Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic lung infection caused by environmental mycobacteria. The clinical course of NTM-PD varies widely among patients. Some individuals remain stable for long periods without treatment, while others experience worsening lung disease that requires antibiotic therapy or may lead to death. Currently available clinical tools are limited in their ability to predict which patients will experience disease progression.
This observational study aims to better understand how the body's immune response and nutritional status are related to disease progression in adults with confirmed or suspected NTM-PD. In particular, the study focuses on T cells, a type of immune cell that plays an important role in controlling mycobacterial infections. Prior research suggests that impaired T-cell function may contribute to disease progression in NTM-PD, but most studies have relied on blood samples rather than immune cells from the lung, where the infection occurs.
In this study, immune cells obtained from bronchoalveolar lavage fluid during clinically indicated bronchoscopy will be analyzed to assess inhibitory and exhausted T-cell profiles in the lung. In addition, systemic T-cell function will be evaluated using the mitogen response from the QuantiFERON-TB Gold Plus blood test. Nutritional status and body composition will also be assessed, as poor nutrition is known to affect immune function and disease outcomes.
Participants will be followed over time as part of routine clinical care. The primary outcome of the study is the time from enrollment to the initiation of antibiotic treatment due to clinical disease progression. Secondary outcomes include identifying immune predictors of treatment initiation, examining the relationship between nutritional status and immune activity, evaluating changes in body composition and immune markers with disease progression, and determining whether immune and nutritional measures improve prediction of mortality beyond established clinical risk scores.
By integrating lung immune profiling, blood-based immune testing, nutritional assessment, and clinical data, this study seeks to improve risk stratification in NTM-PD. The results may help identify patients at higher risk for disease progression and poor outcomes, support more personalized monitoring strategies, and inform future studies targeting immune and nutritional pathways in NTM-PD.
Adults aged 18 years or older
Confirmed or suspected nontuberculous mycobacterial pulmonary disease
Active pulmonary tuberculosis excluded by standard microbiologic testing
Undergoing bronchoscopy as part of routine clinical evaluation or disease monitoring
Active pulmonary tuberculosis confirmed by microbiologic testing
Positive latent tuberculosis infection test
Current active malignancy requiring treatment
History of solid organ transplantation or hematopoietic stem cell transplantation
Participants will be recruited from adults with confirmed or suspected nontuberculous mycobacterial pulmonary disease who are scheduled to undergo bronchoscopy as part of routine clinical evaluation or disease monitoring according to established NTM management guidelines. The study population consists of patients receiving standard-of-care clinical assessment and follow-up, without any additional procedures performed solely for research purposes.
Cohort
Prospective
Not listed
Time to initiation of treatment due to disease progression in nontuberculous mycobacterial pulmonary disease
Time to treatment initiation is defined as the duration from study enrollment to the start of antimicrobial therapy for nontuberculous mycobacterial pulmonary disease due to clinical disease progression. Treatment initiation is determined by the treating physician based on standard clinical practice and guideline-based criteria, including worsening respiratory symptoms, microbiologic findings, and/or radiographic deterioration indicating progression requiring treatment. This primary outcome is used to evaluate the association between time to treatment initiation and immune predictors, including bronchoalveolar lavage-derived inhibitory and exhausted T-cell profiles and systemic T-cell functional capacity, assessed by the QuantiFERON mitogen response, along with other clinical factors.
Proportion of regulatory T cells in bronchoalveolar lavage fluid (BAL) at baseline
Regulatory T cells (Tregs) in BAL fluid are measured by flow cytometry on samples collected at baseline. The outcome is defined as the percentage of CD4⁺ T cells that express regulatory markers (CD3⁺, CD4⁺, CD25\^hi, CD127\^low) in the baseline BAL sample. This immune cell frequency serves as one of the baseline immune parameters in the study.
Proportion of exhausted T cells in BAL fluid at baseline
Exhausted T cells in BAL fluid are measured by flow cytometry at baseline. These are T cells exhibiting an "exhausted" phenotype, characterized by the expression of inhibitory receptors such as PD-1, TIM-3, or CD39. The outcome is the percentage of T cells in the BAL sample that display this exhausted phenotype (CD3⁺, CD4⁺/CD8⁺, PD-1⁺, TIM-3⁺, CD39⁺) at baseline.
QuantiFERON-TB Gold Plus mitogen response at baseline (IU/mL)
The QuantiFERON-TB Gold Plus assay is used to assess systemic T-cell functional capacity at baseline. The outcome is the interferon-gamma concentration (Mitogen minus Nil value, reported in IU/mL) from the mitogen-stimulated tube of the QuantiFERON assay. This value reflects the overall ability of the participant's T cells to produce IFN-γ in response to a non-specific stimulus (mitogen) at baseline.
Body Mass Index (BMI) at baseline (kg/m²)
BMI is calculated as weight in kilograms divided by height in meters squared (kg/m²), measured at baseline. It serves as an anthropometric indicator of the participant's nutritional status. The baseline BMI is documented for each participant as part of the nutritional assessment.
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Seoul National University Hospital
Lead sponsor
SMG-SNU Boramae Medical Center
Collaborator
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