Función pulmonar: ¿Debemos cambiar la forma de calcular la respuesta broncodilatadora en la espirometría en niños? / Should we change the way we calculate the bronchodilator response in children's spirometry?

Tradicionalmente se ha definido la respuesta broncodilatadora (RB) positiva como una mejoría ≥ de 12 % del VEF1. En el año 2022 se publica una Guía sobre la interpretación de función la pulmonar de la Sociedad Americana de Tórax y la Sociedad Europea de Enfermedades Respiratorias, donde se propone que la RB debe expresarse como el cambio porcentual del VEF1 en relación con el VEF1 predicho y que un cambio ≥ 10 % indica una RB positiva. Las sociedades científicas en Chile están evaluando estas recomendaciones para decidir su adecuada implementación en pediatría.

Traditionally, a positive bronchodilator (BR) response has been defined as a ≥ 12% improvement in FEV1. In the year 2022, a Guide on the interpretation of pulmonary function of the American Thoracic Society and the European Society of Respiratory Diseases was published, where it was proposed that BR should be expressed as the percent change in FEV1 relative to predicted FEV1 and that a change ≥ 10% indicates a positive BR. Scientific societies in Chile are evaluating these recommendations to decide their proper implementation in pediatrics.

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Effects of indacaterol versus tiotropium on exercise tolerance in patients with moderate COPD: a pilot randomized crossover study / Efeitos do indacaterol versus tiotrópio na tolerância ao exercício em pacientes com DPOC moderada: estudo cruzado randomizado piloto

Abstract Objective: To compare a once-daily long-acting β2 agonist (indacaterol 150 µg) with a once-daily long-acting anticholinergic (tiotropium 5 µg) in terms of their effects on exercise endurance (limit of tolerance, Tlim) in patients with moderate COPD. Secondary endpoints were their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Methods: This was a randomized, single-blind, crossover pilot study involving 20 patients (mean age, 60.9 ± 10.0 years; mean FEV1, 69 ± 7% of predicted). Spirometric parameters, Transition Dyspnea Index scores, Tlim, and exertional dyspnea were compared after three weeks of each treatment (with a one-week washout period between treatments). Results: Nineteen patients completed the study (one having been excluded because of COPD exacerbation). Improvement in Tlim from baseline tended to be greater after treatment with tiotropium than after treatment with indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0.06). Tlim significantly improved from baseline after treatment with tiotropium (having increased from 396 ± 319 s to 493 ± 347 s; p = 0.010) but not after treatment with indacaterol (having increased from 393 ± 246 to 401 ± 254 s; p = 0.678). There were no differences between the two treatments regarding improvements in Borg dyspnea scores and lung hyperinflation at "isotime" and peak exercise. There were also no significant differences between treatments regarding Transition Dyspnea Index scores (1.5 ± 2.1 vs. 0.9 ± 2.3; p = 0.39). Conclusions: In patients with moderate COPD, tiotropium tends to improve Tlim in comparison with indacaterol. No significant differences were observed between the two treatments regarding their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Future studies, including a larger number of patients, are required in order to confirm our findings and explore mechanistic explanations. (ClinicalTrials.gov identifier: ...

