Please select the eligibility criteria that correspond to the clinical trial below.
Title: Saline Hypertonic in Preschoolers
Brief Summary: The purpose of this study is to assess whether inhalation of 7% hypertonic saline (HS) twice daily for 48 weeks improves the lung clearance index by multiple breath nitrogen washout in comparison with inhalation of 0.9% isotonic saline (IS) in preschool children (ages 3 to 5) with cystic fibrosis.


Options:
A: Inclusion Criteria:

* Diagnosis of CF as defined by 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) has been provided by the subject's parent or legal guardian and the subject
* 6-18 years of age at enrolment
* Able to perform reproducible spirometry
* Clinically stable at enrolment
* Ability to comply with medication use, study visits and study procedures as judged by the site investigator
* FEV1 % predicted \> 70 % as calculated by the Wang reference equations

Exclusion Criteria:

* Respiratory culture positive for:

  * NTM within past year or AFB positive at screening (sputum only)
  * B. cepacia complex within past year or at screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* Investigational drug use within 30 days of screening
* History of alcohol, illicit drug or medication abuse within 1 year of screening
* Other major organ dysfunction excluding pancreatic dysfunction
* History of lung transplantation or currently on lung transplant list
* Physical findings at screening that would compromise the safety of the participant or the quality of the study data
B: 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
C: Inclusion Criteria:

* Diagnosis of CF as evidenced by one or more clinical feature consistent with the CF phenotype or positive CF newborn screen AND one or more of the following criteria:
* A documented sweat chloride ≥ 60 milliequivalents of solute per litre (mEq/L) by quantitative pilocarpine iontophoresis (QPIT)
* A documented genotype with two disease-causing mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene
* Informed consent by parent or legal guardian
* Age ≥ 36 months and ≤72 months at Screening visit
* Ability to comply with medication use, study visits and study procedures as judged by the site investigator
* Ability to perform technically acceptable MBW measurements at the screening and enrollment visits

Exclusion Criteria:

* Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding Screening or Enrollment visit
* Acute wheezing at Screening or Enrollment visit
* Oxygen saturation \< 95% (\<90% in centers located above 4000 feet elevation) at Screening or Enrollment visit
* Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator
* Investigational drug use within 30 days prior to Screening or Enrollment visit
* Treatment with inhaled hypertonic saline at any concentration within 30 days prior to Screening or Enrollment visit
* Chronic lung disease not related to CF
* Inability to tolerate first dose of study treatment at the Enrollment visit
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: C