天津中医药大学学报  2023, Vol. 42 Issue (3): 366-374

文章信息

于亚君, 周之煜, 吕玲, 金鑫瑶, 王昭琦, 刘耀远, 季宏昌, 杨丰文
YU Yajun, ZHOU Zhiyu, LYU Ling, JIN Xinyao, WANG Zhaoqi, LIU Yaoyuan, JI Hongchang, YANG Fengwen
肺结节中西医治疗探讨
Discussion of traditional Chinese medicine and Western medicine treatment of pulmonary nodules
天津中医药大学学报, 2023, 42(3): 366-374
Journal of Tianjin University of Traditional Chinese Medicine, 2023, 42(3): 366-374
http://dx.doi.org/10.11656/j.issn.1673-9043.2023.03.16

文章历史

收稿日期: 2023-03-14
肺结节中西医治疗探讨
于亚君1 , 周之煜2 , 吕玲3 , 金鑫瑶1 , 王昭琦1 , 刘耀远4,5 , 季宏昌1 , 杨丰文1     
1. 天津中医药大学, 天津 301617;
2. 天津中医药大学第二附属医院, 天津 300250;
3. 北京中医医院顺义医院, 北京 101300;
4. 天津中医药大学第一附属医院, 天津 300381;
5. 国家中医针灸临床研究中心, 天津 300381
摘要: 近年来肺结节发病率持续升高,逐渐得到人们关注,其病因和发病机制尚不明确。西医认为肺结节的发病主要与性别、年龄、主动或被动吸烟、遗传、环境和职业、工作及生活压力、接触有毒有害物质、气道菌群状态失调等有关,治疗上以胸部电子计算机断层扫描(CT)随访、局部热消融、糖皮质激素、手术切除等为主。中医认为肺结节多由禀赋不足、饮食失宜、情志内伤、体质及环境等因素导致,患者大多正气亏虚,且痰、瘀、毒等病理因素相互搏结,痹阻于肺络,从而发病。治疗上以温阳、益气、补益脾肺、祛痰、化瘀、解毒、行气解郁、软坚散结等治法为主。中医、西医在治疗肺结节方面各有优势,临床上应取长补短,采用中西医结合治疗。文章分别从中西医方向进行肺结节的诊疗汇总、分析,以期为肺结节的治疗提供新思路、新方向。
关键词: 肺结节    中医治疗    西医治疗    
Discussion of traditional Chinese medicine and Western medicine treatment of pulmonary nodules
YU Yajun1 , ZHOU Zhiyu2 , LYU Ling3 , JIN Xinyao1 , WANG Zhaoqi1 , LIU Yaoyuan4,5 , JI Hongchang1 , YANG Fengwen1     
1. Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;
2. Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China;
3. Beijing Shunyi Hospital of Traditional Chinese Medicine, Beijing 101300, China;
4. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China;
5. National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
Abstract: The gradually increasing incidence of pulmonary nodules has attracted considerable attention over the last few years.The etiology and pathogenesis of this disease are still unclear. Western medicine believes that the causes of pulmonary nodules are mainly related to gender, age, active/passive smoking, genetics, environment and occupation, work and life stress, exposure to toxic and harmful substances, airway flora status, etc. The treatment is based on chest CT follow-up, local thermal ablation, glucocorticoids, and surgical resection. Traditional Chinese medicine thinks that lung nodules are mostly caused by deficient endowment, improper diet, emotional internal injuries, physique and environment, etc. The pathogenesis is deficiency of righteousness, and obstruction of phlegm, stasis and toxin in the lung collaterals. The treatment is based on wenyang, tonifying qi, benefit the spleen and lung, expectorant, dispersing blood stasis, detoxification, regulating qi and alleviating depression, and dissipating mass. Chinese and Western medicine have their own advantages in the treatment of pulmonary nodules. Clinically, they should complement each other and be treated in integrative medicine. This paper summarizes and analyzes the treatment of pulmonary nodules in the direction of Chinese and Western medicine, respectively, in order to provide new ideas and directions for the treatment of pulmonary nodules.
Key words: pulmonary nodule    traditional Chinese medicine treatment    Western medicine treatment    

