A Distinct Bronchoalveolar Lavage Cytokine Signature Characterizes Nontuberculous Mycobacterial Pulmonary Disease

Background: Although diagnosis of pulmonary nontuberculous mycobacterial (NTM) disease typically relies on bronchoscopic sampling, microbiologic testing, and histopathologic evaluation, definitive diagnosis is often difficult. This study investigated whether cytokine profiling of bronchoalveolar lavage (BAL) fluid can help differentiate NTM pulmonary disease (NTM-PD) from other diffuse lung disorders. Methods: From January 2023 to July 2025, we prospectively evaluated 50 patients presenting with undiagnosed micronodular or diffuse pulmonary opacities. BAL fluid was collected during bronchoscopy and analyzed for cytokines and related biomarkers. Eleven patients were clinically diagnosed with NTM-PD based on American Thoracic Society/Infectious Diseases Society of America criteria. Cytokine and cellular profiles were compared between patients with NTM-PD and those with other diffuse lung disorders. A secondary analysis compared infectious granulomatous disease (NTM-PD; n = 11) with noninfectious granulomatous disease (e.g., sarcoidosis; n = 8). Results: BAL fluid from patients with NTM-PD showed significantly higher levels of interleukin-8 (IL-8), interleukin-13 (IL-13), YKL-40, and neutrophils compared to those with other diffuse lung disorders. In subgroup analysis, IL-8, IL-13, and neutrophil proportions remained significantly elevated in infectious granulomatous NTM-PD compared with noninfectious granulomatous disorders. Conclusions: NTM-PD is associated with a distinct BAL cytokine profile characterized by elevated IL-8, IL-13, YKL-40, and neutrophil proportions.