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: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Lucile Packard Children's Hospital, Center of Excellence in Pulmonary Biology, 770 Welch Rd., #350, Stanford University, Palo Alto, CA 94304, United States.
authors.forename: C
authors.initials: C
authors.lastname: Conrad
authors.affiliation: CFFT Therapeutics Development Network Coordinating Center, Seattle, WA. 2001 8th Avenue, Seattle, WA 98121, United States.
authors.forename: J
authors.initials: J
authors.lastname: Lymp
authors.affiliation: CFFT Therapeutics Development Network Coordinating Center, Seattle, WA. 2001 8th Avenue, Seattle, WA 98121, United States.
authors.forename: V
authors.initials: V
authors.lastname: Thompson
authors.affiliation: Lucile Packard Children's Hospital, Center of Excellence in Pulmonary Biology, 770 Welch Rd., #350, Stanford University, Palo Alto, CA 94304, United States.
authors.forename: C
authors.initials: C
authors.lastname: Dunn
authors.affiliation: Lucile Packard Children's Hospital, Center of Excellence in Pulmonary Biology, 770 Welch Rd., #350, Stanford University, Palo Alto, CA 94304, United States.
authors.forename: Z
authors.initials: Z
authors.lastname: Davies
authors.affiliation: University of Utah Pediatric Pulmonology, 100N. Mario Capecchi Dr., Salt Lake City, UT 84113, United States.
authors.forename: B
authors.initials: B
authors.lastname: Chatfield
authors.affiliation: National Jewish Health, 1400 Jackson St., Adult CF Center, Denver, CO 80206, United States.
authors.forename: D
authors.initials: D
authors.lastname: Nichols
authors.affiliation: Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Pulmonary Medicine, OSB 5, Cincinnati, OH 45229, United States.
authors.forename: J
authors.initials: J
authors.lastname: Clancy
authors.affiliation: Pennsylvania State University/Milton S. Hershey Medical Center, PO Box 850, Hershey, PA 17033, United States.
authors.forename: R
authors.initials: R
authors.lastname: Vender
authors.affiliation: Yale University School of Medicine, Yale University School of Medicine, 333 Cedar St., Rm. FMP 526, New Haven, CT 06520, United States.
authors.forename: M E
authors.initials: ME
authors.lastname: Egan
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Quittell
authors.affiliation: St. Louis Children's Hospital, 660 Euclid Ave., CF Center, 10th Floor NW Tower, St. Louis, MO 63110, United States.
authors.forename: P
authors.initials: P
authors.lastname: Michelson
authors.affiliation: University of Alabama at Birmingham, 422 Tinsley Harrison Tower, 1900 University Blvd, Birmingham, AL 35294-0006, United States.
authors.forename: V
authors.initials: V
authors.lastname: Antony
authors.affiliation: Children's Hospital of Pittsburgh of UPMC, 4221 Penn Avenue, AOB Suite 3300, Pittsburgh, PA 15224, United States.
authors.forename: J
authors.initials: J
authors.lastname: Spahr
authors.affiliation: The Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Abramson Research Center, Room 410A, Philadelphia, PA 19104, United States.
authors.forename: R C
authors.initials: RC
authors.lastname: Rubenstein
authors.affiliation: Lucile Packard Children's Hospital, Center of Excellence in Pulmonary Biology, 770 Welch Rd., #350, Stanford University, Palo Alto, CA 94304, United States.
authors.forename: R B
authors.initials: RB
authors.lastname: Moss
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5318, United States.
authors.forename: L A
authors.initials: LA
authors.lastname: Herzenberg
authors.affiliation: CFFT Therapeutics Development Network Coordinating Center, Seattle, WA. 2001 8th Avenue, Seattle, WA 98121, United States.
authors.forename: C H
authors.initials: CH
authors.lastname: Goss
authors.affiliation: 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.
authors.forename: R
authors.initials: R
authors.lastname: Tirouvanziam
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D012129:Respiratory Function Tests / Q000379:methods; D013183:Sputum / Q000187:drug effects / Q000378:metabolism; D013995:Time; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D019272:Leukocyte Elastase; D000111:Acetylcysteine
keywords: Anti-oxidant; Clinical trial; Cystic fibrosis; Glutathione; Lung function