Semmelweis University

THE ROLE OF THE NITRIC OXIDE PATHWAY AND EOSINOPHILIC INFLAMMATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Csoma Balázs

Clinical Medicine

Dr. Reusz György

SE Pulmonológiai Klinika tanterme

2025-01-15 14:00:00

Pulmonológia

Magyar Pál

Dr. Lázár Zsófia

Dr. Kiss Levente

Dr. Barta Imre

Dr. Fekete Andrea

Dr. Czövek Dorottya

Dr. Szabó Mariann

COPD affects over 200 million people worldwide and is responsible for more than 3 million deaths yearly. Cardiovascular diseases are the most common comorbidities, which can influence COPD progression, but can also be affected by the pathological processes of the airway disease. Exacerbations have long-term unfavourable consequences on patients’ quality of life, they accelerate disease progression and are the leading cause of COPD-associated mortality. Easy-to-use biomarkers, predictive of relapses, and the better understanding of the relationship between airway and vascular inflammation are of clinical importance. We described a connection between airway inflammation and impaired endothelial NO synthase activity, a known mechanism involved in endothelial dysfunction. We found that the substrate availability for endothelial NO synthase (reflected by Larginine/ADMA) is decreased in stable and exacerbated COPD, while SDMA is transiently elevated during a relapse. ADMA and SDMA showed correlations to airway inflammatory markers including exhaled NO concentration, sputum inflammatory and neutrophil cell counts. Our findings suggest that the suppression of airway inflammation could also modulate vascular NO signalling in COPD and might favourably affect the development of cardiovascular events. Blood eosinophil granulocyte percentage and number are used to define eosinophilic exacerbations of COPD, which are associated with distinct clinical features. We found that this phenotype is not linked with an increased risk of earlier recurrence of moderate and severe relapses, but the increased number of prior hospitalizations, smoking history and lower FEV1% predicted are associated with a shorter exacerbation-free time with the strongest parameter being the previous exacerbation history. Importantly, upon recurrent exacerbations, the eosinophilic phenotype is less consistent than the non-eosinophilic phenotype. Overall, our findings highlight the need for comprehensive treatment approaches that address both pulmonary and cardiovascular aspects of the disease and indicate no role of BEC during exacerbations to predict future relapses.