fluticasone (25/250mcg) pMDI was safe, well tolerated and non-inferior in efficacy compared to HFA-Propelled Seretide® (25/250mcg) pMDI.

Original salbutamol versus similar salbutamol in children with asthma exacerbation: A randomized, controlled, double-blind study / Salbutamol original contra salbutamol similar en niños con crisis de asma: Estudio aleatorizado, controlado y doble ciego

Introduction.There is clinical evidence suggesting that original salbutamol is more effective than a similar salbutamol product to revert symptoms in acute asthma exacerbation.. Objective. To evaluate the bronchodilator response of both salbutamol medicinal products in children with asthma and to establish, based on the forced expiratory volume, if there is a difference between the group treated with the original salbutamol and the group treated with similar salbutamol. Design. Prospective, randomized, controlled, double-blind study. Material and Methods. One hundred and twenty six children (63 boys, age 9.18 ± 2.83 years old) were included. They were administered a dose of 20 drops (5 mg) of the original salbutamol or similar salbutamol product in nebulizing solution diluted only once in 2 ml saline solution. Preand post-bronchodilator, intra- and inter-group forced expiratory volume was compared at baseline and at 30 minutes. The weight of salbutamol drops was determined by gravimetry, the concentration by chromatography and the number of drops by bottle. Results. The bronchodilator response between the pre- and post-bronchodilator forced expiratory volume was 225 ml (95% CI: 164-286) and 224 ml (95% CI: 163-284) for original salbutamol and similar salbutamol, respectively (p < 0.001). The Delta difference was 1.3 ml (95% CI: -86+83) (p = 0.97). The mean, standard deviation and variation coefficient percentage of the weight of the drop was 364.75 mg (± 6.01, 1.65) and 543.88 mg (± 56.09, 10.31) (p < 0.001) for original salbutamol and similar salbutamol, respectively. Conclusion. There were no differences in the bronchodilator response measured by FEV1 between the original salbutamol and a similar salbutamol product.

Introducción. Existe evidencia clínica que sugiere que el salbutamol original sería más eficaz que el salbutamol similar para revertir los síntomas en el episodio agudo de asma. Objetivo. Evaluar la respuesta broncodilatadora de ambas especialidades farmacéuticas de salbutamol en niños con asma y establecer, mediante el volumen espiratorio forzado, si difiere entre los grupos tratados con salbutamol original y similar. Diseño. Estudio prospectivo, aleatorizado, controlado, a doble ciego. Material y métodos. Se incluyeron 126 niños (63 varones, edad 9,18 ± 2,83 años), que recibieron una dosis de 20 gotas (5 mg) de salbutamol original o similar en solución para nebulizar diluida en 2 ml de solución fisiológica por única vez. Se comparó el volumen espiratorio forzado prebroncodilatador y posbroncodilatador, intragrupos e intergrupos, al inicio y a los 30 minutos. Se determinó el peso de las gotas de salbutamol por gravimetría, la concentración por cromatografía y el número de gotas por envase. Resultados. La respuesta broncodilatadora entre el volumen espiratorio forzado prebroncodilatador y posbroncodilatador fue de 225 ml (IC 95%: 164-286) y 224 ml (IC 95%: 163-284) para salbutamol original y similar, respectivamente (p <0,001). El delta de la diferencia fue de 1,3 ml (IC 95%: -86+83) (p= 0,97). La media, desvío estándar y porcentaje del coeficiente de variación del peso de las gotas fue de 364,75 mg (± 6,01, 1,65) y 543,88 mg (± 56,09, 10,31) (p <0,001) para salbutamol original y similar, respectivamente. Conclusión. No hubo diferencias en la respuesta broncodilatadora medida por el VEF1 entre salbutamol original y similar.

