Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases

Bing Zhong; Lan Yang; Si-Lu Sun; Hong Chen; De-Yun Wang

doi:10.1016/j.mmr.2026.100023

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Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases

REVIEW | Updated：2026-05-11

- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases
- Military Medical Research (2026)
- Affiliations：
  
  Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
  Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
  Department of Pulmonary and Critical Care Medicine, West China Hospital, State Key Laboratory of Respiratory Health and Multimorbidity, Sichuan University, Chengdu 610041, China
  State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  Department of Neurology, Shengli Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China
- Author bio：
  
  *Si-Lu Sun, silusun@scu.edu.cn;
  Hong Chen, cchen4875@gmail.com
- Funds：
- DOI：10.1016/j.mmr.2026.100023
  CLC：
- Received：11 July 2025，
  
  Accepted：23 March 2026，
  
  Published：2026-04
- Accepted：
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Zhong B, Yang L, Sun SL, Chen H, Wang DY. Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases. Mil Med Res. 2026;13(1):100023.
DOI：

Zhong B, Yang L, Sun SL, Chen H, Wang DY. Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases. Mil Med Res. 2026;13(1):100023. DOI： 10.1016/j.mmr.2026.100023.

摘要

Abstract

Hypoxia is a central pathophysiological driver of inflammatory airway diseases

shaping disease progression largely through hypoxia-inducible factor 1α (HIF-1α) signaling. Across these disorders

hypoxia exacerbates airway inflammation through shared mechanisms. As a key signaling hub

HIF-1α disrupts epithelial barrier integrity and initiates inflammatory cascades; reprograms immune responses

promoting the activation and trafficking of eosinophils

T cells

and macrophages while reshaping cytokine profiles

to drive tissue injury; and accelerates airway remodeling

thereby worsening airflow limitation and perpetuating inflammatory cycles. Realizing effective targeted therapies will require rigorous validation of HIF-1α as a therapeutic node and the development of disease-tailored interventions aligned with distinct pathological features. In parallel

strengthened translational and clinical research on hypoxia is essential to build a robust evidence base for practice. This review synthesizes hypoxia-driven mechanisms shared across airway diseases

articulates a unifying framework for HIF-1α signaling across pathological contexts

and highlights the therapeutic implications of fundamental discoveries. By addressing the paucity of cross-disease analyses of hypoxia pathways

it provides both a conceptual foundation and a practical roadmap for developing precise and efficient targeted therapies for inflammatory respiratory diseases.

关键词

Keywords

references

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