Should the Choice of a Long-Acting Bronchodilator in the Long-Term Therapy of Chronic Obstructive Pulmonary Disease Depend Entirely on the Onset of Action?

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Introducing COPD Research and Practice

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From large clinical trials to management of COPD in the real world.

Large clinical trials in chronic obstructive pulmonary disease (COPD) are analyzed and discussed. Unfortunately, all of them have failed to reach their primary endpoint, which has mainly been the effect on the rate of decline in mean FEV1 (forced expiratory volume in 1 second). Nonetheless, almost all trials have demonstrated benefits in important outcomes such as exacerbation frequency, symptoms, quality of life and other measures of health status, which are arguably more meaningful to individual patients than FEV 1 per se

Assessing the clinical value of fast onset and sustained duration of action of long-acting bronchodilators for COPD

Date of Aceptance: 12/02/2015 Acknowledgments The authors were assisted in the preparation of the manuscript by Sarah Filcek, a professional medical writer at CircleScience (Tytherington, UK), part of KnowledgePoint360, an Ashfield Company. This assistance was funded by Novartis Pharmaceuticals. Copyright © 2015. Published by Elsevier Ltd.Peer reviewedPublisher PD

The future of bronchodilation: looking for new classes of bronchodilators

Available bronchodilators can satisfy many of the needs of patients suffering from airway disorders, but they often do not relieve symptoms and their long-term use raises safety concerns. Therefore, there is interest in developing new classes that could help to overcome the limits that characterise the existing classes.At least nine potential new classes of bronchodilators have been identified: 1) selective phosphodiesterase inhibitors; 2) bitter-taste receptor agonists; 3) E-prostanoid receptor 4 agonists; 4) Rho kinase inhibitors; 5) calcilytics; 6) agonists of peroxisome proliferator-activated receptor-γ; 7) agonists of relaxin receptor 1; 8) soluble guanylyl cyclase activators; and 9) pepducins. They are under consideration, but they are mostly in a preclinical phase and, consequently, we still do not know which classes will actually be developed for clinical use and whether it will be proven that a possible clinical benefit outweighs the impact of any adverse effect.It is likely that if developed, these new classes may be a useful addition to, rather than a substitution of, the bronchodilator therapy currently used, in order to achieve further optimisation of bronchodilation

Myeloproliferative neoplasms: From JAK2 mutations discovery to JAK2 inhibitor therapies

Most BCR-ABL1-negative myeloproliferative neoplasms (MPN) carry an activating JAK2 mutation. Approximately 96% of patients with polycythemia vera (PV) harbors the V617F mutation in JAK2 exon 14, whereas the minority of JAK2 (V617F)-negative subjects shows several mutations in exon 12. Other mutation events as MPL, TET2, LNK, EZH2 have been described in chronic phase, while NF1, IDH1, IDH2, ASX1, CBL and Ikaros in blast phase of MPN. The specific pathogenic implication of these mutations is under investigation, but they may have a role in refinement of diagnostic criteria and in development of new prognostic models. Several trials with targeted therapy (JAK inhibitors) are ongoing mostly involving patients with PMF, post-PV MF and post-essential thrombocythemia (ET) MF. Treatment with ruxolitinib and TG101348 has shown clinically significant benefits, particularly in improvement of splenomegaly and constitutional symptoms in MF patients. On the other hand, JAK inhibitors have not thus far shown disease-modifying activity therefore any other deduction on these new drugs seems premature

Indacaterol/Glycopyrronium Combination for COPD

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α1-Antitrypsin deficiency and chronic respiratory disorders

α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments