Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study
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文摘
In a randomised placebo-controlled study in 50 centres, 523 patients with COPD were randomly assigned to 600 mg daily N-acetylcysteine or placebo. Patients were followed for 3 years. Primary outcomes were yearly reduction in forced expiratory volume in 1 s (FEV1) and the number of exacerbations per year. Analysis was by intention to treat.

Findings

The yearly rate of decline in FEV1 did not differ between patients assigned N-acetylcysteine and those assigned placebo (54 mL [SE 6] vs 47 mL [6]; difference in slope between groups 8 mL [9]; 95 % CI −25 to 10). The number of exacerbations per year did not differ between groups (1·25 [SD 1·35] vs 1·29 [SD 1·46]; hazard ratio 0·99 [95 % CI 0·89–1·10, p=0·85]). Subgroup analysis suggested that the exacerbation rate might be reduced with N acetylcysteine in patients not treated with inhaled corticosteroids and secondary analysis was suggestive of an effect on hyperinflation.

Interpretation

N-acetylcysteine is ineffective at prevention of deterioration in lung function and prevention of exacerbations in patients with COPD.


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Corticosteroids in Chronic Obstructive Pulmonary Diseas...
Clinics in Chest Medicine

Corticosteroids in Chronic Obstructive Pulmonary Disease: Clinical Benefits and Risks
Clinics in Chest MedicineVolume 21, Issue 41 December 2000, Pages 739-752
Charlene E. McEvoy, Dennis E. Niewoehner

Abstract
Chronic obstructive pulmonary disease (COPD) is an increasingly important public health problem. It remains one of the leading causes of disability in developed countries and is projected to be the fourth leading cause of death worldwide in 2020.61 The costs of medical care for these patients are enormous and long-term outcomes are poor.21 Bronchodilators, antibiotics, immunizations, smoking cessation, exercise and long-term oxygen cause measurable improvements in clinical outcomes, but the magnitudes of the effects are generally modest.

Over the past 20 years, corticosteroids, both oral and inhaled, have assumed a prominent role in the treatment of COPD. In some clinical settings, nearly one half of patients with COPD receive inhaled corticosteroids, and this number represents a substantial increase from a few years previously.42, 59 and 90 Many physicians now view systemic corticosteroids as standard therapy for severe COPD exacerbations, a practice that was not true a generation ago.59 A small proportion of patients with COPD, approximately 4 % to 10 % , take systemic corticosteroids repeatedly or continuously and are labeled as steroid-dependent.42 and 59

Adoption of these clinical practice patterns was not evidence based. Practice patterns evolved without compelling data that corticosteroids, in any form, improve clinical outcomes in COPD. The rationale for using both inhaled and oral corticosteroids in COPD is partly a result of their well-established effectiveness in the treatment of asthma.40 and 75 Historically, physicians have tended to transfer proven therapies from asthma to COPD, and this transfer may be because of the diagnostic confusion that frequently exists between these two conditions in older patients. In addition, pathophysiologic studies of patients with COPD have demonstrated a low-grade inflammatory reaction in the airways that may lead to occlusive, fibrotic changes over many years.63 Chronic inflammation has also been implicated in the pathogenesis of emphysema.62 Suppression of these inflammatory responses provides a rationale for using corticosteroids.

The question of efficacy is important, however, because corticosteroids may cause major adverse effects, particularly when given systemically. Several large clinical trials have recently been completed or are nearing completion and they should provide better evidence for making informed clinical decisions about the use of both inhaled and systemic corticosteroids in COPD. Analyses and publication of these trials are as yet incomplete, and in the meantime the clinician must evaluate whether the benefits of such therapy outweigh the potential for adverse events. This evaluation is particularly pertinent in the population of patients with COPD, who generally are older, less active, and have significant tobacco use histories, all of which may place them at greater risk for adverse effects.


e79a78d23412cd"" onMouseOver=""InfoBubble.show('infobubble_3','mlktLink_3')"" onMouseOut=""InfoBubble.timeout()"">The effects of inhaled corticosteroids in chronic obstr...
The American Journal of Medicine

The effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials
The American Journal of MedicineVolume 113, Issue 1July 2002, Pages 59-65
Abdullah Alsaeedi, Don D. Sin, Finlay A. McAlister

Abstract

Purpose

Although inhaled corticosteroids are commonly used to treat patients with chronic obstructive pulmonary disease (COPD), their effect on clinical outcomes such as exacerbation and mortality is unknown. This systematic review was conducted to determine whether inhaled corticosteroids improve clinical outcomes for patients with stable COPD.

Subjects and methods

All placebo-controlled randomized trials of inhaled corticosteroids given for at least 6 months for stable COPD were identified by searching MEDLINE (1966–2000), EMBASE (1980–2001), CINAHL (1982–2000), SIGLE (1980–2000), the Cochrane Controlled Trial Registry, and the bibliographies of published studies. We independently extracted data from each of the studies using a specified protocol, and determined the summary risk ratios (RRs) and 95 % confidence intervals (CIs) for exacerbations and deaths.

Results

Nine randomized trials (3976 patients with COPD), including four with a systemic steroid run-in phase, were identified. Use of inhaled corticosteroid therapy reduced the rate of exacerbations (RR = 0.70; 95 % CI: 0.58 to 0.84), with similar benefits in those who were and were not pretreated with systemic steroids. Inhaled corticosteroid therapy was also associated with increased rates of oropharyngeal candidiasis (RR = 2.1; 95 % CI: 1.5 to 3.1), skin bruising (RR = 2.1; 95 % CI: 1.6 to 2.8), and lower mean cortisol levels. No effects were seen on all-cause mortality (RR = 0.84; 95 % CI: 0.60 to 1.18) in the five trials that measured this outcome.

Conclusion

This systematic review demonstrates a beneficial effect of inhaled corticosteroids in reducing rates of COPD exacerbation. Further research is required to define the long-term effects of these medications and the benefit/risk ratio for patients with COPD.


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doi:10.1016/S0140-6736(08)60869-7
Copyright © 2008 Elsevier Ltd All rights reserved.

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Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study

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