No abstract is provided for this article.
New therapeutic options for severe asthma have recently emerged, mostly in the form of monoclonal antibodies ("biologicals") targeting relevant inflammatory pathways. Currently available agents target different aspects of "Type 2" immunity, and their indications often include overlapping patient groups. We present a round-table discussion that took place during the Annual Meeting of the Respiratory Effectiveness Group (REG), on the reasoning behind the use of different add-on medications for severe asthma, and crucially, on selection strategies. The proposed rational is based on current evidence, including real-life studies, as well as on the appreciation of the relevant complexities. Direct head-to-head comparisons of biologicals are lacking; therefore, algorithms for initial choice and potential switch between agents should be based on understanding the key characteristics of different options and the development of a clear plan with predefined targets and shared decision-making, in a structured way.
Objective: The recent appreciation that stenting has improved the short- and long-term outcomes of patients treated with coronary angioplasty has made it imperative to reconsider the comparison between surgery and percutaneous interventions in patients with multivessel disease. Methods: One thousand two hundred five patients were randomly assigned to undergo bypass surgery or angioplasty with stent implantation when there was consensus between the cardiac surgeon and interventional cardiologist as to equivalent treatability. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at 1 year. Major adverse cardiac and cerebrovascular events at 2 years constituted a secondary end point. Results: At 2 years, 89.6% of the surgical group and 89.2% of the stent group were free from death, stroke, and myocardial infarction (log-rank test P =.65). Among patients who survived without stroke or myocardial infarction, 19.7% in the stent group underwent a second revascularization, as compared with 4.8% in the surgical group (P <.001). At 2 years, 84.8% of the surgical group and 69.5% of the stent group were event-free survivors (log-rank test P <.001), and 87.2% in the surgical cohort and 79.6 % in the stent group were angina-free survivors (P =.001). In the diabetes subgroup, 82.3% of the surgical group and 56.3% of the stent group were free from any events after 2 years (log-rank test P <.001). Conclusion: The difference in outcome between surgery and stenting observed at 1 year in patients with multivessel disease remained essentially unchanged at 2 years. Stenting was associated with a greater need for repeat revascularization. In view of the relatively greater difference in outcome in patients with diabetes, surgery clearly seems to be the preferable form of treatment for these patients. J Thorac Cardiovasc Surg 2003;125:809-20
Extract: Asthma has now become one of the most common chronic diseases in industrialized countries and is predicted to increase throughout the world over the next decade, particularly in developing countries. Previously, asthma was viewed as a disease of bronchoconstriction (closing of the airways) and treated predominantly with bronchodilators (drugs which open up the airways), but more recently it has been seen as an inflammatory disease of the airways and the mainstay of modern management is treatment with inhaled corticosteroids. The airway inflammation in asthma is characterized by activation of mast cells, infiltration of eosinophils and increased activated T helper 2 (Th2) lymphocytes. Inhaled corticosteroids have revolutionized the management of asthma, leading to better control of asthma, reduced hospital admissions and a reduced mortality. Corticosteroids and long-acting beta2-agonists (salmeterol and formoterol) in fixed combination inhalers are currently the most effective therapy for asthma and are increasingly used in all patients with persistent symptoms.
Potassium (K+) channels have long been associated with recovery of excitable cells after depolarisation and drugs that block these channels, such as tetraethylammonium and 4- aminopyridine, cause an increase in excita- bility.In airway smooth muscle these K+ channel blocking drugs result in spontaneous action potentials and a reduced threshold of excitation,'2 which may be similar to the elec- trophysiological changes described in asth- matic airways.'The recent development of drugs that open K+ channels in smooth muscle has reawakened interest in potassium channels because such drugs relax airway smooth muscle and may reduce the hyperreactivity of asthma.It is now clear that there is great diversity ofK+ channels in different cells, raising the possibility that selective drugs may be developed for specific cell types, with therapeutic benefit.We review here some ofthe recent developments in under- standing K+ channels in airways and the therapeutic prospects for new K+ channel activators. Potassium channels and their typesRecent electrophysiological studies and the use of new pharmacological agents have shown that K+ channels are present on cells of several types, including nerves, secretory cells, and skeletal and smooth muscle cells.45K+ channels are now seen to be diverse and may be modulated by changes in membrane potential, ion concentration, or receptor activation.All cells in the body are likely to have K+ channels and they may have more than one type.
No currently available treatments reduce the progression of chronic obstructive pulmonary disease (COPD) or suppress the inflammation in small airways and lung parenchyma. However, several new treatments now in development for COPD are targeted at the inflammation process. Antagonists of mediators, such as leukotriene B4, interleukin-8, and tumour necrosis factor-alpha and inhibitors of oxidative and nitrative stress are in clinical development. Phosphodiesterase-4 inhibitors are in clinical trials and drugs that inhibit p38 MAP kinase, nuclear factor-kappaB and phosphoinositide-3 kinase-gamma are now in early development. There is also a search for elastase inhibitors to prevent the development of emphysema and drugs that may even reverse the lung destruction.
