Efficacy of N-acetylcysteine for Patients with Idiopathic Pulmonary Fibrosis: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 FUXiao-wei , TONGXiang , LIUSi-tong ,  FANHong

Department of Respiratory Medicine, West China Hospital, Sichuan University. Chengdu 610041, China;

Corresponding author：

FANHong, Email: fanhongscuhx@163.com

Keywords：

N-acetylcysteine; Idiopathic pulmonary fibrosis; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20140078

Video：

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Objective To systematically review the efficacy and safety of N-acetylcysteine (NAC) for patients with idiopathic pulmonary fibrosis (IPF). Methods We electronically searched PubMed, EMbase, The Cochrane Library (Issue 2, 2014), CNKI, WanFang Data and VIP databases from the date of establishment to February 2014 for all randomized controlled trials (RCTs) on the use of NAC in patients with IPF. Manual search in relevant journals were also performed. The data extraction and quality assessment of included RCTs were conducted by two reviewers independently. Then, meta-analysis was conducted using RevMan 5.1 software. Results A total of 13 RCTs involving 713 patients were included. The results of meta-analysis indicated that the NAC group was better than the control group in clinical effectiveness (RR=1.34, 95%CI 1.19 to 1.51, P < 0.000 1). After treatment, the lung function was also improved in the NAC group than in the control group in the following index:PaO₂ (MD=6.06, 95%CI 3.79 to 8.32, P < 0.000 01), vital capacity (VC) (%) (MD=4.79, 95%CI 0.35 to 9.24, P=0.03) and diffusing capacity of carbon monoxide (Dlco) (%) (MD=5.74, 95%CI 2.67 to 8.81, P=0.000 2). However, no significant difference was found between groups in total lung capacity (TLC) (%) (MD=5.56, 95%CI-1.73 to 12.86, P=0.14). No serious or frequently-happened adverse effect was reported in the NAC group. Conclusion The current evidence suggests that NAC in long term use could improve clinical conditions, PaO₂ and lung function of IPF patients, with less adverse effects.

Citation： FUXiao-wei, TONGXiang, LIUSi-tong, FANHong. Efficacy of N-acetylcysteine for Patients with Idiopathic Pulmonary Fibrosis: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(4): 449-455. doi: 10.7507/1672-2531.20140078 Copy

1.	Raghu G, Collard HR, Egan JJ, et al.An official ATS/ERS/JRS/ALAT statement:idiopathic pulmonary fibrosis:evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med, 2011, 183(6):788-824.
2.	Bjoraker JA, Ryu JH, Edwin MK, et al.Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med, 1998, 157(1):199-203.
3.	Demedts M, Behr J, Buhl R, et al.High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med, 2005, 353(21):2229-2242.
4.	Homma S, Azuma A, Taniguchi H, et al.Efficacy of inhaled Nacetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.Respirology, 2012, 17(3):467-477.
5.	中华医学会呼吸病学分会.特发性肺(间质)纤维化诊断和治疗指南(草案).中华结核和呼吸杂志, 2002, 25(7):387-389.
6.	Higgins J, Green S.Cochrane Handbook for Systematic Review of Interventions Version 5.1.0[updated March 2011].The Cochrane Collaboration, 2011.Available at:www.cochranehand-book.org.
7.	陈风, 李松坤, 刘长波.大剂量富露施(N-乙酰半胱氨酸)在治疗特发性肺间质纤维化的疗效分析.医疗装备, 2008, 21(7):33-34.
8.	贾军, 陈勃江, 蒲青, 等.环磷酰胺、大剂量N-乙酰半胱氨酸治疗特发性肺间质纤维化疗效分析.临床肺科杂志, 2011, 16(6):833-835.
9.	贾莉, 孟红霞.富露施联合强的松治疗特发性肺纤维化临床观察.医学信息(中旬刊), 2010, 5(7):1890-1891.
10.	江爱桂, 卢慧宇, 段德军.N-乙酰半胱氨酸联用甲强龙治疗特发性肺纤维化的疗效观察.实用临床医药杂志, 2009, 13(15):69-70.
11.	蒋艳秋, 江红.N-乙酰半胱氨酸治疗特发性肺纤维化20例临床分析.中国社区医师(医学专业半月刊), 2008, 10(15):43-44.
12.	李明生, 卢明友, 郑晓璐, 等.N-乙酰半胱氨酸对特发性肺纤维化患者血清转化生长因子β1和白细胞介素13的影响.中国医药, 2009, 4(9):691-693.
13.	龙启忠, 杜娟, 张先明, 等.干扰素-γ、N-乙酰半胱氨酸及小剂量强的松联合治疗特发性肺纤维化疗效分析.贵阳医学院学报, 2011, 36(5):465-469.
14.	陆建华, 高静珍.乙酰半胱氨酸联合糖皮质激素治疗特发性肺纤维化中一氧化氮水平变化的研究.中国实验诊断学, 2013, 17(9):1692-1693.
15.	孙英坤, 赵琦, 邵玉霞.N-乙酰半胱氨酸治疗特发性肺纤维化的临床分析.哈尔滨医科大学学报, 2012, 46(5):465-467.
16.	赵琦, 吕福祯, 毛梓源.N-乙酰半胱氨酸治疗特发性肺纤维化的疗效观察.黑龙江医学, 2008, 32(1):30-31.
17.	朱建勇, 曾玉琴, 袁良俊, 等.强的松、N-乙酰半胱氨酸和卡托普利联合治疗特发性肺纤维化.郧阳医学院学报, 2009, 28(6):582-584.
18.	白露, 吴晓梅.大剂量富露施对特发性肺间质纤维化患者肺功能的影响.中国康复理论与实践, 2006, 12(7):618-619.
19.	Kim YH, Kwon SS.Interstitial lung diseases:respiratory review of 2013.Tuberc Respir Dis (Seoul), 2013, 75(2):47-51.
20.	Hunninghake GW.Antioxidant therapy for idiopathic pulmonary fibrosis.N Engl J Med, 2005, 353(21):2285-2287.
21.	Cantin AM, Hubbard RC, Crystal RG.Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis.Am Rev Respir Dis, 1989, 139(2):370-372.
22.	Behr J, Maier K, Degenkolb B, et al.Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis.Adjunctive therapy to maintenance immunosuppression.Am J Respir Crit Care Med, 1997, 156(6):1897-1901.
23.	Das SK, White AC, Fanburg BL.Modulation of transforming growth factor-beta 1 antiproliferative effects on endothelial cells by cysteine, cystine, and N-acetylcysteine.J Clin Invest, 1992, 90(5):1649-1656.
24.	Zafarullah M, Li WQ, Sylvester J, et al.Molecular mechanisms of Nacetylcysteine actions.Cell Mol Life Sci, 2003, 60(1):6-20.

