从气火并治探讨恶性肿瘤免疫相关不良反应的防治

Discuss the Preventive and Treatment for Immune-Related Adverse Events of Malignant Tumors Based on Simultaneous Treatment of Qi and Fire

免疫检查点抑制剂(ICIs)在恶性肿瘤的治疗中可激活抗肿瘤相关免疫,但同时还可引起非特异性的免疫激活,导致免疫相关不良反应(irAEs)的发生。认为ICIs生理情况下可归属于中医学补益剂,发挥温阳益气之效,但免疫应答过激时,ICIs则演变成病理之壮火,对机体具有破坏性。结合免疫治疗不同时期和症状发作程度,将irAEs分为症状发作期(壮火食气耗精)和治疗间歇期(伏火散气势危)两阶段,其中阳动为实火致皮肤、口腔黏膜毒性,气郁化火致胃肠毒性,气闭生火致心脏毒性,气阴两虚致火表现为ICIs相关糖尿病。提出“气火并治”为治疗irAEs的总原则,发作期泻火降气祛药毒以除实火,升阳散火透药毒使火郁发之,通阳行气截药毒使火闭可畅,培气清火制药毒以散虚火,从而达到清壮火、解药毒、缓急症之效;间歇期力图微微生火以温阳气、阻伏火、防复燃,最终通过恢复人体生理之“气”与“阳”的平衡以防治irAEs,提高恶性肿瘤患者生活质量。

Immune checkpoint inhibitors(ICIs)can activate anti-tumour-related immunity in the treatment of malignant tumours,but at the same time,they can also cause non-specific immune activation,leading to the occurrence of immune-related adverse reactions(irAEs).It is believed that under physiological conditions,ICIs can be classified as tonic agents in traditional Chinese medicine,exerting the effect of warming yang and benefiting qi,but when the immune response become over-excited,ICIs evolve into pathogen of exuberant fire,which is destructive to the body.Combining the different periods of immunotherapy and the degree of symptoms,irAEs are divided into two phases:symptom onset phase(exuberant fire consuming qi and essence)and intermittent phase(latent fire dispersing healthy qi in critical condition),in which yang movement is excess fire leading to toxicity of the skin and oral mucous membranes,qi constraint transforming into fire leading to toxicity of gastrointestinal tract,qi block generating fire leading to cardiotoxicity,and qi and yin deficiencies leading to fire manifesting as ICIs-related diabetes.The general principle of“simultaneous treatment of qi and fire”is proposed to guide the treatment of irAEs.During the onset phase,draining fire,directing qi downward,and dispelling drug toxicity are used to remove excess fire;raising yang,dispersing fire,and dispelling drug toxicity are used to disperse fire constraint;promoting the flow of yang and qi and dispelling drug toxicity are used to close fire and smoothen the flow;cultivating qi,clearing fire,and dispelling drug toxicity are used to disperse the deficiency fire,so as to achieve the goal of clearing exuberant fire,eliminating drug toxicity,and alleviating acute symptoms.During the intermittent phase,the aim is to generate fire slightly to warm yang qi,block latent fire,and prevent recurrence,and ultimately restore the balance of qi and yang in human physiology to prevent and treat irAEs and improve the quality of life of patients.