RESUMEN
Background: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers. Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and <80% predicted were randomized to single oral dose of imidafenacin 0.1 mg, imidafenacin 0.2 mg, or placebo. Results: Maximum change in FEV1 with both doses of imidafenacin significantly improved from baseline to 24 hrs after administration when compared with a placebo. Area under the curve in FEV1 during 24 hrs after administration with 0.2 mg, but not 0.1 mg dose, was significantly improved when compared with a placebo, and the improvement was significantly based on dose-dependent manners. Plasma imidafenacin level was positively correlated with change in FEV1. All subjects with both doses of imidafenacin completed without moderate nor severe adverse events. Conclusion: A single oral dose of imidafenacin 0.1 mg or imidafenacin 0.2 mg may contribute to the improvement of pulmonary function with excellent safety and tolerability in patients with COPD. Trial registration: JapicCTI-121760 (Japan Pharmaceutical Information Center - Clinical Trials Information [JapicCTI]; http://www.clinicaltrials.jp/user/cteSearch_e.jsp).
Asunto(s)
Imidazoles/administración & dosificación , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Antagonistas Muscarínicos/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Administración Oral , Anciano , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
A 40-year-old Japanese woman was admitted to Oita University Hospital with progressive dyspnea, consciousness disturbance and severe cytopenias. Her chest roentgenogram showed diffuse bilateral infiltrates. She was therefore forced to receive mechanical ventilation. Bone marrow aspiration disclosed numerous hemophagocytic histiocytes, thus suggesting her condition to be hemophagocytic syndrome. In addition, she also developed myocarditis and renal failure. Pulsed methylprednisolone, gamma-globulin, granulocyte colony-stimulating factor and sivelestat sodium hydrate were administrated, and thereafter the patient recovered from cytopenia and organ failure. Afterwards, influenza A H3N2 was detected from bronchial extracts. We should recognize that an influenza A virus infection can induce hemophagocytic syndrome and acute respiratory failure as the initial manifestations of multiple organ failure.
Asunto(s)
Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Insuficiencia Respiratoria/etiología , Lesión Renal Aguda/etiología , Adulto , Anticuerpos Antivirales/sangre , Bronquios/virología , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Carcinoma/cirugía , Terapia Combinada , Femenino , Glicina/análogos & derivados , Glicina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/virología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Miocarditis/etiología , Complicaciones Posoperatorias/virología , Respiración Artificial , Insuficiencia Respiratoria/terapia , Sulfonamidas/uso terapéutico , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/radioterapia , Neoplasias de la Lengua/cirugía , gammaglobulinas/uso terapéuticoRESUMEN
A 66-year-old man had been given bepridil for the treatment of atrial fibrillation since April 28, 2002. The patient developed exertional dyspnea with hypoxemia in the middle of June 2002 and was admitted to our hospital. The chest X-ray and chest CT scans showed diffuse reticulonodular infiltrates in the lower lung fields. Pulmonary function tests revealed depletion of diffusion capacity for carbon monoxide. Bronchoalveolar lavage fluid contained increased percentages of lymphocytes, neutrophils and eosinophils, and a CD4/8 ratio was low. The transbronchial lung biopsy specimens demonstrated alveolar septal thickening with infiltration of mononuclear cells and intraalveolar organization. As drug-induced pneumonitis was suspected, bepridil was discontinued, resulting in improvement of dyspnea and hypoxemia. The patient was then treated with corticosteroid, which led to complete resolution of infiltration on chest X-ray. According to the clinical data consistent with drug-induced pneumonia, the prompt improvement after cessation of bepridil and the absence of other possible causes, we diagnosed this case as bepridil-induce pnemonitis.