Four inhalation devices for salbutamol; in vivo and in vitro comparison in asthma and COPD.
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KUN Katholieke Universiteit Nijmegen, 23 juni 2004
Promotor : Folgering, H.T.M. Co-promotor : Molema, J.
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SubjectUMCN 2.1: Heart, lung and circulation
Inhalation therapy with bronchodilators is one of the cornerstones of the treatment of asthma and chronic obstructive pulmonary disease (COPD). Several inhalation drug-device combinations are available. Multiple factors, like the inhalation device and the inhalation technique influence the deposition of drug in the airways and consequently the therapeutic efficacy. In this thesis, different elements of inhalation technology and clinical aspects of four currently used inhalation devices (Diskus, Turbuhaler, pressurised metered dose inhaler (pMDI) and Volumatic) were compared. Throughout the studies there was only small evidence for preference or just drawback for the one or the other device. In case of the aerosols, the use of pMDI plus Volumatic seems to be preferable above the pMDI alone. Fewer mistakes were made, even in patients during an exacerbation and a slightly better bronchodilation was found in case of salbutamol delivery via the spacer. Salbutamol via pMDI protected less against bronchoconstriction, suggesting a lower drug deposition. Furthermore, the majority of patients as well in stable phase of the disease as during an exacerbation was unable to use this device correctly. In vitro measurements showed a higher dose output and more respirable particles for Diskus than for Turbuhaler. However, these in vitro differences had no in vivo clinical relevance. The limitations of the use of the Turbuhaler are due to the high restistivity, since the fine particle mass (< 5 m) was dependent of the peak inspiratory flow, especially at the lower range. A minority of patients was not able to generate sufficient flow, even after instruction. These patients should be selected. Delivery system properties and patient's performance should be taken into account when prescribing inhalation therapy in order to achieve a beneficial clinical effect without serious side effects
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