RESEARCH PAPER
The efficacy and safety of inhaled acetylcysteine in comparison with oral acetylcysteine in chronic obstructive pulmonary disease: A randomized single-center study
 
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1
Bogomolets National Medical University, Kyiv, Ukraine
2
National Institute of Phthisiology and Pulmonology named after F. G. Yanovsky, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
CORRESPONDING AUTHOR
Nina Kuzmenko   

Bogomolets National Medical University, Department of Internal Medicine No 3, 26, P. Zaporozhtsa street, Kyiv, Ukraine. Tel.: +380936167200.
Submission date: 2020-02-03
Final revision date: 2020-04-10
Acceptance date: 2020-04-11
Online publication date: 2020-08-06
 
Pol. Ann. Med. 2020;27(2):108–114
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
One-third of all the patients with chronic obstructive pulmonary disease (COPD) additionally take mucolytics as per GOLD recommendation due to complaints of productive cough despite their compliance with the basic treatment regimen.

Aim:
To assess the efficacy and safety of inhaled N-acetylcysteine (NAC) in comparison with oral NAC in patients with COPD.

Material and methods:
The study included 46 patients with stable COPD and difficult expectoration of sputum who were divided into two groups. The first group (n = 22) took 600 mg/day NAC orally, and the second one (n = 24) inhaled 600 mg/day NAC by a nebulizer for 10 days. In the beginning and after the 10-day treatment the questionnaires (CAT, mMRC, CCQ, SGRQ, SF-36), 6-minute walk distance test and day and night cough symptoms were evaluated, spirometry and sputum analysis were performed.

Results and discussion:
In the first group, CCQ showed improvement in the status of patients (by 9.7%). The severity of night cough also decreased. Other indices were not changed statistically. In the other group, positive changes in the CAT (by 13.1%) and SF-36 were reported, night cough decreased. Additionally, forced expiratory volume in 1 s (FEV1) values increased (by 10.3%). No changes in FEV1 2 hours after the first oral usage or inhalation of NAC were found.

Conclusions:
Both oral administration and inhalation of NAC by a nebulizer for 10 days has a similar positive effect on the manifestations of COPD, but the inhalation route of the drug is also accompanied by improved quality of life and lung function test (FEV1) as well.

ACKNOWLEDGEMENTS
We thank Dmytro Fedkov and Liubov Petelytska for comments that greatly improved the manuscript.
CONFLICT OF INTEREST
None declared.
FUNDING
None declared.
 
REFERENCES (33)
1.
Global Initiative for Chronic Obstructive Lung Diseases. Global strategy for diagnosis, management and prevention of chronic obstructive lung disease. 2018 Report. https://goldcopd.org/wp-conten.... Accessed: 20.06.2020.
 
2.
Why chronic obstructive pulmonary disease occurs and how to avoid it. https://moz.gov.ua/article/hea.... Accessed: 22.11.2018 [in Ukrainian].
 
3.
Rogers DF. Mucoactive agents for airway mucus hypersecretory diseases. Respir Care. 2007;52(9):1176–1197.
 
4.
Cazzola M, Rogliani P, Calzetta L, Hanania NA, Matera MG. Impact of mucolytic agents on COPD Exacerbations: A pair-wise and Network meta-analysis. COPD. 2017;14(5):552–563. https://doi.org/10.1080/154125....
 
5.
Cazzola M, Calzetta L, Page C, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: A meta-analysis. Eur Respir Rev. 2015;24(137):451–461. https://doi.org/10.1183/160006....
 
6.
Poole P, Chong J, Cates CJ. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;7: CD001287. https://doi.org/10.1002/146518....
 
7.
Stey C, Steurer J, Bachmann S, Medici TC, Tramèr MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J. 2000;16(2):253–262. https://doi.org/10.1034/j.1399....
 
8.
Zheng JP, Wen FQ, Bai CX, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): A randomised, double-blind placebo-controlled trial. Resp Med. 2014;2(3):187–194. https://doi.org/10.1016/S2213-....
 
9.
Szkudlarek U, Zdziechowski A, Witkowski K, et al. Effect of inhaled N-acetylcysteine on hydrogen peroxide exhalation in healthy subjects. Pulm Pharmacol Ther. 2004;17(3):155–162. https://doi.org/10.1016/j.pupt....
 
10.
App EM, Baran D, Dab I, et al. Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis. Eur Respir J. 2002;19(2):294–302. https://doi.org/10.1183/090319....
 
11.
Shehzad MI, Mannan MA, Alam M, Rauf A, Sharif MI. Airway clearance in bronchiectasis: A randomized control trial with N-acetylcysteine and 3% hypertonic saline. J Islamabad Med Dental Coll. 2019;8(3). https://doi.org/10.35787/jimdc....
 
12.
Masoompour SM, Anushiravani A, Tafaroj Norouz A. Evaluation of the effect of nebulized N-acetylcysteine on respiratory secretions in mechanically ventilated patients: Randomized clinical trial. Iran J Med Sci. 2015;40(4):309–315.
 