Comparación de la aceptabilidad de dos propelentes del salbutamol spray: Ciudad de La Habana, enero-marzo, 2009 / Comparison of the acceptability of two propellants from Salbutamol spray: Ciudad de La Habana during January-March, 2009

El cambio de propelente en la formulación del salbutamol spray por uno protector de la capa de ozono requiere de evidencias que justifiquen su aceptabilidad en la población expuesta a este. En tal sentido se realizó un estudio en Ciudad de La Habana con el propósito de evaluar y comparar la aceptabilidad del producto ventolin con propelente ecológico y el salbutamol spray de producción nacional, posterior a una intervención educativa. Los 841 pacientes incluidos fueron distribuidos entre los municipios de forma proporcional al número de inscriptos para salbutamol spray en cada uno (ponderación municipal de acuerdo con el número de inscriptos). La selección de los pacientes se realizó por conveniencia del total de inscritos en cada farmacia principal municipal. La mayor parte de los encuestados coincide en que el tamaño, la forma del envase y la boquilla son adecuados. El sabor del producto fue considerado agradable discretamente superior en los que emplearon el salbutamol, mientras que la presentación en general fue más aceptada en el caso del ventolin. El control de los síntomas fue similar para ambos grupos. No existieron diferencias marcadas en la aceptabilidad de ambos productos farmacéuticos, a pesar de esto se encontró una aceptabilidad discretamente superior en el caso del ventolin. Estos resultados respaldan la introducción del propelente tetrafluoretano, específicamente el HFC 134, en la fabricación del salbutamol spray dado que el nivel de aceptabilidad del producto ventolin con este propelente ecológico es similar al encontrado para el salbutamol spray producido y comercializado actualmente en Cuba

The change of propellant in spray Salbutamol formula by other of the ozone layer requires of evidences justifying its acceptability in population exposed to it. The aim of present study in Ciudad de La Habana was to assess and to compare the acceptability of Ventolin as an ecological propellant and the Cuban spray Salbutamol, after an educational intervention. The 841 patients included were distributed proportionally to inscribed figure for spray Salbutlamol in each (municipal weighting according to above figure). Patient's selection was made by thing fit for total of inscribed in each municipal drugstore. Most of person polled is satisfied with the size, the packing shape and the mouthpiece. The Ventolin's flavor and presentation were considered as pleasant but not much that of Salbutamol. The symptoms control was similar for both groups of patients. There were not significant differences in acceptability of both pharmaceutical products despite it Ventolin was slightly favored. These results support the introduction of Tetrafluoretane specifically the HCF 134 in the manufacture of spray Salbutamol since the acceptability level of Ventolin with this propellant is similar to that found for spray Salbutamol produced and marketed nowadays in Cuba

Efeito de curto prazo do tiotrópio nos portadores de DPOC em tratamento com B2-agonista / Short-term effect of tiotropium in COPD patients being treated with a B2 agonist

OBJETIVO: Avaliar o impacto de curto prazo do uso de tiotrópio em pacientes com DPOC grave e muito grave com queixas de dispneia apesar do tratamento com outros broncodilatadores. MÉTODOS: Estudo prospectivo incluindo pacientes com DPOC grave ou muito grave, com queixa de dispneia de pequenos esforços ou ao repouso. A cada 15 dias, o tratamento broncodilatador foi modificado: salmeterol, tiotrópio e associação salmeterol+tiotrópio. Ao final de cada regime, foram realizados testes de função pulmonar e teste de caminhada de seis minutos (TC6). Também foram avaliados o grau de dispneia e a capacidade de realização de atividades de vida diária. Para a avaliação das atividades de vida diária, foi utilizada a escala London Chest Activity of Daily Living (LCADL) validado para uso no Brasil. RESULTADOS: Foram avaliados 52 pacientes. Desses, 30 completaram o estudo. A introdução de tiotrópio como monoterapia resultou em uma melhora significativa (p < 0,05) da dispneia basal (média do escore da escala do Medical Research Council de 3,0 para 2,5) e ao final do TC6 (média do escore da escala de Borg de 6,1 para 4,5), e as diferenças foram significativas (p < 0,05 para ambos). O uso da associação salmeterol+tiotrópio resultou em um aumento significativo médio de 81 mL no VEF1 e na melhora de 5,7 pontos no escore da escala LCADL. CONCLUSÕES: A introdução de tiotrópio no tratamento de pacientes com DPOC grave a muito grave em uso de β2-agonistas de longa duração causa melhora na função pulmonar e alivio sintomático perceptível pelos pacientes a curto prazo. Esses resultados, obtidos em regime de atendimento de vida real, dão suporte ao uso da associação salmeterol+tiotrópio em protocolos de assistência específicos a esses pacientes.

