Infectious Disease · Medical Literature
Tracheobronchial invasion by nontuberculous mycobacteria: a rare but overlooked clinical manifestation-a multicenter retrospective analysis.
Abstract
Nontuberculous mycobacteria (NTM) can disseminate and infect various organs throughout the body. However, whether NTM can infect tracheobronchial tissue is rarely reported. This study aimed to address the knowledge gap regarding the epidemiological, demographic, and clinical characteristics of patients with tracheobronchial NTM infection. In this multicenter retrospective cohort study, clinical, demographic, microbiological, and radiological data from hospitalized patients with tracheobronchial NTM infections from January 2015 to May 2025 were collected and analyzed descriptively. Twenty-nine patients (2.3%) were included, and all the patients presented with disseminated NTM infection. Seventeen patients had comorbidities, including 5 with acquired immunodeficiency syndrome and 1 with anti-interferon-γ autoantibody syndrome. Median diagnostic delay was 130 days, and 89.7% of the patients were initially misdiagnosed with tuberculosis or malignancy. The most common symptoms were cough, expectoration, anemia, fever, weight loss, skin lesions, and bone pain. Chest CT revealed nodules, patchy opacities, mass-like shadows, and bronchial stenosis, with or without hilar/mediastinal lymphadenopathy, whereas osteolytic bone destruction was evident in 11 patients. The most common features of bronchoscopy were intraluminal masses/neoplasms/nodules. Metagenomic next-generation sequencing (mNGS) of BALF (n=12) demonstrated 100% positivity, outperforming BALF culture (46.2%, 12/26) and sputum culture (39.3%, 11/28). Mycobacterium colombiense accounted for 24.1% of cases. With respect to therapeutic management, 27 patients received systemic antimicrobial therapy, while 2 did not receive specific anti-N™ treatment. One patient underwent combined endoscopic resection. Overall, 23 patients (79.3%) achieved improvement or cure, 5 showed disease progression, 1 experienced relapse, and 1 died. Tracheobronchial NTM infection is rare but clinically significant, often occurring in the context of disseminated disease with pulmonary involvement. Immunocompromised hosts, particularly those with AIDS or anti-IFN-γ autoantibody syndrome, are highly susceptible. Bronchoscopy typically reveals mass lesions causing luminal stenosis or occlusion. In this cohort, M. colombiense was the most frequently isolated NTM species. Early bronchoscopy, mNGS-based pathogen detection, and timely systemic or endoscopic intervention should be considered to prevent irreversible airway stenosis. Further studies are needed to validate optimal treatment strategies. https://www.ClinicalTrials.gov, identifier NCT07377864.
Clinical relevance
Tracheobronchial NTM infection is a rare but clinically significant manifestation of disseminated NTM disease that has been largely unreported in the literature, creating a critical knowledge gap for clinicians managing immunocompromised patients. The affected population includes predominantly hosts with impaired cell-mediated immunity—particularly those with AIDS or anti-IFN-γ autoantibody syndrome—who are at highest risk for this atypical airway presentation. Given a misdiagnosis rate of nearly 90% (predominantly misclassified as tuberculosis or malignancy) and a median diagnostic delay of 130 days, heightened clinical suspicion and early advanced diagnostic workup are urgently warranted.
Key findings
1. Tracheobronchial NTM infection represented 2.3% of the study cohort (29/~1,261 patients) across a multicenter retrospective analysis spanning January 2015–May 2025, with all 29 patients presenting in the context of disseminated NTM disease. 2. Median diagnostic delay was 130 days, with 89.7% (26/29) of patients initially misdiagnosed with tuberculosis or malignancy, underscoring the profound diagnostic challenge posed by this entity. 3. Immunocompromised states were highly prevalent: 17/29 patients had identifiable comorbidities, including 5 with AIDS and 1 with anti-IFN-γ autoantibody syndrome, confirming impaired cell-mediated immunity as a major predisposing factor. 4. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) demonstrated 100% diagnostic positivity (12/12), significantly outperforming BALF culture (46.2%, 12/26) and sputum culture (39.3%, 11/28), establishing mNGS as the superior diagnostic modality. 5. Mycobacterium colombiense was the most frequently isolated NTM species, accounting for 24.1% (7/29) of cases—a notably high proportion for a species rarely reported as a dominant pathogen in cohort studies. 6. Clinical outcomes with systemic antimicrobial therapy (administered in 27/29 patients, with 1 patient also undergoing combined endoscopic resection) were as follows: 79.3% (23/29) achieved improvement or cure, 5 showed disease progression, 1 experienced relapse, and 1 died.
Practice implications
Clinicians managing immunocompromised patients—especially those with HIV/AIDS or anti-IFN-γ autoantibody syndrome—who present with endobronchial mass lesions, bronchial stenosis, or unexplained airway occlusion on CT should include tracheobronchial NTM infection in the differential diagnosis early, rather than defaulting to tuberculosis or malignancy. Early bronchoscopy with BALF collection for mNGS-based pathogen identification should be prioritized over conventional culture alone, given the markedly superior sensitivity of mNGS (100% vs. 46.2% for BALF culture), which can substantially shorten the current 130-day diagnostic delay. Once tracheobronchial NTM is confirmed, prompt initiation of species-directed systemic antimicrobial therapy is indicated, with consideration of adjunctive endoscopic intervention in select patients with significant luminal obstruction to prevent irreversible airway stenosis.