Advances in combination therapy for asthma and COPD by Jan Lotvall

By Jan Lotvall

content material: Similarities and adjustments within the pathophysiology of bronchial asthma and COPD / Christian Virchow --
Glucocorticoids : pharmacology and mechanisms / Peter Barnes --
Inhaled corticosteroids? medical results in bronchial asthma and COPD / Paul O'Byrne --
LABAS : pharmacology, mechanisms and interplay with anti inflammatory remedies / Gary Anderson --
lengthy and ultra-long appearing beta-2-agonists / Mario Cazzola --
the protection of long-acting beta agonists and the advance of blend cures for bronchial asthma and persistent obstructive pulmonary disorder / Eugene Bleecker --
Inhaled mixture remedy with glucocorticoids and long-acting beta-2-agonists in bronchial asthma and COPD, present and destiny views / Jan Lotvall --
Novel anti inflammatory remedies for bronchial asthma and COPD / Ian Adcock --
Novel biologicals by myself and together in bronchial asthma and hypersensitivity / William Busse --
Anti-infective remedies in bronchial asthma and COPD / Jonathan D.R. Macintyre & Sebastian L. Johnston --
lengthy appearing muscarinic antagonists in bronchial asthma and COPD / Denis O'Donnell --
Phosphodiesterase inhibitors in obstructive lung illness / Jan Lotvall --
organic treatments in improvement for COPD / Riccardo Polosa --
Triple therapy?, within the administration of power obstructive lung ailment (COPD). the worth of mix therapy with inhaled steroid, lengthy performing anticholinergicbronchodilator and lengthy appearing beta 2 agonist bronchodilator in COPD / Ronald Dahl.

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49. Torrego A, Pujols L, Roca-Ferrer J, Mullol J, Xaubet A, Picado C. Glucocorticoid receptor isoforms alpha and beta in in vitro cytokine-induced glucocorticoid insensitivity. Am J Respir Crit Care Med 2004;170:420–5. 50. Sousa AR, Lane SJ, Soh C, Lee TH. In vivo resistance to corticosteroids in bronchial asthma is associated with enhanced phosphorylation of JUN N-terminal kinase and failure of P1: OTA/XYZ JWST083-02 P2: ABC JWST083-L¨otvall 36 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63.

Corticosteroid effects on cell signalling. Eur Respir J 2006;27:413–26. 40. Barnes PJ. Cortoicosteroid effects on cell signalling. Eur Respir J 2006;27(2):413–26. 41. Clark AR. MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids? J Endocrinol 2003;178:5–12. 42. Engelbrecht Y, de Wet H, Horsch K, Langeveldt CR, Hough FS, Hulley PA. Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosphorylation of extracellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines.

45 Certain cytokines (particularly IL-2, IL-4 and IL-13, which show increased expression in bronchial biopsies of patients with steroid-resistant asthma) may induce a reduction in affinity of glucocorticoid receptors in inflammatory cells such as T-lymphocytes, resulting in local resistance to the anti-inflammatory actions of glucocorticoids. 46 The therapeutic implication is that p38 MAP kinase inhibitors now in clinical development might reverse this form of steroid resistance. 18, 47 However, there is no increased expression of GR␤ in the mononuclear cells of patients with steroiddependent asthma who have a reduced responsiveness to glucocorticoids in vitro.

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