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:

* Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND either: (a) A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis or (b) A genotype with two identifiable CF-causing mutations
* Informed consent by parent or legal guardian
* Age 4 months to \< 60 months at Enrollment visit. If participating in Infant Pulmonary Function testing (selected sites), age 4 months to \< 16 months at Enrollment visit.
* Ability to comply with medication use, study visits, and study procedures as judged by the site investigator

Exclusion Criteria:

* Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding Enrollment visit
* Acute wheezing at Enrollment visit (prior to HS test dose), or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
* Oxygen saturation \< 95% (\< 90% in centers located above 4000 feet elevation) at Enrollment visit (prior to HS test dose) or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
* Other major organ dysfunction, excluding pancreatic dysfunction
* Physical findings that would compromise the safety of the subject or the quality of the study data as determined by the site investigator
* Investigational drug use within 30 days prior to Enrollment visit, or within 30 days prior to Infant PFT visit as applicable
* Treatment with inhaled hypertonic saline at any concentration within 30 days of Enrollment visit, or within 30 days prior to Infant PFT visit as applicable
* Chronic lung disease not related to CF
* Intolerance of test dose of HS at Enrollment visit
* A sibling that has been randomized and is still enrolled in ISIS002

Additional Exclusion Criteria for Participation in Infant Pulmonary Function Testing:

* History of adverse reaction to sedation
* Clinically significant upper airway obstruction as determined by the Site Investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea)
* Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy
* Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 2 weeks preceding visit
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:

* Gender: Females or Males. If the subject is female and of childbearing potential (first menses has occurred), she must have a documented negative pregnancy test at screening and prior to each mucociliary clearance study. Those of childbearing potential must be abstinent or using an acceptable method of birth control (i.e. an Intrauterine Contraceptive Device with a failure rate of \<1%, hormonal contraceptives or a barrier method).
* Age: 5-12 years, inclusive
* Diagnosis: Cystic fibrosis documented by a compatible clinical presentation and sweat chloride \> 60 mEq/l or 2 disease causing CFTR mutations.
* Severity of the Disease: Suitable patients will have mild lung disease, as defined by:

  * Pulmonary Function: Each patient must have an FEV1 of greater than or equal to 60% of predicted at the screening visit.
  * Hemoglobin saturation: Patients must have an oxygen saturation of \>92% on room air as determined by pulse oximetry at the screening visit.
* Informed consent - The patient and a parent or legally authorized guardian must agree to the subject's participation in the study by signing and dating the informed consent/assent forms after the nature of the study has been fully explained and all questions have been satisfactorily answered.

Exclusion Criteria:

* Unstable or asthmatic lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 15% below recent (within 6 months) clinical measurements. Patients with a history of co-existent asthma, as manifested by wheezing and significant bronchoreactivity (\>15% increase in FEV1 with bronchodilator), will also be excluded.
* Other medication usage: Patients unable or unwilling to be withdrawn from hypertonic saline therapy for two weeks prior to Visit 1 (baseline MCC visit). Patients using Pulmozyme will be permitted to participate in this trial. Patients on chronic, cycling antibiotics will be required to have completed at least 2 full cycles of the prescribed antibiotic prior to enrollment and should not cycle on or off this therapy during the treatment period of the study.
* Spirometry Performance: Those subjects who are unable to perform acceptable, reproducible spirometry will be excluded from this study.
* Drug allergy: A history of allergy or intolerance to any of the study medications, including albuterol or hypertonic saline.
* Have received an investigational drug or therapy during the preceding 30 days.
* Have had radiation exposure within the past year that would cause them to exceed Federal Regulations by participating in this study.

Answer: B