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.	中華醫學會呼吸病學分會.特發性肺(間質)纖維化診斷和治療指南(草案).中華結核和呼吸雜志, 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.	陳風, 李松坤, 劉長波.大劑量富露施(N-乙酰半胱氨酸)在治療特發性肺間質纖維化的療效分析.醫療裝備, 2008, 21(7):33-34.
8.	賈軍, 陳勃江, 蒲青, 等.環磷酰胺、大劑量N-乙酰半胱氨酸治療特發性肺間質纖維化療效分析.臨床肺科雜志, 2011, 16(6):833-835.
9.	賈莉, 孟紅霞.富露施聯合強的松治療特發性肺纖維化臨床觀察.醫學信息(中旬刊), 2010, 5(7):1890-1891.
10.	江愛桂, 盧慧宇, 段德軍.N-乙酰半胱氨酸聯用甲強龍治療特發性肺纖維化的療效觀察.實用臨床醫藥雜志, 2009, 13(15):69-70.
11.	蔣艷秋, 江紅.N-乙酰半胱氨酸治療特發性肺纖維化20例臨床分析.中國社區醫師(醫學專業半月刊), 2008, 10(15):43-44.
12.	李明生, 盧明友, 鄭曉璐, 等.N-乙酰半胱氨酸對特發性肺纖維化患者血清轉化生長因子β1和白細胞介素13的影響.中國醫藥, 2009, 4(9):691-693.
13.	龍啟忠, 杜娟, 張先明, 等.干擾素-γ、N-乙酰半胱氨酸及小劑量強的松聯合治療特發性肺纖維化療效分析.貴陽醫學院學報, 2011, 36(5):465-469.
14.	陸建華, 高靜珍.乙酰半胱氨酸聯合糖皮質激素治療特發性肺纖維化中一氧化氮水平變化的研究.中國實驗診斷學, 2013, 17(9):1692-1693.
15.	孫英坤, 趙琦, 邵玉霞.N-乙酰半胱氨酸治療特發性肺纖維化的臨床分析.哈爾濱醫科大學學報, 2012, 46(5):465-467.
16.	趙琦, 呂福禎, 毛梓源.N-乙酰半胱氨酸治療特發性肺纖維化的療效觀察.黑龍江醫學, 2008, 32(1):30-31.
17.	朱建勇, 曾玉琴, 袁良俊, 等.強的松、N-乙酰半胱氨酸和卡托普利聯合治療特發性肺纖維化.鄖陽醫學院學報, 2009, 28(6):582-584.
18.	白露, 吳曉梅.大劑量富露施對特發性肺間質纖維化患者肺功能的影響.中國康復理論與實踐, 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. 中華醫學會呼吸病學分會.特發性肺(間質)纖維化診斷和治療指南(草案).中華結核和呼吸雜志, 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. 陳風, 李松坤, 劉長波.大劑量富露施(N-乙酰半胱氨酸)在治療特發性肺間質纖維化的療效分析.醫療裝備, 2008, 21(7):33-34.
8. 賈軍, 陳勃江, 蒲青, 等.環磷酰胺、大劑量N-乙酰半胱氨酸治療特發性肺間質纖維化療效分析.臨床肺科雜志, 2011, 16(6):833-835.
9. 賈莉, 孟紅霞.富露施聯合強的松治療特發性肺纖維化臨床觀察.醫學信息(中旬刊), 2010, 5(7):1890-1891.
10. 江愛桂, 盧慧宇, 段德軍.N-乙酰半胱氨酸聯用甲強龍治療特發性肺纖維化的療效觀察.實用臨床醫藥雜志, 2009, 13(15):69-70.
11. 蔣艷秋, 江紅.N-乙酰半胱氨酸治療特發性肺纖維化20例臨床分析.中國社區醫師(醫學專業半月刊), 2008, 10(15):43-44.
12. 李明生, 盧明友, 鄭曉璐, 等.N-乙酰半胱氨酸對特發性肺纖維化患者血清轉化生長因子β1和白細胞介素13的影響.中國醫藥, 2009, 4(9):691-693.
13. 龍啟忠, 杜娟, 張先明, 等.干擾素-γ、N-乙酰半胱氨酸及小劑量強的松聯合治療特發性肺纖維化療效分析.貴陽醫學院學報, 2011, 36(5):465-469.
14. 陸建華, 高靜珍.乙酰半胱氨酸聯合糖皮質激素治療特發性肺纖維化中一氧化氮水平變化的研究.中國實驗診斷學, 2013, 17(9):1692-1693.
15. 孫英坤, 趙琦, 邵玉霞.N-乙酰半胱氨酸治療特發性肺纖維化的臨床分析.哈爾濱醫科大學學報, 2012, 46(5):465-467.
16. 趙琦, 呂福禎, 毛梓源.N-乙酰半胱氨酸治療特發性肺纖維化的療效觀察.黑龍江醫學, 2008, 32(1):30-31.
17. 朱建勇, 曾玉琴, 袁良俊, 等.強的松、N-乙酰半胱氨酸和卡托普利聯合治療特發性肺纖維化.鄖陽醫學院學報, 2009, 28(6):582-584.
18. 白露, 吳曉梅.大劑量富露施對特發性肺間質纖維化患者肺功能的影響.中國康復理論與實踐, 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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