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《非结核分枝杆菌肺病合并支气管扩张症诊断与治疗中国专家共识》

[Chinese expert consensus on diagnosis and treatment of non-tuberculous mycobacterial pulmonary disease complicated with bronchiectasis].

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2025 Feb 12;48(2):101-115. doi: 10.3760/cma.j.cn112147-20240808-00471.

DOI:10.3760/cma.j.cn112147-20240808-00471
PMID:39914833
Abstract

The incidence and prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) and bronchiectasis have been both increasing. NTM-PD can lead to bronchiectasis, and , with each condition mutually exacerbating the other. Macrolides play a pivotal role in NTM-PD treatment. Additionally, long-term, low-dose oral macrolides are preferred to prevent recurrent acute exacerbations in bronchiectasis patients. However, using macrolides alone may risk inducing non-tuberculous mycobacteria (NTM) resistance in bronchiectasis patients potentially infected with NTM. The European Respiratory Society (ERS) and British Thoracic Society (BTS) guidelines advocate for NTM screening among bronchiectasis patients before receiving long-term, low-dose oral macrolide therapy. Consequently, the focus in clinical practice has shifted towards diagnosing and managing the coexistence of NTM-PD and bronchiectasis. Recognizing these developments, Chinese respiratory experts have established the "."In this expert consensus,systematic reviews were conducted for each of the 10 Population,Intervention,Comparator,Outcome(PICO)questions. Recommendations were formulated,written,and graded using the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach. Fourteen evidence-based recommendations regarding the diagnosis and treatment of NTM-PD in conjunction with bronchiectasis are presented. In the future,it is hoped that this consensus will enhance the diagnosis and treatment of NTM-PD and bronchiectasis comorbidity in China.:Is etiological testing necessary when bronchiectasis is diagnosed in NTM-PD patients?:Bronchiectasis of different etiologies requires distinct treatment strategies and prognoses. Therefore,when NTM-PD patients are diagnosed with bronchiectasis,it is recommended its etiology be investigated. This investigation will aid in the diagnosis,treatment,and prognosis of patients with this comorbidity(1C).:Methods to investigate and evaluate the etiology of bronchiectasis include:(1)obtaining medical history and clinical symptoms;(2)performing a sputum culture,complete blood count,serum immunoglobulin levels(IgG,IgM,IgA),Aspergillus-specific IgE,and serum total IgE levels,and pulmonary function tests;(3)If genetic or autoimmune diseases are suspected,performing additional relevant specialized tests.:What are the clinical characteristics of bronchiectasis patients who should be screened for NTM infection?What tests and samples are recommended?:Bronchiectasis patients meeting the following criteria should be evaluated for possible NTM infection:(1)newly diagnosed bronchiectasis patients;(2)those with unexplained clinical or radiographic exacerbations of bronchiectasis;(3)patients with bronchiectasis planning long-term macrolide therapy(1B).:Recommended specimens for examination include:(1)sputum,induced sputum,bronchial secretions(or lavage fluid),and other respiratory specimens;(2)pathological specimens from lung and mediastinal lymph nodes obtained via puncture and biopsy. Recommended tests encompass acid-fast staining smear and mycobacterial culture(solid or liquid medium)(1a). Molecular tests such as high-throughput sequencing and mass spectrometry offer high diagnostic efficiency and strain-level identification,conditionally recommended to assist in diagnosis as per the relevant expert consensus(2D).:Should patients with bronchiectasis be screened for NTM-PD before initiating long-term macrolide therapy?:Prior to initiating long-term macrolide therapy for bronchiectasis,particularly in patients with a history of NTM-PD,it is crucial to ascertain the presence of active NTM-PD or past MAC-PD. If such conditions are identified,the long-term use of low-dose macrolides alone for bronchiectasis treatment is not recommended(2C).:Should anti-NTM therapy be initiated immediately when a patient with bronchiectasis is also diagnosed with NTM-PD?:In patients with NTM-PD and bronchiectasis comorbidity,initiation of anti-NTM therapy is recommended when there are positive sputum acid-fast staining smears and/or radiographic evidence of cavitary lesions(2B).:How should anti-infective drugs be chosen if bronchiectasis