Duygu ÖZOL, Harun KARAMANLI, Sema UYSAL, Muhammet Ramazan YİĞİTOĞLU, Zeki YILDIRIM

Airway inflammation and tiotropium treatment in stable COPD patients

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung associated with progressive airflow limitation. The aim of this study is to assess the influence of tiotropium treatment on airway inflammation and symptoms in stable COPD patients. Materials and methods: Inflammatory markers were measured in the expired breath condensate fluid (EBC) before starting tiotropium treatment and at the end of the first month. Results: Twenty-two patients (81% men) with a mean age of 65.4 ± 10.1 years completed the study. The mean nitrotyrosine and 8-isoprostane levels for oxidative stress markers in EBC before and after treatment were 4.5 ± 2.3, 3.5 ± 1.9 pg/mL (P = 0.06) and 7.3 ± 10.8, 8.1 ± 11.7 pg/mL (P = 0.28), respectively. The mean interleukin-6 and tumor necrosis factor-alpha levels for inflammation markers in EBC before and after treatment were 1.03 ± 1.1, 0.77 ± 0.8 pg/mL (P = 0.41) and 27.8 ± 2.6, 29.2 ± 5.7 pg/mL (P = 0.36) respectively. The mean symptom scores decreased significantly with tiotropium and a mean increase of 124.6 ± 0.86 mL was observed in a lung function test (FEV1). Conclusion: Although a 4-week treatment with tiotropium did not modify any of the inflammatory or oxidative stress markers in EBC fluid, tiotropium treatment helps to control symptoms in COPD.

Anahtar Kelimeler:

Tiotropium, inflammation, airways, COPD

Airway inflammation and tiotropium treatment in stable COPD patients

Keywords:

Tiotropium, inflammation, airways, COPD,

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Raherison C, Girodet PO. Epidemiology of COPD. Eur Respir Rev 2009; 18: 213–221.
Cosio MG, Guerassimov A. Chronic obstructive pulmonary disease. Inflammation of small airways and lung parenchyma. Am J Respir Crit Care Med 1999; 160: S21–25.
Folchini F, Nonato NL, Feofiloff E, D’Almeida V, Nascimento O, Jardim JR. Association of oxidative stress markers and C-reactive protein with multidimensional indexes in COPD. Chron Respir Dis 2011; 8: 101–108.
Stockley RA. Neutrophils and the pathogenesis of COPD. Chest 2002; 121: 151S–155S.
Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 2004; 59: 574–580.
Louhelainen N, Myllärniemi M, Rahman I, Kinnula VL. Airway biomarkers of the oxidant burden in asthma and chronic obstructive pulmonary disease: current and future perspectives. Int J Chron Obstruct Pulmon Dis 2008; 3: 585– 603.
Hunt J. Exhaled breath condensate: an overview. Immunol Allergy Clin North Am 2007; 27: 587–596.
Rosias PP, Robroeks CM, Kester A, den Hartog GJ, Wodzig WK, Rijkers GT, Zimmermann LJ, van Schayck CP, Jöbsis Q, Dompeling E. Biomarker reproducibility in exhaled breath condensate collected with different condensers. Eur Respir J 2008; 5: 934–942.
Montuschi P. Exhaled breath condensate analysis in patients with COPD. Clin Chim Acta 2005; 356: 22–34.
Kharitonov SA, Barnes PJ. Biomarkers of some pulmonary diseases in exhaled breath. Biomarkers 2002; 7: 1–32.
Marciniuk D, Goodridge D, Hernandez P, Rocker G, Balter M, Bailey P. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J 2011; 18: 69–78.
Rice KL, Kunisaki KM, Niewoehner DE. Role of tiotropium in the treatment of COPD. Int J Chron Obstruct Pulmon Dis 2007; 2: 95–105.
Tashkin DP. Impact of tiotropium on the course of moderate- to-very severe chronic obstructive pulmonary disease: the UPLIFT trial. Expert Rev Respir Med 2010; 4: 279–289.
Anzueto A, Miravitlles M. Efficacy of tiotropium in the prevention of exacerbations of COPD. Ther Adv Respir Dis 2009; 3: 103–111.
Keam SJ, Keating GM. Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD. Treat Respir Med 2004; 3: 247–268.
Gwilt CR, Donnelly LE, Rogers DF. The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? Pharmacol Ther 2007; 115: 208–222.
Pera T, Zuidhof A, Valadas J, Smit M, Schoemaker RG, Gosens R, Maarsingh H, Zaagsma J, Meurs H. Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J 2011; 38: 789–796.
Perng DW, Tao CW, Su KC, Tsai CC, Liu LY, Lee YC. Anti- inflammatory effects of salmeterol/fluticasone, tiotropium/ fluticasone or tiotropium in COPD. Eur Respir J 2009; 33: 778–784.
Patel IS, Roberts NJ, Lloyd-Owen SJ, Sapsford RJ, Wedzicha JA. Airway epithelial inflammatory responses and clinical parameters in COPD. Eur Respir J 2003; 22: 94–99.
Gosens R, Zaagsma J, Meurs H, Halayko AJ. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res 2006; 9: 73.
Ohta S, Oda N, Yokoe T, Tanaka A, Yamamoto Y, Watanabe Y, Minoguchi K, Ohnishi T, Hirose T, Nagase H et al. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy 2010; 40: 1266 – 1275.
Wollin L, Pieper MP. Tiotropium bromide exerts anti- inflammatory activity in a cigarette smoke mouse model of COPD. Pulm Pharmacol Ther 2010; 23: 345–354.
Bühling F, Lieder N, Kühlmann UC, Waldburg N, Welte T. Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro. Respir Med 2007; 10: 2386– 2394.
Bateman ED, Rennard S, Barnes PJ, Dicpinigaitis PV, Gosens R, Gross NJ, Nadel JA, Pfeifer M, Racké K, Rabe KF et al. Alternative mechanisms for tiotropium. Pulm Pharmacol Ther 2009; 22: 533–542.
Powrie DJ, Wilkinson TM, Donaldson GC, Jones P, Scrine K, Viel K, Kesten S, Wedzicha JA. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur Respir J 2007; 30: 472–478.
Morrow JD. The isoprostanes - unique products of arachidonate peroxidation: their role as mediators of oxidant stress. Curr Pharm Des 2006; 12: 895–902.
Montuschi P, Barnes P, Roberts LJ. Insights into oxidative stress: the isoprostanes. Curr Med Chem 2007; 14: 703–717.
Vacca G, Randerath WJ, Gillissen A. Inhibition of granulocyte migration by tiotropium bromide. Respir Res 2011; 27: 24.