Treating chronic obstructive pulmonary disease (COPD) with oral N-acetylcysteine (NAC) does not reduce patients’ risk for acute exacerbation nor improve lung volume decline, according to review and meta-analysis findings published in Therapeutic Advances in Respiratory Disease.
N-acetylcysteine (NAC), with anti-inflammatory and antioxidant properties, is a mucolytic drug that “decreases sputum viscosity and elasticity and improves low airway mucociliary clearance,” although the value of NAC therapy for COPD has yet to be confirmed, study authors noted. They therefore conducted a meta-analysis to examine the long-term efficacy oral NAC therapy in patients with COPD. The primary endpoint was the total number of patients with no acute exacerbations during the study period.
The reviewers searched for randomized controlled trials (RCTs) in all languages comparing outcomes of oral NAC vs placebo in adults with COPD from 2000 through mid-2022 in the Cochrane Library, Web of Science, and PubMed. All included RCTs reported values for at least 1 outcome of the following outcomes: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), glutathione level (GSH), St George’s Respiratory Questionnaire (SGRQ), adverse events, number of patients with no acute exacerbations. Oral NAC dosages ranged from 600 mg every 24 hours to 1800 mg every 12 hours. The reviewers defined acute exacerbation as acute worsening of respiratory symptoms resulting in additional therapy. Secondary endpoints included change in FEV1, FVC, GSH, SGRQ scores, and adverse events.
The meta-analysis included 9 randomized controlled trials (n=1061 NAC group; n=1076 placebo), of which 4 studies had a high risk of bias. Investigators found no significant differences between groups for the primary outcome of number of patients with no acute exacerbations (965 patients NAC therapy vs 979 control group; odds ratio, 1.12, 95% CI, 0.92-1.36, P =.26; I2=51%).
Similarly, no differences were found in the use of NAC therapy vs control for any of the secondary outcomes, including: change in FEV1 (meta-analysis compared 433 patients with NAC therapy vs 447 in control group), change in FVC (177 patients with NAC therapy vs 180 in control group), change in glutathione levels (38 patients with NAC therapy vs 40 in control group), change in SGRQ (128 patients with NAC therapy vs 131 in control group), number of patients with adverse events (832 patients with NAC therapy vs 846 in control group).
In subgroup analysis of NAC dosage (<1200 mg per day vs at least 1200 mg per day) the researchers found no statistically significant difference in the numbers of patients with vs without acute exacerbations. Most common adverse events included diarrhea, nausea, COPD symptoms, dry mouth, leg edema, muscle pain, headache, and dizziness.
Review and meta-analysis limitations included the use of 4 studies with high risk of bias; heterogeneity in the 9 included studies for NAC treatment dose; concomitant COPD treatment; differences in therapy duration; and unknown synergistic effects in patients using oral high-dose NAC (more than 1200mg/day) and inhaled therapy with long-acting bronchodilators.
“The current meta-analysis provided evidence that the number of patients with no acute exacerbations, change in FEV1, change in FVC, change in SGRQ score, and change in GSH level were not significantly different between patients receiving NAC and patients receiving placebo,” investigators stated. They noted that while regular long-term inhaled therapy with long-acting bronchodilators significantly reduces frequency of exacerbations, respiratory symptoms, and risk of mortality in patients with COPD, “NAC did not reduce the risk of acute exacerbation or ameliorate the decline in lung volume in chronic obstructive pulmonary disease patients.”
Huang C, Kuo S, Lin L, Yang Y. The efficacy of N-acetylcysteine in chronic obstructive pulmonary disease patients: A meta-analysis. Ther Adv Respir Dis. 2023; 17:17534666231158563. doi:10.1177/17534666231158563