Advances in Clinical Medicine
Vol. 11  No. 07 ( 2021 ), Article ID: 44150 , 6 pages
10.12677/ACM.2021.117469

肺结核治疗后感染性并发症研究进展

李嫒1,崔金霞2 *

1青海大学,青海 西宁

2青海大学附属医院呼吸内科,青海 西宁

收稿日期:2021年6月21日;录用日期:2021年7月11日;发布日期:2021年7月26日

摘要

随着人们对已治疗的肺结核患者更多关注与随访,发现感染更有可能发生在这类患者中。因为肺结核是一个破坏性的过程,会导致肺组织纤维化、实质改变、支气管扩张、肺部瘢痕形成等,导致肺体积减少,进而影响肺功能。除了结核病的复发和再次感染外,对于治疗后的结核病患者还越来越多地认识到其他病原体的感染。本文旨在总结如何处理新发肺部感染的肺结核患者,以确保最佳的治疗和康复。

关键词

肺结核,非结核分枝杆菌,支气管扩张症

Research Progress of Infectious Complications after Pulmonary Tuberculosis Treatment

Ai Li1, Jinxia Cui2*

1Qinghai University, Xining Qinghai

2Department of Respiratory Medicine, Affiliated Hospital of Qinghai University, Xining Qinghai

Received: Jun. 21st, 2021; accepted: Jul. 11th, 2021; published: Jul. 26th, 2021

ABSTRACT

With the increasing attention and follow-up to patients who have been treated for pulmonary tuberculosis, infection is more likely to occur in these patients. Because TB is a destructive process, it can lead to fibrosis of lung tissue, parenchymal changes, bronchiectasis, scarring of the lungs, resulting in reduced lung volume, which in turn affects lung function. In addition to the recurrence and re-infection of TB, patients following TB treatment are increasingly aware of infection with other pathogens. The purpose of this article is to summarize and guide the management of pulmonary tuberculosis patients with new signs and symptoms of pulmonary infection to ensure optimal treatment and recovery.

Keywords:Pulmonary Tuberculosis, Non-Tuberculous Mycobacterium, Bronchiectasis

Copyright © 2021 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

结核病是一种严重威胁全球公共健康安全的流行病,被列为全球十大死因之一。它是由结核分枝杆菌引起的一种具有高度传染性的疾病。其中约80%的病例为肺结核,另外也可以影响机体的其他组织,即肺外结核病,包括肠道、脑膜、淋巴结、骨骼、关节、肾脏及皮肤等。

从流行病学方面来看,结核病依然是世界上一个关键的全球性公共卫生问题,尤其在低收入及中等收入国家。据2020年世界卫生组织报告,2019年全球新报告病例710万例,较2019~2012年间维持在每年570~580万例水平有大幅提升。尽管目前已经在治疗上取得了进展,全球发病率每年下降约2%,但因耐药结核病的出现,结核病正在迅速成为一种全球性公共卫生危机 [1]。另外肺结核患者,即使在治愈后,也可能进一步发展为呼吸道感染疾病和肺部相关疾病,这有可能成为慢性疾病,导致更高的疾病发病率和死亡率 [2]。肺结核病治疗后慢性阻塞性肺疾病(COPD)、支气管扩张和肺炎的加重更为频繁 [3] [4]。特别是在吸烟和大气污染的情况下肺老化可明显加剧 [5]。在有一定程度肺组织破坏的个体中非结核分枝杆菌和烟曲霉菌的定植和感染也很常见 [6]。除了肺结核复发或再感染外,当发现肺结核患者治疗后出现相关症状、肺功能恶化和肺结核后遗症的证据时,所有这些情况都需要在鉴别诊断中考虑到。

肺结核治疗后感染可能具有与肺结核相似的临床特征,咯血就是一种常见的临床表现。因此建议在结核病治疗结束时行胸部X光检查,这对未来进行前后比较时有很大的参考作用。在结核病治疗后的2年内进行6个月左右的呼吸科门诊随访,可能有助于监测和管理部分慢性肺病患者可能出现的COPD和支气管扩张。临床医生也应该意识到肺结核分支杆菌–曲霉菌混合感染的可能性和相关的较高死亡率情况 [7] [8]。

2. 慢性肺曲霉菌病的临床表现和治疗

慢性肺曲霉菌病包括一系列疾病类型,通常有相互的重叠。慢性肺曲霉菌病的主要亚型包括慢性空洞型曲霉病、慢性纤维性曲霉病、曲菌球和曲霉菌结节。据估计,肺结核治疗后残留肺空洞为2厘米左右的患者有1/5的机会发展为曲菌球 [9]。对于可以获得治疗的慢性肺曲霉菌病患者研究,对患者死亡率总体估计短期内为20%~33%,在5年内为33%~80% [10] [11]。

