Introduction: The mechanisms underlying the development of pulmonary hypertension (PH) and its severity in chronic lung diseases (CLD) are unknown. The study aimed to assess the protein expression profile in plasma in patients with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD), according to the presence and severity of PH, and explore similarities with idiopathic pulmonary arterial hypertension (iPAH).

Methods: We analysed 115 patients with CLD: 40 non-PH (19 COPD, 21 ILD), 41 with moderate PH (22 COPD, 19 ILD) and 34 with severe PH (21 COPD, 13 ILD); and 38 patients with iPAH. Plasma samples were analysed by liquid chromatography-mass spectrometry. Student t-tests were used to calculate each comparison and false discovery rates computed. Proteins with a fold change >|1.5|, p-value<0.05 and present in >80% cases of the cohort were selected.

Results: CLD-PH had up-regulated proteins from the immunoglobulin superfamily (IgSF) compared with non-PH. Compared with CLD patients with moderate PH, those with severe PH had 6 IgSF proteins and lysozyme up-regulated; and keratin-1 down-regulated. Compared with iPAH, patients with CLD- severe PH had up-regulated 6 IgSF proteins, orosomucoid-1 and tenascin-C; and down-regulated IGF-binding protein-3 and tetranectin.

Conclusions: Patients with CLD and PH show a distinct proteomic profile, particularly in IgSF expression, which is further amplified in severe PH. Patients with CLD- severe PH also differ from iPAH, specially in IgSF. Further studies are warranted to assess the functionality of IgSF proteins and their clinical implications in CLD-PH.

Supported by PI18/00383 (ISCiii) and FCHP grants. OTC by MS contract, CP17/00114 (ISCiii)