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      Effect of carbocisteine on patients with COPD: a systematic review and meta-analysis

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          Abstract

          Background

          COPD is the fourth leading cause of death in the world. It is a common, progressive, treatable and preventable disease. The exacerbation of COPD is associated with the peripheral muscle force, forced expiratory volume in 1 second (FEV 1), the quality of life and mortality. Many studies indicated that the mucoactive medicines could reduce the exacerbations of COPD. This study summarized the efficacy of carbocisteine as a treatment for COPD.

          Methods

          We searched the randomized controlled trials (RCTs) following electronic bibliographic databases: MedLine, Embase, Cochrane Library and Web of Science. We additionally searched gray literature database: OpenSIGLE. We also additionally searched the clinical trial registers: ClinicalTrials.gov register and International Clinical Trials Registry Platform Search Portal. We used RCTs to assess the efficacy of the treatments. We included studies of adults (older than 18 years) with COPD. We excluded studies that were published as protocol or written in non-English language (Number 42016047078).

          Findings

          Our findings included data from four studies involving 1,357 patients. There was a decrease in the risk of the rate of total number of exacerbations with carbocisteine compared with placebo (−0.43; 95% confidence interval [CI] −0.57, −0.29, P<0.01). Carbocisteine could also improve the quality of life (−6.29; 95% CI −9.30, −3.27) and reduce the number of patients with at least one exacerbation (0.86; 95% CI 0.78, 0.95) compared with placebo. There was no significant difference in the FEV 1 and adverse effects and the rate of hospitalization.

          Interpretation

          Long-term use of carbocisteine (500 mg TID) may be associated with lower exacerbation rates, the smaller number of patients with at least one exacerbation and higher quality of life of patients with COPD.

          Related collections

          Most cited references 21

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          Interpreting thresholds for a clinically significant change in health status in asthma and COPD.

          Health status (or Health-Related Quality of Life) measurement is an established method for assessing the overall efficacy of treatments for asthma and chronic obstructive pulmonary disease (COPD). Such measurements can indicate the potential clinical significance of a treatment's effect. This paper is concerned with methods of estimating the threshold of clinical significance for three widely used health status questionnaires for asthma and COPD: the Asthma Quality of Life Questionnaire, Chronic Respiratory Questionnaire and St George's Respiratory Questionnaire. It discusses the methodology used to obtain such estimates and shows that the estimates appear to be fairly reliable; ie. for a given questionnaire, similar estimates may be obtained in different studies. These empirically derived thresholds are all mean estimates with confidence intervals around them. The presence of these confidence intervals affects the way in which the thresholds may be used to draw inferences concerning the clinical relevance of clinical trial results. A new system of judging the magnitude of clinically significant results is proposed. Finally, an attempt is made to translate these thresholds into scenarios that illustrate what a clinically significant change with treatment may mean to an individual patient.
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            Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I.

            Chronic obstructive pulmonary disease (COPD) is often associated with peripheral muscle weakness, which is caused by several factors. Acute exacerbations may contribute, but their impact on muscle force remains unclear. Correlations between peripheral muscle force and inflammatory and anabolic markers have never been studied in COPD. The effect of an acute exacerbation on quadriceps peak torque (QPT) was therefore studied in hospitalised patients, and the aforementioned correlations were examined in hospitalised and in stable patients. Lung function, respiratory and peripheral muscle force, and inflammatory and anabolic markers were assessed in hospitalised patients on days 3 and 8 of the hospital admission and 90 days later. The results on day 3 (n=34) were compared with those in clinically stable outpatients (n=13) and sedentary healthy elderly subjects (n=10). Hospitalised patients had lowest mean (SD) QPT (66 (22)% predicted) and highest median (IQR) levels of systemic interleukin-8 (CXCL8, 6.1 (4.5 to 8.3) pg/ml). Insulin-like growth factor I (IGF-I) tended to be higher in healthy elderly subjects (p=0.09). QPT declined between days 3 and 8 in hospital (mean -5% predicted (95% CI -22 to 8)) and partially recovered 90 days after admission to hospital (mean 6% predicted (95% CI -1 to 23)). QPT was negatively correlated with CXCL8 and positively correlated with IGF-I and lung transfer factor in hospitalised and in stable patients. Peripheral muscle weakness is enhanced during an acute exacerbation of COPD. CXCL8 and IGF-I may be involved in the development of peripheral muscle weakness in hospitalised and in stable patients with COPD.
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              Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study.

              Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD. We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio (FEV(1)/FVC) of less than 0.7 and an FEV(1) between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry (http://umin.ac.jp/ctr/index/htm) number UMIN-CRT C000000233. 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1.01 [SE 0.06] vs 1.35 [SE 0.06]), risk ratio 0.75 (95% CI 0.62-0.92, p=0.004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated. Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2017
                02 August 2017
                : 12
                : 2277-2283
                Affiliations
                [1 ]Respiratory Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
                [2 ]Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China
                [3 ]Department of Pediatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital
                [4 ]Respiratory Medicine, Southwest Medical University, Chengdu Military General Hospital, Chengdu, Sichuan, People’s Republic of China
                Author notes
                Correspondence: Zhenliang Xiao, Southwest Medical University, Respiratory Medicine, The Original General Hospital of Chengdu Military, No 270 Rongdu Road, LongQuan Section, Chengdu, Sichuan, People’s Republic of China, Email xiaozhenliang2001@ 123456aliyun.com
                Article
                copd-12-2277
                10.2147/COPD.S140603
                5546781
                © 2017 Zeng et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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