The following is a summary of “Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions,” published in the April 2024 issue of Pulmonology by Liu et al.

Endothelial dysfunction is a well-recognized hallmark of chronic airway diseases, encompassing chronic obstructive pulmonary disease (COPD) and asthma; however, its precise manifestation within the context of asthma-COPD overlap (ACO) remains elusive. Neopterin (NP), a metabolite of guanosine triphosphate, has emerged as a novel biomarker heralding heightened risk for adverse cardiovascular events. Against this backdrop, the study endeavors to unravel the intricate association between NP levels and endothelial dysfunction, alongside impaired lung function, among patients afflicted with COPD, asthma, and ACO.

A meticulously designed prospective cohort comprising 77 subjects was assembled for comprehensive evaluation. Each participant underwent various assessments, including lung function tests, endothelial function evaluations encompassing pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample analyses. Additionally, the impact of NP on endothelial cells (ECs) in hypoxic environments was scrutinized in vitro.

The findings revealed a significant attenuation in endothelial function among COPD and  patients with ACO compared to healthy controls (P < 0.05). Notably, forced expiratory volume in 1 second (FEV1) exhibited inverse correlations with PWV and positive associations with FMD (P < 0.05), underscoring the intricate interplay between pulmonary function and endothelial health. Moreover, NP levels were significantly elevated in individuals with chronic respiratory ailments relative to the control cohort, with patients with COPD demonstrating the highest levels, followed by asthma, and ACO exhibiting the lowest (P < 0.05). 

Furthermore, plasma NP levels exhibited negative correlations with FEV1 and positive associations with PWV (P < 0.05), emphasizing the potential utility of NP as a surrogate marker for disease severity and endothelial dysfunction. In vitro investigations unveiled a dose-dependent escalation in reactive oxygen species (ROS) levels alongside a decline in mitochondrial membrane potential (ΔΨm) within ECs under hypoxic conditions in response to elevated NP levels (P < 0.05), shedding light on the mechanistic underpinnings of NP-mediated endothelial dysfunction.

In summary, the study delineates the intricate relationship between NP levels, disease severity in chronic airway diseases, and endothelial dysfunction. Identifying NP as a potential therapeutic target offers promising avenues for evaluating and managing endothelial dysfunction in the context of chronic airway diseases.

Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02784-4