非结核分枝杆菌肺病(NTM-PD)和支气管扩张症(简称支扩)的发病率和患病率均呈现增长趋势。NTM-PD可导致支扩,而支扩也是NTM-PD常见的易患因素,两种疾病在病情发生发展中互为因果、相互促进。大环内酯类药物是治疗NTM-PD的核心药物,小剂量口服大环内酯类药物也是预防支扩患者反复急性加重的首选治疗方案;然而对于潜在NTM感染的支扩患者,大环内酯类药物的单药使用存在诱发NTM耐药的风险。欧洲呼吸协会(ERS)和英国胸科协会(BTS)指南建议支扩患者在接受小剂量大环内酯类抗菌药物口服治疗前进行NTM筛选,因此NTM-PD与支扩复合病的诊断、治疗成为了临床关注的焦点。为规范化NTM-PD与支扩复合病的诊治,由我国NTM-PD专家、呼吸病学专家、方法学专家组成的编写组经过系统的文献分析、多轮线上线下讨论和问卷调查,制定了我国NTM-PD与支扩复合病的诊断和治疗专家共识。本共识提出了10个核心问题,内容涵盖病因学检查、诊断、治疗、预后转归及管理等方面,最终形成了14条推荐意见。共识使用调整后的推荐分级的评估、制定和评价(GRADE)方法对证据评价和推荐意见进行分级。希望通过本共识,提高我国NTM-PD与支扩复合病的诊断和治疗水平。
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 vice versa, 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 " Expert consensus on diagnosis and treatment of non-tuberculous mycobacterial pulmonary disease and bronchiectasis." 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. Question 1:Is etiological testing necessary when bronchiectasis is diagnosed in NTM-PD patients? Recommendation 1: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). Recommendation 2: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. Question 2:What are the clinical characteristics of bronchiectasis patients who should be screened for NTM infection?What tests and samples are recommended? Recommendation 3: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). Recommendation 4: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). Question 3:Should patients with bronchiectasis be screened for NTM-PD before initiating long-term macrolide therapy? Recommendation 5: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). Question 4:Should anti-NTM therapy be initiated immediately when a patient with bronchiectasis is also diagnosed with NTM-PD? Recommendation 6: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). Question 5:How should anti-infective drugs be chosen if bronchiectasis infection worsens during anti-NTM treatment in patients with NTM-PD and bronchiectasis? Recommendation 7: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 Pseudomonas aeruginosa 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). Question 6:How should patients with NTM-PD and bronchiectasis,who have failed anti-NTM treatment or who cannot tolerate regular anti-NTM therapy,be treated? Recommendation 8: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). Question 7:What are the recommendations for the use of glucocorticoids in patients with NTM-PD and bronchiectasis comorbidity who require glucocorticoid treatment for other conditions? Recommendation 9: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). Question 8:What are the recommendations for surgical treatment in patients with NTM-PD and bronchiectasis comorbidity? Recommendation 10: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). Recommendation 11: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 Mycobacterium abscessus 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). Recommendation 12: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). Question 9:How should the therapeutic effect and outcome of NTM-PD and bronchiectasis comorbidity be evaluated? Recommendation 13: 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. Question 10:How should recurrence be managed and prevented in patients with NTM-PD and bronchiectasis after bacteriological negative conversion or cure? Recommendation 14: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).
中华医学会结核病学分会,中华医学会呼吸病学分会. 非结核分枝杆菌肺病与支气管扩张症复合病的诊断与治疗专家共识[J]. 中华结核和呼吸杂志,2025,48(02):101-115.