infection worsens during anti-NTM treatment in patients with NTM-PD and bronchiectasis?:Prior to initiating antibiotic therapy,perform a comprehensive etiological testing of sputum and/or respiratory secretions,including bacterial and fungal cultures and drug sensitivity testing(1A). Empirical antimicrobial therapy should be started before etiological results are available. Antibiotic selection should be guided by prior drug sensitivity testing. For patients with moderate to severe bronchiectasis without prior etiological culture results,routine coverage for during treatment is recommended(1B). Apart from bacteria,other pathogens such as viruses and fungi may also contribute to acute exacerbations of the disease,necessitating differential diagnosis(2C).:How should patients with NTM-PD and bronchiectasis,who have failed anti-NTM treatment or who cannot tolerate regular anti-NTM therapy,be treated?:For patients who have failed anti-NTM therapy or are unable to tolerate standard anti-NTM regimens,it is recommended to focus on the treatment and management of bronchiectasis(2C).:What are the recommendations for the use of glucocorticoids in patients with NTM-PD and bronchiectasis comorbidity who require glucocorticoid treatment for other conditions?:Regular use of glucocorticoids for symptom control in patients with NTM-PD and bronchiectasis comorbidity is not recommended. Inhaled bronchodilators are recommended for patients with obstructive ventilation dysfunction. In cases where conditions such as asthma,systemic lupus erythematosus,rheumatoid arthritis,or other diseases necessitate glucocorticoid use for disease control,caution should be exercised based on the diagnosis and treatment guidelines of the respective diseases or consensus(2C).:What are the recommendations for surgical treatment in patients with NTM-PD and bronchiectasis comorbidity?:Surgical treatment should be approached with caution,and surgery is not recommended if anti-mycobacterial treatment is effective(1A). Lung resection surgery for NTM pulmonary disease should only be considered after expert multidisciplinary assessment in a center experienced in managing NTM-pulmonary disease(1B).:Patients with concentrated and limited lung lesions,acceptable cardiopulmonary function without contraindications,and who meet one of the following conditions may be candidates for surgery:(1)multiple drug susceptibility tests showing macrolide-resistant NTM strains and regular antimycobacterial therapy failure;or patients infected with macrolide-resistant who have not responded adequately to medical treatment;(2)patients experiencing refractory hemoptysis,which poses a potential life-threatening risk,despite improvement in other symptoms following drug treatment;(3)repeated NTM infections that significantly impact patients' daily life and work(1B).:Following thoracic surgery in patients with NTM-PD complicated by bronchiectasis,it is recommended that anti-NTM treatment be continued post-operatively for a minimum of 12 months until sputum culture conversion is achieved(1B).:How should the therapeutic effect and outcome of NTM-PD and bronchiectasis comorbidity be evaluated? When evaluating treatment effect and outcomes in patients with NTM-PD and bronchiectasis comorbidity,both the "prognostic criteria of NTM-PD" and "symptom indicators of bronchiectasis" should be considered(1B). Treatment outcomes can be categorized into three grades:(1)cure stage:meeting any of the criteria ①-④ for NTM-PD and in a stable period of bronchiectasis;(2)improvement stage:meeting any of the criteria ①-④ for NTM-PD,or in a stable period of bronchiectasis;(3)treatment failure:meeting any of the criteria ⑤-⑦ for NTM-PD,and experiencing repeated acute exacerbations of bronchiectasis(2D);(3)for patients with immune dysfunction or long-term use of immunosuppressants/hormones,the dosage or duration of immunosuppressants/hormones are supposed to be reduced as much as possible without affecting the efficacy of the original disease under the guidance and supervision of the professional doctors. Meanwhile,it is recommended to regularly recheck chest CT and sputum mycobacterial culture.:How should recurrence be managed and prevented in patients with NTM-PD and bronchiectasis after bacteriological negative conversion or cure?:It is recommended to modify lifestyle and habits to reduce environmental exposure to NTM(1B). For patients with a low body mass index and/or a history of weight loss,nutritional assessment and intervention should be considered(2D).