OBJECTIVE: To evaluate the short-term impact of tiotropium in patients with severe or very severe COPD who complain of dyspnea despite being currently treated with other bronchodilators. METHODS: A prospective study including patients with severe or very severe COPD and complaining of dyspnea at rest or on minimal exertion. Every 15 days, the bronchodilator treatment regimen was altered, from salmeterol to tiotropium to salmeterol+tiotropium. At the end of each regimen, pulmonary function tests and the six-minute walk test (6MWT) were performed. The degree of dyspnea and the ability to perform activities of daily living were also assessed. To evaluate patient ability to perform activities of daily living, we employed the London Chest Activity of Daily Living (LCADL), validated for use in Brazil. RESULTS: We evaluated 52 patients, 30 of whom completed the study. The use of tiotropium in isolation resulted in significant improvement in dyspnea at baseline (mean Medical Research Council scale score reduced from 3.0 to 2.5) and at the end of 6MWT (mean Borg scale score reduced from 6.1 to 4.5), and the differences were significant (p < 0.05 for both). The use of the salmeterol+tiotropium combination resulted in a significant (81 mL) increase in FEV1 and a 5.7 point improvement in the LCADL score. CONCLUSIONS: The introduction of tiotropium into the treatment of patients with severe or very severe COPD and using long-acting β2 agonists improves pulmonary function and provides symptomatic relief, as perceived by patients in the short term. These results, obtained under real life treatment conditions, support the use of the salmeterol+tiotropium combination in specific treatment protocols for these patients.

Levosalbutamol vs racemic salbutamol in the treatment of acute exacerbation of asthma.

Objective. To compare efficacy and tolerability of levosalbutamol (Group 1) and racemic salbutamol (Group 2) for the treatment of acute exacerbation of asthma in children age 5 to 18 yr. Methods. A randomized double blind clinical study involving 60 children was undertaken between October ’06 to December ’07. Results. The following baseline clinical characteristic were recorded initially and after giving 3 nebulizations at 20 min intervals in the Ist hour of presentation viz respiratory rate (RR), heart rate (HR), oxygen saturation in room air SPO2, PEFR (peak expiratory flow rate), serum K+ level and asthma score. In Group 1 patients (levosalbutamol), there was significant increment in SPO2 and PEFR (P<0.05) values with decrease in tachypnea and asthma score while no significant difference was found in pre and post treatment HR & Serum K+ levels. In Group 2 patients although there was clinical improvement in terms of SPO2, PEFR, RR and asthma score, it resulted in significant tachycardia and decrease in K+ levels. Conclusion. Levosalbutamol appears to be more efficacious than racemic salbutamol in terms of improvement in PEFR, SPO2 and asthma score while deleterious effects of tachycardia and fall in serum K+ were seen with racemic salbutamol.

Efeito da obstrução de vias aéreas nas variações das propriedades resistivas e elásticas do sistema respiratório de asmáticos, mediadas pelo uso de salbutamol / Effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of patients with asthma

OBJETIVO: Investigar os efeitos da obstrução de vias aéreas nas variações das propriedades resistivas e elásticas do sistema respiratório de asmáticos adultos mediadas pelo uso de salbutamol. MÉTODOS: Foram analisados 24 indivíduos controles e 69 asmáticos, todos não tabagistas, divididos em três grupos segundo o nível de obstrução de vias aéreas (leve, moderada e acentuada). Cada grupo foi dividido em dois subgrupos de acordo com a resposta broncodilatadora: resposta broncodilatadora positiva (RB+) ou negativa (RB-). A espirometria foi utilizada para a avaliação da obstrução, e a técnica de oscilações forçadas, para a análise das propriedades resistivas e elásticas, sendo realizadas antes e após a utilização de 300 µg de salbutamol. RESULTADOS: A resistência no intercepto (R0) apresentou maior redução nos grupos com maior obstrução. Essa redução foi mais evidente nos subgrupos RB+ do que nos RB- (p < 0,02 e p < 0,03, respectivamente). Houve diferença significativa entre o grupo controle e a o subgrupo com obstrução acentuada RB+ (p < 0,002). As reduções na elastância dinâmica (Edyn) se acentuaram significativamente com a obstrução, tanto para os subgrupos RB- (p < 0,03), quanto para os RB+ (p < 0,003). As reduções da Edyn foram significativamente maiores nos subgrupos com obstrução moderada RB- (p < 0,008) e com obstrução acentuada RB+ (p < 0,0005) do que no grupo controle. CONCLUSÕES: Em asmáticos, o aumento da obstrução de vias aéreas resulta na elevação das variações em R0 e Edyn com o uso de salbutamol. Pacientes com RB+ apresentam variações mais elevadas que indivíduos com RB-.

