Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Abstract

Background: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR). Methods: Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC 20 for histamine of <8 mg/ ml. Patients received either 2 × 500 µg FP or placebo for 6 months. Expiratory volumes were measured at monthly visits, BHR was determined at the start of the study and after 3 and 6 months, and bronchial biopsy specimens were taken at the start and after 6 months of treatment. Biopsy specimens from asymptomatic smokers served as controls. Results: In contrast to asthma, indices of BHR were not significantly influenced by treatment with FP. Forced expiratory volume in 1 second (FEV 1 ) showed a steep decline in the placebo group but remained stable in patients treated with FP. FEV 1 /FVC, and maximal expiratory flows at 50% and 25% FVC (MEF 50 , MEF 25 ) were significantly increased in the FP treated patients compared with the placebo group. Biopsy specimens were analysed for the presence of CD3+, CD4+, CD8+, MBP+, CD15+, CD68+, CD1a, and tryptase cells. FP treatment resulted in marginal reductions in these indices of inflammation. Conclusion: In patients with COPD and BHR, FP has a positive effect on indices of lung function compared with placebo. Bronchial inflammation analysed in bronchial biopsy specimens is only marginally reduced.

Outcomes for COPD pharmacological trials: from lung function to biomarkers

“…These studies usually involve either a baseline biopsy and a second biopsy after a defined period of treatment, or a single biopsy at the end of active treatment with a biopsy in a parallel group of patients taking placebo therapy. Overall, inhaled corticosteroids seem to have little effect on the airway inflammation typical of COPD, while they are able to reduce mast cells, an effect which is associated with a reduction in exacerbation numbers [484,485]. More encouraging results have been obtained after treatment with either a phosphodiesterase-4 inhibitor or with the combination of corticosteroids and bronchodilators [486,487].…”

Contemporary Management of Chronic Obstructive Pulmonary Disease

“…The mechanisms by which inhaled corticosteroids exert their beneficial effects on COPD outcomes are unclear. However, they attenuate airway hyperresponsiveness, 67,127 which may be an important predictor of COPD mortality, 128 and reduce some [129][130][131][132] but not all 133,134 components of airway inflammation and oxidative stress. Some caution should be exercised in using inhaled corticosteroids because they are associated with increased risk of certain adverse effects including thrush, oral candidiasis, and bruising.…”

Decreased Maturation of Dendritic Cells in the Central Airways of COPD Patients Is Associated with VEGF, TGF-β and Vascularity

“…However, a low number of subjects and a low number of biopsies per subject are common limitations in biopsy studies. Finally, the use of inhaled corticosteroids, especially in the most severe stages of COPD, could influence DC numbers and differentiation, even if it has been shown that inhaled corticosteroids did not affect at least the number of immature DC cells in bronchial biopsies of COPD patients [32]. Despite all of these limitations, we believe that studies on bronchial biopsies provide a unique opportunity to investigate the complex relationship between airway inflammation and remodeling in COPD.…”