RESUMO Objetivo: Comparar um β2-agonista de longa duração administrado uma vez por dia (indacaterol 150 µg) a um anticolinérgico de longa duração administrado uma vez por dia (tiotrópio 5 µg) quanto a seus efeitos na resistência ao exercício (limite de tolerância, Tlim) em pacientes com DPOC moderada. Os desfechos secundários foram seus efeitos na hiperinsuflação pulmonar, na dispneia causada pelo exercício e na dispneia na vida diária. Métodos: Estudo piloto randomizado cruzado e simples cego com 20 pacientes (média de idade: 60,9 ± 10,0 anos; média do VEF1: 69 ± 7% do previsto). Parâmetros espirométricos, pontuação no Transition Dyspnea Index, Tlim e dispneia aos esforços foram comparados após três semanas de cada tratamento (com uma semana de intervalo entre os tratamentos). Resultados: Dezenove pacientes completaram o estudo - um foi excluído por causa de exacerbação da DPOC. A melhora no Tlim tendeu a ser maior com tiotrópio do que com indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0,06). Em comparação com os valores basais, o Tlim melhorou significativamente com tiotrópio (aumentando de 396 ± 319 s para 493 ± 347 s; p = 0,010), mas não com indacaterol (aumentando de 393 ± 246 para 401 ± 254 s; p = 0,678). Não houve diferença entre os tratamentos quanto à melhora na pontuação na escala de dispneia de Borg e na insuflação pulmonar no "isotempo" e no pico do exercício. Também não houve diferenças significativas entre os tratamentos quanto à pontuação no Transition Dyspnea Index (1,5 ± 2,1 vs. 0,9 ± 2,3; p = 0,39). Conclusões: Em pacientes com DPOC moderada, o tiotrópio tende a melhorar o Tlim em comparação com o indacaterol. Não houve diferenças significativas entre os tratamentos quanto a seus efeitos na insuflação pulmonar, na dispneia durante o exercício e na dispneia na vida diária. São necessários mais estudos, com um número maior de pacientes, para confirmar nossos achados e explorar explicações mecanicistas. (ClinicalTrials.gov ...

Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility / Avaliação da resposta ao broncodilatador em pacientes pediátricos com bronquiolite obliterante pós-infecciosa: uso de diferentes critérios de identificação de reversibilidade das vias aéreas

ABSTRACT Objective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications.

RESUMO Objetivo: A bronquiolite obliterante pós-infecciosa (BOPI) é uma entidade clínica que tem sido classificada como obstrução fixa e constritiva do lúmen por tecido fibrótico. Entretanto, estudos recentes utilizando oscilometria de impulso relataram resposta ao broncodilatador em pacientes com BOPI. O objetivo deste estudo foi avaliar a resposta broncodilatadora em pacientes pediátricos com BOPI, comparando critérios diferentes para a definição da resposta. Métodos: Foram avaliados pacientes pediátricos com diagnóstico de BOPI tratados em um de dois ambulatórios de pneumologia pediátrica na cidade de Porto Alegre (RS). Parâmetros espirométricos foram medidos de acordo com recomendações internacionais. Resultados: Foram incluídos 72 pacientes pediátricos com BOPI no estudo. As médias dos valores pré- e pós-broncodilatador foram claramente inferiores aos valores de referência para todos os parâmetros, especialmente FEF25-75%. Houve uma melhora pós-broncodilatador. Quando medidos como aumentos percentuais médios, VEF1 e FEF25-75% melhoraram em 11% e 20%, respectivamente. Entretanto, quando os valores absolutos foram calculados, as médias de VEF1 e FEF25-75% aumentaram somente em 0,1 l. Verificamos que a idade da agressão viral, história familiar de asma e alergia não tiveram efeitos significativos na resposta ao broncodilatador. Conclusões: Pacientes pediátricos com BOPI têm uma obstrução das vias aéreas periféricas que responde ao tratamento, mas não uma reversão completa com o broncodilatador. O conceito de BOPI como obstrução fixa e irreversível parece não se aplicar a essa população. Nossos dados sugerem que a obstrução de vias aéreas em pacientes com BOPI é variável, e esse achado pode ter importantes implicações clínicas.

Estudio cualitativo del efecto del consumo de tintura madre de Allium sativum L. en la concentración de lisozima y proteínas totales en niños menores de 6 años con infecciones respiratorias agudas (I.R.A.) en el consultorio de Hualqui, VIII Región, Chile / Qualitative study of the effect on consumption of the mother tincture of Allium sativum (garlic) in the lysozyme concentration and total protein in children under 6 years old with acute respiratory infection in the Hualqui Medic´s office, VIII Region of Chile

Sampled population was children under 6 years with acute respiratory infection and the sample were obtained from sputum. The aim was to determine the changes in the concentrations ob both, lisozyme and total protein, before and after the intervention with the garlic mother tincture. It was a pilot study quantitative and through a system of nonrandomness simple of the probabilistic a sample of 25 individuals for determining if you belong to the treatment group (mother tincture) or control (placebo). The results indicate a decrease in the concentration of lysozyme and total proteins in the treatment group between 3 to 5 days after initiated treatment, on the other hand the control group showed an increase in the measurements. Only the treatment group showed positive changes in type symptomatical of the disease. Mother Tincture of garlic is a phytotherapeutic alternative excellent for effectively combat acute respiratory infections in children.