慢性肺曲霉菌病的临床特征通常是无特异性的,起病较缓慢。常见症状包括体重减轻、慢性咳嗽、疲劳、呼吸困难和咯血 [12]。没有并发慢性空洞型曲霉病/慢性纤维性曲霉病的单纯性曲菌球通常很少或没有症状。胸部影像是一种重要的诊断手段,胸部X光或CT断层扫描可显示肺部一个或多个空洞,通常位于肺上叶,大小不一,可伴有胸膜增厚和肺纤维化 [13]。空洞可以表现为薄壁空洞或厚壁空洞,且有可能含有真菌球。诊断的主要手段是检测血清中的曲霉菌特异性IgG抗体 [14] [15]。

治疗主要取决于疾病的类型及范围,以及患者是否适合行手术切除 [16]。对于每个患者都必须去考虑治疗的风险与益处。且目前关于治疗的最佳持续时间和抗真菌药物的选择相关数据是非常局限的。伏立康唑、异乌康唑或伊曲康唑是慢性空洞型曲霉病/慢性纤维性曲霉病患者的一线治疗药物 [17] [18]。血清药物浓度监测对于最初优化给药至关重要 [19]。如果上述治疗方案失败、患者不耐受或出现耐药现象时,两性霉素B、米卡芬净或卡泊芬净是静脉注射用替代药品 [17]。

建议慢性空洞型曲霉病患者的最短疗程为4~6个月 [16]。而对于疾病进展较快、药物反应不良或持续性免疫抑制的个体可能需要更长的治疗病程。其中有一部分进展性疾病患者需要终身性治疗 [18]。胸膜增厚和真菌球缩小及胸部X线变化消退可以用于评估药物的治疗反应及效果 [20]。对于单纯性曲菌球患者,手术切除可以预防或治疗大咯血情况 [18]。

3. 支气管扩张症的临床特点、治疗和康复

支气管扩张症可以出现在活动性肺结核的病程发展中,也可能出现在肺结核的后遗症中。一项系统研究以肺结核患者为研究对象,并通过胸部CT成像评估患者康复后肺部改变,结果显示有35%~86%的患者远期出现了支气管扩张 [21]。肺结核后患者的支气管管道狭窄、结疤以及淋巴结肿大对支气管的外部压迫均可导致气管内分泌物滞留,有反复感染的风险,进而导致气道管壁的破坏和扩张。另外肺实质的纤维化和破坏也可以通过实质收缩牵拉而引起支气管扩张 [22]。

支气管扩张的主要并发症之一是由于反复感染、肺功能逐渐恶化以及机体运动耐力和生活质量降低而导致的疾病频繁德恶化。这种反复出现的感染恶性循环是由于肺的结构性损伤、持续性炎症、呼吸道细菌与真菌定植以及纤毛上皮功能不全之间相互作用而引起的。支气管扩张症患者频繁发生感染有较高的住院率及死亡率,对于公共卫生系统以及患者家庭产生严重负担。支气管扩张的临床表现主要包括咳嗽、咳痰、咯血等。胸膜炎性胸痛、呼吸困难、发烧、疲劳和体重减轻是常见的临床特征 [23]。

肺结核治疗后出现非囊性支气管扩张的患者,远期引起反复感染的微生物是有限的。然而,相关数据完全可以从非囊性支气管扩张患者的研究中推断出来,尤其是在结核病高流行率地区中。引起感染病情恶化的常见相关微生物包括:铜绿假单胞菌、流感嗜血杆菌、卡他莫拉菌和金黄色葡萄球菌等 [24]。洋葱伯克霍尔德氏菌复合体、嗜麦芽窄食单胞菌和假单胞菌科的其他成员目前越来越被认为是相关致病微生物 [25]。对于种变化可以归因于目前微生物诊断技术的进步、痰培养及检测的加强以及长期应用抑制性抗生素治疗 [26]。在有感染加重的支气管扩张患者中,也经常被培养分离出来 [27]。

