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.
Author(s): Conrad C(1), Lymp J(2), Thompson V(2), Dunn C(1), Davies Z(1), Chatfield B(3),
Nichols D(4), Clancy J(5), Vender R(6), Egan ME(7), Quittell L(8), Michelson
P(9), Antony V(10), Spahr J(11), Rubenstein RC(12), Moss RB(1), Herzenberg
LA(13), Goss CH(2), Tirouvanziam R(14).
Affiliation(s): Author information:
(1)Lucile Packard Children's Hospital, Center of Excellence in Pulmonary Biology,
770 Welch Rd., #350, Stanford University, Palo Alto, CA 94304, United States.
(2)CFFT Therapeutics Development Network Coordinating Center, Seattle, WA. 2001 8th
Avenue, Seattle, WA 98121, United States.
(3)University of Utah Pediatric Pulmonology, 100N. Mario Capecchi Dr., Salt Lake
City, UT 84113, United States.
(4)National Jewish Health, 1400 Jackson St., Adult CF Center, Denver, CO 80206,
United States.
(5)Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Pulmonary
Medicine, OSB 5, Cincinnati, OH 45229, United States.
(6)Pennsylvania State University/Milton S. Hershey Medical Center, PO Box 850,
Hershey, PA 17033, United States.
(7)Yale University School of Medicine, Yale University School of Medicine, 333 Cedar
St., Rm. FMP 526, New Haven, CT 06520, United States.
(8)Morgan Stanley Children's Hospital of New York, Division of Pediatric
Pulmonology, Columbia University Medical Center, 3959 Broadway CHC 7-701, New
York, NY 10032, United States.
(9)St. Louis Children's Hospital, 660 Euclid Ave., CF Center, 10th Floor NW Tower,
St. Louis, MO 63110, United States.
(10)University of Alabama at Birmingham, 422 Tinsley Harrison Tower, 1900 University
Blvd, Birmingham, AL 35294-0006, United States.
(11)Children's Hospital of Pittsburgh of UPMC, 4221 Penn Avenue, AOB Suite 3300,
Pittsburgh, PA 15224, United States.
(12)The Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Abramson
Research Center, Room 410A, Philadelphia, PA 19104, United States.
(13)Department of Genetics, Stanford University School of Medicine, Stanford, CA
94305-5318, United States.
(14)Emory+Children's Center for CF and Airways Disease Research, 2015 Uppergate Dr.,
Rm. 344, Emory University School of Medicine, Atlanta, GA 30322, United States.
Publication date & source: 2014, J Cyst Fibros. ,
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.
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