Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD

Abstract

The anti-inflammatory effects of salmeterol/fluticasone (SFP), tiotropium/fluticasone (Tio+FP) and tiotropium (Tio) alone were investigated on the inflammatory cells and mediators in sputum induced from chronic obstructive pulmonary disease patients.Subjects were either newly diagnosed or had not taken any medication for 3 months prior to the study. Subjects (n599) were randomised (not double blinded) and received either SFP (100/ 1,000 mg daily), Tio+FP (18/1,000 mg daily) or Tio (18 mg daily) for 12 weeks. Induced sputum and serum C-reactive protein (CRP) were analysed prior to and at the end of treatment.The results showed that treatment with SFP caused a significant reduction in interleukin (IL)-8 and matrix metalloprotease (MMP)-9 in induced sputum, compared with treatment with Tio alone. There were no treatment differences between the SFP and Tio+FP groups in decreasing IL-8 and MMP-9 levels. The reduction in IL-8 showed significant association with the reduction in MMP-9. All treatment groups failed to significantly reduce the numbers of total cells, neutrophils, macrophages and eosinophils in induced sputum; in addition, there were no treatment differences in terms of improvement of forced expiratory volume in one second, forced vital capacity, CRP or quality of life between the three groups.The anti-inflammatory effects of salmeterol/fluticasone probably contribute to the clinical benefits seen in chronic obstructive pulmonary disease patients.

Airway inflammation and tiotropium treatment in stable COPD patients

“…Only 12 weeks of treatment with salmeterol/fluticasone caused a significant reduction in IL-8 and matrix metallopeptidase-9 compared with tiotropium alone. Thus, in this clinical trial, the authors also failed to show any antiinflammatory effect of tiotropium (18). Similarly, Powrie et al (25) also found that there were no differences between the start and the end of a 1-year course of tiotropium in sputum, serum IL-6, and myeloperoxidase levels in 48 COPD patients in vivo.…”

“…Although the role of tiotropium in the management of COPD is well documented, its effect on airway inflammation in stable COPD is not clear. A number of studies have been performed examining these effects of tiotropium upon various measures of inflammation with conflicting results (17,18). The aim of this study was to see if airway inflammation and oxidative stress markers in EBC would be changed by a 4-week course of tiotropium therapy, given at a dose of 18 µg daily.…”

Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice

“…Patients who have more exacerbations demonstrate increased levels of inflammatory markers at stable state [38,39]. However, in two recent studies, no direct evidence for an anti-inflammatory effect was found, since IL-6 and IL-8 levels in the sputum of patients with COPD were not decreased after anticholinergic therapy [40,41]. However, both studies have substantial limitations as discussed by the authors.…”

Effect of tiotropium on quality of life in COPD: a systematic review

“…[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] Of the 24 publications that met the inclusion criteria for this systematic review (see Table 1), 16 compared tiotropium with placebo, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] seven compared tiotropium with an active comparator, [66][67][68][69][70][71][72] and one compared tiotropium with both placebo and an active comparator. 73 The QoL outcomes reported in the 24 included publications were mostly SGRQ and/or TDI (Tables 2 and 3).…”