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The following is a summary of “Vascular Remodeling and TSLP/Angiogenin Overexpression in Severe Mixed Asthma,” published in the February 2025 issue of the Respiratory Research by Bertolini et al.

Asthma with a neutrophilic or mixed inflammatory profile represents a challenging clinical phenotype that is often difficult to control with conventional therapies. While airway remodeling is a well-recognized feature of asthma pathophysiology, the specific contributions of vascular and extracellular matrix remodeling in neutrophilic or mixed inflammation remain poorly understood. This study aimed to evaluate the distinct patterns of vascular, smooth muscle, and matrix-associated airway remodeling in eosinophilic (EOS) and mixed/neutrophilic (MIXED) asthma phenotypes and to explore their relationship with asthma severity and exacerbation frequency. 

In this cross-sectional study, bronchial biopsy specimens from 40 patients with mild-to-severe asthma (EOS: n = 19; MIXED: n = 19/2) and 7 healthy control subjects (CTRL) were analyzed for key markers of airway remodeling. The study assessed α-SMA+ cells (within 100µM beneath the basement membrane [BM]), BM thickness, and vascular remodeling-related biomarkers, including angiogenin, vascular endothelial growth factor (VEGF), CD31, and protease-activated receptor 2 (PAR2). Additionally, the expression of alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL-33) was evaluated. Results demonstrated a significantly higher number of CD31+ and angiogenin+ cells in MIXED compared to EOS asthmatics (p < 0.05). Severe MIXED asthma was characterized by an increased number of CD31+, TSLP+, α-SMA+, and angiogenin+ cells relative to mild MIXED, mild EOS, or severe EOS asthma (p < 0.05). 

However, BM thickness was significantly greater in severe EOS compared to mild EOS (p < 0.05). Among patients with frequent exacerbations in the MIXED group, there was a notable increase in CD31+ and TSLP+ cells, while non-exacerbators in the MIXED phenotype exhibited a higher number of PAR2+ cells. CD31+ cell count correlated with several indicators of disease severity, including pulmonary function impairment, exacerbation frequency, inhaled corticosteroid (ICS) dose, bronchial neutrophil presence, angiogenin, α-SMA, TSLP, and IL-33 levels (p < 0.05). Furthermore, predictive analysis identified CD31 > 97.17 cells/mm², angiogenin > 35.36 cells/mm², and functional parameters such as FEV1, FEV1/FVC, total lung capacity (TLC), and functional residual capacity (FRC) (% predicted) as potential indicators of severe MIXED asthma. 

These findings suggest that severe or frequently exacerbating asthma with a mixed inflammatory profile is characterized by extensive vascular remodeling and the overexpression of TSLP and angiogenin, implicating a mechanistic link between eosinophilic and neutrophilic inflammation in airway remodeling. These insights highlight the need for targeted therapeutic approaches addressing vascular remodeling in asthma subtypes with mixed inflammatory characteristics.

Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-025-03133-9