Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Oct 2011
Randomized Controlled Trial Multicenter StudySafety and tolerability of an oral MMP-9 and -12 inhibitor, AZD1236, in patients with moderate-to-severe COPD: a randomised controlled 6-week trial.
Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). This phase IIa study investigated the safety and tolerability of oral AZD1236, an MMP-9 and MMP-12 inhibitor, in patients with COPD. Efficacy analyses were included on an exploratory basis. ⋯ For most of these COPD patients, with the particular exception of one who experienced a serious AE, AZD1236 at 75 mg twice daily was generally well tolerated and had an acceptable safety profile. Therapeutic efficacy could not be demonstrated, possibly due to the stable disease and background medications of the patients enrolled in this small, short-term study.
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Pulm Pharmacol Ther · Oct 2011
Multicenter StudyReevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study.
Sivelestat, a neutrophil elastase inhibitor, has been approved in Japan for the treatment of patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS). The Pharmaceuticals and Medical Devices Agency (PMDA) has ordered to conduct a postmarket clinical study in order to reevaluate the efficacy and safety of Sivelestat in actual clinical settings in Japan. ⋯ Sivelestat contributed to early weaning from the mechanical ventilation, while showing no negative effect on the long-term outcomes of ALI associated with SIRS. The results of this study suggest the clinical usefulness of Sivelestat in this patient population.
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Pulm Pharmacol Ther · Oct 2011
ReviewThe dynamic face of respiratory research: understanding the effect of airway disease on a lung in constant motion.
The lungs are in a constant state of motion. The dynamic nature of tidal breathing, whereby cycles of pressure changes across the lungs cause the chest wall, lung tissue and airways to repeatedly expand and contract, ventilates the lung tissue and allows respiration to occur. However, these regular cycles of tidal inspirations and expirations are punctuated by breaths of differing volumes, most particularly periodic deep inspirations. ⋯ On the other hand, DI bronchoprotection is completely absent in asthma. Although the mechanisms behind these abnormalities remain unclear, the inability for deep inspirations to both protect against and fully reverse bronchoconstriction in patients with asthma appears critical in the development of airway hyperresponsiveness. As such, determining the pathophysiology responsible for the malfunction of deep inspirations in asthma remains critical to understanding the disease and is likely to pave the way for novel therapeutic targets.
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Pulm Pharmacol Ther · Oct 2011
Statins and outcome after hospitalization for COPD exacerbation: a prospective study.
Retrospective studies have shown that the use of statins is associated with reduced mortality and decreased hospitalizations from COPD, but data from prospective studies are lacking. ⋯ The use of statins in patients hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and severe ECOPD and improved HRQoL. These data support a possible beneficial role for these agents in COPD.