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

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

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

Reversibilidad espirométrica en pacientes con enfermedad pulmonar obstructiva crónica: ¿debe emplearse 200 ó 400 µg de salbutamol? / Spirometric reversibility in COPD patients: 200 or 400 mg salbutamol should be used?

The optimal dose of salbutamol for testing spirometric reversibility in patients with chronic obstructive pulmonary disease (COPD) has not been determined and either 200 or 400 µg are commonly used. The purpose of the present study is to test both doses in a group of patients with mild to severe COPD. Forty stable COPD patients were included to receive in random order both doses of salbutamol, with spirometry being performed before and after 15 min of their administration. Absolute and percent predicted changes were evaluated. For the latter, an increase in forced expiratory volume in one second (FEV1), slow vital capacity (SVC), forced vital capacity (FVC) and inspiratory capacity (IC) equal or greater than 10 percent predicted was considered clinically significant. No differences were found in absolute post-bronchodilator values between the two doses. In addition, the proportion of responders to 200 and 400 µg of salbutamol according to the percent predicted changes was similar with both doses. This was particularly true when all variables related to volume changes (SVC, FVC, and IC) were included in the analysis. In conclusion, the present results indicate that for testing spirometric reversibility in COPD patients the 200 µg dose of salbutamol is as effective as the 400 µg dose.

La óptima dosis de salbutamol que se debe emplear para evaluar la reversibilidad espirométrica en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) no ha sido establecida, por lo que 200 ó 400 mg son corrientemente utilizados. El propósito del presente estudio fue evaluar el efecto de ambas dosis de salbutamol en un grupo de pacientes con enfermedad leve a grave. El estudio incluyó a 40 pacientes con EPOC estable a los cuales se les realizó una espirometría antes y 15 minutos después de recibir en orden aleatorio 200 ó 400 µg de salbutamol en dos días consecutivos. Los cambios se evaluaron en valores absolutos y en porcentaje del valor teórico. Se midió los cambios en VEF1, CVF, capacidad vital lenta (CVL) y capacidad inspiratoria (CI). Se consideró clínicamente significativo un aumento igual o mayor al 10 por ciento del valor teórico. No se observó diferencias en los valores absolutos post broncodilatador entre las dos dosis como tampoco expresados en porcentaje del valor teórico. Además, la proporción de pacientes que respondieron con 200 y 400 µg de salbutamol fue similar. Esto fue particularmente importante cuando se incluyó en el análisis todas las variables relacionadas con el cambio de volumen (CVL, CVF y CI). Concluimos que para evaluar la reversibilidad espirométrica en pacientes con EPOC, 200 µg de salbutamol son tan efectivos como 400 µg.

Beneficios clínicos y funcionales de agregar teofilina a la terapia inhalatoria con broncodilatadores de acción corta en pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD

Background: Although theophylline is considered a third line bronchodilator drug for the treatment of chronic obstructive pulmonary disease (COPD), it is widely used in Chile, because it is administered orally and has a moderate cost. Aim: To evaluate if theophylline adds clinical and/or functional benefits when associated to standard recommended inhaled bronchodilator therapy. Subjects and methods: Thirty-eight stable COPD patients who accepted to participate in the study approved by the Ethics Committee of our institution were studied. Using a randomized double-blind placebo-controlled study, theophylline (250 mg) or placebo was administered twice a day for 15 days in addition to inhaled salbutamol and ipratropium bromide. Prior to and at the end of the study, patients underwent: a) a spirometry to evaluate changes in dynamic pulmonary hyperinflation using slow vital capacity (SVC) and inspiratory capacity (IC), b) the 6 min walking distance (6 MWD); and c) measurement of maximal inspiratory and expiratory pressures. Dyspnea and quality of life (QoL) were evaluated using appropriate questionnaires. Results: Compared to placebo, patients on theophylline showed significant increases in SVC (p=0.014), IC (p=0.002), and 6 MWD (p=0.005). They also experienced an improvement in dyspnea (p=0.042) and QoL (p=0.011). All patients improved at least one of these parameters with 53% of the patients showing an improvement in 3 or more. Conclusions: Our results indicate that adding theophylline to standard treatment with inhaled bronchodilators provides additional benefits in stable COPD patients by reducing dynamic pulmonary hyperinflation, improving exercise tolerance, dyspnea and QoL.

Effect of salbutamol on pulmonary responsiveness in chronic pulmonary allergic inflammation in guinea pigs

Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 ± 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergen-specific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG1-specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of ß2-agonists results in a loss of some of their protective effects against the allergen.

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.

Correccion rapida de la hiperkalemia aguda con salbutamol en nebulizacion / Rapid correction of acute hyperkalemia with nebulized salbutamol

En 15 pacientes en hemodiálise crónica y con hiperkalemia aguda, se relizaron 22 tratamientos con 20 mg de salbutamol en nebulización, para descender la potasemia, hasta que se pudiera efectuar la hemodiálisis. Los controles de laboratorio realizados a los 20, 40, 60, 90 y 180 minutos, revelaron que los descensos de los niveles de potasio en plasma fueron significativos a los 40 minutos, máximos a los 90 minutos (1,12 ñ 0,10 mEql) y persistieron descendidos hasta por lo menos 3 horas (en 3 casos hasta 6 horas), luego del tratamiento. Alcanzó significación el descenso de la tensión arterial sistólica y diastólica, y el incremento en las frecuencias cardíacas y respiratoria. Esta modalidad terapéutica fue efectiva en todos los casos en que se la realizó. Los efectos secundarios a la administración de la droga fueron moderados y tolerables: taquicardia sinusal, temblor fino y sensación de ansiedad, en 6,4 y 1 pacientes, respectivamente