Therapeutic advances in respiratory disease
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Pulmonary mycoses are among the most feared infections encountered in immunocompromised patients. The problem is amplified by the increasing numbers of chronically immunocompromised patients that have substantially increased both the prevalence and clinical severity of infections caused by fungi. ⋯ Fortunately, recent advances in diagnostics and antifungal therapy, and their direct application to specific diseases, provide important new approaches to this complex and often seriously ill patient population. In this article we review the commonly occurring pulmonary fungal infections in the immunocompromised population with a particular focus on their management.
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Sphingolipids form a broad class of lipids with diverse functions ranging from membrane constituents to intracellular second messengers and extracellular mediators. They can be rapidly generated or converted into each other and they play pivotal roles in various cellular processes, many of which are broadly associated with inflammation and apoptosis. Among the numerous sphingolipids, ceramide and sphingosine-1-phosphate (S1P) have received the greatest attention. ⋯ S1P is a potent chemotaxin for many leukocytes, it organizes lymphocyte trafficking and is involved in several key symptoms of asthma such as airway hyperresponsiveness and pulmonary eosinophil sequestration. S1P is formed by sphingosine kinases that have been identified as possible drug targets for the treatment of asthma. Based on these findings, several new drugs have recently been developed to specifically target sphingomyelinases, sphingosine kinases and S1P receptors for the treatment of COPD, cystic fibrosis, asthma and acute lung injury.
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Ther Adv Respir Dis · Oct 2011
Review Comparative StudyProfiling the bronchodilator effects of the novel ultra-long-acting β2-agonist indacaterol against established treatments in chronic obstructive pulmonary disease.
Indacaterol is a novel, inhaled, ultra-long-acting β(2)-agonist providing 24-h bronchodilation with once-daily (od) dosing for maintenance use in patients with chronic obstructive pulmonary disease (COPD). This article reviews the bronchodilator properties of indacaterol compared with other treatments used in COPD. Data from five published placebo-controlled studies were reviewed. ⋯ In the fourth study, the onset of the bronchodilator effect of indacaterol was similar to that of salbutamol. In the fifth study, the bronchodilator effect of indacaterol on trough FEV(1) was maintained at a significant and clinically relevant level over 52 weeks, whereas the bronchodilator effect of formoterol diminished over time. To conclude, indacaterol is a highly effective bronchodilator that is superior to or at least as effective as other available long-acting bronchodilators for COPD.
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Ther Adv Respir Dis · Jun 2011
ReviewThe potential for inhaled treprostinil in the treatment of pulmonary arterial hypertension.
Inhaled treprostinil is a safe and well-tolerated approved pharmaceutical for the treatment of pulmonary arterial hypertension. In a series of open-label studies and in the pivotal trial with 253 patients, this long-acting prostacyclin analogue demonstrated pronounced pulmonary selectivity of vasodilatory effects, improved physical capacity and excellent tolerability and safety following aerosol administration. For efficient treatment, only four daily inhalations of treprostinil are necessary compared with six to nine in iloprost aerosol therapy. ⋯ Pulmonary arterial hypertension remains, however, a severe, life-threatening disease, in spite of the enormous progress in specific drug therapy over the last decade. Therefore, further improvement of drug therapy will be essential, with clear potential for inhaled treprostinil: a reduction of inhalation frequency and duration would markedly improve quality of life and compliance, and a longer-lasting local prostanoid effect might further enhance the efficacy of inhaled treprostinil. The advantageous pharmacological properties of treprostinil offer the opportunity to establish a convenient metered dose inhaler as a delivery system, to combine inhaled treprostinil with available or future drugs for pulmonary arterial hypertension, or to develop sustained release formulations of treprostinil suitable for inhalation based on liposomes or biodegradable nanoparticles.
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Ther Adv Respir Dis · Jun 2011
Comparative Study Controlled Clinical TrialAntifungal medication is efficient in the treatment of sarcoidosis.
Fungi have been suspected of contributing to the pathogenesis of sarcoidosis. A previous intervention study demonstrated an improvement in the clinical condition in 15 out of 18 patients with a long-term history of sarcoidosis when antifungal medication was added to corticosteroids. The present study was performed to compare the effects of antifungal treatment with corticosteroid treatment in sarcoidosis. ⋯ The results suggest that antifungal treatment is as efficient as corticosteroid treatment against the granulomatous and inflammatory manifestations of sarcoidosis. This is probably because this treatment is directed towards the causative agent. Additional studies are required to define the phenotype, where the antifungal treatment was not efficient (4/22) and to perform long-term follow up to determine the risk of recurrence.