Asthma is a common clinical respiratory disease with typical symptoms such as coughing, wheezing, chest tightness, shortness of breath, and dyspnea, which tend to worsen at night or in the early morning. Its pathogenesis is closely related to factors such as oxidative stress, immune imbalance, and abnormal cell regulation. In recent years, it has been found that ferroptosis is closely associated with asthma. This article explores the effects of environmental factors and genetic background on ferroptosis through the mechanism of ferroptosis in asthma, as well as therapeutic strategies targeting ferroptosis, providing a new perspective for clinical translational research on asthma.

Ziyue Min, Liming Fan, Wei Xiao. The Mechanism of Ferroptosis in Asthma and Targeted Therapy: A New Perspective on Environmental Interaction and Clinical Translation. International Journal of Frontiers in Medicine (2025), Vol. 7, Issue 4: 26-32. https://doi.org/10.25236/IJFM.2025.070404.

[1] CHOWDHURY N U, GUNTUR V P, NEWCOMB D C, et al. Sex and gender in asthma [J/OL]. European Respiratory Review, 2021, 30 (162) : 210067. DOI: 10.1183/16000617.0067-2021.

[2] LI M, LI M, HOU Y, et al. Ferroptosis triggers airway inflammation in asthma[J/OL]. Therapeutic Advances in Respiratory Disease, 2023, 17: 17534666231208628 DOI: 10.1177/17534666231208628.

[3] DAI Y, CUI C, JIAO D, et al. JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases[J/OL]. Cancer Cell International, 2025, 25: 83. DOI:10.1186/s12935-025-03681-6.

[4] PHILIPPOT Q, DESLEE G, ADAIR-KIRK T L, et al. Increased Iron Sequestration in Alveolar Macrophages in Chronic Obtructive Pulmonary Disease[J/OL]. PLoS ONE, 2014, 9 (5) : e96285. DOI: 10.1371 / journal pone. 0096285.

[5] HAN F, LI S, YANG Y, et al. Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid Peroxidation and disrupting iron homeostasis [J/OL]. Bioengineered, 12 (1) : 5279-5288. The DOI: 10.1080/21655979.2021.1964158.

[6] ALI M K, KIM R Y, BROWN A C, et al. Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma [J/OL]. European Respiratory Journal, 2020, 55 (4) [2025-03-16]. HTTP://https://publications.ersnet.org/content/erj/55/4/1901340. DOI: 10.1183/13993003.01340-2019.

[7] WANG Y, WANG M, LIU Y, et al. Integrated regulation of stress responses, autophagy and survival by altered intracellular iron stores [J/OL]. Redox Biology, 2022, 55: 10.1016 DOI: 102407 / j.r edox. 2022.102407.

[8] LV X, DONG M, TANG W, et al. Ferroptosis, novel therapeutics in asthma [J/OL]. Biomedicine & Pharmacotherapy, 2022, 153: 10.1016 DOI: 113516 /j.b iopha. 2022.113516.

[9] SONG J, ZHANG H, TONG Y, et al. Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway Inflammation [J/OL]. Redox Biology, 2023, 68:102970. DOI: 10.1016 / j.r edox.2023.102970.

[10] LIU S, CHEN L, SHANG Y. CEACAM5 exacerbates asthma by inducing ferroptosis and autophagy in airway epithelial cells through the JAK/STAT6- dependent pathway [J/OL]. Redox Report : Communications in Free Radical Research, 30(1): 10.1080 DOI: 2444755/13510002.2024.2444755.

[11] RICE M B, LJUNGMAN P L, WILKER E H, etc. Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart Study [J/OL]. American Journal of Respiratory and Critical Care Medicine, 2015, 191(6): 656-664. DOI:10.1164/rccm.201410-1875OC.

[12] LIU K, HUA S, SONG L. PM2.5 Exposure and Asthma Development: The Key Role of Oxidative Stress [J/OL]. Oxidative Medicine and Cellular Longevity, 2022, 2022(1): 3618806. The DOI: 10.1155/2022/3618806.

[13] WANG A, LIU J, LI Z, et al. CC16 alleviates P2.5-induced lung epithelial cell injury and airway inflammation in asthmatic mice by inhibiting Ferroptosis [J/OL]. Ecotoxicology and Environmental Safety, 2025, 289:117417. DOI: 10.1016 / j. coenv. 2024.117417.

[14] TAO P, SU B, MAO X, et al. Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis [J/OL]. Redox Biology, 2025, 82: 10.1016 DOI: 103594 / j.r edox. 2025.103594.

[15] CHEN X, CHEN H, ZHANG P, et al. Coke oven emissions exacerbate allergic asthma by promoting ferroptosis in airway epithelial cells [J/OL]. Journal of Hazardous Materials, 2024, 478:135542. DOI: 10.1016 / j.j hazmat. 2024.135542.

[16] WANG Y, YANG L, ZHANG X, et al. Epigenetic regulation of ferroptosis by H2B monoubiquitination and p53 [J/OL]. EMBO reports, 2019, 20(7): E47563. DOI: 10.15252 / embr. 201847563.

