Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial

Brightling, Christopher E.; Monteiro, William; Ward, Richard J.; Parker, Debbie; Morgan, Michael; Wardlaw, Andrew J.; Pavord, Ian D.

doi:10.1016/s0140-6736(00)02872-5

Cited by 524 publications

(432 citation statements)

References 26 publications

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“…36 Recent findings show that eosinophilic airway inflammation is common in patients with stable moderate and severe COPD. 11 In our study no significant differences in changes in cellular indices were detected between the treatment groups. The CD8+ lymphocytes were markedly decreased in the lamina propria of both the FP and placebo groups.…”

Section: Discussionmentioning

confidence: 53%

“…10 It has recently been reported that prednisolone has a beneficial effect in patients with COPD who have increased numbers of sputum eosinophils. 11 In a large multicentre trial in patients with respiratory symptoms, the effect of an inhaled steroid on the course of forced expiratory volume in 1 second (FEV 1 ) was found to be most prominent in those with more severe bronchial hyperresponsiveness (BHR). 12 BHR is usually seen as a distinguishing characteristic of asthma, but is found surprisingly often in patients with COPD and in smokers.…”

mentioning

confidence: 99%

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Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Verhoeven

Hegmans²,

Mulder³

et al. 2002

Thorax

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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.

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Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Verhoeven

Hegmans²,

Mulder³

et al. 2002

Thorax

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“…Similarly, IL-5 was more often detectable in COPD (15%) than in healthy subjects (0%), a finding in agreement with the observation that some COPD may display airway eosinophilia. 25,26 There are other models looking at cytokines in the airway by using sputum samples. We previously showed that measuring cytokines after 24 h sputum cell culture could provide biological signals distinguishing asthmatics 27 and COPD 4 from healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Sputum cytokine levels in patients undergoing hematopoietic SCT and comparison with healthy subjects and COPD: a pilot study

Moermans

Bonnet

Willems

et al. 2014

Bone Marrow Transplant

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Patients undergoing hematopoietic SCT (HSCT) display an airway neutrophilic inflammation before transplantation that persists over the years. In this study, we have investigated the cytokine profile over a period of 1 year in the sputum supernatant of patients who underwent HSCT. We have measured sputum supernatant levels of TNF-α, TGF-β1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17 and IFN-γ in 49 HSCT patients and compared the results with those found in 40 chronic obstructive pulmonary disease (COPD) and 54 healthy subjects matched for age. Compared with healthy subjects, before transplantation, HSCT patients exhibited raised levels of IL-6 (P o0.001) and IL-8 (P o 0.05) while the other cytokines were generally poorly detectable. This picture was rather similar to that seen in COPD even if cytokine levels were much greater in the latter, with IL-8 being significantly greater in COPD than in HSCT patients (P o0.0001). In the 1 year following transplantation, sputum IL-6 and IL-8 did not differ from those in healthy subjects. Overall in HSCT patients, sputum IL-8 and IL-6 correlated with sputum neutrophil counts (r = 0.4, P o 0.0001; r = 0.42, P o 0.0001, respectively). In conclusion, sputum IL-6 and IL-8 may play a role in neutrophilic airway inflammation seen in patients undergoing HSCT.

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“…A 2005 meta-analysis of the effect of ICS treatment on sputum markers in COPD indicated that there was an overall effect of ICS in reducing neutrophil and lymphocyte counts to a small extent provided they were given over a prolonged period of time of greater than 6 weeks [61]. More recent studies of 6-month duration with budesonide showed no effect on sputum neutrophil count, although sputum eosinophil counts were reduced [62]; indeed, the presence of eosinophilic inflammation in COPD has been proposed as a marker of clinical responsiveness to ICS [63,64]. A biopsy study showed that fluticasone treatment for 3 months had no effect on the number of CD8+, CD68+ and neutrophils, although CD8/CD4 ratio in epithelium and subepithelial mast cells was reduced [65].…”

Section: Anti-inflammatory Effects Of Ics In Copdmentioning

confidence: 99%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

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International audienceInhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV and the rate of exacerbations. A reduction in the rate of decline in FEV of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases

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Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial

Cited by 524 publications

References 26 publications

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Sputum cytokine levels in patients undergoing hematopoietic SCT and comparison with healthy subjects and COPD: a pilot study

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

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