肺结节是一种慢性进展性疾病,以非干酪样坏死性上皮细胞肉芽肿为病理特征[1],该病起病隐匿,病程缓慢,多数患者早期未见典型临床症状,随病情发展会出现肺实质浸润,并伴有持续存在的慢性炎症,逐渐形成肺纤维化,严重者可转变为肺癌甚至死亡[2]。近年来肺结节的检出率和发病率日渐增高,逐渐引起人们重视。目前,肺癌是全世界发病率和病死率较高的恶性肿瘤之一[3],肺结节被认为是肺癌的早期危险信号,对患者的生命及生活造成了一定威胁及负担。因此,尽早准确辨别、治疗肺结节是防止其癌变的关键。肺结节的发病机制尚未明确,治疗方法较为单一。中医治疗肺结节具有一定疗效,根据患者处于疾病的不同时期以及不同的临床症状,进行辨证施治以减轻病症,缓解焦虑状态,改善生活质量。本文将分别从中医、西医两个方向探讨肺结节的治疗,以期防治癌变并提高疗效。

1 对肺结节的认识 1.1 西医对肺结节的认识 1.1.1 肺结节的定义及分类

肺结节是指在肺脏内直径≤3 cm的类圆形或不规则形病灶,影像学表现为密度增高的实性或亚实性肺部阴影,不伴肺不张、肺门淋巴结肿大及胸腔积液。

肺结节按照数量可分为单个病灶的孤立性肺结节和两个及以上病灶的多发性肺结节。按照结节密度可分为实性肺结节和亚实性肺结节,其中亚实性肺结节又分为纯磨玻璃结节和部分实性结节(磨玻璃密度和实性密度均有的为混杂性结节)。恶性率最高的是部分实性结节,其次为磨玻璃结节、实性结节。按照结节大小可分为结节直径 < 5 mm的微小结节和直径为5~10 mm的小结节。此外,若结节直径达到10~30 mm应尽早诊治[4]

1.1.2 肺结节的病因及临床表现

目前研究认为肺结节的发病原因主要与性别、年龄、主动或被动吸烟、遗传、环境和职业、工作及生活压力、接触有毒有害物质、气道菌群状态失调等有关。此外,一些慢性呼吸系统疾病,如慢性阻塞性肺疾病、肺结核、慢性肺炎、肺部良性肿瘤等也可导致肺结节的发生[5-6]

多数肺结节患者早期无临床症状,或临床症状不典型,仅表现有干咳、胸部憋闷等症状,50%~70%患者可伴随周身乏力不适的症状[7]。随着病情的发展会出现进行性呼吸困难、咳嗽、胸闷气短,严重的患者可能会伴有发绀、杵状指等症状[2]

1.1.3 肺结节的诊断

1)影像学诊断:主要包括胸部X线、胸部电子计算机断层扫描(CT)、正电子发射断层成像-X线计算机断层成像(PET-CT)、磁共振成像(MRI)等检查。其中胸部CT是临床诊断肺结节最常用的检测手段。2)非手术活检:包括支气管镜检查和经胸壁肺穿刺活检术。单纯通过影像学检查很难判断肺结节的性质,所以需要病理检测才能明确诊断。3)手术活检:包括胸腔镜检查和纵膈镜检查。适用于以上检查无法进行或进行后仍无法确诊的情况。4)实验室检查:如血常规中的淋巴细胞、嗜酸性粒细胞、单核细胞、中性粒细胞,或血清血管紧张素转化酶、C-反应蛋白、血沉、血钙、尿钙等指标也需要关注,因其不具有特异性,目前仅作为辅助诊断,明确诊断仍需病理学检查[2]

