Distinct plasma proteome in severe pulmonary hypertension associated with chronic lung disease

The mechanisms underlying the development and severity of pulmonary hypertension (PH) in chronic lung diseases (CLD) remain incompletely understood. To identify relevant pathobiological pathways, we analyzed the protein expression profile in plasma of patients with chronic obstructive pulmonary disease (COPD) and fibrosing interstitial lung disease (ILD), stratified by the presence and severity of PH, and explored similarities with idiopathic pulmonary arterial hypertension (iPAH).

Plasma samples from 114 patients with CLD-36 without PH (17 COPD, 19 ILD), 33 with nonsevere PH (18 COPD, 15 ILD), and 45 with severe PH (28 COPD, 17 ILD)-and 38 with iPAH were analyzed using liquid chromatography-tandem mass spectrometry. We examined differential protein expression across groups and associations with hemodynamic measurements. Functional enrichment and protein interaction analyses were used to identify relevant biological pathways. Predictive protein combinations were analyzed using stepwise logistic regression.

Patients with COPD and ILD showed distinct proteomic profiles in relation to their hemodynamic status. In COPD, the presence and severity of PH were associated with dysregulation of extracellular matrix homeostasis and cell adhesion pathways, among others. Patients with ILD showed fewer differentially expressed proteins linked to PH, with the most conspicuous differences involving proteins related to immune and inflammatory response pathways. Patients with severe COPD- or ILD-associated PH displayed proteomic signatures distinct from those of iPAH.

The pathophysiological mechanisms underlying the development of PH differ between COPD and ILD, and the proteomic profile of severe PH in both conditions is distinct from that observed in iPAH.