13.
Sadowska AM, Verbraecken J, Darquennes K, De Backer WA. Role of N-acetylcysteine in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(4):425–434. https://dx.doi.org/10.2147%2Fc....
 
14.
Moore VC. Spirometry: step by step. Breathe. 2012;8(3):232–240. https://doi.org/10.1183/207347....
 
15.
Celli B, Tetzlaff K, Criner, et al. The 6-minute-walk distance test as a chronic obstructive pulmonary disease stratification tool. Insights from the COPD Biomarker Qualification Consortium. Am J Respir Crit Care Med. 2016;194(12):1483–1493. https://doi.org/10.1164/rccm.2....
 
16.
Gupta N, Pinto LM, Morogan A, Bourbeau J. The COPD assessment test: a systematic review. Eur Respir J. 2014;44(4):873–884. https://doi.org/10.1183/090319....
 
17.
Munari AB, Gulart AA, Dos Santos K, Venâncio RS, Karloh M, Mayer AF. Modified Medical Research Council Dyspnea Scale in GOLD Classification Better Reflects Physical Activities of Daily Living. Respir Care. 2018;63(1):77–85. https://doi.org/10.4187/respca....
 
18.
Kon S, Dilaver D, Mittal M, et al. The Clinical COPD Questionnaire: response to pulmonary rehabilitation and minimal clinically important difference. Thorax. 2014;69(9):793–798. https://doi.org /10.1136/thoraxjnl-2013-204119.
 
19.
Müllerova H, Gelhorn H, Wilson H, et al. St George’s Respiratory Questionnaire Score Predicts Outcomes in Patients with COPD: Analysis of Individual Patient Data in the COPD Biomarkers Qualification Consortium Database. Chronic Obstr Pulm Dis. 2017;4(2):141–149. https://dx.doi.org/10.15326%2F....
 
20.
Soyyiğit S, Erk M, Güler N, Kilinç G. [The value of SF-36 questionnaire for the measurement of life quality in chronic obstructive pulmonary disease]. Tuberk Toraks. 2006;54(3):259–266. https://www.ncbi.nlm.nih.gov/p... [in Turkish].
 
21.
Decalmer SC, Webster D, Kelsall AA, McGuinness K, Woodcock AA, Smith JA. Chronic cough: How do cough reflex sensitivity and subjective assessments correlate with objective cough counts during ambulatory monitoring? Thorax. 2007;62:329–334. https://doi.org/10.1136/thx.20....
 
22.
Sanguinetti CM. N-acetylcysteine in COPD: Why, how, and when? Multidiscip Respir Med. 2016;11:8. https://doi.org/10.1186/s40248....
 
23.
Turner RD, Bothamley GH. N-acetylcysteine for COPD: The evidence remains inconclusive. Resp Med. 2014;2(4):e3. https://doi.org/10.1016/S2213-....
 
24.
Millar AB, Pavia D, Agnew JE, Lopez-Vidriero MT, Lauque D, Clarke SW. Effect of oral N-acetylcysteine on mucus clearance. Br J Dis Chest. 1985;79(3):262–266. https://doi.org/10.1016/0007-0....
 
25.
Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study Group. Am J Respir Crit Care Med. 1997;156(2 Pt 1):341–357. https://doi.org/10.1164/ajrccm....
 
26.
Dueholm M, Nielsen C, Thorshauge H, et al. N-acetylcysteine by metered dose inhaler in thetreatment of chronic bronchitis: a multi-centre study. Resp Med. 1992;86(2):89–92. https://doi.org/10.1016/s0954-....
 
27.
Tarrant BJ, Maitre C, Romero L, et al. Mucoactive agents for chronic, non-cystic fibrosis lung disease: A systematic review and meta-analysis. Respirology. 2017;22(6):1084–1092. https://doi.org/10.1111/resp.1....
 
28.
Tong Sun, Jing Liu, De Wei Zhao. Efficacy of N-acetylcysteine in idiopathic pulmonary fibrosis. Medicine. 2016;95(19):1–7. https://doi.org/10.1097/MD.000....
 
29.
Sakamoto S, Muramatsu Y, Satoh K, et al. Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study. Respirology. 2015;20(3):445–452. https://doi.org/10.1111/resp.1....
 
30.
Okuda R, Matsushima H, Oba T, et al. Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis: A prospective, single-arm study. Respir Investig. 2016;54(3):156–161. https://doi.org/10.1016/j.resi....
 
31.
Pappová L, Kazimierová I, Kocmálová M. Effect of inhaled and oral n-acetylcysteine on airway defense mechanism. Eur Pharm. J. 2017;64(1):17–21. https://doi.org/10.1515/afpuc-....
 
32.
Kandasamy J, Carlo WA. Pharmacologic Therapies IV: Other Medications. In: Goldsmith JP, Karotkin E, Suresh G, Keszler M. Assisted Ventilation of the Neonate. 6th Ed. Philadelphia, PA: Elsevier;2017:366–379. https://doi.org/10.1016/B978-0....
 
33.
Jargin SV. On the use of acetylcysteine as a mucolytic drug. J Invest Biochem. 2016;52(3):52–53. https://doi.org/10.5455/jib.20....