Hypertension, Pulmonary

Inclusion Criteria

- Diagnosis of an interstitial lung disease (usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP] or sarcoidosis) with high resolution CT and a total lung capacity (TLC) ≤ 90% or scleroderma associated pulmonary arterial hypertension (PAH) with total lung capacity (TLC) ≤ 80%.
 - Interstitial lung disease (ILD) must have been stable for at least 3 months (decrease in forced vital capacity (FVC)< 10% and diffusing capacity of lung for carbon monoxide (DLco) < 15 % in 3 months), i.e. no significant changes in pulmonary function testing and stable medication in terms of ILD (e.g., corticosteroids, immunosuppressants)
 - Mean pulmonary vascular resistance (PVR) > 400 dyne sec cm-5 or mean pulmonary arterial pressure (PAP mean) > 30 mmHg
 - Pulmonary capillary wedge pressure (PCWP) < 15 mmHg
 - Hemodynamic parameters at baseline (PAP, PCWP, cardiac output [CO], systemic mean arterial pressure [SAP])
 - High resolution computer tomography (HRCT) (should not be older than 12 months prior start of the study)
 - Heart rate > 55 beats per minute (BPM) and < 105 BPM at rest
 - Systolic blood pressure (SBP) > 90 mmHg
 -World Health Organisation (WHO) functional class II, III and IV
 - 6 Minute Walking Test (6MWT) > 100m and < 450 m
 - Stable controlled arterial hypertension according to current guidelines
 - Women of childbearing potential will be included in the study if the pregnancy test is negative and combination of condoms with a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain intra-uterine devices [IUDs]) is granted.

Exclusion Criteria

- Co-medication:
 -- Patients pretreated with specific medication for pulmonary arterial hypertension (PAH) like endothelin receptor antagonists, prostaglandins or phosphodiesterase type 5 (PDE 5) blockers are excluded from the trial.
 -- Requirement for concomitant use of nitrates are contraindicated.
 - Pre-existing clinically relevant lung disease other than ILD including.
 -- Bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD) with a forced expiratory volume in one second (FEV1)/FVC <60% pred., active tuberculosis
 -- Pulmonary hypertension of another WHO group (I, II, IV and V)
 -- Severe congenital abnormalities of the lungs, thorax and diaphragm
 -- Clinical or radiological evidence of a pulmovenoocclusive disease (PVOD)
 - Systemic hemodynamics
 -- Acute or severe chronic left heart failure (ejection fraction (EF) < 50%)
 -- Severe coronary artery disease (CAD; EF < 50%);  CAD patients must be asymptomatic and stable
 -- Congenital or acquired valvular or myocardial disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension
 - Pulmonary function
 -- TLC predicted < 30%
 -- FEV1 (related to FVC) < 60% predicted
 - Blood gases at room air
 -- Arterial partial carbon dioxide pressure (Pa CO2) > 45 mmHg 
 -- Arterial partial oxygen pressure (Pa O2) < 50 mmHg at O2 supply >/= 4 L/min
 - Peripheral organ function
 -- Moderate or severe hepatic insufficiency (Child-Pugh Class Band C and/or total bilirubin > 2.5 mg/dl (0.043 mmol/L); and/or hepatic transaminases >3 upper limit normal [ULN]) 
 -- Moderate or severe renal insufficiency (creatinine > 2 mg/dl) or creatinine clearance according to Cockroft-Gault formula < 35 mL/ min