CARBOCISTEINE IMPROVES QUALITY OF LIFE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2007)

To the Editor: Chronic obstructive pulmonary disease (COPD) is a major cause of disability throughout the world. The risk of airflow limitation is significantly greater with older age.1 Patients with COPD are prone to exacerbations, and health-related quality of life (QOL) is partly attributed to exacerbation frequency.2 Exacerbations adversely affect QOL, and recovery occurs only slowly, over a period of weeks or months. QOL may deteriorate more rapidly in patients with frequent exacerbations.3 Evaluation of QOL may provide sensitive measurements of disturbance in daily life, whereas measures of lung function such as forced expiratory volume in 1 second (FEV1) may not correspond to the extent of disability. Treatment of COPD has been focused on improving lung function and relieving symptoms with the use of inhaled long-acting bronchodilators. These drugs also reduce exacerbations and improve QOL. One of the triggers for COPD exacerbation is respiratory virus infection. Rhinoviruses are the major cause of the common cold and are also associated with exacerbations of COPD.4 Carbocisteine reduces intercellular adhesion molecule-1 expression and blocks entry of rhinovirus ribonucleic acid into the endosomes.5 Therefore, carbocisteine may be useful in the prevention of common colds and exacerbations in COPD patients. The preventive effects of carbocisteine on acute exacerbations of COPD were investigated in a multicenter (n=23), parallel-group, randomized study. One hundred forty-two clinically stable patients with COPD (mean age±standard error 70.1±0.6), whose percentage of FEV1 (FEV1%; FEV1/forced vital capacity) was less than 70% and less than 80% of predicted, were prospectively and randomly assigned to two groups: a study group and a control group. Patients with COPD with two or more exacerbations in the preceding 2 years were enrolled in this trial. Study group patients (n=72) were administered 1,500 mg (3 doses of 500 mg) of carbocisteine daily in addition to inhaled bronchodilators for 12 months, whereas control group patients (n=70) continued to inhale the previously prescribed bronchodilators. The proportion of usage of long-acting bronchodilators were similar between two groups (71% vs 69%). There were no significant differences between the two groups regarding age, sex, or FEV1%. The primary endpoint of this study was to examine whether treatment with carbocisteine decreases frequency of exacerbations, and secondary endpoints were to examine whether it improves QOL, as evaluated using the St. George's Respiratory Questionnaire (SGRQ), disease-specific QOL measures, and whether it decreases frequency of common colds. The patients recorded their symptoms in a daily diary. An exacerbation was diagnosed based on changes in the following symptoms from their stable condition according to the Anthonisen criteria: dyspnea, sputum purulence, sputum volume, cold, wheeze, cough, fever, and change in respiratory rate or heart rate of 20%.6 The frequency of common colds was measured according to changes in symptoms in the daily diary and clinical information at each visit (coryzal symptoms, headache, sore throat, cough, and feverishness) (Table 1). No apparent adverse effects due to carbocisteine therapy were observed during the study period. The mean number of common colds for 12 months was significantly lower in the study group than in the control group (risk ratio (RR)=0.74, 95% confidence interval (CI)=0.56–0.99). The number of exacerbations for 12 months was also significantly lower in the study group than in the control group (RR=0.37, 95% CI=0.22–0.62). SGRQ total score and component scores (Impacts, Symptoms, and Activities) were similar between the groups at the start of the study. SGRQ total score decreased in the study group but not in the control group, indicating that carbocisteine improved patient QOL. In addition, all three component scores decreased in the study group, suggesting that carbocisteine administration improved both physical and mental aspects of QOL. FEV1 was not significantly changed during the study period in either group. Carbocisteine treatment reduced frequency of COPD exacerbation and common cold and improved QOL. The lower rate of exacerbation observed in this study is consistent with previous reports.7, 8 Carbocisteine may have a preventive effect on exacerbations in patients with COPD. The Preventive Effects on Acute Exacerbations of COPD with Carbocisteine (PEACE study) Group consists of the following investigators: Takayuki Kuriyama, Department of Respirology, Graduate School of Medicine, Chiba University; Mutsuo Yamaya, Department of Geriatrics and Gerontology, Tohoku University School of Medicine; Keishi Kubo, First Department of Internal Medicine, Shinshu University School of Medicine; Masashi Mikami, Department of Respiratory Medicine, Saitama Medical Center, Saitama Medical University; Michiaki Mishima, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University; Masakazu Ichinose, Third Department of Internal Medicine, Wakayama Medical University; Hisamichi Aizawa, Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine; Masaharu Nishimura, First Department of Medicine, Hokkaido University Graduate School of Medicine; Takahide Nagase, Department of Respiratory Medicine, University of Tokyo, Graduate School of Medicine; Atsushi Nagai, First Department of Medicine, Tokyo Women's Medical University; and Yoshinosuke Fukuchi, Department of Respiratory Medicine, Juntendo University School of Medicine. Financial Disclosure: Koichiro Tatsumi was supported by a grant to the Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan. Author Contributions: Koichiro Tatsumi: acquisition of subjects, data analysis, interpretation of data, and preparation of manuscript. Yoshinosuke Fukuchi: director of the study, interpretation of data. Sponsor's Role: None.