Hypertonic Saline and Mucociliary Clearance in Children
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Previously, the investigators and others have shown that mucociliary clearance (MCC) is
      defective in patients with cystic fibrosis (CF) and it is now thought that alterations in
      airway mucus rheology figure prominently in the impairment. Mucociliary clearance works by
      trapping toxic particles, bacteria and viruses in the lung mucus and then quickly removing
      the mucus out of the lungs. Defects in MCC typically lead to the accumulation of mucus in the
      airways, and this in turn is associated with acute infections, chronic bacterial colonization
      and chronic inflammation. One treatment strategy that is gaining acceptance as an important
      therapy for improving MCC in adults with CF is the inhalation of the osmotic stimulus,
      hypertonic saline (HS). A number of studies have shown that acute inhalation of HS (7%
      saline) significantly improves MCC in adults with CF and results from a recent study indicate
      that two weeks of inhaling HS leads to a significant increase in MCC that is sustained for 8
      hours post inhalation and is associated with significant improvements in FEV1, FVC and
      FEF25-75 values. Since MCC in patients with CF appears to be impaired by adulthood, any drug
      that disrupts or slows the impairment in childhood could prove enormously beneficial in the
      long-term prognosis of the disease. Nevertheless, no studies have been conducted to determine
      if HS treatment improves MCC in children with CF. This is most problematic for physicians who
      care for children with CF who have normal FEV1 and FVC values, since it is unclear if they
      should treat these children with HS or not. This research study is designed to begin to
      answer this question. The investigators hypothesize that acute inhalation of hypertonic
      saline (7%) will improve MCC in CF children with normal pulmonary function. Our hypothesis
      will be tested in a one-year clinical trial that will be randomized and placebo-controlled.
      Twelve children with CF who are 7-12 years old and have normal FEV1 and FVC values will
      participate. Our goal will be to compare MCC in these children on two study visits after
      acute inhalations of placebo (0.12% saline) or hypertonic saline (HS) (7% saline) aerosol.
      The investigators predict that MCC values after acute inhalation of 7% HS aerosol will be
      statistically significantly greater than after placebo inhalation.
    

Detailed description: 
      Several studies report that mucociliary clearance (MCC) is impaired in adults with CF.
      Because MCC is an important airway defense mechanism, drugs that slow impairment of MCC in
      children could prove beneficial in the long-term prognosis of the disease. A few studies have
      shown that inhalation of hypertonic saline (HS) significantly improves MCC in adults with CF
      and improvement is associated with increases in pulmonary function and decreases in pulmonary
      exacerbations. Nevertheless, no studies have examined if HS improves MCC in CF children. This
      is problematic for physicians who care for CF children with normal pulmonary function, since
      it is unclear if they should treat with HS or not. This study was designed to begin to answer
      this question. Twelve children with CF (7-12 yrs; 5 males) and normal pulmonary function
      (FEV1 and FVC > 90% of predicted values) participated in a screening visit and two study
      visits. On the screening visit, children underwent an induced sputum test. On the two study
      visits, they inhaled 0.12% saline (placebo), or HS, in a double-blind, randomized, cross-over
      study. Following inhalation of placebo or HS, patients inhaled the radioisotope 99mtechnetium
      and underwent sequential imaging of their lungs with a gamma camera for 90 min and
      approximately 24 hrs later. Mucociliary clearance was quantified at 60 min (MCC60), 90 min
      (MCC90) and 24 hrs (MCC24hrs) after inhalation of the radioisotope. Between the 60 min and 90
      min measurements, children coughed 30 times.
    

Intervention name(s): 0.12% saline; 7% saline
Intervention type(s): Drug; Drug
Intervention description(s): 5mL of 0.12% saline inhaled once over 20 minutes; 5mL 7% saline inhaled once over 20 minutes
Other intervention name(s): hypertonic saline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: mucociliary clearance; children; cystic fibrosis; hypertonic saline