Effects of Different Combined Bronchodilator Therapies on Airway Inflammation in COPD

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterised by chronic progressive airway obstruction and inflammation. Only a few studies have evaluated the effects of bronchodilator therapy on airway inflammation in patients with COPD.

Objective: The aim of this study was to investigate the effects of different combinations of bronchodilator therapies on airway inflammation in COPD.

Methods: Thirty patients with COPD and ten healthy nonsmoker subjects were included in the study. COPD patients were randomly classified into three groups. Groups 1, 2 and 3 were treated with ipratropium bromide plus formoterol (IP + FOR), theophylline plus ipratropium bromide (IP + THEO), and formoterol plus theophylline (FOR + THEO), respectively, for 12 weeks. Pulmonary function tests were performed, blood was drawn for arterial blood gas analyses, and sputum was induced before and after treatment. The induced sputum total and differential cell counts, serum and sputum inflammatory markers including interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and leukotriene (LT)-B4 were measured.

Results: When compared with the control group, total sputum cell counts, number of neutrophils, and sputum and serum inflammatory marker levels were significantly higher in COPD patients. Although there were no statistically significant differences among the groups, inflammatory parameters were found to be significantly reduced in all three treatment groups at the end of treatment. Total cell counts were: 2.4 +/- 0.9 versus 1.28 +/- 0.5 x 10(6)cells/g in the IP + FOR group (p < 0.05), 2.32 +/- 0.4 versus 1.37 +/- 0.6 x 10(6)cells/g in the IP + THEO group (p < 0.05), and 3.05 +/- 1.3 versus 1.6 +/- 0.8 x 10(6)cells/g in the FOR + THEO group (p < 0.05). Sputum IL-8 levels were: 1738.5 +/- 292 versus 848 +/- 262 ng/L in the IP + FOR group (p < 0.05), 1543.2 +/- 378 versus 800.2 +/- 224 ng/L in the IP + THEO group (p < 0.05), and 1561.2 +/- 412 versus 815.7 +/- 259 ng/L in the FOR + THEO group (p < 0.05).

Conclusion: Different combinations of bronchodilator therapies caused significant changes in sputum and blood IL-8, TNF-alpha and LTB4 levels of COPD patients without significantly improving pulmonary function tests or arterial blood gas parameters.