title: Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial.
abstract: BACKGROUND
  Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted.
  
  
  OBJECTIVE
  To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ).
  
  
  METHODS
  Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30.
  
  
  RESULTS
  461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups.
  
  
  CONCLUSIONS
  Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated.
  
  
  BACKGROUND
  NCT00669331.
authors.affiliation: Department of Respiratory Medicine, Royal Brompton Hospital, London, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Bilton
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Centre, Philadelphia, Pennsylvania, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Tino
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Barker
authors.affiliation: Queensland Lung Transplant Service, The Prince Charles Hospital, Chermside, Queensland, Australia School of Medicine, The University of Queensland, Herston, Queensland, Australia.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chambers
authors.affiliation: Institute of Cellular Medicine Newcastle University & Sir William Leech Centre, Freeman Hospital, Newcastle-upon-Tyne, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: De Soyza
authors.affiliation: UZL University Hospital Leuven, Leuven, Belgium.
authors.forename: Lieven J A
authors.initials: LJ
authors.lastname: Dupont
authors.affiliation: Department of Respiratory Medicine, Middlemore Hospital, Auckland, New Zealand.
authors.forename: Conor
authors.initials: C
authors.lastname: O'Dochartaigh
authors.affiliation: Atrium MC Pulmonology Department, Heerlen, The Netherlands.
authors.forename: Eric H J
authors.initials: EH
authors.lastname: van Haren
authors.affiliation: Hospital Interzonal Especializado en Agudos y Cronicos "Dr Antonio A. Cetrangolo", Partido de Vicente Lopez Provincia de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Luis Otero
authors.initials: LO
authors.lastname: Vidal
authors.affiliation: Medizinische Hochschule Hannover, Klinik fur Pneumologie, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Pharmaxis Ltd, Frenchs Forest, Sydney, NSW, Australia.
authors.forename: Howard G
authors.initials: HG
authors.lastname: Fox
authors.affiliation: Pharmaxis Ltd, Frenchs Forest, Sydney, NSW, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Pharmaxis Ltd, Frenchs Forest, Sydney, NSW, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Charlton
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001987:Bronchiectasis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000150:complications; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005100:Expectorants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008353:Mannitol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D055118:Medication Adherence; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects; D011788:Quality of Life; D012008:Recurrence; D013183:Sputum / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005100:Expectorants; D008353:Mannitol
keywords: Bronchiectasis; Respiratory Infection