title: Mucus clearance and lung function in cystic fibrosis with hypertonic saline.
abstract: BACKGROUND
  Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense. Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function.
  
  
  METHODS
  A total of 24 patients with cystic fibrosis were randomly assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent sodium chloride) four times daily with or without pretreatment with amiloride. Mucus clearance and lung function were measured during 14-day baseline and treatment periods.
  
  
  RESULTS
  Long-term inhalation of hypertonic saline without pretreatment with amiloride (i.e., with placebo pretreatment) resulted in a sustained (> or =8 hours) increase in 1-hour rates of mucus clearance, as compared with those with amiloride pretreatment (14.0+/-2.0 vs. 7.0+/-1.5 percent, respectively; P=0.02) and increased 24-hour rates of mucus clearance over baseline. Furthermore, inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second (FEV1) between the baseline period and the treatment period (mean difference, 6.62 percent; 95 percent confidence interval, 1.6 to 11.7; P=0.02), whereas hypertonic saline with amiloride did not improve FEV1 (mean difference, 2.9 percent; 95 percent confidence interval, -2.2 to 8.0; P=0.23). Forced vital capacity (FVC), the forced expiratory flow between 25 and 75 percent of FVC (FEF25-75), and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo, whereas the residual volume as a proportion of total lung capacity (RV:TLC) did not change in either group. A comparison of the changes in lung function in the two groups showed no significant difference. In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance, whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit.
  
  
  CONCLUSIONS
  In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease.
authors.affiliation: University of North Carolina at Chapel Hill Cystic Fibrosis Research and Treatment Center, Chapel Hill 27599, USA. scott_donaldson@med.unc.edu
authors.forename: Scott H
authors.initials: SH
authors.lastname: Donaldson
authors.forename: William D
authors.initials: WD
authors.lastname: Bennett
authors.forename: Kirby L
authors.initials: KL
authors.lastname: Zeman
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.forename: Robert
authors.initials: R
authors.lastname: Tarran
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008450:Maximal Midexpiratory Flow Rate / Q000187:drug effects; D009079:Mucociliary Clearance / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D011292:Premedication; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D014797:Vital Capacity / Q000187:drug effects; D014867:Water / Q000502:physiology
chemical_list: D012462:Saline Solution, Hypertonic; D026941:Sodium Channel Blockers; D014867:Water; D000584:Amiloride