This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Culpitt, S. V. Articles by Barnes, P. J. Search for Related Content PubMed PubMed Citation Articles by Culpitt, S. V. Articles by Barnes, P. J.

Effect of Theophylline on Induced Sputum Inflammatory Indices and Neutrophil Chemotaxis in Chronic Obstructive Pulmonary Disease

Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom

Correspondence and requests for reprints should be addressed to Sarah V. Culpitt, Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, SW3 6LY, London, UK. E-mail: duncan.rogers{at}ic.ac.uk

Chronic obstructive pulmonary disease (COPD) is characterized by a neutrophilic airway inflammation that can be demonstrated by examination of induced sputum. Theophylline has antiinflammatory effects in asthma, and in the present study we investigated whether a similar effect occurs in COPD patients treated with low doses of theophylline. Twenty-five patients with COPD were treated with theophylline (plasma level of 9–11 mg/L) for 4 weeks in a placebo-controlled, randomized, double-blind crossover study. Theophylline was well tolerated. Induced sputum inflammatory cells, neutrophils, interleukin-8, myeloperoxidase, and lactoferrin were all significantly reduced by about 22% by theophylline. Neutrophils from subjects treated with theophylline showed reduced chemotaxis to N-formyl-met-leu-phe ( 28%) and interleukin-8 ( 60%). Neutrophils from a healthy donor showed reduced chemotaxis ( 30%) to induced sputum samples obtained during theophylline treatment. These results suggest that theophylline has antiinflammatory properties that may be useful in the long-term treatment of COPD.

Key Words: COPD • sputum • theophylline • neutrophil • chemotaxis

This article has been cited by other articles:

				M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers Eur. Respir. J., February 1, 2008; 31(2): 416 - 469. [Abstract] [Full Text] [PDF]

				P J Barnes Theophylline for COPD. Thorax, September 1, 2006; 61(9): 742 - 743. [Full Text] [PDF]

				T Hirano, T Yamagata, M Gohda, Y Yamagata, T Ichikawa, S Yanagisawa, K Ueshima, K Akamatsu, M Nakanishi, K Matsunaga, et al. Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline. Thorax, September 1, 2006; 61(9): 761 - 766. [Abstract] [Full Text] [PDF]

				P. J. Barnes, B. Chowdhury, S. A. Kharitonov, H. Magnussen, C. P. Page, D. Postma, and M. Saetta Pulmonary Biomarkers in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 6 - 14. [Abstract] [Full Text] [PDF]

				P. J. Barnes Theophylline in Chronic Obstructive Pulmonary Disease: New Horizons Proceedings of the ATS, November 1, 2005; 2(4): 334 - 339. [Abstract] [Full Text] [PDF]

				P. J. Barnes and R. A. Stockley COPD: current therapeutic interventions and future approaches Eur. Respir. J., June 1, 2005; 25(6): 1084 - 1106. [Abstract] [Full Text] [PDF]

				P. J. Barnes, I. M. Adcock, and K. Ito Histone acetylation and deacetylation: importance in inflammatory lung diseases Eur. Respir. J., March 1, 2005; 25(3): 552 - 563. [Abstract] [Full Text] [PDF]

				S. L. Traves, S. J. Smith, P. J. Barnes, and L. E. Donnelly Specific CXC but not CC chemokines cause elevated monocyte migration in COPD: a role for CXCR2 J. Leukoc. Biol., August 1, 2004; 76(2): 441 - 450. [Abstract] [Full Text] [PDF]

				E. Gamble, D. C. Grootendorst, C. E. Brightling, S. Troy, Y. Qiu, J. Zhu, D. Parker, D. Matin, S. Majumdar, A. M. Vignola, et al. Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 976 - 982. [Abstract] [Full Text] [PDF]

				M Profita, G Chiappara, F Mirabella, R Di Giorgi, L Chimenti, G Costanzo, L Riccobono, V Bellia, J Bousquet, and A M Vignola Effect of cilomilast (Ariflo) on TNF-{alpha}, IL-8, and GM-CSF release by airway cells of patients with COPD Thorax, July 1, 2003; 58(7): 573 - 579. [Abstract] [Full Text] [PDF]

				R.O. Crapo, R.L. Jensen, and F.E. Hargreave Airway inflammation in COPD: physiological outcome measures and induced sputum Eur. Respir. J., June 1, 2003; 21(41_suppl): 19S - 28s. [Abstract] [Full Text] [PDF]

				B. Balbi COPD: Is Chemotaxis the Key? Chest, April 1, 2003; 123(4): 983 - 986. [Full Text] [PDF]

				P. J. Barnes Theophylline: New Perspectives for an Old Drug Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 813 - 818. [Full Text] [PDF]

				M. J. Tobin Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 356 - 370. [Full Text] [PDF]

				K. F. Rabe On Theophylline, Leukocytes, and Chicken Soup Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1351 - 1352. [Full Text] [PDF]