[17] SHAHEEN S O, RUTTERFORD C M, LEWIS S J, et al. Maternal selenium status in pregnancy, offspring glutathione peroxidase 4 genotype, and childhood asthma [J/OL]. The Journal of Allergy and Clinical Immunology, 2015, 135(4): 1083-1085. The e3. DOI: 10.1016 / j.j. Aci 2014.10.035.

[18] Li Jingyi, Li Yujian, Lai Shenglin, et al. Research progress on N6-adenylate methylation and ferroptosis in allergic rhinitis - asthma syndrome in children [J]. Chinese Journal of Contemporary Pediatrics, 2025, 27(2): 242-247.

[19] LIN L, HU X, LI Q, et al. Methyltransferase-like 3 (METTL3) Epigenetically Modulates Glutathione Peroxidase 4 (GPX4) Expression to Affect Asthma [J/OL]. Iranian Journal of Allergy, Asthma and Immunology, 2023, 22 (6) : 551-560. The DOI: 10.18502 / ijaai v22i6. 14644.

[20] YU S, JIA J, ZHENG J, et al. Recent Progress of Ferroptosis in Lung Diseases [J/OL]. Frontiers in Cell and Developmental Biology, 2021, 9: 10.3389 DOI: 789517 / fcell. 2021.789517.

[21] DOLL S, FREITAS F P, SHAH R, et al. FSP1 is a glutathione-independent ferroptosis suppressor [J/OL]. Nature, 2019, 575(7784): 693-698. DOI:10.1038/s41586-019-1707-0.

[22] Sun Congcong, Cui Wenjing, Zhang Jintao, et al. The role of ferroptosis in airway remodeling in bronchial asthma [J]. Journal of Shandong University (Medical Science Edition), 2024, 62(7): 1-9.

[23] FAN B Y, PANG Y L, LI W X, et al. Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4[J/OL]. Neural Regeneration Research, 2020, 16(3): 561-566. DOI:10.4103/1673-5374.293157.

[24] WANG Y, WAN R, PENG W, et al. Quercetin alleviates ferroptosis accompanied by reducing M1 macrophage polarization during neutrophilic airway Inflammation [J/OL]. European Journal of Pharmacology, 2023, 938:175407. DOI: 10.1016 / j. jphar. 2022.175407.

[25] Dai Xiaohan, Zhao Xia, Yan Hua, et al. Effects of Guben Fangxiao Yin on oxidative stress and AMPK/Nrf2/HO-1 pathway in lung tissue of bronchial asthma remission model mice [J/OL]. Chinese Journal of Traditional Chinese Medicine, 2024, 65(2): 205-212. DOI:10.13288/j.11-2166/r.2024.02.015.

[26] Luyts J, Burnay N, Piguet E, et al. Structured timeline mapping as a data collection methodology: a new perspective for research on environmental adaptation[J]. Journal of Clinical Immunology, 2024.

[27] Liu Yu-Tong, Che Nan, Li Li, et al. Anthocyanins regulate airway inflammation in asthma through the Nrf-2/HO-1 signaling pathway [J/OL]. Journal of immunology, 2019, 35 (1): 36-41. DOI: 10.13431 / j.carol carroll nki. J immunol. J. 20190005.

[28] Zhao Yuzhe, Jiang Jingzhi, Ye Jing, et al. Polygonatum side alleviates airway inflammation in mouse asthma models through the p38 MAPK/Nrf2/HO-1 pathway [J]. Chinese Pharmacological Bulletin, 2018, 34(6): 851-856.

[29] Zhong Changhui, Qian Jin, Yang Yuanzheng, et al. The effect of amygdalin on the KELch-like epichlorohydrin-1 / nuclear factor E2-related factor 2 signaling pathway in bronchial asthmatic rats [J/OL]. Chinese Journal of Clinical Pharmacology, 2022, 38(18): 2157-2161. DOI:10.13699/j.cnki.1001-6821.2022.18.010.

[30] Jiang Xiao-Cui, Xiao Min, Zhao Min, et al. Shugan Bushen Yulin Decoction improves sperm quality in mice with liver depression and kidney deficiency oligoasthenospermia by inhibiting ferroptosis of testicular cells through the Keap1/Nrf2/GPX4 pathway [J/OL]. Chinese Journal of Traditional Chinese Medicine, 2024, 42(5): 46-51, 275-277. DOI:10.13193/j.issn.1673-7717.2024.05.010.

[31] Zhang Zhengze, Liu Hao, He Yuewen, et al. Study on the mechanism of electroacupuncture in alleviating ferroptosis in lung tissue of asthmatic mice through the Keap1/Nrf2 pathway [J]. Acupuncture Research, 2024: 1-15.

[32] WANG H, JIA Y, GU J, et al. Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment[J/OL]. Frontiers in Pharmacology, 2023, 14:1087557. DOI: 10.3389 / fphar. 2023.1087557.

[33] MOHAMMAD TAHERI M, JAVAN F, POUDINEH M, et al. Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy [J/OL]. Journal of Translational Medicine, 2024, 22(1): 736. DOI:10.1186/s12967-024-05534-8.

[34] WANG Y, FAN J, TONG Y, et al. Bioinformatics analysis of ferroptosis- related gene AKR1C3 as a potential biomarker of asthma and its identification in BEAS - 2 b cells [J/OL]. Computers in Biology and Medicine, 2023, 158:106740. DOI:10.1016/j.com pbiomed. 2023.106740.