此外,肺结节的患者也应注意监测一些肿瘤标志物的指标,如胃泌素释放肽前体、神经特异性烯醇化酶、癌胚抗原、细胞角蛋白片19、鳞状细胞癌抗原等指标,若这些指标出现进行性增高的情况,需要警惕。

1.2 中医对肺结节的认识 1.2.1 病名及临床症状

肺结节是随着西医影像学的不断发展而被发现的,在中医并没有与之对应的病名。现在大多医家将其归属于“咳嗽”“积聚”“痰核”“肺痹”“肺积”“喘证”等病。

该病起病隐匿,患者在早期并没有典型的临床症状。随着病情的进展可能会出现咳嗽、胸闷胸痛、呼吸困难、乏力等症状。

1.2.2 病因病机

肺结节发病机制复杂,现代医家对于该病的病因病机有着不同的见解,但大多数医家认为肺结节的病因无外乎本虚标实,多由禀赋不足、饮食失宜、情志内伤、体质及环境等因素所导致。本虚主要责之于阳虚、气虚,标实主要为痰、瘀、毒等相互搏结,痹阻肺络,从而发为本病。其病位在肺,涉及脾、肾。

若阳气亏虚,体内的气血津液等物质疏布异常,形成痰湿、瘀血、浊毒等病理产物,停聚在体内相互搏结发为本病,并且阳虚易生内寒,寒主收引、凝聚,更易招致阴邪积聚[8-9]

痰邪黏滞、重浊,在体内可阻滞气机,使津液疏布障碍,长期凝聚可形成结节;瘀血为停留在体内的离经之血,与痰邪相同,瘀血形成后也可加重气机阻滞,影响血液运行,积聚成肿块、结节;浊毒由藏于体内组织器官中的多种病理产物相互结合产生,长时间积聚体内,既可自身转化为结节组织,又可与其他代谢产物结合,相互影响共同转化为可以致病的肺部结节。痰、瘀、毒相互搏结、凝滞,痹阻肺络,使肺中气血无法交接,日久终成结节[1, 10-11]

2 肺结节的治疗 2.1 西医治疗 2.1.1 定期CT随访

中、低危肺结节患者一般采取胸部CT定期随访观察,若肺结节为中、高危则应缩短随访时间,并需要尽快确定结节性质,便于及时治疗,一般随访的时间根据结节的大小、性质及临床症状决定[12]

2.1.2 手术治疗

对于高度恶性的肺结节一般采取手术切除,现在临床首选的是电视辅助胸腔镜手术,相比于传统的开胸手术,能最大限度保留患者的肺功能,其创伤较小且术后并发症较少[13]

2.1.3 局部热消融术

局部热消融技术是利用热产生的生物学效应直接导致病灶组织中的肿瘤细胞发生不可逆损伤或凝固性坏死的一种微创治疗技术。目前主要包括射频消融术、微波消融术和冷冻消融术,其中应用最广泛的是射频消融术[14]

2.1.4 药物治疗

1)糖皮质激素:为治疗肺结节的一线用药,主要目的是改善患者症状,抑制和限制肉芽肿性炎症的持续发展,其缺点是不良反应较多,部分患者在减药或停药后会有症状反复的趋势。

2)免疫抑制药物:对糖皮质激素治疗无效或无法忍受其不良反应的患者,临床常使用甲氨蝶呤、硫唑嘌呤、来氟米特等替代治疗。其中甲氨蝶呤是首选二线用药,它既能够单独用于治疗也可以联合糖皮质激素一起治疗。

3)抗肿瘤坏死因子-α(TNF-α)药物:被认为是治疗肺结节的一种新的治疗方法,常作为三线用药使用,包括英夫利昔单抗、阿达木单抗和依那西普等药物,主要应用于一、二线药物治疗后均无效的患者。

