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 ...

Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae: a case-case-control study / Factores de riesgo para infección con Klebsiella pneumoniae resistente a carbapenémicos: estudio caso-caso-control

Objective: To evaluate the association between quinolone exposure and the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and to estimate CRKP-specific mortality. Methods: Case-case-control study implemented in a tertiary care institution. Three groups of patients were analyzed: 61 consecutive cases of infection with CRKP (Group I); 61 randomly chosen cases of patients infected with carbapenem-sensitive Klebsiella pneumoniae (CSKP; Group II); and 122 randomly chosen controls without CRKP or CSKP infection. Matching was based on the length of stay in intensive care unit and the date of bacterial isolation. An active search was performed for patients with CRKP and CSKP infection, and prospective cases were included in the study. We compared the results for Groups I and II against those for the controls by using two conditional logistic regression analyses that included infection as the dependent variable and controlled for time at risk and co-morbidities. Results: Exposure to quinolones was not associated with CRKP infection: no association was found in the analysis of CRKP with the controls (OR = 1.7; 95% CI: 0.2-6.5) or in the analysis of CSKP against the controls (OR = 0.6; 95% CI: 0.2-1.6). Use of carbapenems (OR = 3.3; 95% CI: 1.2-9.3) and colonization with CRKP (OR = 3.3; 95% IC: 1.2-9.3) were specific risk factors for infection with CRKP. Mortality associated with CRKP was 61.3%. Conclusion: No association was found between exposure to quinolones and infection with CRKP; however, colonization by CRKP and use of carbapenems are risk factors for infection with CRKP.

Resumen Objetivo: Evaluar la asociación entre la exposición a quinolonas y la aparición de infección por Klebsiella pneumoniae resistente a Carbapenémicos (CRKP) y estimar la mortalidad específica por CRKP. Métodos: Estudio caso-caso-control realizado en una institución de tercer nivel de atención. Se adelantó búsqueda activa y prospectiva de los casos. Se analizaron tres grupos: 61 casos consecutivos de infección por CRKP, 61 casos elegidos al azar de los pacientes con infección por Klebsiella pneumoniae sensible a Carbapenémicos (CSKP) y 122 controles sin infección por CRKP ni por CSKP, elegidos al azar. Se realizó emparejamiento por estancia en unidad de cuidados intensivos y fecha del aislamiento bacteriano. Los datos se extractaron de la historia clínica electrónica. Se comparó los casos CRKP y los casos CSKP contra los controles mediante dos análisis de regresión logística condicional, con la infección como variable dependiente y controlando por el tiempo en riesgo y la comorbilidad. Resultados: La exposición a quinolonas no se asoció a infección con CRKP: no se encontró asociación en el análisis de CRKP contra controles (OR 1.7 IC 95%: 0.2-6.5) ni en el análisis de CSKP contra controles (OR 0.6 IC 95%: 0.2-1.6). El uso de carbapenémicos (OR 3.3 IC 95%: 1.2-9.3) y la colonización por KPRC (OR 16,2 IC 95%: IC 95%: 3.3-79.1) fueron factores de riesgo específicos para infección por CRKP. La mortalidad específica asociada a CRKP fue de 61.3%. Conclusión: No se encontró asociación entre la exposición a quinolonas y la infección por KPRC, pero la colonización por CRKP y el uso de carbapenémicos son factores de riesgo asociados a la infección por KPRC.