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

C. Conrad; J. Lymp; V. Thompson; C. Dunn; Z. Davies; B. Chatfield; D. Nichols; J. Clancy; R. Vender; M. E. Egan; L. Quittell; P. Michelson; V. Antony; J. Spahr; R. C. Rubenstein; R. B. Moss; L. A. Herzenberg; C. H. Goss; R. Tirouvanziam

doi:10.1016/j.jcf.2014.08.008

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

C. Conrad, J. Lymp, V. Thompson, C. Dunn, Z. Davies, B. Chatfield, D. Nichols, J. Clancy, R. Vender, M. E. Egan, L. Quittell, P. Michelson, V. Antony, J. Spahr, R. C. Rubenstein, R. B. Moss, L. A. Herzenberg, C. H. Goss, R. Tirouvanziam

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

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 24weeks. 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 FEF_25-75%) 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 (24week FEV₁ treatment effect=150mL, 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.

Original language	English
Pages (from-to)	219-227
Number of pages	9
Journal	Journal of Cystic Fibrosis
Volume	14
Issue number	2
DOIs	https://doi.org/10.1016/j.jcf.2014.08.008
State	Published - Mar 1 2015

Keywords

Anti-oxidant
Clinical trial
Cystic fibrosis
Glutathione
Lung function

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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. (2015). 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. Journal of Cystic Fibrosis, 14(2), 219-227. https://doi.org/10.1016/j.jcf.2014.08.008

@article{d8f48152ca0640c9a0440e02aa81a0cf,

title = "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",

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 24weeks. 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 (24week FEV1 treatment effect=150mL, 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",

author = "C. Conrad and J. Lymp and V. Thompson and C. Dunn and Z. Davies and B. Chatfield and D. Nichols and J. Clancy and R. Vender and Egan, {M. E.} and L. Quittell and P. Michelson and V. Antony and J. Spahr and Rubenstein, {R. C.} and Moss, {R. B.} and Herzenberg, {L. A.} and Goss, {C. H.} and R. Tirouvanziam",

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year = "2015",

month = mar,

day = "1",

doi = "10.1016/j.jcf.2014.08.008",

language = "English",

volume = "14",

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Conrad, C, Lymp, J, Thompson, V, Dunn, C, Davies, Z, Chatfield, B, Nichols, D, Clancy, J, Vender, R, Egan, ME, Quittell, L, Michelson, P, Antony, V, Spahr, J, Rubenstein, RC, Moss, RB, Herzenberg, LA, Goss, CH & Tirouvanziam, R 2015, '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', Journal of Cystic Fibrosis, vol. 14, no. 2, pp. 219-227. https://doi.org/10.1016/j.jcf.2014.08.008

TY - JOUR

T1 - Long-term treatment with oral N-acetylcysteine

T2 - Affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial

AU - Conrad, C.

AU - Lymp, J.

AU - Thompson, V.

AU - Dunn, C.

AU - Davies, Z.

AU - Chatfield, B.

AU - Nichols, D.

AU - Clancy, J.

AU - Vender, R.

AU - Egan, M. E.

AU - Quittell, L.

AU - Michelson, P.

AU - Antony, V.

AU - Spahr, J.

AU - Rubenstein, R. C.

AU - Moss, R. B.

AU - Herzenberg, L. A.

AU - Goss, C. H.

AU - Tirouvanziam, R.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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 24weeks. 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 (24week FEV1 treatment effect=150mL, 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.

AB - 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 24weeks. 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 (24week FEV1 treatment effect=150mL, 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.

KW - Anti-oxidant

KW - Clinical trial

KW - Cystic fibrosis

KW - Glutathione

KW - Lung function

UR - http://www.scopus.com/inward/record.url?scp=84924340525&partnerID=8YFLogxK

U2 - 10.1016/j.jcf.2014.08.008

DO - 10.1016/j.jcf.2014.08.008

M3 - Article

C2 - 25228446

AN - SCOPUS:84924340525

SN - 1569-1993

VL - 14

SP - 219

EP - 227

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 2

ER -

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

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