摘要

非结核分枝杆菌肺病(NTM-PD)和支气管扩张的发病率及患病率均呈上升趋势。NTM-PD可导致支气管扩张,反之亦然,二者相互加剧病情。大环内酯类药物在NTM-PD治疗中起关键作用。此外,长期小剂量口服大环内酯类药物是预防支气管扩张患者急性加重复发的首选方法。然而,单独使用大环内酯类药物可能会使潜在感染NTM的支气管扩张患者产生NTM耐药风险。欧洲呼吸学会(ERS)和英国胸科学会(BTS)指南提倡在支气管扩张患者接受长期小剂量口服大环内酯类药物治疗前进行NTM筛查。因此,临床实践的重点已转向诊断和管理NTM-PD与支气管扩张的共存情况。认识到这些进展后,中国呼吸专家制定了“……”。在本专家共识中,针对10个“人群、干预措施、对照、结局”(PICO)问题分别进行了系统评价。采用推荐分级的评估、制定与评价(GRADE)方法制定、撰写并分级推荐意见。提出了14条关于NTM-PD合并支气管扩张诊断和治疗的循证推荐意见。希望本共识未来能提高中国NTM-PD和支气管扩张合并症的诊断和治疗水平。:NTM-PD患者诊断为支气管扩张时是否需要进行病因检测?:不同病因的支气管扩张需要不同的治疗策略和预后。因此,NTM-PD患者诊断为支气管扩张时,建议对其病因进行调查。该调查将有助于此类合并症患者的诊断、治疗和预后评估(1C)。:调查和评估支气管扩张病因的方法包括:(1)获取病史和临床症状;(2)进行痰培养、全血细胞计数、血清免疫球蛋白水平(IgG、IgM、IgA)、曲霉特异性IgE和血清总IgE水平检测以及肺功能测试;(3)若怀疑有遗传性或自身免疫性疾病,进行其他相关专项检测。:应筛查NTM感染的支气管扩张患者的临床特征有哪些?推荐哪些检测和样本?:符合以下标准的支气管扩张患者应评估是否可能感染NTM:(1)新诊断的支气管扩张患者;(2)支气管扩张有不明原因的临床或影像学加重的患者;(3)计划进行长期大环内酯类药物治疗的支气管扩张患者(1B)。:推荐的检查样本包括:(1)痰液、诱导痰、支气管分泌物(或灌洗液)及其他呼吸道样本;(2)经穿刺和活检获取肺部及纵隔淋巴结的病理样本。推荐的检测包括抗酸染色涂片和分枝杆菌培养(固体或液体培养基)(1a)。高通量测序和质谱等分子检测具有较高的诊断效率和菌株水平鉴定能力,根据相关专家共识有条件推荐用于辅助诊断(2D)。:支气管扩张患者在开始长期大环内酯类药物治疗前是否应筛查NTM-PD?:在开始对支气管扩张患者进行长期大环内酯类药物治疗前,尤其是有NTM-PD病史的患者,确定是否存在活动性NTM-PD或既往MAC-PD至关重要。若发现此类情况,不建议单独长期使用小剂量大环内酯类药物治疗支气管扩张(2C)。:支气管扩张患者同时诊断为NTM-PD时是否应立即开始抗NTM治疗?:对于NTM-PD和支气管扩张合并症患者,痰涂片抗酸染色阳性和/或有空洞性病变的影像学证据时,建议开始抗NTM治疗(2B)。:NTM-PD和支气管扩张患者抗NTM治疗期间支气管扩张感染加重时应如何选择抗感染药物?:在开始抗生素治疗前,对痰液和/或呼吸道分泌物进行全面病因检测,包括细菌和真菌培养及药敏试验(1A)。在病因结果出来之前应开始经验性抗菌治疗。抗生素选择应以既往药敏试验为指导。对于中度至重度支气管扩张且无既往病因培养结果的患者,治疗期间建议常规覆盖……(1B)。除细菌外,病毒和真菌等其他病原体也可能导致疾病急性加重,需要进行鉴别诊断(2C)。:NTM-PD和支气管扩张患者抗NTM治疗失败或无法耐受常规抗NTM治疗时应如何治疗?:对于抗NTM治疗失败或无法耐受标准抗NTM方案的患者,建议重点关注支气管扩张的治疗和管理(2C)。:对于因其他情况需要使用糖皮质激素治疗的NTM-PD和支气管扩张合并症患者,糖皮质激素的使用有哪些建议?:不建议常规使用糖皮质激素控制NTM-PD和支气管扩张合并症患者的症状。对于存在阻塞性通气功能障碍的患者,建议使用吸入性支气管扩张剂。对于哮喘、系统性红斑狼疮、类风湿关节炎等疾病需要使用糖皮质激素控制病情的情况,应根据各自疾病的诊断和治疗指南或共识谨慎使用(2C)。:NTM-PD和支气管扩张合并症患者的手术治疗有哪些建议?:手术治疗应谨慎,抗分枝杆菌治疗有效时不建议手术(1A)。NTM肺病的肺切除术应仅在经验丰富的NTM肺病管理中心进行专家多学科评估后考虑(1B)。:肺部病变集中且局限、心肺功能可接受且无禁忌证,且符合以下条件之一的患者可能适合手术:(1)多次药敏试验显示对大环内酯类耐药的NTM菌株且常规抗分枝杆菌治疗失败;或感染对大环内酯类耐药的……且药物治疗效果不佳的患者;(2)尽管药物治疗后其他症状有所改善,但仍有难治性咯血,存在潜在生命危险;(3)反复NTM感染严重影响患者日常生活和工作(1B)。:NTM-PD合并支气管扩张患者胸科手术后,建议术后继续抗NTM治疗至少12个月,直至痰培养转阴(1B)。:应如何评估NTM-PD和支气管扩张合并症的治疗效果和结局?评估NTM-PD和支气管扩张合并症患者的治疗效果和结局时,应同时考虑“NTM-PD的预后标准”和“支气管扩张的症状指标”(1B)。治疗结局可分为三个等级:(1)治愈阶段:符合NTM-PD标准①-④中的任何一条且支气管扩张处于稳定期;(2)改善阶段:符合NTM-PD标准①-④中的任何一条,或支气管扩张处于稳定期;(3)治疗失败:符合NTM-PD标准⑤-⑦中的任何一条,且支气管扩张反复急性加重(2D);(3)对于免疫功能低下或长期使用免疫抑制剂/激素的患者,在专业医生的指导和监督下,应尽可能减少免疫抑制剂/激素的剂量或使用时间,同时不影响原疾病的疗效。同时,建议定期复查胸部CT和痰分枝杆菌培养。:NTM-PD和支气管扩张患者细菌学转阴或治愈后应如何管理和预防复发?:建议改变生活方式和习惯,减少环境中NTM暴露(1B)。对于体重指数低和/或有体重减轻病史的患者,应考虑进行营养评估和干预(2D)。

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