Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Bosentan on Exercise Capacity at High Altitude
Brief Summary: This study is to determine whether bosentan will alter exercise capacity after rapid ascent to high altitude.

We hypothesize that bosentan administration will improve arterial oxygenation and exercise capacity.


Options:
A: Main inclusion criteria:

* Systemic Sclerosis diffuse or limited
* Significant Interstitial Lung Disease on HRCTscan
* DLco \< 80% predicted
* Dyspnea on exertion
* Walk not limited by musculoskeletal reasons

Main exclusion criteria:

* Interstitial Lung Disease due to other conditions than SSc
* End stage restrictive or obstructive lung disease
* Severe cardiac or renal diseases
* Significant pulmonary arterial hypertension
* Smoker (\> 5cig./day)
* Treatment with immunosuppressive, antifibrotic drugs, high dose corticosteroids (within 4 weeks of randomization)
B: Inclusion Criteria:

1. Patients \>=18yrs, \<80yrs
2. Patients with idiopathic pulmonary fibrosis (IPF) or idiopathic fibrotic non-specific interstitial pneumonitis (NSIP) confirmed by their respiratory physician according to ATS/ERS criteria.
3. Patients with pulmonary hypertension on right heart catheter (mean pulmonary arterial pressure \>=25mmHg with pulmonary artery occlusion pressure, left atrial pressure or left ventricular end-diastolic pressure \<15mmHg).
4. Patients providing written informed consent.

Exclusion Criteria:

1. Patients \<18, \>80yrs.
2. Patients with unstable disease, or an acute exacerbation of their underlying fibrotic lung disease.
3. Patients with significant other organ co-morbidity including hepatic or renal impairment.
4. Patients with systolic BP \< 85mmHg
5. Patients with other conditions that may affect the ability to perform a 6-minute walk test.
6. Patients unable to provide informed consent and comply with the patient protocol.
7. Patients receiving excluded medications (including: epoprostenol, or prostacyclin analogues, phosphodiesterase inhibitors, other endothelin receptor antagonists, drugs with potential interaction with bosentan such as glibenclamide, fluconazole, cyclosporin A, or tacrolimus, and other investigational agents).
8. Patients with planned surgical intervention during the study period.
9. Pregnant patients or women of child-bearing age, who are not using a reliable contraceptive method.
10. Patients with clinically overt ischaemic heart disease.
11. Patients with predominant emphysema on high resolution CT scan (emphysema greater in extent than interstitial changes).
C: Inclusion Criteria:

* Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) due to the following:

  a. idiopathic or heritable PAH b. PAH associated with: i. connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease, systemic lupus erythematosus, or overlap syndrome) ii. drugs or toxins iii. Human Immunodeficiency Virus (HIV) infection iv. congenital heart defects repaired greater than 1 year prior to screening (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) NB: subjects with portopulmonary hypertension and pulmonary veno-occlusive disease are NOT eligible for the study
* Subject must have a current diagnosis of being in World Health Organisation (WHO) Functional Class II or III.
* Subject must meet all of the following haemodynamic criteria by means of a right heart catheterization prior to screening:

  i. mPAP of ≥25 mmHg ii. PVR ≥ 300 dynes/sec/cm5 iii. PCWP or LVEDP of ≤12 mmHg if PVR ≥300 to \<500 dyne/sec/cm5 , or PCWP/LVEDP ≤ 15 mmHg if PVR ≥500 dynes/sec/cm5
* Subject must walk a distance of ≥125m and ≤500m at the screening visit

Exclusion Criteria:

* Subject received previous PAH therapy (phosphodiesterase type 5 inhibitor (PDE5i), endothelin receptor antagonist (ERA), chronic prostanoid\*) within 4 weeks prior to the screening visit (\*Chronic prostanoid use is considered \>7 days of treatment)
* Subject received ERA treatment (e.g., bosentan or sitaxentan) or PDE5i treatment (e.g. Sildenafil) at any time AND discontinued due to tolerance issues other than those associated with liver function abnormalities
* Subjects who have previously discontinued ambrisentan or tadalafil in either another clinical study or commercial product (Volibris/Letairis or Adcirca) for safety or tolerability reasons.
D: Inclusion Criteria:

* Normal healthy subjects aged 18 - 55 years

Exclusion Criteria:

* Pregnancy
* Heart, lung or liver disease
* Use of glyburide, cyclosporin A

Answer: D