Clinical Characteristics and Immune Escape Mechanism of Nontuberculous Mycobacterial Lung Disease in South China

Overview

Nontuberculous Mycobacterial lung disease (NTM-LD) is a significant infectious challenge. The precise causes remain unclear, diagnosis can be complex, treatment outcomes are often unsatisfactory, and the disease can severely affect a patient's quality of life. Environmental factors, such as the warm and humid climate in South China, may contribute to unique characteristics of NTM in this region, but systematic research is currently lacking. This study aims to improve the understanding of NTM-LD in South China. It consists of two complementary parts: 1. The first part is a retrospective review of medical records from approximately 1,500 NTM patients across multiple hospitals in South China. This analysis seeks to identify common patterns in symptoms, diagnostic findings, and treatment responses within this population. 2. The second part is a prospective study involving about 106 current NTM-LD patients. Blood and lung fluid samples will be collected to analyze, using advanced laboratory techniques, how the patient's immune system responds to the infection. This investigation aims to uncover clues about why some cases are difficult to treat. The overall goal of this research is to generate evidence that can aid healthcare providers in South China in diagnosing and managing NTM-LD more effectively. Please note that this is an observational study; no new drugs or experimental treatments are being tested.

1. Background and Rationale NTM-LD presents significant clinical challenges due to its unclear pathogenesis, diagnostic complexity, suboptimal treatment outcomes, and poor prognosis. The unique climatic (hot, humid) and demographic factors in South China suggest potential regional variations in NTM epidemiology and clinical presentation. However, a systematic investigation into its clinical characteristics and underlying mechanisms in this region is lacking, impeding the development of localized precision medicine strategies. 2. Study Objectives Primary Objective: To systematically characterize the epidemiological patterns, clinical phenotypes, and prognostic determinants of NTM-LD in the South China population. Secondary Objectives: To analyze the distribution of NTM species and their correlation with disease severity and radiological findings. To investigate host immune microenvironment alterations post-NTM infection, focusing on inflammatory responses and immune cell functional states. To explore molecular mechanisms associated with treatment refractoriness in NTM disease. 3. Study Design This is a hybrid observational study comprising two distinct parts: * Part 1: A multicenter, retrospective, non-interventional survey study. * Part 2: A prospective observational study involving biospecimen collection and laboratory analysis. 4. Study Populations and Sample Size * Part 1: Approximately 1,500 patients diagnosed with NTM lung disease per standard guidelines between January 2015 and May 2025 across multiple collaborating centers in South China. * Part 2: A subset of 106 consecutively enrolled, confirmed NTM patients from the collaborating network for prospective biospecimen collection. 5. Methods and Procedures * Part 1 (Retrospective Survey): Data on demographics, clinical symptoms, imaging features (chest CT), microbiology, treatment regimens, and outcomes will be extracted from electronic health records. Statistical analyses will include descriptive summaries, correlation studies, and multivariable regression modeling to identify prognostic factors. * Part 2 (Prospective Study): Peripheral blood and bronchoalveolar lavage fluid (BALF) will be collected. Analyses will include: Molecular Biology: Real-time quantitative PCR for cytokine expression profiling; Western blot for protein-level assessment. Single-Cell Sequencing: To delineate immune cell composition, transcriptional states, and cell-cell interaction networks within the pulmonary immune microenvironment. 6. Statistical Analysis For Part 1, appropriate statistical tests (e.g., Chi-square, t-test, ANOVA, Kaplan-Meier survival analysis, Cox regression) will be applied based on data types and distribution. For Part 2, bioinformatics pipelines specific for single-cell RNA sequencing data will be employed for clustering, differential expression, and pathway analysis. A p-value \<0.05 will be considered statistically significant. 7. Ethics and Data Management The study protocol will be submitted for approval to The Eighth Affiliated Hospital of Sun Yat-Sen University Ethics Committee of all participating centers prior to initiation. Patient informed consent will be obtained for the prospective Part 2. All data will be de-identified, coded, and stored on secure, password-protected servers in compliance with data protection regulations. 8. Significance This study is expected to generate a comprehensive clinical profile of NTM lung disease in South China and provide novel insights into its pathogenesis at the immune-microenvironment level. The findings may contribute to more accurate diagnostic criteria, prognostic models, and inform the future development of targeted therapeutic strategies for this refractory infection.