Hypertonic Saline and Mucociliary Clearance in Children
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: 0.12% saline; 7% saline
Intervention description: 5mL of 0.12% saline inhaled once over 20 minutes; 5mL 7% saline inhaled once over 20 minutes
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 17.0
Sex: All
Minimum age: 7 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: mucociliary clearance; children; cystic fibrosis; hypertonic saline

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females

          -  Age 7-12 years old

          -  Diagnosis of cystic fibrosis by sweat chloride > 60 meq/L, or presence of two CFTR
             mutations known to cause CF

          -  Routinely treated with the short-acting bronchodilator albuterol

          -  FEV1 > 90% of predicted values

        Exclusion Criteria:

          -  FEV1 < 90% of predicted values

          -  Routine use of hypertonic saline, mannitol, or amiloride

          -  Allergic bronchopulmonary aspergillosis (ABPA)

          -  Sputum colonization with Burkholderia cepacia or multiple antibiotic resistant
             organisms

          -  Evidence of a pulmonary exacerbation within past two weeks

          -  Treated with intravenous or oral antibiotics in the past two weeks for a pulmonary
             exacerbation

          -  Presence of an acute respiratory illness characterized by:

               -  Coughing above baseline values

               -  Wheezing

               -  Respiratory distress

               -  Hemoptysis

          -  Cannot perform the inhalation maneuvers that are required for drug inhalation or
             radioaerosol administration