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

Claudio M Sanguinetti

doi:10.1186/s40248-016-0039-2

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.

Highlights

The antioxidant and anti-inflammatory properties of NAC are based on a consistent amount of proofs obtained in vitro and in vivo and new information is continuously yielded about the useful involvement of this drug into the most intimate mechanisms playing a decisive role in triggering and maintaining respiratory inflammation
The inflammatory nature of Chronic Obstructive Pulmonary Disease (COPD) has already been well demonstrated [126], so as that oxidative stress has a close inter-relationship with the inflammatory process [5, 11, 20, 21, 33]
NAC has the potential to interfere with the processes that underline COPD pathogenesis and, as a matter of fact, the respiratory level of oxidants is decreased after its administration [7]

Summary

Background

Chronic Obstructive Pulmonary Disease (COPD), a common, preventable and treatable disease, is characterized by a chronic airflow obstruction that is usually progressive and scarcely reversible,caused by a variable association of chronic bronchitis, small airways damage and pulmonary emphysema, consequent to inhalation of noxious particles and gases, especially tobacco smoke, inducing a chronic airway inflammation, and frequently associated with several comorbidities [1, 2]. In a comment on high-dose N-acetylcysteine in COPD Cazzola and Matera [124] do not exclude the potential usefulness of NAC for the treatment of COPD patients, even if they rely more on the mucolytic properties of the drug than on its antioxidant effect These authors once more point out the lack in PANTHEON trial of a phenotypization of patients that likely would have clarified the exact role of the antioxidant therapy in COPD, as already demonstrated in the post-hoc analysis of HIACE study where the efficacy against exacerbations occurred only in the high-risk COPD patients, that is a well defined group of patients where the disease has a more severe connotation and poorer outcome. This evidence is present in the GOLD recommendations [2]

Conclusions

Findings

Methods