Association of Nutrition and T Cell Immune Activity With Disease Progression in Nontuberculous Mycobacterial Pulmonary Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Time to initiation of treatment due to disease progression in nontuberculous mycobacterial pulmonary disease
研究概览
简要总结
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.
详细描述
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic and heterogeneous infectious lung disease caused by a variety of environmental mycobacteria, including Mycobacterium avium complex (MAC), Mycobacterium abscessus subspecies, Mycobacterium kansasii, and other rapidly or slowly growing species. Despite increasing global prevalence, the clinical course of NTM-PD remains highly variable. Some patients experience long-term stability without treatment, whereas others develop progressive lung destruction, recurrent exacerbations, treatment failure, or death. This heterogeneity highlights limitations in current prognostic tools and underscores the need for biologically informed risk stratification.
The BACES score (Body mass index <18.5 kg/m², Age ≥65 years, Cavitary disease, Elevated erythrocyte sedimentation rate, and male Sex) is a validated clinical scoring system for mortality prediction in NTM-PD. While clinically practical, BACES relies exclusively on demographic, nutritional, inflammatory, and radiographic variables and does not incorporate direct measures of host immune function. Increasing evidence suggests that host immune dysregulation-particularly impairment of adaptive T-cell-mediated immunity-plays a central role in disease progression and may explain outcome differences among patients with similar clinical features.
Recent translational studies using lung tissue, spatial transcriptomics, and peripheral blood immunophenotyping have demonstrated a characteristic immune imbalance in NTM-PD. These studies consistently show hyperactivation of innate immune pathways (e.g., macrophage and monocyte inflammatory signaling) alongside functional suppression of T-cell-mediated adaptive immunity. This T-cell dysfunction is characterized by reduced antigen-specific interferon-gamma (IFN-γ) production, decreased co-stimulatory signaling (such as CD28 downregulation), and increased expression of inhibitory immune checkpoint receptors, including programmed death-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3). Additionally, CD39-expressing T cells-associated with adenosine-mediated immunosuppression and terminal exhaustion-have been implicated in chronic infectious and inflammatory states.
Importantly, increased frequencies of PD-1-positive or TIM-3-positive CD4+ T cells have been associated with higher mycobacterial burden, cavitary disease, low body mass index, and adverse clinical outcomes in NTM-PD. These inhibitory and exhausted T-cell phenotypes appear to reflect chronic antigenic stimulation and impaired immune control of infection. However, most prior studies have relied on peripheral blood samples, which may not accurately represent the immune microenvironment within the lung, the primary site of disease activity.
Bronchoalveolar lavage (BAL) fluid provides direct access to immune cells within affected lung segments and offers a unique opportunity to characterize local pulmonary immune responses. BAL-derived T-cell immunophenotyping may therefore yield more clinically relevant insights into disease pathogenesis and progression than blood-based analyses alone. Nonetheless, systematic evaluation of inhibitory and exhausted T-cell subsets in BAL fluid and their association with clinically meaningful outcomes in NTM-PD remains limited.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Able and willing to provide written informed consent
排除标准
- •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
- •Use of systemic immunosuppressive medications
- •Diagnosis of autoimmune disease
- •Use of biologic agents or planned initiation of biologic therapy
- •Acute lower respiratory tract infection requiring treatment within 4 weeks prior to bronchoscopy
- •Pregnancy
研究组 & 干预措施
NTM-PD cohort
This cohort includes adults (≥18 years) with confirmed or suspected nontuberculous mycobacterial pulmonary disease (NTM-PD) in whom active pulmonary tuberculosis has been excluded and who are undergoing bronchoscopy as part of routine clinical care. Participants receive standard-of-care evaluation and management according to established NTM clinical guidelines. There are no experimental interventions assigned in this study. Residual bronchoalveolar lavage fluid remaining after clinically indicated testing is used for immunologic analyses, including flow cytometric assessment of inhibitory and exhausted T-cell subsets. Clinical data, nutritional status, imaging findings, and laboratory results are collected prospectively, and participants are followed longitudinally to assess time to initiation of antimicrobial treatment due to clinical disease progression and other clinically relevant outcomes.
结局指标
主要结局
Time to initiation of treatment due to disease progression in nontuberculous mycobacterial pulmonary disease
时间窗: From enrollment to initiation of nontuberculous mycobacterial treatment, up to 24 months
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.
次要结局
- Proportion of regulatory T cells in bronchoalveolar lavage fluid (BAL) at baseline(Baseline)
- Proportion of exhausted T cells in BAL fluid at baseline(Baseline)
- QuantiFERON-TB Gold Plus mitogen response at baseline (IU/mL)(Baseline)
- Body Mass Index (BMI) at baseline (kg/m²)(Baseline)
- Mini Nutritional Assessment (MNA) score at baseline(Baseline)
- Pectoralis muscle area (PMA) at baseline (cm²)(Baseline)
- Visceral fat area (VFA) at baseline (cm²)(Baseline)
- Subcutaneous fat area (SFA) at baseline (cm²)(Baseline)
- Change in BAL Fluid Regulatory T-Cell Proportion from Baseline to Disease Progression(At time of disease progression requiring treatment (within up to 24 months).)
- Change in BAL Fluid Exhausted T-Cell Proportion from Baseline to Disease Progression(At time of disease progression requiring treatment (within up to 24 months))
- Change in Pectoralis Muscle Area (PMA) from Baseline to Disease Progression Description(At time of disease progression requiring treatment (within up to 24 months))
- Change in Visceral Fat Area on CT at T12 Level from Baseline to Disease Progression(At time of disease progression requiring treatment (within up to 24 months))
- Change in Subcutaneous Fat Area on CT at T12 Level from Baseline to Disease Progression(At time of disease progression requiring treatment (within up to 24 months))
- All-Cause Mortality within 24 Months (Comparison of BACES vs Immune-Augmented Score)(From enrollment through 24 months of follow-up)
研究者
Deog Kyeom Kim
Clinical Professor, Department of Pulmonary and Critical Care Medicine, SMG-SNU Boramae Medical Center
Seoul National University Hospital