The Effects of Fluticasone with or without Salmeterol on Systemic Biomarkers of Inflammation in Chronic Obstructive Pulmonary Disease

Sin, Don D.; Man, S. F. Paul; Marciniuk, Darcy; Ford, Gordon; FitzGerald, Mark; Wong, Eric; York, Ernest L.; Mainra, Rajesh; Ramesh, Warren; Melenka, Lyle; Wilde, Eric; Cowie, Robert L.; Williams, Dave; Gan, Wen Qi; Rousseau, Roxanne

doi:10.1164/rccm.200709-1356oc

Cited by 189 publications

(135 citation statements)

References 54 publications

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“…We were unable to confirm this finding, and so do others recently [24]. Anyway, there is no convincing evidence, at present, that inhaled corticosteroids are effective in reducing the all-cause mortality rate in COPD [25].…”

Section: Discussioncontrasting

confidence: 58%

Prognostic value of C-reactive protein in chronic obstructive pulmonary disease

et al. 2011

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To establish whether C-reactive protein (CRP) is an independent predictor of all-cause mortality and hospitalization in chronic obstructive pulmonary disease (COPD), we followed 200 patients with COPD and 201 age-and gender -matched controls for a median time of 4.2 years (range, 0.2-5.1 years). Airflow obstruction was rated moderate if forced expiratory volume in one second (FEV 1 ) was 50-69% of the predicted value, or severe if FEV 1 was \50%. The CRP level was categorized as low (B3 mg/L) or high ([3 mg/L). The hazard of death was estimated by a proportional hazard regression model, using controls with low CRP as the reference category. Fifty subjects died: 41 (21%) among the COPD and 9 (4%) among the controls (p \ 0.0001). The hazard of death in moderate COPD was not significantly higher than in the reference category, independently of the CRP level. In severe COPD with a low CRP, the hazard of death is 3.4 times higher than in the reference category (p = 0.008); in severe COPD and a high CRP it is 9.6 times higher (p \ 0.0001). The rate of hospitalization in COPD patients with a high CRP is 1.9 times higher than in those with a low CRP [95% confidence interval (CI), 1.2-3.2]. In severe COPD, it is 6.9 times higher than in moderate COPD (95% CI, 3.8-12.7). A high CRP level is a significant amplifier of the risk of death only in severe COPD. The degree of airflow obstruction is a strong independent predictor of COPD-related outcomes.

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Section: Discussioncontrasting

confidence: 58%

Prognostic value of C-reactive protein in chronic obstructive pulmonary disease

et al. 2011

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“…However, a prospective study of high-dose ICS in COPD patients (TORCH study) showed a minimal reduction in all causes of mortality, indicating that it is unlikely that there is a significant clinical benefit of ICS on COPD comorbidities such as cardiovascular disease or lung cancer, which are the commonest causes of death [93]. A controlled trial of high-dose ICS with or without a LABA showed no reduction in systemic inflammation in COPD patients, as measured by circulating IL-6 and CRP concentrations, indicating likely corticosteroid resistance of systemic as well as local inflammation in COPD patients [164]. However, there was a reduction in SP-D, indicating that ICS may reduce the production of lung-specific markers of inflammation.…”

Section: Inhaled Corticosteroidsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,465

1,113

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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“…Thus, ICS therapy leads to a reduction in systemic levels in inflammatory markers such as C-reactive protein or surfactant-D [68,69].…”

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

121

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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The Effects of Fluticasone with or without Salmeterol on Systemic Biomarkers of Inflammation in Chronic Obstructive Pulmonary Disease

Cited by 189 publications

References 54 publications

Prognostic value of C-reactive protein in chronic obstructive pulmonary disease

Prognostic value of C-reactive protein in chronic obstructive pulmonary disease

Systemic manifestations and comorbidities of COPD

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

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