Please select the eligibility criteria that correspond to the clinical trial below.
Title: Acute Inhalation of Hypertonic Saline Does Not Improve Mucociliary Clearance in All Children With Cystic Fibrosis
Brief 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.


Options:
A: Inclusion Criteria:

* Subject has a confirmed diagnosis of cystic fibrosis based on: 2 positive sweat chloride tests and/or genetic characterization
* Subject is 8 years of age or older
* informed consent of the patient or legal representative
* Women of childbearing potential are only included into the study, if they are using an effective method of birth control during the protocol (failure rate \<1% e.g. implants, combined oral contraceptives, injectables, some intrauterine devices, sexual abstinence or vasectomised partner)

Exclusion Criteria:

* Subject has no chronic rhinosinusitis (European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS-criteria)
* Subject has a critical condition defined as: forced expiratory volume at one second \< 30% and / or arterial oxygen saturation \< 93% without O2-substitution; need of O2-substitution
* Subject had an ENT surgery within 6 months prior to study
* Subject participates in another clinical trial within 30 days prior to study entry
B: 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
C: Inclusion Criteria:

* Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
* Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
* 6-18 years of age at enrolment and able to perform reproducible spirometry
* Clinically stable at enrolment
* FEV1 % predicted ≥ 80 % as calculated by the Wang reference equations
* Ability to comply with medication use, study visits and study procedures

Exclusion Criteria:

* Respiratory culture positive for NTM or B. cepacia complex within past year or screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* Investigational drug use within 30 days of screening
* Physical findings at screening that would compromise the safety of the participant or the quality of the study data
D: Inclusion Criteria:

* diagnosis of Cystic Fibrosis (genotyping and sweat test)
* \> 8 year-old
* clinically and therapeutically stable disease in the last 30 days;
* Forced Expiratory Volume in one second (FEV1) ≥ 50% of predicted value;
* intolerance (cough, throat irritation, saltiness) to previous administration of 5.8% hypertonic saline solution.

Exclusion Criteria:

* decrease in FEV1 \>15% after first inhalation of hypertonic saline;
* Burkholderia cepacia infection;
* infective exacerbation requiring antibiotic treatment in the 15 days preceding enrolment;
* patient non compliant to standard therapy;
* Lung transplant;
* Patient unable to perform reproducible spirometry;
* Intolerance to β2 bronchodilators;
* Concurrent enrolment in other clinical trials;
* Plasmatic creatinine and transaminases more than twice the normal values.

Answer: B