1. Raghu G, Collard HR, Egan JJ, et al.An official ATS/ERS/JRS/ALAT statement:idiopathic pulmonary fibrosis:evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med, 2011, 183(6):788-824.
2. Bjoraker JA, Ryu JH, Edwin MK, et al.Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med, 1998, 157(1):199-203.
3. Demedts M, Behr J, Buhl R, et al.High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med, 2005, 353(21):2229-2242.
4. Homma S, Azuma A, Taniguchi H, et al.Efficacy of inhaled Nacetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.Respirology, 2012, 17(3):467-477.
5. 中华医学会呼吸病学分会.特发性肺(间质)纤维化诊断和治疗指南(草案).中华结核和呼吸杂志, 2002, 25(7):387-389.
6. Higgins J, Green S.Cochrane Handbook for Systematic Review of Interventions Version 5.1.0[updated March 2011].The Cochrane Collaboration, 2011.Available at:www.cochranehand-book.org.
7. 陈风, 李松坤, 刘长波.大剂量富露施(N-乙酰半胱氨酸)在治疗特发性肺间质纤维化的疗效分析.医疗装备, 2008, 21(7):33-34.
8. 贾军, 陈勃江, 蒲青, 等.环磷酰胺、大剂量N-乙酰半胱氨酸治疗特发性肺间质纤维化疗效分析.临床肺科杂志, 2011, 16(6):833-835.
9. 贾莉, 孟红霞.富露施联合强的松治疗特发性肺纤维化临床观察.医学信息(中旬刊), 2010, 5(7):1890-1891.
10. 江爱桂, 卢慧宇, 段德军.N-乙酰半胱氨酸联用甲强龙治疗特发性肺纤维化的疗效观察.实用临床医药杂志, 2009, 13(15):69-70.
11. 蒋艳秋, 江红.N-乙酰半胱氨酸治疗特发性肺纤维化20例临床分析.中国社区医师(医学专业半月刊), 2008, 10(15):43-44.
12. 李明生, 卢明友, 郑晓璐, 等.N-乙酰半胱氨酸对特发性肺纤维化患者血清转化生长因子β1和白细胞介素13的影响.中国医药, 2009, 4(9):691-693.
13. 龙启忠, 杜娟, 张先明, 等.干扰素-γ、N-乙酰半胱氨酸及小剂量强的松联合治疗特发性肺纤维化疗效分析.贵阳医学院学报, 2011, 36(5):465-469.
14. 陆建华, 高静珍.乙酰半胱氨酸联合糖皮质激素治疗特发性肺纤维化中一氧化氮水平变化的研究.中国实验诊断学, 2013, 17(9):1692-1693.
15. 孙英坤, 赵琦, 邵玉霞.N-乙酰半胱氨酸治疗特发性肺纤维化的临床分析.哈尔滨医科大学学报, 2012, 46(5):465-467.
16. 赵琦, 吕福祯, 毛梓源.N-乙酰半胱氨酸治疗特发性肺纤维化的疗效观察.黑龙江医学, 2008, 32(1):30-31.
17. 朱建勇, 曾玉琴, 袁良俊, 等.强的松、N-乙酰半胱氨酸和卡托普利联合治疗特发性肺纤维化.郧阳医学院学报, 2009, 28(6):582-584.
18. 白露, 吴晓梅.大剂量富露施对特发性肺间质纤维化患者肺功能的影响.中国康复理论与实践, 2006, 12(7):618-619.
19. Kim YH, Kwon SS.Interstitial lung diseases:respiratory review of 2013.Tuberc Respir Dis (Seoul), 2013, 75(2):47-51.
20. Hunninghake GW.Antioxidant therapy for idiopathic pulmonary fibrosis.N Engl J Med, 2005, 353(21):2285-2287.
21. Cantin AM, Hubbard RC, Crystal RG.Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis.Am Rev Respir Dis, 1989, 139(2):370-372.
22. Behr J, Maier K, Degenkolb B, et al.Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis.Adjunctive therapy to maintenance immunosuppression.Am J Respir Crit Care Med, 1997, 156(6):1897-1901.
23. Das SK, White AC, Fanburg BL.Modulation of transforming growth factor-beta 1 antiproliferative effects on endothelial cells by cysteine, cystine, and N-acetylcysteine.J Clin Invest, 1992, 90(5):1649-1656.
24. Zafarullah M, Li WQ, Sylvester J, et al.Molecular mechanisms of Nacetylcysteine actions.Cell Mol Life Sci, 2003, 60(1):6-20.

Chinese Journal of Evidence-Based Medicine

Efficacy of N-acetylcysteine for Patients with Idiopathic Pulmonary Fibrosis: A Meta-Analysis

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