4)Acthar凝胶:是一种长效、高纯度的注射用促肾上腺皮质激素制剂,现在该药的使用数量已减少很多,是治疗肺结节的四线药物。

5)其他药物:除上述药物外,白细胞介素-6(IL-6)抑制剂、间充质干细胞疗法、程序性死亡受体1(PD-1)/PD-1配体(PD-L1)抑制剂、内皮素受体拮抗剂等药物也可应用于肺结节的治疗,但其使用风险和不良反应仍不容忽视。

2.2 中医治疗

根据肺结节本虚标实的病机,各医家在治疗肺结节时从扶正、祛邪角度出发,采用温阳、益气、补益脾肺、祛痰、化瘀、解毒等方法治疗肺结节。

2.2.1 扶正

1)温阳:常用的温阳类方剂有温阳补血、散寒通滞的阳和汤;温化痰饮、健脾渗湿的苓桂术甘汤;补肾助阳的肾气丸;温阳益气的参附汤;回阳救逆的四逆汤;温阳散寒的吴茱萸汤;温阳化饮的当归四逆汤、苓甘五味姜辛汤等[8, 15-28]。用药上还可选用淫羊藿、肉苁蓉、附子、肉桂、干姜、杜仲、补骨脂、吴茱萸、仙灵脾、桂枝、鹿角等温阳类药物补肾助阳、温阳化气[8-9, 19-21]

2)益气:常用的方剂有健脾益气的四君子汤、六君子汤、补中益气汤等[18-19, 22];补益肺气的补肺汤[26-27];益气固表的玉屏风散;益气滋阴的沙参麦冬汤、麦门冬汤、百合固金汤[20, 28]。此外根据不同证型,各医家酌情选用黄芪、党参、灵芝、茯苓、白术、山药等药物补益肺脾之气,复气化之动力[19-20];或使用沙参、黄精、百合、石斛、太子参、西洋参、玄参等药物以达益气养阴之效[10, 21, 26-27]

3)补益脾肺:既能直接补益肺气,又能通过健脾间接补益肺气,以达培土生金之效。常用的方剂如补肺气、养肺阴的黄芪四君子汤、香砂六君子汤、补肺汤、沙参麦冬汤、麦门冬汤[17, 25, 29];补脾升清的黄芪赤风汤、六君子汤[17]。也有医家使用自拟方药治疗肺脾两虚型肺结节,如王诚喜教授自拟黄芪益肺汤,以补肺健脾[30];李素云教授自拟补肺健脾方、补肺益肾方,以补肺健脾、益肺补肾[24];郑心教授自拟肺康方,以补脾益肺、理气化痰行瘀[31]

在用药方面,可使用黄芪、白术、党参、太子参以补益肺气[29, 32-34];沙参、生地黄、熟地黄、麦冬、天冬、百合、石斛、玉竹等补益肺阴[32-35];黄芪、党参、白术、茯苓、猪苓、山药、薏苡仁等健脾益气[36-37],也可辅用升麻、柴胡、葛根、防风、羌活、桔梗等质轻味薄、辛温升散之品提升脾气,以达培土生金之效[38];还可使用太子参、玄参、麦冬滋阴益胃;干姜、肉豆蔻、砂仁等温中补阳[39]

2.2.2 祛邪

1)祛痰:痰既是导致肺结节发生的病因之一,也是一种病理产物,其性质胶着黏滞,且变化多端,因此祛痰散结法对于治疗肺结节极为重要。常用的方剂有燥湿祛痰散结的二陈汤、六君子汤;理气化痰散结的温胆汤;清热化痰、宽胸散结的桑贝小陷胸汤、千金苇茎汤、清金化痰汤、大陷胸汤;温阳化痰散结的瓜蒌薤白半夏汤等[23, 25, 40-46]。若痰湿较重可选用葶苈子、白芥子、浙贝母、厚朴、石菖蒲、皂角刺、苦杏仁、苍术、厚朴、茯苓、猫爪草、穿山甲、紫苏子、三叶青、僵蚕等药物祛痰除湿、宽胸散结[21, 33, 39, 47-51];若痰热较重可选用胆南星、瓜蒌、射干、麻黄、浙贝母、枇杷叶、清半夏、夏枯草、金荞麦、黄芩、蒲公英等药物清热化痰散结[19, 32-33, 35, 39, 52-53]