La población muestreada fueron niños menores de 6 años con I.R.A y la muestra fue obtenida de la expectoración. El objetivo fue determinar los cambios en la concentraciones de lisozima y proteínas totales, antes y después de la intervención con la tintura madre de ajo. Fue un estudio cuantitativo experimental y a través de un sistema de aleatoriedad simple del tipo probabilístico se toma una muestra de 25 individuos para determinar si pertenecerán al grupo tratamiento (tintura madre) o control (placebo). Los resultados obtenidos indican una disminución en la concentración de lisozima y proteínas totales del grupo tratamiento entre los 3 a 5 días después de iniciado el tratamiento, en cambio el grupo control reveló un aumento en las mediciones. Solamente el grupo tratamiento evidenció cambios positivos de tipo sintomatológico de la enfermedad. La tintura madre de ajo es una excelente alternativa fitoterapeútica para el combate eficaz contra las infecciones respiratorias agudas en niños.

Características funcionais pulmonares e uso de broncodilatador em pacientes com fibrose cística / Pulmonary function parameters and use of bronchodilators in patients with cystic fibrosis

OBJETIVO: Analisar as características funcionais pulmonares, a resposta farmacodinâmica a um broncodilatador e sua prescrição em pacientes com diagnóstico de fibrose cística (FC). MÉTODOS: Estudo de coorte retrospectivo de pacientes (6-18 anos) com diagnóstico de FC acompanhados em um centro de referência, capazes de realizar testes de função pulmonar (TFP) entre 2008 e 2010. Foram analisados CVF, VEF1 e FEF25-75%, em percentual do previsto, antes e após prova broncodilatadora (pré-BD e pós-BD, respectivamente) de 312 TFP. Foram realizadas ANOVA para medidas repetidas e comparações múltiplas. RESULTADOS: Foram incluídos no estudo 56 pacientes. Desses, 37 e 19, respectivamente, tinham resultados de TFP entre 2008 e 2010 e apenas em 2009-2010, formando dois grupos. No grupo com TFP nos três anos estudados, houve redução significativa em VEF1 pós-BD em 2008-2010 (p = 0,028) e 2009-2010 (p = 0,036) e em FEF25-75% pré-BD e pós-BD em todas as comparações múltiplas (2008 vs. 2009; 2008 vs. 2010; e 2009 vs. 2010). No grupo com TFP apenas em 2009-2010, não houve diferenças significativas em nenhuma das comparações das variáveis estudadas. Dos 312 TFP, somente 24 (7,7%) apresentaram resposta significativa ao broncodilatador e pertenciam a pacientes sem prescrição de broncodilatador durante o período estudado. CONCLUSÕES: Houve perda funcional, com indicação de doença pulmonar progressiva, nos pacientes com FC estudados. Houve maiores alterações no FEF25-75%, sugerindo o comprometimento inicial de vias aéreas menores.

