the mainstay of the current administration, is a logical approach to improve existing bronchodilators.? once per day by inhalation Agonists are in clinical development, but the inhaled anticholinergic tiotropium long BMS 378806 BMS-806 time has recently been in some L Change available. Tiotropium bromide is a long-acting anticholinergic tiotropium bromide with a unique selectivity T slow dissociation kinetics fromM1 andM3muscarinic receptors.17 18 clinical trials in COPD now show that inhaled tiotropium once t Resembled an effective bronchodilators in patients with COPD and is more efficient than herk Mmliche ipratropium bromide four times daily.19 21 Long-term studies with tiotropium showed a significant improvement of the symptoms and the improvement of my Lebensqualit t and an unexpected reduction of 23 exacerbations.
22 tiotropium is likely to be the choice of the bronchi in COPD and may have additive effects with long-acting ? Agonists. More mediator antagonists of inflammatory mediators k Can in COPD many inflammatory cells may be involved and structural cells are activated, and there is an ongoing inflammatory process, even in patients smoking.24 The profile of mediators deposed COPD is different from that in asthma, are drugs so different likely to be effective. Since COPD is characterized by neutrophilic inflammation, has drawn attention to mediators in the recruitment and activation of neutrophils or reactive species of oxygen for increased FITTINGS oxidative stress in COPD stakeholders.
Leukotriene B4 is a potent inhibitors of LTB4 neutrophil chemotactic factor obtained Ht, and in the sputum of patients with COPD.25 Ren is usually from alveol Derived macrophages and neutrophils, and k Can synergistic with interleukin-8. Two subtypes of LTB4 receptor have been described BLT1 receptors expressed primarily on granulocytes and monocytes, whereas BLT2 receptors expressed on T lymphocytes.26 BLT1 antagonists such LY29311 developed for the treatment of neutrophils inflammation.27 LY293111 inhibits neutrophil chemotactic activity t of sputum patients with COPD demonstrate the potential clinical value of these drugs.28 LTB4 receptor-selective antagonist currently in development, including SC 53228, PO Box 105696, SB201146 and BIIL284.
LTB4 is synthesized out of 5 ? Lipoxygenase inhibitors, which there are several, although there are problems in the clinical development of this class of drugs because of side effects. Chemokine Inhibitors several chemokines involved in neutrophil chemotaxis and especially to the CXC family, whose most prominent member is IL go 8 Ren. IL-8 levels were significantly increased in the sputum of COPD patients Ht and correlate with disease at severity.29 blocking antique Body to IL-8 and related chemokines, certain types of neutrophilic inflammation in experimental animals and reduce the chemotactic response of neutrophils sputum of COPD patients 0.25 Human monoclonal antique body to IL-8 blocked the chemotactic response of neutrophils to IL-8, and is effective in animal models of inflammation.30 This neutrophil antique body is currently in clinical trials, but less effective k tha can