2)化瘀:血瘀为主的肺结节患者,治疗时常使用桃红四物汤、血府逐瘀汤等以达活血化瘀散结之效[43]。亦可选用活血化瘀、散结消癥药物,如赤芍、牡丹皮、桃仁、红花、三七、郁金、川芎、丹参、当归、姜黄、鸡血藤、血竭等。此外,血瘀甚者可酌情加用三棱、莪术等破血之药[21, 27, 32-33, 36-37, 39-40, 42, 47-51, 53-54]。肺脏脉络大多细微,若患者久病入络,治疗时应当深入肺络,祛除伏邪,在活血化瘀的基础上加入“搜剔络邪”之通络药物,如蜈蚣、全蝎、僵蚕、水蛭、地龙、蜂房、土鳖虫等,可增强通利散结之功,以达活血化瘀、攻坚消积之效。虫类药物功善走窜,有通经活络之功效,正如叶天士所言:“久则邪正混处其间,草木不能见效,当以虫蚁疏逐。”[19, 22, 26, 36, 42, 49-52, 54]

3)解毒:伏邪胶结难解,蕴久化热,郁久成毒,为热毒蕴结之表现,临床上可选用白花蛇舌草、半枝莲、山慈菇、鱼腥草、蒲公英、石见穿、鬼箭羽、夏枯草、败酱草、金荞麦、土茯苓、土贝母、板蓝根、仙鹤草、猫爪草等防癌散结[10, 26-27, 33, 37, 42, 49-50, 53, 55-56]

4)行气解郁:指使用行气解郁、疏肝理气等方药治疗肺结节。常用的方剂如:疏肝行气散结的柴胡疏肝散、逍遥散、四逆散和升降散;行气解郁、降气化痰的柴朴汤等,使肝气调达舒畅,进而助肺气宣发肃降[34, 42-45, 57-58]。常用的疏肝解郁、理气散结药物有柴胡、佛手、香橼、郁金、合欢皮、玫瑰花、延胡索、香附、木香、青皮、川楝子、荔枝核、木香、陈皮、枳实、白芍等[19, 33, 36-37, 40, 42, 48, 52-53]。亦可酌情加入枳实、枳壳、厚朴、紫苏子、紫苏梗,调畅胸中气机以复肝主疏泄之性[50]

5)祛风、解表、宣肺(开玄):玄府、肺络是根植于肺脏的微观脏腑结构,风药不仅可开透郁闭的玄府,亦可开宣肤表毛孔,建立祛邪外出的顺畅通道,其善行发散的特性亦符合肺为华盖的特点,可有效引导药物直达肺部,发挥“定向”协同增效的治疗功效[59-60]。代表方剂有解表扩络、透郁开玄之麻黄连翘赤小豆汤[60-62]。常用的药物有麻黄、细辛、荆芥、羌活等解表祛风的药物,亦可配伍地龙、僵蚕、蜈蚣、全蝎、青风藤、海风藤、络石藤等虫类、藤类的祛风药深入肺络,搜风通络,引他药入肺络以清伏邪[43, 59]

6)软坚散结:《素问·至真要大论》提出“结者散之”的治法,临床上在治疗肺结节时也会着重使用软坚散结类的药物,如鳖甲、牡蛎、龙骨、夏枯草、昆布、海藻、瓦楞子等治疗肺结节[27, 33, 39, 42, 53, 56]

