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

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 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）.