Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
Brief Summary: This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).


Options:
A: Inclusion Criteria:

* Subject has a confirmed diagnosis of cystic fibrosis based on: 3 positive sweat chloride tests and/or genetic characterisation
* Subject is 5 years of age or older
* Subject has chronic or recurrent rhinosinusitic disorders
* Subject is able to comply with the procedures scheduled in the protocol
* Women of childbearing potential are only included into the study, if they are using an effective method of birth control during the protocol (e.g. implants, combined oral contraceptives, injectables, some IUDs, sexual abstinence or vasectomised partner)

Exclusion Criteria:

* Subject has a critical condition defined as: FEV1 \< 30% and / or SaO2 \< 93% without O2-substitution; need of O2-substitution
* Subject had an ENT surgery within 6 months prior to study
* Subject shows signs of nasal bleeding
* Subject has an ear drum perforation
* Subject had an acute rhinosinusitis or a pulmonary exacerbation at study entry with need of additional systemic antibiotic therapy
* Subject has a new therapy with nasal topic steroids during treatment interval
* Subject has a new systemic steroid therapy
* Subject is unlikely to comply with the procedures scheduled in the protocol
* Subject has a known allergic reaction to the medication
* Subject is pregnant or breastfeeding
* Patient participates in another clinical trial within 30 days prior to study entry or 30 days after end of the study.
B: 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
C: Inclusion Criteria:

* Male and female patients, \>/= 6 years of age
* Confirmed diagnosis of cystic fibrosis (CF)
* Receiving Pulmozyme once daily chronically for treatment of CF for at least 6 months prior to screening
* Percent predicted FEV1 \>/= 40% at screening based on the Wang (males \< 18 years, females \< 16 years) or Hankinson (males \>/= 18 years, females \>/= 16 years) standardized equations
* Able to reproducibly perform spirometry testing and comply with study assessments

Exclusion Criteria:

* An acute respiratory infection or pulmonary exacerbation within 4 weeks prior to randomization
* Initiation of any new chronic therapy (e.g. inhaled corticosteroids, inhaled oral antibiotics, high-dose ibuprofen, hypertonic saline, ivacaftor) for respiratory disease within 4 weeks prior to randomization
* Changes in chest physiotherapy schedule within 4 weeks prior to randomization
* Hospitalization within 4 weeks prior to randomization
* Planned hospitalization during the 6-week study
* History of organ transplantation
* Participation in an investigational drug or device study within 30 day prior to screening
D: Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis (sweat test/genotype)
2. Aged 8 years or older
3. Have FEV1 between 40% and 80% of predicted for height, age and gender OR a decrease in FEV1 of 20% or more than that recorded 6-12 months previously.
4. As determined by the investigator, are capable and willing to

   * Use the study diary as required for this protocol
   * Able to perform all of the techniques necessary to measure lung function
   * Able to administer the dry powder mannitol
5. Are capable of and have given informed consent
6. Clinically stable at study entry

Exclusion Criteria:

1. Investigators, site personnel directly affiliated with this study, and their immediate families.
2. Subjects under the age of 8 years.
3. Subjects with currently active asthma
4. Subjects using hypertonic saline treatment in the last 2 weeks
5. Considered "terminally ill" or listed for transplantation
6. Requiring home oxygen or assisted ventilation
7. Colonisation with Burkholderia cepacia
8. Significant episode of hemoptysis (\>60 mls) in the previous 12 months
9. Myocardial Infarction in the six months prior to enrolment.
10. Cerebral Vascular Accident in the six months prior to enrolment.
11. Ocular surgery in the three months prior to enrolment.
12. Abdominal surgery in the three months prior to enrolment.
13. Subjects who are breast feeding or pregnant.
14. Female subjects of reproductive capability, not using a reliable form of contraception
15. Inability to obtain informed consent from the subject or subject's authorised representative.
16. Subjects who have participated in another investigative drug study parallel to, or within 4 weeks of study entry.
17. Known intolerance to mannitol or beta2 agonists.
18. Uncontrolled hypertension - systolic BP \> 160 and or diastoli

Answer: B