Effect of switching tiotropium HandiHaler® to Respimat® Soft Mist™ Inhaler in patients with COPD: the difference of adverse events and usability between inhaler devices.

BACKGROUND: Recently, tiotropium Respimat® Soft Mist™ Inhaler has been developed. Respimat is a multidose and propellant-free kit. The aerosol generated from Respimat improved lung drug deposition and required a lower dose of drug than HandiHaler®. The aim of this study is to assess the effect of switching from tiotropium HandiHaler to Respimat in patients with chronic obstructive pulmonary disease (COPD). METHODS: Thirty-four patients with COPD who received 18 µg of tiotropium delivered by the HandiHaler once daily were enrolled in this study between May and September 2010. Symptoms, adverse events, pulmonary functions, and usability of inhaler devices were assessed before and 12 weeks after switching from HandiHaler to 5 µg of tiotropium delivered by the Respimat. Symptoms and adverse events were also assessed 4 and 12 weeks after switching. Dyspnea was evaluated using the British Medical Research Council dyspnea scale. The usability of inhaler devices was scored using a 12-step checklist. RESULTS: Twenty-nine patients were followed until 12 weeks after switching. The median FEV1 (forced expiratory volume in 1 sec) values before and 12 weeks after switching to Respimat were 1.41 L and 1.60 L, respectively. Dry mouth appeared to improve after switching to Respimat. Cough just after inhalation was observed in seven patients until 4 weeks after switching. However, six patients overcame cough as they got used to Respimat. Regarding the handling of inhaler devices, patients were not good at breathing out before inhalation and holding their breath just after inhalation both with HandiHaler and with Respimat. However, in general, both inhalers were considered to be easy to use. Twenty-one patients replied that handling of Respimat was easier than that of HandiHaler. CONCLUSIONS: There was no major problem in switching from tiotropium HandiHaler to Respimat. Respimat and HandiHaler showed similar effects and usability. However, we should be aware of cough just after inhalation with Respimat.

Spermidine regulates insulin synthesis and cytoplasmic Ca(2+) in mouse beta-TC6 insulinoma cells.

In order to assess the functional role of the polyamines spermidine and spermine in pancreatic beta-cells, we examined the effect of spermidine and spermine synthase inhibitors, trans-4-methylcyclohexylamine (MCHA) and N-(3-aminopropyl)cyclohexylamine (APCHA), on cellular polyamine and insulin contents, insulin secretion, and cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in mouse insulin-secreting Beta-TC6 cells. The cellular spermidine and spermine contents were reduced 90% and 64% by cultivation of cells in the presence of MCHA and APCHA for 3 days, respectively. Addition of spermidine or spermine reversed the polyamine level reduced by MCHA or APCHA, respectively. Insulin secretion was decreased 40~60% in the cells treated with MCHA or APCHA. The reduction by MCHA was reversed to the untreated level by adding spermidine exogenously, while the effect of APCHA was not reversed by treatment with spermine. The cellular insulin content was also reduced by treatment with MCHA but not the expression of insulin 1 and 2 genes, suggesting that spermidine was involved in the translation of insulin mRNAs. The elevation of [Ca(2+)](i), a key event triggering insulin secretion induced by glucose, was reduced in Beta-TC6 cells by MCHA treatment. The spermidine synthase inhibitor also augmented the sustained [Ca(2+)](i) rise induced by carbamylcholine but not by a high concentration of KCl or nicotine. These results suggested that spermidine rather than spermine plays an important role in the regulation of insulin synthesis and the glucose-induced [Ca(2+)](i) rise in Beta-TC6 cells.