Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effects of Long Term Inhalation of Hypertonic Saline in Subjects With Cystic Fibrosis
Brief Summary: The effect of long term inhalation of hypertonic saline in subjects with cystic fibrosis on lung function, incidence of respiratory tract infections, quality of life, quantitative microbiology and sputum cytokine profile. The hypothesis is that regular inhalation of nebulised hypertonic saline will have a beneficial effect on lung function and other clinical outcomes with no adverse effects on infection and inflammation in adults and children with cystic fibrosis.


Options:
A: Inclusion Criteria:

* Confirmed diagnosis of CF (sweat tests/genotype)
* The subject, or their legal guardian for children under 18 years old, must provide written informed consent.
* The subject must be in stable clinical condition at the time of and for a period of 14 days prior to their recruitment into the study.
* Age \> 6 years old
* FEV1 \> 40% predicted for height, age and gender
* Proven or anticipated compliance with therapy or study protocol
* Regular attendee at a Cystic Fibrosis Clinic (\> 2 visits per year)
* Able to reproducibly perform lung function tests (spirometry)
* Relatively stable nutritional status (\< 2 kg weight loss in last 6 months and \< 5 kg weight loss in last year)
* Known to have "normal" (for CF subject) laboratory tests - haematology, biochemistry, immunology, coagulation, etc.

Exclusion Criteria:

* Requiring home oxygen (pO2 \<55mmHg or pCO2 \>50mmHg) or assisted ventilation.
* Considered "terminally ill" or listed for transplantation (either lung or liver). Subjects that are listed for transplant after being enrolled in the trial are eligible to continue in the trial.
* Subjects colonised with Burkholderia cepacia. However, if a subject becomes colonised with B. cepacia during the trial, they should continue in the trial. Subjects should be considered to be B. cepacia positive if they have had even a single lifetime isolate. In these subjects, spirometry should be measured on a dedicated spirometer.
* Cigarette smoker.
* Exposure to investigational drugs within the past 30 days.
* Major haemoptysis (\> 60 mL in a single episode) within the last twelve months.
* Concurrent illnesses eg. cor pulmonale, clinically significant liver disease (portal hypertension, varices).
* Known allergy to quinine sulphate, Glucose 6-phosphate dehydrogenase deficiency.
* Immune thrombocytopaenic purpura.
* Pregnant or lactating females.
* At risk females unwilling to use appropriate contraception to prevent pregnancy for the duration of their enrolment in the study.
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:

* Has a diagnosis of CF via standard criteria
* Is aged 18 years or older
* Is capable of providing written informed consent in English to participate in the study.
* Has a forced expiratory volume in 1 second (FEV1) \>= 40% and \< 110% predicted normal for age, gender, and height at Screening.
* Has a body mass index (BMI) \< 30 kg/m2
* Can tolerate cessation of treatment with HS for 72 hours and rhDNase for 24 hours prior to each treatment visit until discharge from Visits 2 and 3.
* Can tolerate cessation of treatment with long-acting beta-agonists (LABAs) for 12 hours and short-acting beta-agonists (SABAs) for 6 hours prior to radioaerosol administration for each MCC measurement and at least until discharge from Visits 2 and 3
* Is on a stable medication regimen for at least 28 days before start of dosing and can continue such regimen for duration of study
* Tolerates the 30 minute administration of 7% HS by the tPAD device at screening without subjective intolerance, oxyhemoglobin desaturation, or significant change in spirometry (\>10% reduction from pre-dose value in FEV1, measured 30 minutes after completion of the aerosol administration)

Exclusion Criteria:

* Has evidence of an acute upper or lower respiratory infection or clinically significant illness at screening or within 28 days prior to the start of dosing
* Required an acute intervention with antibiotics (oral, inhaled, or IV) or systemic corticosteroids within the last 28 days for a respiratory illness
* Has a history of intolerance to a beta-agonist or hypertonic saline
* Has evidence of significant nasal obstruction that impairs the ability to breathe through the nose
* Has a clinical diagnosis of sleep apnea
* Has current symptoms of allergic rhinitis
* Is unable to maintain a stable dosage regimen of any concomitant medication throughout the duration of the trial.
* Has participated in a clinical drug or investigational device trial within the past 28 days
* Has a history of positive test for Burkholderia cepacia
* Has a present history of any clinically significant and uncontrolled neurologic, gastrointestinal, renal, hepatic, cardiovascular (including hyper/hypotension and tachy/bradycardia), psychological, pulmonary, metabolic, endocrine, or hematological disorder or disease, or any other major disorder or disease, in the opinion of the investigator
* Has a history of smoking within the last 12 months
* Is known to be pregnant, has a positive urine pregnancy test or is nursing (female subjects only)
* Should not participate in the study, in the opinion of the Principal or Clinical investigator
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: A