OBJECTIVE: To analyze pulmonary function parameters and pharmacodynamic response to a bronchodilator, as well as the prescription of bronchodilators, in cystic fibrosis (CF) patients. METHODS: This was a retrospective cohort study involving patients 6-18 years of age, diagnosed with CF, and followed at a referral center between 2008 and 2010. We evaluated only those patients who were able to perform pulmonary function tests (PFTs). We analyzed FVC, FEV1, and FEF25-75%, expressed as percentages of the predicted values, prior to and after bronchodilator tests (pre-BD and post-BD, respectively), in 312 PFTs. Repeated measures ANOVA and multiple comparisons were used. RESULTS: The study included 56 patients, divided into two groups: those whose PFT results spanned the 2008-2010 period (n = 37); and those whose PFT results spanned only the 2009-2010 period (n = 19). In the 2008-2010 group, there were significant reductions in post-BD FEV1 between 2008 and 2010 (p = 0.028) and between 2009 and 2010 (p = 0.036), as was also the case for pre-BD and post-BD FEF25-75% in all multiple comparisons (2008 vs. 2009; 2008 vs. 2010; and 2009 vs. 2010). In the 2009-2010 group, there were no significant differences between any of the years for any of the variables studied. Among the 312 PFTs, significant responses to the bronchodilator occurred in only 24 (7.7%), all of which were from patients for whom no bronchodilator had been prescribed during the study period. CONCLUSIONS: In the CF patients studied, there was loss of pulmonary function, indicating progressive lung disease, over time. The changes were greater for FEF25-75% than for the other variables, which suggests the initial involvement of small airways.

Possible mechanism[s] of the relaxant effects of Achillea wilhelmsii on guinea-pig tracheal chains

Achillea wilhelmsii have been used in folk remedies. The relaxant effects of the extract of A. wilhelmsii on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of the extract, theophylline and saline were examined by their relaxant effects on precontracted tracheal chains of guinea pig by KCl [group 1], 10 micro M methacholine [group 2], incubated tissues by atropine, propranolol and chlorpheniramine and contracted by KCl [group 3] and incubated tissues by propranolol and chlorpheniramine and contracted by methacholine [group 4]. In group 1 and 2, all concentrations of theophylline and three higher concentrations [4, 6 and 8 mg/mL] of the extract showed significant relaxant effects compared to that of saline. In groups 3 and 4 experiments also all concentrations of the extract showed significant relaxant effects compared to that of saline. The relaxant effect of three higher concentrations [4, 6 and 8 mg/mL] of the extract in group 1 were significantly greater than those of group 2 and in group 3 were significantly lower than those of group 1. There were significant positive correlations between the relaxant effects and concentrations for theophylline in groups 1 and 2 and the extract in all four groups of experiments. These results showed a potent relaxant effect for the extract from A. wilhelmsii on tracheal chains of guinea pigs. A muscarinc receptor blockade was also suggested for the extract

Relaxant effects of different fractions from Tymus vulgaris on guinea-pig tracheal chains

In previous studies, the relaxant effect of Tymus vulgaris has been demonstrated on guinea pig tracheal chains. Therefore, in the present study, the relaxant effects of n-hexane, dichloromethane, methanol and aqueous fractions of Tymus vulgaris on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of each fraction (0.4, 0.8, 1.2 and 1.6 g%) in comparison to saline as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6 and 0.8 mM) were examined for their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 ìÌ methacholine (group 2, n = 7 for each group). In group 1, all concentrations of the n-hexane fraction and theophylline and three last concentrations (0.8, 1.2 and 1.6 g%) of dichloromethane and two higher concentrations (1.2 and 1.6 g%) of methanol fractions showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). In group 2, all concentrations of theophylline, n-hexane and dichloromethane fractions and three concentrations (0.8, 1.2 and 1.6 g%) of methanol and two higher concentrations (1.2 and 1.6 g%) of aqueous fractions showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). In addition, with group 1, the relaxant effect of all concentrations of all fractions except the n-hexane fraction, were significantly less than those of theophylline (p<0.05 to p<0.001). The n-hexane fraction showed higher relaxant effect than theophylline. The relaxant effect of all concentrations of the n-hexane fraction and the three last concentrations (0.8, 1.2 and 1.6 g%) of dichloromethane and aqueous fractions were significantly greater in group 2 than in group 1 (p<0.05 to p<0.001). There were significant positive correlations between the relaxant effects and concentrations for theophylline and all fractions (except aqueous fraction in group 1) in both groups, but a negative correlation for the aqueous fraction in group 1 (p<0.05 to p<0.001). These results showed a potent relaxant effect for n-hexane and weaker relaxant effect for other fractions from Tymus vulgaris on tracheal chains of guinea pigs.

