Scholarlink

Background <p>Asthma with neutrophilic/mixed inflammation is a difficult-to-control clinical phenotype. Currently, vascular and matrix airway remodeling in asthma with neutrophilic/mixed inflammation is not well known. We aimed to evaluate the differences in vascular/smooth muscle/matrix related asthma remodeling in eosinophilic (EOS) and mixed/neutrophilic (MIXED) bronchial phenotypes in relation to asthma severity and exacerbation frequency.</p> Methods <p>In this cross-sectional study, α-SMA<sup>+</sup> cells (100µM beneath the basement membrane [BM]), BM thickness, vascular remodeling-related biomarkers (angiogenin, vascular endothelial growth factor [VEGF], CD31 and Protease-activated receptor 2 [PAR2]), alarmins (TSLP and Interleukin (IL)-33) were evaluated in bronchial sections from 40 mild-to-severe asthmatics (EOS: <i>N</i> = 19 and mixed/neutrophilic: <i>N</i> = 19/2) and 7 control subjects (CTRL).</p> Results <p>The number of CD31<sup>+</sup> and angiogenin<sup>+</sup> cells was higher in MIXED than in EOS asthmatics (<i>p</i> &lt; 0.05). In severe MIXED CD31<sup>+</sup>, TSLP<sup>+</sup>, α-SMA<sup>+</sup>, and angiogenin<sup>+</sup> cells increased compared to mild MIXED/EOS or severe EOS (<i>p</i> &lt; 0.05), but BM thickness was higher in severe vs. mild EOS (<i>p</i> &lt; 0.05). MIXED frequent exacerbators had higher numbers of CD31<sup>+</sup> and TSLP<sup>+</sup> cells, whereas MIXED non-exacerbators had increased PAR2<sup>+</sup> cells. CD31<sup>+</sup> cells correlated with impairment of pulmonary functions, number of exacerbations, ICS dose, bronchial neutrophils, angiogenin, α-SMA, TSLP and IL-33 (<i>p</i> &lt; 0.05). Finally, CD31 &gt; 97.17 cells/mm<sup>2</sup>, angiogenin &gt; 35.36 cells/mm<sup>2</sup>, and functional parameters such as FEV<sub>1</sub>, FEV<sub>1</sub>/FVC, TLC and FRC (%pred.) were found to be predictors of severe MIXED asthma.</p> Conclusion <p>The severe or frequent exacerbator asthmatics with bronchial mixed inflammatory profile are characterized by increased number of vessels and overexpression of TSLP and angiogenin, suggesting a pathogenetic link between mixed eosinophilic and neutrophilic inflammation and vascular remodeling.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Vascular remodeling and TSLP/angiogenin overexpression in severe mixed asthma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月28日

查看全文
  • Francesca Bertolini,
  • Vitina M.A. Carriero,
  • Elisa Arrigo,
  • Giuseppe Guida,
  • Stefano Levra,
  • Stefano Pizzimenti,
  • Mirella Profita,
  • Isabella Gnemmi,
  • Antonino Di Stefano,
  • Fabio L.M. Ricciardolo

摘要

Background

Asthma with neutrophilic/mixed inflammation is a difficult-to-control clinical phenotype. Currently, vascular and matrix airway remodeling in asthma with neutrophilic/mixed inflammation is not well known. We aimed to evaluate the differences in vascular/smooth muscle/matrix related asthma remodeling in eosinophilic (EOS) and mixed/neutrophilic (MIXED) bronchial phenotypes in relation to asthma severity and exacerbation frequency.

Methods

In this cross-sectional study, α-SMA+ cells (100µM beneath the basement membrane [BM]), BM thickness, vascular remodeling-related biomarkers (angiogenin, vascular endothelial growth factor [VEGF], CD31 and Protease-activated receptor 2 [PAR2]), alarmins (TSLP and Interleukin (IL)-33) were evaluated in bronchial sections from 40 mild-to-severe asthmatics (EOS: N = 19 and mixed/neutrophilic: N = 19/2) and 7 control subjects (CTRL).

Results

The number of CD31+ and angiogenin+ cells was higher in MIXED than in EOS asthmatics (p < 0.05). In severe MIXED CD31+, TSLP+, α-SMA+, and angiogenin+ cells increased compared to mild MIXED/EOS or severe EOS (p < 0.05), but BM thickness was higher in severe vs. mild EOS (p < 0.05). MIXED frequent exacerbators had higher numbers of CD31+ and TSLP+ cells, whereas MIXED non-exacerbators had increased PAR2+ cells. CD31+ cells correlated with impairment of pulmonary functions, number of exacerbations, ICS dose, bronchial neutrophils, angiogenin, α-SMA, TSLP and IL-33 (p < 0.05). Finally, CD31 > 97.17 cells/mm2, angiogenin > 35.36 cells/mm2, and functional parameters such as FEV1, FEV1/FVC, TLC and FRC (%pred.) were found to be predictors of severe MIXED asthma.

Conclusion

The severe or frequent exacerbator asthmatics with bronchial mixed inflammatory profile are characterized by increased number of vessels and overexpression of TSLP and angiogenin, suggesting a pathogenetic link between mixed eosinophilic and neutrophilic inflammation and vascular remodeling.