OBJECTIVE: To investigate the effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of adult patients with asthma. METHODS: This study comprised 24 healthy controls and 69 patients with asthma, all of whom were nonsmokers. The patients were divided into three groups according to the severity of airway obstruction (mild, moderate or severe). Each of the three groups was divided into two subgroups according to the bronchodilator response (BR): positive (BR+) or negative (BR-). Airway obstruction was determined by means of spirometry, and the resistive and elastic properties were determined by means of the forced oscillation technique. These measurements were conducted before and after albuterol use (300 µg). RESULTS: The resistance at the intercept (R0) presented greater reductions in the groups with higher obstruction. This reduction was more evident in the BR+ subgroups than in the BR- subgroups (p < 0.02 and p < 0.03, respectively). There was a significant difference between the control group and the BR+ subgroup with severe obstruction (p < 0.002). The reductions in dynamic elastance (Edyn) were significantly greater in proportion to the degree of obstruction, in the BR- subgroups (p < 0.03), and in the BR+ subgroups (p < 0.003). The reductions in Edyn were significantly greater in the BR- subgroup with moderate obstruction (p < 0.008) and in the BR+ subgroup with severe obstruction (p < 0.0005) than in the control group. CONCLUSIONS: In patients with asthma, increased airway obstruction results in greater reductions in R0 and Edyn after albuterol use. These reductions are greater among BR+ patients than among BR- patients.

Evaluation of asthma control using patient based measures and peak expiratory flow rate / Evaluación del control del asma usando medidas basadas en el paciente y tasas de flujo expiratorio máximo

OBJECTIVE: Asthma control has not been formally evaluated in the Caribbean. This study evaluated disease control on The Asthma Control Test (ACT), The Royal College of Physicians "Three questions" for Assessing Asthma Control (RCP), peak expiratory flow rate (PEFR) and patients'self-assessment of control. SUBJECTS AND METHODS: Asthma control was examined in a cross-section of 205 asthmatics above 16 years of age using the ACT, RCP and on the PEFR % predicted. Scores below 20 and equal to or above 1 on the ACT and RCP respectively, and PEFR below 80% predicted indicated uncontrolled asthma. Patients stated whether they perceived their asthma was controlled or uncontrolled. RESULTS: Overall there were more females (63.9%, p < 0.001) than males (36.1%). Males aged between 17-30 years predominated (60.8%, p < 0.001) with gender reversal beyond 30 years of age (33.2%, p < 0.002) years. Self-assessed control was higher (69.3%, p < 0.001) than control evaluated by the ACT and RCP tests, which were comparable (p > 0.05). Fewer patients (13.2%) achieved control on PEFR > 80% predicted than on the ACT (22.4%) and RCP (18%). The Kappa statistic indicated good reproducibility of the RCP and ACT and concordance between the PEFR and RCP (0.63) and the PEFR and ACT (0.56). Higher education was associated with control on the ACT (p < 0.0005) and RCP (p < 0.002) but not on PEFR or self-assessment (p > 0.05). CONCLUSION: Approximately 80% of study asthmatics were uncontrolled, and patients tended to overestimate their disease control. The ACT and RCP instruments were comparable with the PEFR. Efforts to study their validity and formal evaluation of asthma control in Trinidad are recommended.