The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

OBJECTIVE: To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs. METHODS: Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50 percent of the maximum response (EC50) was determined. Tracheal responses to 0.1 percent ovalbumin and white blood cell counts in the lung lavage fluid were also examined. RESULTS: The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases). CONCLUSIONS: These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.

Pharmacologic bronchodilation response to salbutamol in COPD patients.

Background: Airway hyperresponsiveness (AHR) is the most characteristic feature of asthma, which is reported in COPD patients and smokers. Increased airway responsiveness to ί-agonists is also demonstrated in asthmatics as well as smokers. However, there is no report regarding AHR to ί-agonist drugs in COPD patients. Therefore, in this study pharmacologic bronchodilation response to salbutamol in COPD patients was examined. Materials and Methods: The threshold concentrations of inhaled salbutamol required for a 20% change in forced expiratory flow in 1 sec (FEV 1 ) as PC 20 , or a 35% change in specific airway conductance (sGaw) as PC 35 was measured in 14 COPD patients and 14 normal subjects. Results: Airway responsiveness to salbutamol in COPD patients (PC 20 = 14.14 ± 1.62 and PC 35 = 9.70 ± 1.48 mg/l) was significantly lower than normal subjects (PC 20 = 224.57 ± 16.62 and PC 35 = 81.87 ± 8.16 mg/l, P < 0.001 for both cases). The values of FEV 1 and sGaw in COPD patients (56.43 ± 14.45 and 0.081 ± 0.120 respectively) were significantly lower than those of normal subjects (104.07 ± 5.72 and 0.194 ± 0.041 respectively), (P < 0.001 for FEV 1 and P < 0.005 for sGaw). There was a significant correlation between FEV 1 with PC 20 salbutamol (r = 0.862, P < 0.001). The correlations between PC 20 and PC 35 was also statistically significant (r = 0.862, P < 0.001). Conclusion: These results showed increased airway responsiveness of most COPD patients to salbutamol which was highly correlated to airway caliber.

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.

Beta 2 agonistas de acción prolongada en el tratamiento del asma en niños / Long acting beta 2 agonists in the treatment in children with asthma

A pesar del uso de corticoides inhalados en el tratamiento del asma bronquial existe un número variable de pacientes que no logran el control de su enfermedad. En estos casos, una de las alternativas terapéuticas propuesta por diversas guías clínicas es la adición de beta 2 agonistas de acción prolongada. Este articulo, revisa las características farmacológicas, posibles efectos adversos y las indicaciones en niños.

Emerging Molecular Targets for the Treatment of Asthma.

Current therapeutic approaches for the treatment of asthma have limitations in their ability to target all the features of the disease. Indeed, existing pharmacological asthma therapies are based on decades old strategies that were developed prior to the rapid growth in knowledge stemming from cell and molecular biology in the past decade. Thus, there is an unmet need for developing new drugs to target these features along with improved efficacy and safety. In the present review, the limitations of prevalent pharmacological asthma therapy are discussed briefly, and some explanations are suggested as to why new therapeutic targets are required to treat asthma, and finally directions for novel asthma therapies are proposed.

Doxofylline: The next generation methylxanthine.

Methylxanthines are widely used in the treatment of asthma. Being one of the few drugs that can be administered orally, they are especially helpful in resource restricted settings. Theophylline, the commonly used methylxanthine drug is associated with a wide range of adverse effects accounting for the poor compliance and high drop-out rates. Moreover, a narrow therapeutic index warrants routine monitoring of its levels in the blood. Doxofylline, a new methylxanthine derivative, is shown to have similar efficacy with significantly less side effects in both animal studies as well as human adults. However, there is a paucity of studies in children with asthma. Retrospective data suggest that 11% patients experienced some side effects, but only 5% reported moderate side effects. Available evidence suggests that it improves spirometric parameters in children with asthma as compared to placebo. Extrapolating data from adult patients, it may be used in place of theophylline as an add on therapy in step 3 and step 4 in children with asthma. Dosage recommended for children> 6 yrs of age is 6 mg/Kg/dose BID. Doxofylline produces stable serum concentrations, hence plasma monitoring is required only in patients with hepatic insufficiency and intolerance to xanthine drugs.

