Buha, I. (44460972900)I. (44460972900)BuhaMirić, M. (57193772097)M. (57193772097)MirićAgić, A. (57698117600)A. (57698117600)AgićSimić, M. (55847076300)M. (55847076300)SimićStjepanović, M. (55052044500)M. (55052044500)StjepanovićMilenković, B. (23005307400)B. (23005307400)MilenkovićNagorni-Obradović, L. (57189629141)L. (57189629141)Nagorni-ObradovićŠkodrić-Trifunović, V. (23499690800)V. (23499690800)Škodrić-TrifunovićIlić, B. (56806538200)B. (56806538200)IlićPopević, S. (54420874900)S. (54420874900)PopevićDimic-Janjic, S. (57208444020)S. (57208444020)Dimic-JanjicIlić, A. (7004055911)A. (7004055911)Ilić2025-06-122025-06-122022https://doi.org/10.26355/eurrev_202207_29206https://www.scopus.com/inward/record.uri?eid=2-s2.0-85134207957&doi=10.26355%2feurrev_202207_29206&partnerID=40&md5=320a0e7b8480960c7976d1c5ce15e378https://remedy.med.bg.ac.rs/handle/123456789/3765OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) accelerate the progressive impairment of lung function and general health. Together with maintenance therapy for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) and natural propolis have demonstrated pharmacological properties that address crucial pathophysiological processes underlying COPD and may prevent AECOPDs. This study aims at responding to dose-dependent efficacy and safety concerns regarding a propolis-NAC combination for the reduction of COPD exacerbation rates. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, phase IV trial with three treatment arms: Placebo and two active substance groups, one (AS-600) received 600 mg of NAC + 80 mg of propolis while the other (AS-1,200) received 1,200 mg of NAC + 160 mg of propolis. Following an AECOPD, frequent-exacerbation phenotype patients (n=46) were assigned a once-daily three-month therapy with the study drug and one year follow-up. The primary endpoint was the COPD exacerbation incidence rate during the follow-up period as a measure of dose-dependent efficacy of NAC-propolis combination compared to placebo. RESULTS: There was a statistically significant difference in the AECOPD incidence rate: 52.6% in patients that received placebo, 15.4% that received AS-600 and only 7.1% that received AS-1,200 (Fisher’s exact test, p = 0.013). Compared to placebo, AECOPD frequency was significantly lower only in AS-1,200 (p=0.009). Compared to placebo, the relative risk for exacerbation was 0.29 in AS-600 and 0.13 in AS-1,200. No adverse events related to the treatment were reported. CONCLUSIONS: Oral combination of natural propolis with NAC confirmed formulation efficiency with a favorable safety profile. Our results need to be confirmed by larger clinical trials. © 2022 Verduci Editore s.r.l. All rights reserved.COPDDose-dependentEfficacyExacerbationNACPropolisSupplement