Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase IV Study on the Effects of Sildenafil in Combination With Pulmonary Rehabilitation Program on Exercise Tolerance in Patients With COPD and Pulmonary Hypertension
Brief Summary: Sildenafil is a phosphodiesterase-5 inhibitor that has been approved for the treatment of pulmonary arterial hypertension with orphan drug designation. Sildenafil modulates the nitric oxide (NO) pathway in the vessel wall. Since this pathway is impaired in pulmonary arteries of patients with pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD), the investigators hypothesized that sildenafil might improve pulmonary hemodynamics and increase exercise tolerance in this condition.


Options:
A: Inclusion Criteria:

* \>18 years
* Written inform consent
* PH secondary to diastolic left heart failure defined as
* PAP mean \>25 mmHg
* Wedge mean \>15 mmHg
* Normal systolic left ventricular (LV) function on echo/nuclear imaging (left ventricular ejection fraction (LVEF) \> or =45%)
* New York Heart Association class (NYHA) II-IV despite heart failure therapy

Exclusion Criteria:

* Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonary disease)
* Other cause of PH besides diastolic heart failure
* Coronary ischemia or recent myocardial infarction (\<6 months)
* Hypotension ( \<90/50 mmHg)
* Ongoing nitrate therapy
* Ongoing therapy with citochrome P450 3A4 ( CYP3A4) inhibitors (ketoconazole, erythromycin, cimetidine, clarithromycin, itraconazole, voriconazole and protease inhibitors) or CYP3A4 inductors(carbamacepine, phenytoin, phenobarbital, rifampicin, Sint Janskruid ). Furthermore patients will be informed not to drink grapefruit juice while on study medication because of the known impact of grape fruit on pharmacokinetics of Sildenafil.
* Ongoing therapy with alpha -inhibitors
* Significant mitral or aortic valve dysfunction
* Severe liver dysfunction
* Pregnancy
* Unable to read and comprehend Dutch language
B: Inclusion Criteria:

* Patients of ES with age greater than or equal to 14 years and weight greater than or equal to 30 kgs in World Health Organisation (WHO) functional class II and III attending our congenital clinic were invited to participate in the study

Exclusion Criteria:

* WHO class IV,
* congestive heart failure or had PCWP \> 15mmHg,
* left ventricular ejection fraction \<40%,
* atrial fibrillation,
* patent ductus arteriosus,
* complex congenital heart defects,
* restrictive lung disease(total lung capacity \< 70% of predicted), obstructive lung disease ( forced expiratory volume in 1 second \[FEV1\] \< 70% of predicted with FEV1/ Forced vital capacity \[FVC\] \< 60%),
* previously diagnosed coronary artery disease requiring nitrate therapy,
* abnormal biochemical profile and
* hypersensitivity to PDE- 5 inhibitors.
C: Inclusion Criteria:

* COPD, FEV1 \< 80% ref. and FEV1/FVC \< 0.7 post bronchodilator
* Age 40-80 years
* Pulmonary hypertension
* Consent to participate in the study

Exclusion Criteria:

* Pulmonary or extrapulmonary disease that modifies gas exchange or pulmonary hemodynamics
* Recent exacerbation (\<4 weeks) (temporally)
* Patients treated with nitrates or CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir)
* Ischemic optic neuropathy
* Patients treated with phosphodiesterase-5 inhibitors
* Patients with ischemic cardiopathy
* Systemic disease that could modified the results
* Patients unable to practise exercise
D: Inclusion Criteria:

* Must have participated and discontinued in the previous PAH placebo controlled study due to clinical worsening on placebo or tadalafil 2.5 mg, 10mg, or 20 mg
* Must have completed Week 16 of the previous PAH study and had either no clinical worsening or became clinically worse at the Week 16 visit on placebo or tadalafil 2.5 mg, 10mg, or 20 mg
* Females who have a negative urine pregnancy test and are willing to use 2 types of birth control
* Be 12 years or older (country specific regulations apply) with parental approval

Exclusion Criteria:

* Participated in the placebo controlled study and had clinical worsening on 40 mg tadalafil
* Have left-sided heart disease
* Have a musculoskeletal disorder that limits being able to get around
* Nitrate use
* Certain current systemic treatments

Answer: C