Lead acetate induced contraction in rat tracheal smooth muscle is independent of epithelium.

Airways are the primary target of lead exposure from atmospheric pollution, its effect on airway smooth muscle and their responsiveness to bronchoactive agents is not clearly understood. In the present investigation the effect of lead on the isolated airway smooth muscle activity was studied in organ bath set-up. Further the involvement of airway epithelium was examined and the responsiveness of airway smooth muscle to adenosine, acetylcholine (bronchoconstrictors) and isoproterenol (bronchodilator) was also investigated. Lead in concentration of 10(-12) M to 10(-4) M produced concentration-dependant contractile response in rat tracheal rings. Acetylcholine and adenosine induced concentration-dependent contractile response was slightly inhibited after lead exposure. The relaxant response to isoproterenol was also inhibited in lead exposed tissues. Epithelium removal did not significantly change the contractile response to lead suggesting that the lead induced contraction of airway smooth muscle is epithelium independent.

Easy Diagnosis of Asthma: Computer-Assisted, Symptom-Based Diagnosis

Diagnosis of asthma is often challenging in primary-care physicians due to lack of tools measuring airway obstruction and variability. Symptom-based diagnosis of asthma utilizing objective diagnostic parameters and appropriate software would be useful in clinical practice. A total of 302 adult patients with respiratory symptoms responded to a questionnaire regarding asthma symptoms and provoking factors. Questions were asked and recorded by physicians into a computer program. A definite diagnosis of asthma was made based on a positive response to methacholine bronchial provocation or bronchodilator response (BDR) testing. Multivariate logistic regression analysis was used to evaluate the significance of questionnaire responses in terms of discriminating asthmatics. Asthmatic patients showed higher total symptom scores than non-asthmatics (mean 5.93 vs. 4.93; p<0.01). Multivariate logistic regression analysis identified that response to questions concerning the following significantly discriminated asthmatics; wheezing with dyspnea, which is aggravated at night, and by exercise, cold air, and upper respiratory infection. Moreover, the presence of these symptoms was found to agree significantly with definite diagnosis of asthma (by kappa statistics). Receiver-operating characteristic curve analysis revealed that the diagnostic accuracy of symptom-based diagnosis was high with an area under the curve of 0.647+/-0.033. Using a computer-assisted symptom-based diagnosis program, it is possible to increase the accuracy of diagnosing asthma in general practice, when the facilities required to evaluate airway hyperresponsiveness or BDR are unavailable.

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.

Reversibilidad espirométrica en la enfermedad pulmonar obstructiva crónica: efecto diferencial del salbutamol sobre el volumen espiratorio forzado del primer segundo y el volumen pulmonar / Spirometric reversibility to Salbutamol in chronic obstructive pulmonary disease (COPD): differential effects on FEV1 and on lung volumes

Background: In recent years it has been suggested that in COPD, lung volumes can be modified more than expiratory flows, with bronchodilators. Aim: To study the acute effects of salbutamol on FEV1 and lung volumes at rest. Subjects and Methods: Forty stable COPD patients were studied using a single dose of salbutamol (200 µg). Forced expiratory volumen in 1 second (FEV1), slow vital capacity (SVC), forced vital capacity (FVC), and inspiratory capacity (IC) were measured at baseline and after salbutamol administration. Results: After salbutamol, 39/40 patients exhibited a clinically significant increase in volumes (SVC, FVC or IC ×10 percent predicted). A significant increase in FEV1 (×10 percent predicted) was observed in only 13 patients. Conclusions: Our results demonstrate that changes in lung volumes, and consequently in dynamic lung hyperinflation, take place more frequently than changes in maximal expiratory flows during the spirometric test in patients with COPD. Assessment of spirometric reversibility based only on changes in FEV1 underestimates the effect of bronchodilator drugs in these patients.