Please select the eligibility criteria that correspond to the clinical trial below.
Title: Acute Effects of a Single Dose of Sildenafil (20mg/40mg) on Pulmonary Haemodynamics and Gas Exchange at Rest and During Exercise in COPD Patients With 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), we hypothesized that sildenafil might improve pulmonary hemodynamics and increase exercise tolerance in this condition. However, in COPD sildenafil may also impair gas exchange due to the inhibition of pulmonary hypoxic vasoconstriction. The research project is aimed to evaluate these effects.

It is a prospective, randomized, double-blind study to evaluate the acute effects of a single dose of 20 or 40 mg of sildenafil on gas exchange and pulmonary hemodynamics. Subjects: 20 patients (10 in each group). Measurements: pulmonary hemodynamics, arterial blood gasses and ventilation-perfusion distributions; at rest and during sub-maximal exercise.


Options:
A: Inclusion Criteria:

* Clinical diagnosis of IPF
* 40-85 years of age
* 6-minute walk distance 150-500 m
* FVC 40-90% predicted
* DLCO 30-90% predicted

Exclusion Criteria:

* Severe pulmonary hypertension
* Severe heart failure
* FEV1/FVC \< 0.7
B: Inclusion Criteria:

* Participant in Apex 2 high altitude expedition

Exclusion Criteria:

* Previous history of high altitude pulmonary edema
C: Inclusion Criteria:

* COPD (FEV1/FVC\<0.7)
* Age 40-75
* Pulmonary hypertension (Vmax TI\>=2.8m/sec)

Exclusion Criteria:

* Treatment with CYP3A4 inhibitors, nitrates, PDE-5 inhibitors
* Coronary disease
* Ischemic optical neuritis
D: Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-mandated procedure
2. Males or females \>=12 years of age (except for countries where this age limit is contrary to specific regulatory requirements).

   - Women of childbearing potential must have a negative pretreatment pregnancy test and must use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.

   ·Reliable methods of contraception are:

   O Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.

   O Intrauterine devices. O Oral, transdermal, injectable or implantable contraceptives only in combination with a barrier method.
   * Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception.
   * Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.

     * Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or documented surgically or naturally sterile.
3. Patients with symptomatic PAH
4. Patients with the following types of PAH belonging to WHO Group I:

   * Idiopathic (IPAH)
   * Familial (FPAH)
   * Associated with (APAH):

     i. Collagen vascular disease with normal left ventricular function (ejection fraction (EF) \> 50%) ii. Congenital systemic-to-pulmonary shunts at least 2 years post surgical repair iii. Drugs and toxins
5. PAH diagnosed by right heart catheter showing:

   * Mean pulmonary arterial pressure (mPAP) \>= 25 mm Hg AND
   * Pulmonary capillary wedge pressure (PCWP) =\< 15 mm Hg or left ventricular end diastolic pressure (LVEDP) =\< 15 mmHg If both PCWP and LVEDP are available then the LVEDP value is retained for inclusion.
6. Treatment with a stable dose of sildenafil equal to or greater than 20 mg t.i.d. for at least 12 weeks prior to randomization (no sildenafil dosage adjustment should occur in this period) 7)150 m =\< 6-minute walk test (6MWT) =\< 480 m, documented by 2 tests with second 6MWT within 15% of first 6MWT distance or a third test required

Exclusion Criteria :

1. PAH belonging to WHO group II-V
2. PAH associated with portal hypertension and HIV infection
3. PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy
4. PAH associated with significant venous or capillary involvement (PCWP \> 15 mmHg): pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis
5. Persistent pulmonary hypertension of the newborn
6. Significant valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization (i.e. patients with tricuspid or pulmonary insufficiency secondary to PAH can be included)
7. Restrictive lung disease: total lung capacity (TLC) \< 60% of normal predicted value (see Appendix 3)
8. Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) \< 0.5
9. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
10. Known HIV infection
11. Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements or that may interfere with the safety or the evaluation of the study, such as chronic infection, chronic renal failure etc.
12. Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
13. Pregnancy or breast-feeding
14. Condition that prevents compliance with the protocol or adherence to therapy
15. Systolic blood pressure \< 85 mmHg
16. Body weight \< 40 kg
17. Hemoglobin \<75% of the lower limit of the normal range
18. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal ranges
19. Known hypersensitivity or history of drug-related adverse events with bosentan (e.g. increase in liver function test results), or any of the excipients of its formulation
20. Receipt of an investigational product other than sildenafil within 3 months before start of study treatment
21. Treatment with endothelin receptor antagonists (ERAs), prostanoids or phosphodiesterase (PDE) 5 inhibitors other than sildenafil within 3 months prior to randomization
22. Concomitant systemic treatment within 1 week prior to randomization with

    * calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus and everolimus
    * glibenclamide (glyburide)
    * both cytochrome P2C9 (CYP2C9) and cytochrome P3A4 (CYP3A4) (e.g., fluconazole, amiodarone, voriconazole)
    * combination of drugs that inhibit CYP2C9 and CYP3A4
23. Treatment with nitrates and alpha-blockers at time of randomization
24. In the opinion of the investigator - patients in need for treatment with any prostanoid up to Visit 4
25. Significant left ventricular dysfunction

Answer: C