Understanding Nontuberculous Mycobacterial Pulmonary Disease as a Chronic Lung Disease

Nontuberculous mycobacterial pulmonary disease (NTM-PD), although undeniably infectious disease, is increasingly recognised as a chronic, relapsing respiratory disorder. Its management challenges include not only timely diagnosis and treatment but also prevention of recurrence, quality of life assessment, and follow-up for post-infectious sequelae [1, 2]. Early recognition of NTM-PD and identification of at-risk populations are critical. NTM-PD often presents with small airway inflammation and tree-in-bud nodular opacities on chest CT, progressing over time [3]. Without appropriate attention, diagnosis may be delayed by years or decades. Bronchiectasis represents a major risk factor, with incidence rates up to 19 times higher than in the general population [4]. Repeated infections, impaired mucociliary clearance, and structural lung damage perpetuate a cycle favouring NTM infection. Among bronchiectasis patients, those with advanced age, female sex, prior tuberculosis, prolonged macrolide use, frequent exacerbations, and radiographic progression are at heightened risk [4, 5]. These high-risk individuals warrant close surveillance for NTM-PD development. Despite prolonged multidrug therapy, microbiological cure rates remain suboptimal: approximately 60% for Mycobacterium avium complex PD and 45% for Mycobacterium abscessus PD [6, 7]. Recurrence rates are also high. Given the link between environmental exposure and reinfection [1, 2], patients should be advised to minimise environmental exposure to NTM. As persistent respiratory symptoms are common, integrating patient-reported outcomes into clinical practice is essential. Treatment success should be measured not only by culture conversion but also by improvements in patient well-being. Tools such as the Quality of Life-Bronchiectasis questionnaire effectively capture meaningful clinical improvements [8]. Future strategies must incorporate symptom burden and quality of life measures to better assess treatment effectiveness. Emerging evidence suggests that NTM-PD is not merely secondary to underlying lung disease but actively contributes to chronic airway damage. Persistent inflammation, bronchiolitis, and cavitary destruction lead to irreversible airflow limitation. Longitudinal studies report a 2.5-fold increased risk of chronic obstructive pulmonary disease (COPD) among NTM-PD patients compared to controls [9]. Furthermore, annual FEV1 decline is greater in NTM-PD patients (−77.6 mL/year) than in non-NTM individuals (−47.3 mL/year). Disease severity, measured by the BACES score (body mass index, age, cavity, erythrocyte sedimentation rate, and sex), correlates strongly with accelerated FEV1 decline, emphasising the need for early and active intervention [10]. NTM-PD is an escalating public health burden, particularly in the Asia-Pacific region [11]. In South Korea, healthcare expenditures related to NTM-PD have increased nearly six fold, reaching approximately 18 million USD annually [12]. Costs peak at diagnosis but persist throughout long-term management [13]. Similarly, in Japan, NTM-PD markedly elevates hospitalisation rates and healthcare utilisation, especially among patients with pre-existing bronchiectasis and COPD [14]. Thus, the financial burden on patients warrants consideration throughout the disease course. In conclusion, the updated understanding of NTM-PD underscores its nature as a progressive, chronic, and relapsing disease, not a single infectious event. High progression rates, poor treatment success, frequent recurrences, and irreversible lung function decline result in increased mortality, reduced quality of life, and substantial healthcare costs. A multidisciplinary, patient-centred approach—integrating pulmonologists, infectious disease specialists, radiologists, rehabilitation experts, and social workers—is essential (Figure 1). Future research should prioritise both novel anti-mycobacterial therapies and strategies to alleviate the long-term burden of this disease. Hyung-Jun Kim is currently participating as an institutional PI in a clinical trial sponsored by LigaChem Biosciences Inc. Jae-Joon Yim has participated or is currently participating as the overall PI or institutional PI in multiple clinical trials sponsored by Insmed Incorporated, AN2 Therapeutics, LigaChem Biosciences Inc., and Mannkind Corporation.