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

• Published in: Journal of cystic fibrosis Vol. 14; no. 2; pp. 219 - 227
• Main Authors: Conrad, C, Lymp, J, Thompson, V, Dunn, C, Davies, Z, Chatfield, B, Nichols, D, Clancy, J, Vender, R, Egan, M.E, Quittell, L, Michelson, P, Antony, V, Spahr, J, Rubenstein, R.C, Moss, R.B, Herzenberg, L.A, Goss, C.H, Tirouvanziam, R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2015
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - adverse effects; Administration, Oral; Adolescent; Adult; Anti-oxidant; Antioxidants - administration & dosage; Antioxidants - adverse effects; Child; Clinical trial; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - drug therapy; Cystic Fibrosis - metabolism; Cystic Fibrosis - physiopathology; Double-Blind Method; Drug Monitoring; Female; Glutathione; Humans; Inflammation - drug therapy; Inflammation - metabolism; Leukocyte Elastase - metabolism; Lung - drug effects; Lung - metabolism; Lung - physiopathology; Lung function; Male; Oxidative Stress - drug effects; Pulmonary/Respiratory; Respiratory Function Tests - methods; Sputum - drug effects; Sputum - metabolism; Time; Treatment Outcome; Cystic fibrosis; Clinical trial; Lung function; Anti-oxidant; Glutathione
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2014.08.008

Abstract 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). Log10 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.