OBJETIVO: El control del asma no ha sido evaluado formalmente en el Caribe. El estudio evaluó el control de la enfermedad utilizando el Test de Control del Asma (TCA), las "tres preguntas" del Colegio Real de Médicos para evaluar el control del asma (CRM), y la tasa de flujo expiratorio máximo (FEM) así como la autoevaluación del control por parte de los pacientes. SUJETOS Y MÉTODOS: El control del asma fue examinado en una sección transversal de 205 asmáticos de más de 16 años de edad, mediante el TCA, el CRM, y la predicción del FEM%. Las puntuaciones por debajo de 20 e iguales o por encima de 1 en el TCA y el CRM respectivamente, por debajo del 80% de predicción de la FEM, indicaban asma no controlada. Los pacientes informaban si percibían su asma como controlada o no controlada. RESULTADOS: En general hubo más (p < 0.001) mujeres (63.9%) que hombres (36.1%). Los hombres predominaron (p < 0.001) entre los 17 - 30 años (60.8%) con reversión del género (p < 0.002) pasados los 30 (33.2%) años. El control autoevaluado (69.3%) fue mayor (p < 0.001) que el control evaluado por las pruebas TCA y CRM, que fueron comparables (p > 0.05). Menos pacientes (13.2%) lograron un control con FEM > 80% de predicción que con TCA (22.4%) y CRM (18%). La estadística Kappa indicó una buena reproductibilidad de CRM y TCA, así como concordancia entre FEM y CRM (0.63) y FEM y TCA (0.56). Un nivel de educación más alto estuvo asociado con el control en TCA (p < 0.0005) y CRM (p < 0.002) pero no en FEM o autoevaluación (p > 0.05). CONCLUSIÓN: Aproximadamente el 80% de los asmáticos fueron no controlados, y los pacientes sobrestiman su control de la enfermedad. Los instrumentos TCA y CRM fueron comparables con la FEM. Se recomienda hacer esfuerzos por estudiar la validez de estos, así como la evaluación formal del control del asma en Trinidad.

Broncodilatação na DPOC: muito além do VEF1-efeito do salbutamol nas propriedades resistivas e reativas do sistema respiratório / Bronchodilation in COPD: beyond FEV1-the effect of albuterol on resistive and reactive properties of the respiratory system

OBJETIVO: Atualmente existem importantes debates na literatura sobre a resposta broncodilatadora em pacientes com DPOC e se a variação do VEF1 pode ser considerada uma indicação completa de reversibilidade neste caso particular. O objetivo deste estudo foi investigar o efeito do salbutamol nas propriedades resistivas e elásticas do sistema respiratório de portadores de DPOC. MÉTODOS: Foram avaliados 70 indivíduos com DPOC, classificados através da espirometria em dois grupos: broncodilatador (BD)-negativo (n = 39); e BD-positivo (n = 31). Utilizou-se a técnica de oscilações forçadas (TOF) para avaliar os seguintes parâmetros: a resistência no intercepto (R0), associada à resistência total do sistema respiratório; a resistência média (Rm), relacionada à resistência de vias aéreas centrais; e a complacência dinâmica (Cdyn); assim como o coeficiente angular da resistência (S) e a reatância média (Xm), relacionados com a homogeneidade do sistema respiratório. RESULTADOS: O uso do salbutamol resultou em reduções significativas de R0 (p < 0,00002) e Rm (p < 0,0002). Foram também observadas elevações significativas em S (p < 0,0001), Cdyn (p < 0,0001) e Xm (p < 0,00004). Estas alterações ocorreram tanto nos dois grupos, tendo sido observadas maiores modificações nos parâmetros da TOF do que nos parâmetros da espirometria. CONCLUSÕES: O uso de salbutamol melhorou o comportamento dos componentes resistivos e reativos do sistema respiratório dos pacientes com DPOC estudados. Estas mudanças ocorreram independentemente da classificação do exame empregando o VEF1, o que indica que a utilização deste parâmetro isoladamente pode não ser suficiente para identificar completamente os efeitos fisiológicos envolvidos.

