Inhalation of Corticosteroids in Smoking and Non-smoking Asthmatics.

Summary

People with asthma suffer from breathlessness because the small tubes (bronchioles) that carry air in and out of the lungs become inflamed and narrow. Steroids reduce the inflammation, and are commonly used to control asthma, but they do not work well in some asthmatics, particularly those who smoke. This study is done to find out more about why smokers with asthma do not benefit from steroid treatment. In this study, the effect of Flixotide (fluticasone propionate), a steroid widely used to treat asthma, is tested in smokers and non-smokers with mild asthma. 16 smokers and 16 non-smokers, aged 18-55 years will be enrolled in this study. Subjects will take each of the following treatments: * 100 micrograms Flixotide twice daily for 7 days; * 500 micrograms Flixotide twice daily for 7 days; and * placebo (dummy medicine) twice daily for 7 days. Study design: subjects will have a screening visit (over 2 days), and will take part in 3 treatment periods (which are separated by interval of at least 14 days); a follow-up visit is scheduled 7 days after the last intake of study treatment. The order in which order the subjects will take the treatments is defined at random. Total study duration: about 11 weeks. To test the effects of Flixotide, the subject's responses to : * an inhaled allergen test * a PC20 methacholine test * blood, urine and sputum PD markers will be analysed. This study will take place in 2 centres: 1 in the United Kingdom and 1 in Belgium. The units will recruit participants by advertising (newspaper, radio, and websites), word of mouth, from volunteer databases, and via the centres' websites.

Timeline

Start

2011-07-20

Primary completion

2012-12-01

Completion

2012-12-12

Publications

• Background Adcock IM, Barnes PJ. Molecular mechanisms of corticosteroid resistance. Chest. 2008 Aug;134(2):394-401. doi: 10.1378/chest.08-0440.
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• Background Chaudhuri R, Livingston E, McMahon AD, Lafferty J, Fraser I, Spears M, McSharry CP, Thomson NC. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006 Jul 15;174(2):127-33. doi: 10.1164/rccm.200510-1589OC. Epub 2006 Apr 27.
• Background Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol. 1987 May;79(5):734-40. doi: 10.1016/0091-6749(87)90204-1.
• Background Gauvreau GM, Wood LJ, Sehmi R, Watson RM, Dorman SC, Schleimer RP, Denburg JA, O'Byrne PM. The effects of inhaled budesonide on circulating eosinophil progenitors and their expression of cytokines after allergen challenge in subjects with atopic asthma. Am J Respir Crit Care Med. 2000 Dec;162(6):2139-44. doi: 10.1164/ajrccm.162.6.2001120.
• Background GlaxoSmithKline Document Number GM2003/00619/00 Study ID EL110002. A single-centre, randomised, double-blind, double-dummy, placebo-controlled, 3-period crossover study to evaluate the effect of pre-treatment with repeat doses of GW842470X (6mg inhaled once daily via the Cyclohaler for 7 days) on the allergen induced late asthmatic response in subjects with mild to moderate asthma, using fluticasone propionate (250 mcg twice daily for 7 days) as a positive control. Report Date 24-Jun-2004.
• Background GlaxoSmithKline Document Number YM2009/00265/00 Study ID LPA111834. A randomised, double-blind, placebo-controlled, 2-period crossover study to evaluate the effect of treatment with GSK2190915 on the allergen-induced asthmatic response in subjects with mild asthma. Report Date 26-Mar-2010.
• Background GlaxoSmithKline Document Number YM2010/00033/00 Study ID SIG110762. A randomised, placebo-controlled, incomplete block, three-way crossover study to evaluate the effect of treatment with repeat inhaled doses of GW870086 on the allergen-induced early and late asthmatic response in subjects with mild asthma. Report Date 10-May-2010.
• Background Grzelewska-Rzymowska I, Gondorowicz K, Cieslewicz G, Rozniecki J. [Course of non-specific bronchial reactivity to histamine after bronchospasm induced by allergen challenge in patients with bronchial asthma]. Pneumonol Alergol Pol. 1995;63(5-6):273-80. Polish.
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• Background Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2006 Mar;117(3):522-43. doi: 10.1016/j.jaci.2006.01.032.
• Background Johnston NW, Sears MR. Asthma exacerbations . 1: epidemiology. Thorax. 2006 Aug;61(8):722-8. doi: 10.1136/thx.2005.045161.
• Background Kidney JC, Boulet LP, Hargreave FE, Deschesnes F, Swystun VA, O'Byrne PM, Choudry N, Morris MM, Jennings B, Andersson N, Andreasson A, Cockcroft DW. Evaluation of single-dose inhaled corticosteroid activity with an allergen challenge model. J Allergy Clin Immunol. 1997 Jul;100(1):65-70. doi: 10.1016/s0091-6749(97)70196-9.
• Background Moerloose KB, Robays LJ, Maes T, Brusselle GG, Tournoy KG, Joos GF. Cigarette smoke exposure facilitates allergic sensitization in mice. Respir Res. 2006 Mar 29;7(1):49. doi: 10.1186/1465-9921-7-49.
• Background O'Shaughnessy KM, Wellings R, Gillies B, Fuller RW. Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1472-6. doi: 10.1164/ajrccm/147.6_Pt_1.1472.
• Background O'Byrne PM, Gauvreau GM, Brannan JD. Provoked models of asthma: what have we learnt? Clin Exp Allergy. 2009 Feb;39(2):181-92. doi: 10.1111/j.1365-2222.2008.03172.x.
• Background Singh D, Petavy F, Macdonald AJ, Lazaar AL, O'Connor BJ. The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Respir Res. 2010 Mar 1;11(1):26. doi: 10.1186/1465-9921-11-26.
• Background Thomson NC, Spears M. The influence of smoking on the treatment response in patients with asthma. Curr Opin Allergy Clin Immunol. 2005 Feb;5(1):57-63. doi: 10.1097/00130832-200502000-00011.
• Background Tomlinson JE, McMahon AD, Chaudhuri R, Thompson JM, Wood SF, Thomson NC. Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax. 2005 Apr;60(4):282-7. doi: 10.1136/thx.2004.033688.
• Background Van Hove CL, Moerloose K, Maes T, Joos GF, Tournoy KG. Cigarette smoke enhances Th-2 driven airway inflammation and delays inhalational tolerance. Respir Res. 2008 May 20;9(1):42. doi: 10.1186/1465-9921-9-42.
• Cahn A, Boyce M, Mistry S, Musani N, Rambaran C, Storey J, Ventresca P, Michel O. Randomized trial of allergen-induced asthmatic response in smokers and non-smokers: effects of inhaled corticosteroids. Clin Exp Allergy. 2015 Oct;45(10):1531-41. doi: 10.1111/cea.12610.

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Indications