Efficacy and Safety of -acetylcysteine Therapy for Idiopathic Pulmonary Fibrosis: An Updated Systematic Review and Meta-analysis

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2019 Jul 2

PMID 31258714

Citations 20

Authors

Fanchao Feng

Jiarui Zhang

Zhichao Wang

Qi Wu

Xianmei Zhou

Affiliations

Soon will be listed here.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease with poor prognosis and limited treatment options. -acetylcysteine (NAC), an anti-oxidant drug, has promising potential in the treatment of IPF. In the present systematic review and meta-analysis, the efficacy and safety of NAC for IPF were investigated. The following databases were comprehensively searched for relevant studies published until August 2018: Pubmed, Embase, Cochrane library, Chinese National Knowledge Infrastructure, Wangfang Database, VIP and the Chinese Biology Medical Database. A total of 21 controlled trials assessing the efficacy and safety of NAC therapy for IPF were identified and primary outcomes [forced vital capacity (FVC), adverse side effects] and secondary outcomes [diffusing capacity for carbon monoxide (DLCO) and its percentage predicted value (DLCO%), vital capacity (VC), partial arterial oxygen pressure (PaO), 6-min walking distance test and mortality] were extracted for the meta-analysis. The risk ratio and mean difference or standardized mean difference with 95% confidence interval were calculated using RevMan 5.3 software. Analysis of the pooled data revealed that, compared with control treatments (routine treatment or drugs other than anti-oxidants), NAC therapy reduced the decline in lung function, as indicated by the FVC and DLCO, and slowed the progression of the disease, as indicated by the PaO, while complications and mortality were similar. These results suggest good efficacy, tolerability and safety of the treatment. Furthermore, subgroup analysis revealed that combined therapy including NAC for IPF might be more effective than NAC monotherapy, while oral administration of NAC was safer than inhalation. In conclusion, the results of the present review and meta-analysis provide important information that may serve as a guide regarding NAC therapy for IPF in clinical practice.

Citing Articles

Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective.

Santus P, Signorello J, Danzo F, Lazzaroni G, Saad M, Radovanovic D J Clin Med. 2024; 13(14).

PMID: 39064168 PMC: 11278452. DOI: 10.3390/jcm13144127.

Molecular Mechanisms of N-Acetylcysteine in RSV Infections and Air Pollution-Induced Alterations: A Scoping Review.

Wrotek A, Badyda A, Jackowska T Int J Mol Sci. 2024; 25(11).

PMID: 38892239 PMC: 11172664. DOI: 10.3390/ijms25116051.

Comparison of Longevity in Patients with Idiopathic Pulmonary Fibrosis Using Pirfenidone Versus Triple Therapy with Prednisolone, Azathioprine, and Acetylcysteine.

Asl M, Motakef Z, Behgam N, Attaran S, Mirsadraee M Tanaffos. 2023; 22(1):129-135.

PMID: 37920315 PMC: 10618587.

N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals.

Tieu S, Charchoglyan A, Paulsen L, Wagter-Lesperance L, Shandilya U, Bridle B Antioxidants (Basel). 2023; 12(10).

PMID: 37891946 PMC: 10604897. DOI: 10.3390/antiox12101867.

Advances in the Use of -Acetylcysteine in Chronic Respiratory Diseases.

Mokra D, Mokry J, Barosova R, Hanusrichterova J Antioxidants (Basel). 2023; 12(9).

PMID: 37760016 PMC: 10526097. DOI: 10.3390/antiox12091713.

References

Birmingham C . Total parenteral nutrition in the critically ill patient. Lancet. 1999; 353(9159):1116-7. DOI: 10.1016/s0140-6736(99)00006-9. View

Hagiwara S, Ishii Y, Kitamura S . Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice. Am J Respir Crit Care Med. 2000; 162(1):225-31. DOI: 10.1164/ajrccm.162.1.9903129. View

Kinnula V, Fattman C, Tan R, Oury T . Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J Respir Crit Care Med. 2005; 172(4):417-22. PMC: 2718525. DOI: 10.1164/rccm.200501-017PP. View

Tomioka H, Kuwata Y, Imanaka K, Hashimoto K, Ohnishi H, Tada K . A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis. Respirology. 2005; 10(4):449-55. DOI: 10.1111/j.1440-1843.2005.00725.x. View

Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen H . High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005; 353(21):2229-42. DOI: 10.1056/NEJMoa042976. View

Borok Z, Buhl R, Grimes G, Bokser A, Hubbard R, Holroyd K . Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet. 1991; 338(8761):215-6. DOI: 10.1016/0140-6736(91)90350-x. View

Kliment C, Oury T . Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis. Free Radic Biol Med. 2010; 49(5):707-17. DOI: 10.1016/j.freeradbiomed.2010.04.036. View

Bando M, Hosono T, Mato N, Nakaya T, Yamasawa H, Ohno S . Long-term efficacy of inhaled N-acetylcysteine in patients with idiopathic pulmonary fibrosis. Intern Med. 2010; 49(21):2289-96. DOI: 10.2169/internalmedicine.49.4011. View

Raghu G, Collard H, Egan J, Martinez F, Behr J, Brown K . 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. PMC: 5450933. DOI: 10.1164/rccm.2009-040GL. View

10.

Wynn T . Integrating mechanisms of pulmonary fibrosis. J Exp Med. 2011; 208(7):1339-50. PMC: 3136685. DOI: 10.1084/jem.20110551. View

11.

Homma S, Azuma A, Taniguchi H, Ogura T, Mochiduki Y, Sugiyama Y . Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis. Respirology. 2012; 17(3):467-77. DOI: 10.1111/j.1440-1843.2012.02132.x. View

12.

Raghu G, Anstrom K, King Jr T, Lasky J, Martinez F . Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012; 366(21):1968-77. PMC: 3422642. DOI: 10.1056/NEJMoa1113354. View

13.

Noble P, Barkauskas C, Jiang D . Pulmonary fibrosis: patterns and perpetrators. J Clin Invest. 2012; 122(8):2756-62. PMC: 3408732. DOI: 10.1172/JCI60323. View

14.

Sakamoto S, Itoh T, Muramatsu Y, Satoh K, Ishida F, Sugino K . Efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis. Intern Med. 2013; 52(22):2495-501. DOI: 10.2169/internalmedicine.52.8498. View

15.

Strand M, Sprunger D, Cosgrove G, Fernandez-Perez E, Frankel S, Huie T . Pulmonary function and survival in idiopathic vs secondary usual interstitial pneumonia. Chest. 2014; 146(3):775-785. PMC: 4151362. DOI: 10.1378/chest.13-2388. View

16.

Martinez F, de Andrade J, Anstrom K, King Jr T, Raghu G . Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370(22):2093-101. PMC: 4116664. DOI: 10.1056/NEJMoa1401739. View

17.

Richeldi L, du Bois R, Raghu G, Azuma A, Brown K, Costabel U . Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370(22):2071-82. DOI: 10.1056/NEJMoa1402584. View

18.

Sakamoto S, Muramatsu Y, Satoh K, Ishida F, Kikuchi N, Sano G . Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study. Respirology. 2015; 20(3):445-52. DOI: 10.1111/resp.12477. View

19.

Hutchinson J, Fogarty A, Hubbard R, McKeever T . Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J. 2015; 46(3):795-806. DOI: 10.1183/09031936.00185114. View

20.

Oldham J, Ma S, Martinez F, Anstrom K, Raghu G, Schwartz D . TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2015; 192(12):1475-82. PMC: 4731723. DOI: 10.1164/rccm.201505-1010OC. View