淋巴循环障碍与塑型性支气管炎
2018年7期

中华泌尿外科杂志,第41卷第7期 第551页-第553页

何丽,侯小萌,沈文彬,徐凯峰

  正文

塑型性支气管炎(plastic bronchitis,PB),又称纤维素性支气管炎、Hofman支气管炎、管型性支气管炎、假膜性支气管炎或纤维蛋白性支气管炎,是一种以凝胶状支气管树样管型物形成并黏附填充气道为特征的罕见的可致死性肺部疾病[1],可因局部或广泛气道阻塞而出现呼吸功能障碍,严重者可因呼吸窘迫危及生命。该病各年龄段均可发病,儿童多见,严重程度不一,易被忽视。临床报道不多,具体病因及发病机制不明确,缺乏有效的治疗方法。随着认识的不断深入,越来越多的证据表明,许多不明原因的PB可能由肺部淋巴循环异常所致[2],目前认为,至少部分PB可能为淋巴循环疾病中的一种,且治疗方法也有了突破性进展。PB发病率低,真实的发病率不清。儿童发病率高于成人,常继发于心肺疾病。临床医师对该病认识不足,症状轻的患者常被漏诊或误诊。

20世纪50年代前,感染是PB的主要原因,随着抗生素的广泛使用,过敏性疾病及先天性心脏病的报道逐渐增多[1]。临床上继发性PB占80%左右[3],常见的病因:(1)心脏病:常见于先天性心脏病患者单心室矫正术后,超过4%的Fontan术后的患儿可发生PB[4,5,6,7];此外,PB偶可发生在Glenn分流术、法洛四联症修复术及动脉转接术等心脏手术后[4]。(2)肺部疾病:常见于支气管哮喘、变应性支气管肺曲霉病或流感病毒感染[8,9,10,11],但囊性纤维化[12]、肺结核及支气管扩张等少见[1,3]。(3)淋巴源性:淋巴管自身病变所致淋巴循环疾病,如广泛性淋巴管异常(generalized lymphatic anomaly, GLA),包括淋巴管扩张和淋巴管瘤病[13,14]。(4)其他疾病,如有毒气体吸入或镰状细胞贫血等[1,15]。PB有多种分类方法。最近,由于PB发病机制有了突破性进展,Itkin等[2]根据是否为淋巴循环障碍所致分为淋巴循环障碍相关的PB与其他原因的PB,而淋巴循环障碍相关的PB可原发于淋巴管本身疾病,如淋巴管扩张和淋巴管瘤病,亦可为继发性(如Fontan术后)。

目前,有关PB的淋巴循环障碍机制已初步阐明,从而为PB的诊断和治疗提供了新的途径。1989年,Wiggins等[16]发现PB可能与肺部淋巴结或淋巴循环异常有关。作者报道1例49岁的男性患者,23年中反复咳出支气管树样管型,病理学显示管型由酸性黏液、纤维素及成熟淋巴细胞组成;右肺中叶手术标本可见肺门部位淋巴管扩张和管壁增厚,远端终末细支气管周围淋巴细胞聚集。2005年,Madsen等[1]发表了有关淋巴循环异常所致PB的文章。近年来,随着淋巴管造影术的发展,PB的淋巴循环障碍才得以明确。2012年,Nadolski和Itkin[17]首先采用超声引导下经双侧腹股沟淋巴结内造影术(intranodal lymphangiogram,IL)显影胸导管并行胸导管栓塞术成功治疗6例乳糜胸患者,病例对照研究结果证实,IL比传统的经足淋巴管造影术操作时间更短。随后Dori等[18]经动物实验证实磁共振动态增强淋巴管造影(dynamic contrast-enhanced magnetic resonance lymphangiography,DCMRL)可显示中央淋巴系统,并将该技术应用于Fonton术后及先天性心脏病的PB患者,证实了该类患者的PB与肺部淋巴循环异常有关,胸导管栓塞术是有效的治疗手段[19,20]。不仅如此,Itkin等[2]将DCMRL这一新技术成功用于非心源性PB患者,在7例入院诊断为支气管哮喘(2例)、慢性咳嗽(3例)、组织胞浆菌病合并脱屑性间质性肺炎(1例)及肺泡蛋白沉积症(1例)的成人PB患者中,发现6例肺部淋巴管循环异常,提示部分可能被认为是特发性或继发性PB的患者存在肺部淋巴系统异常,故Itkin等将PB分为淋巴循环障碍性和非淋巴循环障碍性两大类。

