title: Inhaled hypertonic saline in infants and toddlers with cystic fibrosis: short-term tolerability, adherence, and safety.
abstract: BACKGROUND
  Inhaled hypertonic saline (HS) is an attractive agent for chronic maintenance therapy in infants and toddlers with cystic fibrosis (CF) because it improves defective mucociliary clearance. Prior to undertaking a clinical trial of HS efficacy in young children with CF, tolerability, adherence, and safety must be established.
  
  
  METHODS
  Three-center, open label evaluation of the short-term tolerability, adherence, and safety of 7% HS administered twice daily for 14 days in children with CF 12-30 months of age. The primary objective was to evaluate the proportion of participants unable to tolerate single and repeated doses of 7% HS according to protocol-defined criteria. Participants inhaled a test dose of HS at the enrollment visit; test dose intolerance was defined as fulfillment of at least one of 4 criteria. Participants who tolerated the test dose inhaled 7% HS twice daily for 14±2 days.
  
  
  RESULTS
  Twenty children were enrolled. One was withdrawn due to maternal concern over fussiness with application of the facemask for the test dose. Of the 19 participants administered the test dose, 1 was withdrawn due to test dose intolerance (5%, 95% confidence interval 0, 26%). Eighteen participants completed the study; 1 was intolerant (95% CI 0, 27%) at the final visit due to new wheezes on exam in association with an upper respiratory infection and otitis media. Home symptom diaries demonstrated cough as the main symptom in the hour following inhalation, which decreased in frequency over the study period. Adherence as assessed by daily home diary and returned study drug ampoules was high. Participants reported receiving both treatments on a median of 100% of days; a median of 25 ampoules were used during a median of 13 days.
  
  
  CONCLUSIONS
  7% HS appears well tolerated for up to 14 days in infants and toddlers with CF, with high adherence. These results provide encouraging short-term tolerability and adherence data for future trials assessing the safety and efficacy of 7% HS in young children with CF.
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, 4800 Sandpoint Way NE, Seattle, WA 98105, USA. margaret.rosenfeld@seattlechildrens.org
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Stephanie
authors.initials: S
authors.lastname: Davis
authors.forename: Lyndia
authors.initials: L
authors.lastname: Brumback
authors.forename: Stephen
authors.initials: S
authors.lastname: Daniel
authors.forename: Ron
authors.initials: R
authors.lastname: Rowbotham
authors.forename: Robin
authors.initials: R
authors.lastname: Johnson
authors.forename: Sharon
authors.initials: S
authors.lastname: McNamara
authors.forename: Renee
authors.initials: R
authors.lastname: Jensen
authors.forename: Carol
authors.initials: C
authors.lastname: Barlow
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D000280:Administration, Inhalation; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D055118:Medication Adherence; D009079:Mucociliary Clearance / Q000187:drug effects; D010865:Pilot Projects; D012119:Respiration / Q000187:drug effects; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D012462:Saline Solution, Hypertonic