DOI:10.3760/cma.j.cn112147-20240808-00471版权归中华医学会所有。
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证据质量 | 具体描述 | 研究类型 | 表达字母 |
---|---|---|---|
高 | 非常确信真实的效应值接近效应估计值 | 高质量的随机对照试验(RCT);系统评价/Meta 分析 | A |
中 | 对效应估计值有中等程度的信心;真实值有可能接近估计值,但仍存在二者大不相同的可能性 | 有研究缺陷的RCT;低质量的系统评价/Meta分析;高质量的观察性研究 | B |
低 | 对效应估计值的确信程度有限;真实值可能与估计值大不相同 | 非随机对照病例研究;其他观察性研究 | C |
极低 | 对效应估计值没有信心;真实值很可能与估计值大不相同 | 病例报道;专家意见 | D |
推荐强度 | 具体描述 | 表达数字 |
---|---|---|
支持使用某项干预措施的强推荐 | 评价者确信干预措施利大于弊 | 1 |
支持使用某项干预措施的弱推荐 | 利弊不确定或无论高低质量的证据均显示利弊相当 | 2 |
反对使用某项干预措施的弱推荐 | 利弊不确定或无论高低质量的证据均显示利弊相当 | 2 |
反对使用某项干预措施的强推荐 | 评价者确信干预措施弊大于利 | 1 |
病因 | 临床表现 | 检查及评估方法 |
---|---|---|
既往下呼吸道感染 | ||
婴幼儿和儿童时期下呼吸道感染是支气管扩张症最常见的病因,如麻疹、百日咳、肺结核、肺炎(细菌、病毒、支原体)。其中铜绿假单胞菌的感染或定植与支扩病情发生发展的关系尤为密切 | 下呼吸道感染症状 | 需详细询问患者的病史和合并症,尤其是幼年下呼吸道感染病史 |
免疫功能缺陷 | ||
原发性:低免疫球蛋白血症 | - | 免疫球蛋白水平(IgG、IgM、IgA) |
继发性:长期服用免疫抑制药物、HIV感染 | - | 病史询问、HIV抗体和病毒载量、全血细胞计数、外周血淋巴细胞亚群计数 |
气道阻塞或误吸 | 病史询问,有无误吸史。影像学检查、局灶性疾病的支气管镜检查 | |
变应性支气管肺曲霉病 | 支气管哮喘症状 | 曲霉特异性IgE,血清总IgE水平 |
慢阻肺病或支气管哮喘 | 咳、痰、喘 | 肺功能检查 |
遗传因素 | ||
囊性纤维化 | 发病早,鼻窦炎、胰腺炎或吸收不良,男性不育症 | 汗液氯化物检测,囊性纤维化跨膜传导调节蛋白(CFTR)基因突变 |
原发性纤毛运动障碍 | 发病早,鼻窦炎,慢性扁桃体炎,男性不育症 | 鼻呼出气一氧化碳(FeNO)浓度检测、基因检测、纤毛功能评估 |
α1-抗胰蛋白酶缺乏症 | 肺气肿 | α1-抗胰蛋白酶水平与表型 |
先天支气管病变:巨大气管-支气管症、软骨塌陷等 | - | CT检查 |
自身免疫性疾病 | ||
类风湿性关节炎 | 晨僵等 | 类风湿因子 |
干燥综合征 | 口干、鼻干、眼干等 | 抗环瓜氨酸肽 |
硬皮病 | 面具脸等 | 抗核抗体 |
炎症性肠病 | 腹泻、便血 | 肠镜黏膜活检 |
注:-表示无症状
项目 | 内容 |
---|---|
临床表现 | 具有呼吸系统症状和(或)全身性症状 |
影像学 | 经胸部影像学检查发现空洞性阴影、多灶性支气管扩张以及多发性小结节病变 |
并且 | 排除其他肺部疾病 |
微生物学 | 在确保标本无外源性污染的前提下,符合以下条件之一者可诊断为 NTM 肺病 |
1. 2份分开送检的痰标本NTM培养阳性并鉴定为同一致病菌,和(或)NTM 分子生物学检测均为同一致病菌; | |
2. 支气管冲洗液或支气管肺泡灌洗液NTM培养和(或)分子生物学检测1次阳性; | |
3. 经支气管镜或其他途径肺活组织检查发现分枝杆菌病组织病理学特征性改变(肉芽肿性炎症或抗酸染色阳性),并且NTM培养和(或)分子生物学检测阳性; | |
4. 经支气管镜或其他途径肺活组织检查发现分枝杆菌病组织病理学特征性改变(肉芽肿性炎症或抗酸染色阳性),并且1次及以上的痰标本、支气管冲洗液或支气管肺泡灌洗液中NTM培养和(或)分子生物学检测阳性。 |

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