目前认识到,部分PB患者存在淋巴循环异常。淋巴循环障碍包括外周淋巴管或中央淋巴系统如胸导管、乳糜池及其分支的循环障碍。自胸导管到肺实质的淋巴循环异常是肺淋巴疾病的重要原因,可累及纵隔、肺、胸膜及支气管黏膜下层,因此,Itkin等将其称为"肺淋巴灌注综合征(pulmonary lymphatic perfusion syndrome,PLPS)",并认为PLPS是一种先天性淋巴管解剖变异[21]。如图1,图2所示,若异常的淋巴液渗出波及支气管黏膜,可在支气管内形成支气管样管型。

PB临床上常表现为咳嗽、咯血、喘息、胸痛、发热、呼吸困难及低氧血症,典型者可出现患侧呼吸音降低和哮鸣音,且常可咳出或经支气管镜取出凝胶状支气管树样管型(图3),将其放置于生理盐水中可散开呈支气管树枝状,外观呈白色、黄色、浅红色,有韧性。管型物的大小及形状不同,一般而言,由淋巴系统异常所致的PB形成的支气管样塑型较大(可长达30 cm),呈多角形,而支气管哮喘或肺部感染性疾病患者形成的支气管塑型一般较小,且结构简单。较小的管型容易漏诊。常用的检查方法有X线胸片、胸部CT及支气及支气管镜等。

与传统的淋巴管造影方法相比,IL和DCMRL这两项新技术是诊断淋巴源性PB的重要方法[22]。IL是将细套管针穿刺入腹股沟淋巴结,然后从套管内注射一种油性造影剂,使其能够继续流动至中央淋巴导管。与传统的经足淋巴管造影术比较,该技术操作迅速、并发症少且成功率高。DCMRL是在超声或透视引导下行淋巴结穿刺,行淋巴管造影的增强核磁,获得时间相关的动态MRI增强序列。

PB发病率低,病因不完全明确,治疗效果常不满意,原则上应针对可能产生PB的基础疾病和发生机制进行个体化治疗。若出现较大管型危及生命时,可经支气管镜取出管型[12]

关于PB治疗方法的研究较少[23,24]。文献报道的方法有:(1)可能有效:选择性淋巴管介入治疗或手术[2,19,20,25,26];低脂饮食[26,27,28,29],肝素雾化吸入治疗[30,31,32],雾化吸入高渗盐水[33],支气管镜下治疗[11,33,34,35,36] 。(2)疗效不确定:小剂量口服大环内酯类药物[33,34,37,38],口服或吸入糖皮质激素(适用于嗜酸粒细胞铸型)[34,35,39,40,41]。(3)慎用:吸入β-受体激动剂无效[33];祛痰药物,如N-乙酰半胱氨酸和愈创甘油醚无效[33,38]

部分PB与先天性心脏病、肺部淋巴管或淋巴引流异常所致的淋巴循环异常有关。淋巴循环异常的PB可采用胸导管结扎术[25,26]。随着微创技术的发展,淋巴管介入技术越来越多地用于淋巴管疾病的治疗[21]。MRI引导下选择性淋巴管栓塞术最初用于先天性心脏病术后的PB患者。Dori等[19,20]采用DCMRL技术对单心腔的PB患儿行肺部淋巴显像,然后选择性的进行肺部异常淋巴管栓塞术,可缓解症状。Itkin等[2]将这一技术用于成人,通过DCMRL在平均反复发作4年、多种治疗方案无效的7例PB患者中发现6例肺部淋巴管异常,并进行选择性肺淋巴管栓塞术,术后患者症状出现不同程度的缓解。其他可能有效的治疗手段包括淋巴管静脉吻合分流术[2]。此外,采用物理疗法如高频胸部震荡可改善气道廓清功能,有利于分泌物的排出。

PB病因繁多,对淋巴循环障碍机制的认识为PB的诊断与治疗提供了新的思路,有助于指导PB的精准治疗。明确不同病因PB的淋巴回流状况,将有助于识别那些原因不明的PB。PB新的认识和分类将有助于治疗方案的选择。未来尚需收集更多的病例进行研究,并对PLPS发生的具体机制进行深入探讨。选择性的异常淋巴管栓塞术的远期疗效需要进一步观察,其他针对胸导管或异常淋巴管的介入或手术治疗方法也需要评估。


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