N-acetylcysteine in COPD: why, how, and when?

Abstract

Oxidants have long been recognized to have an important role in the pathogenesis of COPD, and in this cigarette smoke has a strong responsibility, because it generates a conspicuous amount of oxidant radicals able to modify the structure of the respiratory tract and to enhance several mechanisms that sustain lung inflammation in COPD. In fact, oxidative stress is highly increased in COPD and natural antioxidant capacities, mainly afforded by reduced glutathione, are often overcome. Thus an exogenous supplementation of antioxidant compounds is mandatory to at least partially counteract the oxidative stress. For this purpose N-acetylcysteine has great potentialities due to its capacity of directly contrasting oxidants with its free thiols, and to the possibility it has of acting as donor of cysteine precursors aimed at glutathione restoration. Many studies in vitro and in vivo have already demonstrated the antioxidant capacity of NAC. Many clinical studies have long been performed to explore the efficacy of NAC in COPD with altern results, especially when the drug was used at very low dosage and/or for a short period of time. More recently, several trials have been conducted to verify the appropriateness of using high-dose NAC in COPD, above all to decrease the exacerbations rate. The results have been encouraging, even if some of the data come from the most widely sized trials that have been conducted in Chinese populations. Although other evidence should be necessary to confirm the results in other populations of patients, high-dose oral NAC nevertheless offers interesting perspectives as add-on therapy for COPD patients.

Keywords: Antioxidants; COPD; Exacerbations; High dose oral N-acetylcysteine; Oxidative stress.

Fig. 1

Mean values of H₂O₂ in expired breath condensate (EBC) of COPD patients, treated with usual therapy plus NAC or with usual therapy only, before the study and at 15, 30, and 60 days after the start of the study. Mod from [7]

Fig. 2

a Mean time to first exacerbation; b mean cumulative exacerbation frequency in Chinese COPD patients treated with high-dose NAC or placebo in adjunct to usual therapy for one year and divided according to basal high or low exacerbation risk. Mod. from [111]

Fig. 3

a Total number of COPD exacerbations occurred in one year in NAC group and in placebo group; b number of exacerbations/patient/year in the two groups of patients. Mod from [119]