对于肺结核后支气管扩张患者,临床管理上应注重肺康复治疗(胸部理疗、吸入高渗盐水、适当运动及清除气道),旨在降低复发感染的频率与严重程度,并提高运动耐量和生活质量。长期口服抗生素的目的主要是为了防止病情反复及进一步恶化,打破恶性循环。多项随机对照试验表明,与安慰剂相比,长期使用大环内酯类药物治疗(6个月或12个月)的患者恶化频率呈显著降低 [28] [29]。然而,这种做法可能会导致选择性大环内酯类耐药性微生物的出现。吸入型抗生素也用于减轻细菌负担,与口服抗生素相比,通常副作用较少。然而,吸入型抗生素的对于患者的耐受性和可用性可能是一个问题。

4. 非结核分枝杆菌感染

有证据表明,全球非传染性疾病感染的负担正在增加。从肺部样本中分离出的最常见的非结核分枝杆菌是鸟–胞内复合体分枝杆菌 [30]。堪萨斯分枝杆菌是导致进行性肺部疾病的另一项重要原因。患有先前存在的结构性肺部疾病的患者(包括支气管扩张和既往结核病)有发展成非结核分枝杆菌肺病的风险 [31]。据估计,NTM肺病可发生在7%~11%的肺结核患者中 [32]。

鸟–胞内复合体分枝杆菌肺病的临床特征是复杂可变且非特异性的,主要包括咳嗽、疲劳、呼吸困难、胸部不适、咯血、体重减轻和发热。堪萨斯分枝杆菌肺病有更明显的临床表现。两者的放射学表现都包括实质浸润、结节和空洞 [33]。诊断标准主要包括符合临床特征及影像学特点,支气管灌洗或痰标本培养到一种或两种微生物阳性结果,以及组织活检具有特定的组织病理学特征 [34]。

对于符合诊断标准的患者,是否开始治疗受到疾病的严重程度、进展风险、合并症、治疗的耐受性和治疗目标的影响。肺纤维空洞的存在对疾病的进展有促进作用,故需要迅速开始治疗 [34]。治疗方案的选择取决于对大环内酯类药物的敏感性。有指南建议由利福平、乙胺丁醇和阿奇霉素或克拉霉素组成的三联疗法来进行治疗 [35]。对于轻中度严重且没有纤维空洞形成的患者,抗生素可以每周服用三次。而对于重度或有纤维空洞形成的患者需要每天服用利福平、乙胺丁醇和阿奇霉素或克拉霉素,并考虑使用静脉注射或雾化吸入第四种药物阿米卡星 [35]。治疗持续时间至少为痰培养转阴后1年。目前仍然迫切得需要进一步研究治疗非结核分枝杆菌感染的新型药物或现有药物的新组合。

5. 预防和接种疫苗

有流行病学数据表明,在流感大流行和季节性流行期间,肺结核病患者与健康人群相比,患流感相关疾病的频率和严重程度都有所增加 [36] [37]。流感和结核分支杆菌混合感染会损害宿主免疫功能,导致患者对继发性细菌感染的易感性明显增加 [38]。通过对可能感染流感的个体进行及时的经验性抗病毒治疗,可能会缓解感染流感而增加的严重后果。在接受治疗的肺结核病患者中,由于肺部疾病的严重程度和持续时间有所不同,因此应特别考虑对那些患有慢性呼吸道疾病的患者接种流感疫苗。

吸烟是肺部感染的风险因素,也是导致肺功能迅速恶化、机体运动耐力下降和生活质量受损的共同危险因素 [39]。基于肺结核人群的研究已经证明吸烟与不良结果的发展、复发和耐药结核病的发展之间存在相关性 [40]。因此对于肺结核病人,完善全面的戒烟及肺康复计划很可能是减少肺部疾病患者感染性恶化的重要战略 [41]。

6. 总结

目前对肺结核治疗后远期肺部健康的认识越来越多,并得到了更多的关注。并且越来越多的人认识到,完成肺结核治疗的患者应该得到及时的随访,特别是有明显的肺部纤维空洞的患者。有COPD及支气管扩张症的患者尤其可能经过进一步的反复感染使得肺功能下降,并影响生活质量。

因此在治疗结束后,定期行肺活量测定、痰抗酸杆菌检查、曲霉菌筛查以及胸部X光检查对评估随后可能复发的结核病、非特异性感染、肿瘤或其他后遗症都很有帮助。另外戒烟、接种疫苗、预防性使用抗生素和肺部康复训练都有可能助于遏制病情恶化与进展,减少肺功能下降,从而提高生活质量。

文章引用

李 嫒,崔金霞. 肺结核治疗后感染性并发症研究进展
Research Progress of Infectious Complications after Pulmonary Tuberculosis Treatment[J]. 临床医学进展, 2021, 11(07): 3232-3237. https://doi.org/10.12677/ACM.2021.117469

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  42. NOTES

    *通讯作者。

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