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

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, FEV1 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 (FEV1 and FEF25-75%) remained stable or increased slightly in the NAC group but decreased in the placebo group (p = 0.02 and 0.02). Log(10) FINE activity remained equal between cohorts (difference 0.21, 95% CI -.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 < .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. (C) 2014 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.