Hypertonic Saline and Mucociliary Clearance in Children
Hypertonic Saline and Mucociliary Clearance in Children
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.
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.
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