[Role of "gut lung axis-NETs" pathway in chronic obstructive pulmonary disease based on theory of "deficiency, phlegm, stasis, and toxin"].

Authors

Fang-Yuan Yu, Yu-Fei Chen, Han-Tao Zhao, Zheng Hong, Rui-Tao Wang, Xiao-Man Zhong, Jian-Jun Wu

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 14. Pages 3972-3980.

Abstract

Chronic obstructive pulmonary disease(COPD) is a systemic disease characterized by persistent airflow limitation and airway inflammation, with a consistently high incidence and a lack of effective clinical interventions to reverse disease progression. Based on the core TCM pathogenesis theory of "deficiency, phlegm, stasis, and toxin", this paper systematically explores the critical role of the "gut lung axis-neutrophil extracellular traps(NETs)" pathway in the occurrence and development of COPD, as well as its intrinsic association with TCM pathogenesis. Specifically, dysbiosis of the intestinal microecology and dysregulation of pulmonary NETs persist throughout the disease course. Among these, "deficiency of healthy Qi" serves as the initiating factor; disruption of the gut microbiota and deficiency of metabolic products lead to decreased pulmonary defensive function and immunometabolic imbalance. Furthermore, impairment of the intestinal barrier results in the translocation of lipopolysaccharide(LPS) into the bloodstream. As an "endogenous toxin", LPS activates pulmonary neutrophils, triggers oxidative stress, and promotes the formation of NETs. Moreover, the explosive release of pulmonary NETs represents the microscopic entity of the pathological products of "phlegm, stasis, and toxin". The highly viscous DNA backbone of NETs contributes to the formation of "tenacious phlegm" that obstructs the airways; NETs-induced immunothrombosis leads to "stasis obstructing lung collaterals"; and the cytotoxic proteins carried by NETs act as "virulent toxins" that directly damage the lung parenchyma. These pathological processes are the microscopic manifestations of the core pathogenesis of COPD, namely "deficiency leading to excess", "intertwining of phlegm and stasis", and "toxin damaging lung collaterals". In this context, spleen Qi deficiency drives dysregulation of the gut-lung microecology; the influx of endogenous toxins induces NETs activation; and the accumulation of phlegm, stasis, and toxin aggravates lung tissue remodeling. Accordingly, this paper proposes the application of the "consolidating the foundation and clearing the source" method to reconstruct intestinal microecology and block the origin of endogenous toxins, as well as the "removing toxins and dredging collaterals" method to target NETs regulation for resolving phlegm and removing stasis. Through dual "gut-lung" targeting to restore systemic homeostasis, this study provides a theoretical basis and new insights for the integrated TCM and western medicine prevention and treatment of COPD.

PMID:
42543328
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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