Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial

J Cyst Fibros. 2015 Mar;14(2):219-27. doi: 10.1016/j.jcf.2014.08.008. Epub 2014 Sep 13.


Purpose: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways.

Methods: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks.

Endpoints: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF.

Results: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14).

Conclusions: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.

Keywords: Anti-oxidant; Clinical trial; Cystic fibrosis; Glutathione; Lung function.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine* / administration & dosage
  • Acetylcysteine* / adverse effects
  • Administration, Oral
  • Adolescent
  • Adult
  • Antioxidants / administration & dosage
  • Antioxidants / adverse effects
  • Child
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / metabolism
  • Cystic Fibrosis* / physiopathology
  • Double-Blind Method
  • Drug Monitoring
  • Female
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Leukocyte Elastase / metabolism
  • Lung* / drug effects
  • Lung* / metabolism
  • Lung* / physiopathology
  • Male
  • Oxidative Stress / drug effects*
  • Respiratory Function Tests / methods
  • Sputum / drug effects
  • Sputum / metabolism
  • Time
  • Treatment Outcome


  • Antioxidants
  • Leukocyte Elastase
  • Acetylcysteine