Effect of Symbicort ® on GR in Sputum in COPD

Summary

The purpose of the research (or "knowledge gap" this research is designed to fill) is to understand the science of how the combination therapy of 2 drugs (inhaled longacting beta-agonists(LABA) and inhaled corticosteroids (ICS), which are commonly used in chronic obstructive pulmonary disease (COPD) patients, is better than each drug alone. ICS and LABA both have antiinflammatory properties; that is, they dampen the inflammation in the cells of the airways in the lungs. The combination of LABA and ICS has also been shown to improve clinical effectiveness in asthma patients. The addition of a LABA to LOW doses of ICS has been shown to be more clinically beneficial in asthma than the use of HIGH doses of ICS alone. This has allowed a reduction in the total ICS dose and minimised the adverse side effects of inhaled corticosteroids. Recent evidence suggests that the use of combination therapy of LABA and ICS may also improve clinical effectiveness in COPD patients. Investigators will address this hypothesis by examining the inflammation cells of COPD direct from the site of disease (the airways) by looking at sputum/mucus. This research will build on the existing knowledge of the science of how these drugs work in asthma and COPD and allows us to understand the molecular science, which may support new future drug targets for patients with COPD, which are greatly needed.

Timeline

Start

2013-01

Primary completion

2014-12

Completion

2015-04

Publications

• Background Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000 Sep;20(18):6891-903. doi: 10.1128/MCB.20.18.6891-6903.2000.
• Background Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997 Feb;155(2):542-8. doi: 10.1164/ajrccm.155.2.9032192.
• Background Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1635-9. doi: 10.1164/ajrccm.160.5.9811058.
• Background Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C; TRial of Inhaled STeroids ANd long-acting beta2 agonists study group. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003 Feb 8;361(9356):449-56. doi: 10.1016/S0140-6736(03)12459-2.
• Background Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J. 2003 Dec;22(6):912-9. doi: 10.1183/09031936.03.00027003.
• Background Essilfie-Quaye S, Ito K, Ito M, Kharitonov SA, Barnes PJ. Comparison of Symbicort(R) versus Pulmicort(R) on steroid pharmacodynamic markers in asthma patients. Respir Med. 2011 Dec;105(12):1784-9. doi: 10.1016/j.rmed.2011.08.020. Epub 2011 Sep 7.

Drugs

Indications