7)复合治疗:肺结节发病机制复杂,迁延难愈,故在治疗时各医家常将多种治法联合使用以散结消积。刘鑫教授在治疗肺结节时用血府逐瘀汤合桑贝小陷胸汤或温胆汤、连朴饮、苇茎汤等进行化裁,以豁痰化瘀、解毒散结[43];沈佳教授选用泽漆汤加减治疗肺结节,全方以化痰活血祛邪为主,适当佐以扶正[63];李仝教授使用双合汤以化痰行瘀、通络散结[23];张晓梅教授自拟益肺散结方为基础方,以益肺、化痰、散瘀、通络[64];周平安教授自拟芪银归草散结汤以益气活血化痰[65];谢刚主任使用三楞煎加减治疗肺结节,以达活血逐瘀、化痰散结之效[44]。另有医家以理气、消瘀、化痰、滋阴为基本原则,创立结节方,理气、化痰与通络并行,使气机得畅,痰瘀得去,病灶自除[49]。也可选用二陈汤、三子养亲汤、补阳还五汤、血府逐瘀汤等加减以化痰祛瘀散结[66]

2.2.3 其他疗法

临床也有医家采取自血疗法、穴位贴膏、刺血等外治法治疗肺结节。陈生教授发现中医药联合自血疗法治疗肺结节颇有疗效,自血疗法是抽取自身静脉血2 mL注入特定穴位中以达持续刺激经络之效,主要选取足三里、血海、丰隆、曲池、肺俞、脾俞、肾俞、太冲等穴位进行治疗[56];刘小虹教授在治疗肺结节时,除内治法外,还辅以肺结节穴位贴膏,主要选择肺俞、天突、大椎、中脘、膻中、涌泉等穴位以达补益肺脾之气、通行经络之效[67];王翠芳等[68]在治疗肺结节时选取双侧肝俞、胆俞、脾俞等穴位进行背俞穴刺血治疗。

3 小结

中医认为肺结节可归属于“肺积”“积聚”“痰核”“肺痹”等范畴,多为本虚标实之疾,本虚主要是阳虚和气虚,标实主要为痰、瘀、毒等相互搏结,痹阻于肺络,从而发病。其病位主要在肺、脾、肾,故治疗时应攻补兼施,扶正与祛邪并用,扶正以温阳、益气、补益脾肺为主,祛邪以祛痰、化瘀、解毒、行气解郁、解表宣肺、软坚散结等为主,根据患者的症状选取不同药物进行治疗。

临床上大多数肺结节患者被检出时并无明显症状,西医通常采用胸部CT随访来进行观察,并无相应治疗措施。中医素有“未病先防,既病防变”的治病理念,对于此类起病隐匿、病程较长的慢性疾病,具有其独特优势。医者可以从患者体质着手,根据患者不同症状或体质进行辨证论治,对症下药,不仅能够改善患者的临床症状,延缓或控制疾病发展,还可以调整患者的偏颇体质,从而祛除病邪,达到标本兼治之效。同时早期的干预治疗不仅填补了胸部CT随访观察过程中的治疗“空窗期”,一定程度上也可以缓解患者查出疾病而不进行治疗产生的焦虑,改善了患者的身心状态。

对于中高危的肺结节,或者已经恶化的结节,西医的靶向治疗或手术切除治疗仍是首选治疗方式,可以杜绝肺结节的恶化、转移。但在靶向治疗或手术治疗时不免会损伤患者正气,造成患者气血阴阳虚弱的情况,此时可以联合中医药协同治疗,扶其正气,使患者尽快恢复健康状态。

但是目前中医对肺结节的治疗尚未达成共识,病因病机及证型分类缺乏统一标准,缺少高质量的循证医学证据,并且基础研究也相对欠缺。因此应及时开展高质量的循证研究和基础研究,从而提高中医药治疗肺结节的疗效和证据级别,进一步完善中医药治疗肺结节的治疗方案。

中医、西医对于肺结节的治疗有着各自的优势与不足,在临床诊疗中可以尝试中西医联合治疗,取长补短,发挥各自不同的优势,对肺结节进行全方位的诊疗,也为临床治疗肺结节带来新的角度与思路,值得深入研究、传承。

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