Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Crossover Mucociliary Clearance Study of Aerosolized 7% NaCl Solution Administered Overnight by the tPAD Device to Subjects With Cystic Fibrosis
Brief Summary: The primary objective of this study is to determine whether a single overnight, eight-hour administration of a 7% NaCl solution delivered by the Parion Sciences transnasal Pulmonary Aerosol Delivery (tPAD) device has a significant effect on mucociliary clearance in subjects with cystic fibrosis, as compared to no treatment. This study will be conducted at the University of Pittsburgh Medical Center.


Options:
A: 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
B: 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.
C: Inclusion Criteria:

1. Male or female patients with a documented diagnosis of CF aged ≥18 years.
2. Written informed consent.
3. At least day 10 - 14 of IV antibiotic therapy during a hospital admission for a pulmonary exacerbation.
4. Patients must be able to perform acceptable spirometric manoeuvres, according to the American Thoracic Society/ERS (ATS/ERS) standards (Miller, Hankinson et. al. 2005).
5. Patient with an FEV1% predicted of ≥ 40%predicted (Stanojevic, Wade et al. 2008).
6. Patients who are productive of sputum from screening visit to study visit 1 (≥10g over 24 hours).
7. Patients who have been prescribed HTS (Nebusal 7%) and have successfully completed a challenge test.
8. Any other chronic medication must have commenced therapy 4 weeks prior to screening and be willing to continue this therapy for the entire duration of the study.

Exclusion Criteria:

1. Day 1-9 of IV antibiotic therapy during a hospital admission.
2. Patients who are colonized with Burkholderia cepacia complex.
3. Patient who are HTS naive.
4. Patients who have an intolerance to HTS.
5. Patients who are currently participating in another study or have participated in another study with an investigational drug within one month of screening.
6. Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

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D: 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

Answer: D