Aim: to investigate the role of inflammation and auto-immunity in pulmonary arterial hypertension by using the profile of volatile organic compounds.

Hypothesis: first, the investigators hypothesize that at time of diagnosis the VOC profiles will discriminate patients with PAH-CTD and idiopathic PAH (IPAH) from patients with systemic sclerosis or systemic lupus erythematosus (CTD) without PAH, supporting the contention that there is a overlapping inflammatory and auto-immune pathway in PAH. During follow-up, the investigators will measure the VOC profiles of patients in all three groups who will be treated according standard clinical care. The hypothesis is that VOC profiles are affected by therapy.

Inclusion Criteria:

1. PAH-CTD patients, inclusion criteria:

   • classification as definite systemic sclerosis or systemic lupus erythematosus according to respectively the ACR-EULAR criteria (16) and SLICC criteria (17)
   • minimal age of 18 year
   • diagnosis of pulmonary arterial hypertension: mean pulmonary artery pressure (mPAP) of ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and a pulmonary vascular resistance (PVR) ≥240 dynes.s.cm-5 measured by right heart catherization.

2. IPAH patients, inclusion criteria:

   • diagnosis of pulmonary arterial hypertension: mean pulmonary artery pressure (mPAP) of ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and a pulmonary vascular resistance (PVR) ≥240 dynes.s.cm-5 measured by right heart catherization.
   • no family history of PAH
   • triggering factor is excluded: connective tissue disease, drugs or toxins, human immunodeficiency virus, congenital heart disease, portal hypertension, schistosomiasis (2)
   • minimal age of 18 year

3. SSc and SLE (CTD) patients without PAH, inclusion criteria:

   • classification as definite systemic sclerosis or systemic lupus erythematosus according to respectively the ACR-EULAR criteria (16) and SLICC criteria (17)
   • minimal age of 18 year
   • no signs of PAH at screening visit

Exclusion Criteria:

• active or treated malignancy
• tuberculosis or hepatitis B/C infection in case of start immunosuppressive therapy
• need to start immediately with therapy
• already use of immune suppression

See eligibility criteria