N-acetylcysteine: evidence based consensus document on the therapeutic advantages in respiratory diseases (NECTAR)

N-acetylcysteine (NAC) is a key precursor of glutathione (GSH), the lung's principal antioxidant. First developed as a mucolytic, NAC is now recognized for broader antioxidant, anti-inflammatory, immunomodulatory, and anti-biofilm effects, prompting its use as an adjuvant in treatment of chronic respiratory conditions. This document consolidates existing evidence to this effect, and adds insights from practicing clinicians to guide about use of NAC in clinical practice.

An expert working group (EWG) comprising ten pulmonologists and a multidisciplinary drafting committee reviewed data from in vitro, mechanistic, animal and observational studies, randomized trials, reviews and meta-analyses for role of NAC in respiratory diseases. Eight respiratory conditions: stable COPD, acute exacerbations of COPD (AECOPD), tuberculosis (TB), and anti-tubercular drug-induced liver injury (AT-DILI), non-cystic fibrosis bronchiectasis, cystic fibrosis (CF), bacterial and viral infections, interstitial lung disease (ILD), and asthma were studied and discussed. A modified Delphi process was conducted to establish expert consensus on the role of NAC in each of these conditions. Consensus was defined as ≥70% agreement on predefined statements.

Experts agreed that NAC is useful as an adjunct in COPD especially chronic bronchitis phenotypes mainly for preventing exacerbations at 600 mg twice daily. During AECOPD, low dose NAC may aid recovery. In TB and AT-DILI, NAC is safe, lowers oxidative stress and may limit lung damage. In non-CF bronchiectasis, NAC may reduce exacerbations in frequent exacerbators. In CF, NAC improves lung function, mucociliary clearance, and disrupts biofilms. NAC is useful in bacterial and viral infections but data for ILDs and asthma does not support routine use. NAC was consistently rated safe and well-tolerated.

This consensus underscores the role of NAC in chronic respiratory diseases beyond its mucolytic properties and reiterates that NAC's antioxidant, anti-inflammatory, immunomodulatory and anti-biofilm properties provide significant clinical utility. It is a proven adjunctive therapy for COPD, bronchiectasis, and cystic fibrosis. While promising for TB and respiratory infections, further evidence is required. Its efficacy in asthma and ILDs remains uncertain. These findings guide clinical practice while highlighting research priorities to fully establish NAC's therapeutic potential in respiratory medicine.