Hypertonic Saline Inhalation for Nontuberculous Mycobacterial Lung Disease

This multicenter randomized controlled trial evaluates the clinical and microbiological effects of inhaled 3% hypertonic saline in treatment-naïve patients with nontuberculous mycobacterial lung disease (NTM-LD). Participants are randomized in a 1:1 ratio to either early initiation of 3% hypertonic saline for 6 months or delayed initiation consisting of normal saline inhalation during the first 3 months followed by 3% hypertonic saline during the subsequent 3 months. The primary objective is to compare respiratory symptom improvement between hypertonic saline and normal saline at Month 3. Secondary objectives include evaluating sputum microbiological outcomes, radiographic changes, inflammatory markers, small airway function, treatment initiation, safety, and within-participant changes before and after switching from normal saline to hypertonic saline in the delayed-initiation arm. The first participant was enrolled on October 3, 2025.

Inclusion Criteria: 1. Adults aged 18 years or older. 2. Diagnosis of nontuberculous mycobacterial lung disease (NTM-LD) according to ATS/ERS/ESCMID/IDSA diagnostic criteria, including compatible clinical symptoms, radiographic findings, and microbiological evidence. 3. Not receiving anti-NTM antibiotic treatment at the time of screening. 4. Able and willing to provide written informed consent. 5. Able to perform nebulized inhalation therapy using a mesh nebulizer at home. Exclusion Criteria: 1. Active tuberculosis. 2. Human immunodeficiency virus (HIV) infection. 3. Receiving active treatment for malignancy. 4. Uncontrolled asthma. 5. Frequent or clinically significant hemoptysis. 6. History of intolerance, bronchospasm, or hypersensitivity during inhalation testing with hypertonic saline. 7. Inability to prepare a mesh nebulizer or perform inhalation therapy at home. 8. Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study participation.