OBJECTIVE: Current debates on the bronchodilator response in COPD patients and whether the variation in FEV1 can be considered as an indicator of complete reversibility in such patients motivated us to conduct this study. The objective of the study was to determine the effect of albuterol on the resistive and reactive properties of the respiratory system in COPD patients. METHODS: We evaluated 70 patients with COPD, divided into two groups based on spirometry findings: bronchodilator (BD)-negative (n = 39); and BD-positive (n = 31). We used the forced oscillation technique (FOT) to evaluate the following parameters: resistance at the intercept (R0), associated with the total resistance of the respiratory system; mean resistance (Rm), associated with central airway resistance; dynamic compliance (Cdyn); and the slope of resistance (S) and mean reactance (Xm), both of which are associated with the homogeneity of the respiratory system. RESULTS: The use of albuterol resulted in significant reductions in (p < 0.00002) and Rm (p < 0.0002). There were also significant increases in S (p < 0.0001), Cdyn (p < 0.0001) R0 and Xm (p < 0.00004).These modifications occurred in both groups, the changes in FOT parameters being greater than those observed for spirometric parameters. CONCLUSIONS: The use of albuterol improved the resistive and reactive properties of the respiratory system of the COPD patients under study. These changes occurred regardless of the FEV1-based classification, thereby indicating that the use of this parameter in isolation might not suffice to identify the physiological effects involved.

Treatment of moderate chronic obstructive pulmonary disease (stable) with doxofylline compared with slow release theophylline--a multicentre trial.

An open, randomised trial was conducted at Burdwan Medical College and Midnapore Medical College in West Bengal to investigate therapeutic efficacy and tolerability of doxofylline compared with slow release theophylline in 75 patients (45 males and 30 females) aged between 40 and 70 years who had been suffering from moderate chronic obstructive pulmonary disease. After one week of washout, the two drugs were administered orally to two groups one of 40 patients on doxofylline (400mg twice daily) and 35 patients on slow released theophylline (400mg once a day at evening); treatment and follow-up lasted 4 weeks on both groups patients. Both drugs significantly increased spirometric parameter (doxofylline p<0.01 and theophylline p<0.04) and significantly reduced salbutamol consumption (p<0.001 for both drugs). Doxofylline was better tolerated than theophylline considering either the number of unwanted side-effects: (Doxofylline 8 and theophylline 25) or number of drop-out side-effects (doxofylline 5 and theophylline 10). From these results, doxofylline seemed to be a good alternative to theophylline in the treatment of chronic obstructive pulmonary disease.

Are we adequately managing children with wheeze using the standard case management guidelines?

INTRODUCTION: Prevalence of wheezing is increasing, bronchodilators are sub-optimally utilized and antibiotics are over-prescribed. In Thailand, current case management guidelines based on WHO guidelines, recommend two doses of rapid-acting bronchodilator for children with audible wheeze and fast breathing (FB) and/or lower chest indrawing (LCI). OBJECTIVE: To document the response of children with wheeze with FB and/or LCI to up to three doses of bronchodilator therapy and followed children whose FB and LCI disappeared for 7 days. MATERIAL AND METHOD: We documented response to up to three dose of inhaled salbutamol in consecutively assessed eligible children 1-59 months of age presenting with auscultatory/audible wheeze and FB [WHO defined non-severe pneumonia (NSP)] and/or LCI [WHO defined severe pneumonia (SP)] at the outpatient department of a referral hospital. Data were collected for up to 7 days in responders to bronchodilator therapy. RESULTS: Of 534 children were screened from November 2001 to February 2003, 263 (49.3%) had wheeze and NSP and 271 (50.7%) had wheeze and SP Forty-eight children (9%) had audible wheeze. At screening, 224/263 (85.2%) children in the NSP group and 195/271 (72.0%) in the SP group responded to inhaled salbutamol. 86/419 (20.5%) responded to the third dose of bronchodilator Four hundred and nineteen responders were enrolled and followed up. On follow-up, 14/217 (6.5%) responders among the NSP group and 24/190 (12.6%) among the SP group showed deterioration. Age 1-11 months at screening was identified as an independent predictor of subsequent deterioration. Two seasonal peaks from December to March and from August to October were documented. CONCLUSION: A third dose of bronchodilator therapy at screening will improve the specificity of case management guidelines and reduce antibiotic use. Physicians should use auscultation for management of wheeze.