A joint work by the Biomedical Research Networking Center (CIBER) has revealed that the biopathological mechanisms that cause pulmonary hypertension are "markedly" different in chronic obstructive pulmonary disease (COPD) and diffuse interstitial lung disease (DILD), despite both sharing similar hemodynamic features.
The study, published in the journal 'The Journal of Heart and Lung Transplantation', examined the plasma proteome of 114 people with chronic lung disease, either COPD or DILD, with different levels of pulmonary hypertension, as well as 38 patients with idiopathic pulmonary arterial hypertension (IPAH).
To carry out the study, advanced proteomics techniques based on liquid chromatography coupled with mass spectrometry were used, which made it possible to detect differentiated patterns of protein expression linked to both the presence and intensity of pulmonary hypertension in these pathologies.
The data show that, in COPD, severe pulmonary hypertension is related to variations in proteins associated with the extracellular matrix, cell adhesion processes, and immune system activation, suggesting active vascular remodeling accompanied by inflammation.
The authors point out that these results suggest that pulmonary hypertension in COPD constitutes a biologically aggressive vasculopathy, and not just a secondary consequence of lung tissue deterioration.
In contrast, in pulmonary hypertension linked to DILD, a protein pattern associated with endothelial dysfunction and structural loss of the vascular bed predominates, with fewer global changes in the proteome. This supports the idea that, in DILD, pulmonary hypertension is more closely connected with the fibrotic process of the lung.
Differences compared to idiopathic PAH
The analysis also shows that the proteomic profiles detected in severe pulmonary hypertension associated with COPD or DILD are "clearly different" from those observed in idiopathic PAH, even when the degree of pulmonary hypertension is similar.
This result calls into question whether both entities share the same biological mechanisms and helps to understand why numerous drugs effective in PAH have offered limited benefits in patients with pulmonary hypertension linked to chronic respiratory diseases.
"These results indicate that patients with similar pulmonary pressures may have biologically different diseases," said Joan Albert Barberà, a researcher from the Respiratory Diseases area of CIBER (CIBERES) and the Hospital Clínic-August Pi i Sunyer Biomedical Research Institute (IDIBAPS).
Barberà, one of those responsible for the research, added that the molecular characterization of these patients may allow specialists to move towards a more refined classification of the pathology and, in the medium term, towards more individualized therapies.
In addition to delving into the biological bases of the disease, the work describes combinations of proteins capable of discriminating between patients with and without pulmonary hypertension, as well as between mild and severe forms, which opens the door to the development of plasma biomarkers applicable in clinical practice.
The researchers emphasize that this is an exploratory study and that, therefore, the results must be confirmed in independent cohorts and in longitudinal research. Nevertheless, they highlight that the study represents an "important step" towards the definition of molecular endotypes in pulmonary hypertension associated with chronic respiratory diseases and towards the design of future targeted therapeutic strategies.
Teams from the Bellvitge Biomedical Research Institute, the Hospital del Mar, and the Vall d'Hebron University Hospital linked to CIBERES, along with the Parc Taulí Hospital of Sabadell and the Bioinformatics Platform of the CIBER of Hepatic and Digestive Diseases (CIBEREHD), also collaborated in the project.