Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
Brief Summary: The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients.


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:

* 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 defined by two or more clinical features of CF and a documented sweat chloride concentration \> 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
* 14 years of age and older at enrollment
* Clinically stable at enrollment
* Ability to comply with medication use, study visits and study procedures
* FEV1 % predicted \> 40% \< 80 % as calculated by reference equations

Exclusion Criteria:

* Respiratory culture positive for: B. cepacia complex within past year or at screening
* Use of systemic corticosteroids within 30 days of screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* History of biliary cirrhosis, portal hypertension, or splenomegaly
* Other major organ dysfunction
* History of lung transplantation or currently on lung transplant list
* Supplemental oxygen therapy
* Oxygen saturation \< 95 % on room air
* Positive pregnancy test at screening
* Investigational drug use within 30 days of screening
* History of alcohol, illicit drug or medication abuse within 1 year of screening
* Acute respiratory symptoms
* Inability to take any form of bronchodilator
* Wheezing at the time of study
D: Inclusion Criteria:

* Subject has a confirmed diagnosis of cystic fibrosis based on: 2 positive sweat chloride tests and/or genetic characterization
* Subject is 8 years of age or older
* informed consent of the patient or legal representative
* Women of childbearing potential are only included into the study, if they are using an effective method of birth control during the protocol (failure rate \<1% e.g. implants, combined oral contraceptives, injectables, some intrauterine devices, sexual abstinence or vasectomised partner)

Exclusion Criteria:

* Subject has no chronic rhinosinusitis (European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS-criteria)
* Subject has a critical condition defined as: forced expiratory volume at one second \< 30% and / or arterial oxygen saturation \< 93% without O2-substitution; need of O2-substitution
* Subject had an ENT surgery within 6 months prior to study
* Subject participates in another clinical trial within 30 days prior to study entry

Answer: C