Bronchiectasis, Nontuberculous Mycobacterial Lung Disease
Conditions
Keywords
Hypertonic saline inhalation, Airway clearance therapy, Nontuberculous Mycobacterial Lung Disease, Bronchiectasis, Mycobacterium avium complex, Mycobacterium abscessus, Respiratory Severity Score, Nebulized Hypertonic Saline, NTM-LD
Brief summary
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.
Detailed description
Nontuberculous mycobacterial lung disease (NTM-LD) is a chronic pulmonary infection that frequently progresses despite conservative management. Because prolonged multidrug antibiotic therapy is associated with substantial treatment burden, potential toxicity, and variable effectiveness, additional non-antibiotic treatment strategies are needed, particularly for patients who defer, cannot tolerate, or are not yet indicated for antibiotic treatment. Hypertonic saline inhalation facilitates airway clearance and sputum removal and has been increasingly used as an adjunctive treatment in specialized NTM centers. However, prospective randomized data remain limited, particularly in Asian populations. This multicenter randomized controlled trial investigates whether early initiation of inhaled 3% hypertonic saline improves respiratory symptoms and microbiological outcomes compared with delayed initiation. To ensure treatment safety, all participants undergo a supervised inhalation tolerance assessment before randomization. During this assessment, inhaled salbutamol (Ventolin) premedication is administered, followed by inhalation of 3% hypertonic saline. Participants demonstrating clinically significant intolerance, severe bronchospasm, or other safety concerns are excluded from study treatment. Following successful completion of the tolerance assessment, participants are randomized to one of two groups. The early-initiation group receives inhaled 3% hypertonic saline for 6 months. The delayed-initiation group receives inhaled normal saline during Months 0-3, followed by inhaled 3% hypertonic saline during Months 4-6. The primary randomized comparison is performed at Month 3 between participants receiving hypertonic saline and those receiving normal saline. Additional analyses evaluate within-participant changes in the delayed-initiation arm before and after switching from normal saline to hypertonic saline. Throughout the study, participants continue routine clinical care. Initiation of anti-NTM antibiotic treatment remains at the discretion of the treating physician.
Interventions
DRUGNebulized 3% Hypertonic Saline
Nebulized 3% hypertonic saline, 5 mL once daily via mesh nebulizer. Administered during Months 0-6 in the early-initiation arm and during Months 4-6 in the delayed-initiation arm after completion of the Month 3 assessment.
Nebulized 0.9% normal saline, 5 mL once daily via mesh nebulizer during Months 0-3 in the delayed-initiation arm.
Sponsors
Taipei Veterans General Hospital, Taiwan
National Science and Technology Council, Taiwan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomized in a 1:1 ratio to either early initiation of 3% hypertonic saline inhalation for 6 months or delayed initiation consisting of normal saline inhalation during Months 0-3 followed by 3% hypertonic saline during Months 4-6. The primary comparison is performed at Month 3 between the two parallel groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Respiratory Severity Score (RSS) From Baseline to Month 3 | Baseline and Month 3 | Total Respiratory Severity Score (RSS) ranges from 0 to 60 and is calculated from six visual analog scales evaluating cough, sputum production, dyspnea, fatigue, sleep disturbance, and overall respiratory symptoms. Higher scores indicate worse symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Acid-Fast Bacilli (AFB) Sputum Smear Grade Over Time | Baseline, Month 3, and Month 6 | AFB sputum smear grade assessed using standard semi-quantitative microscopy (negative, scanty, 1+, 2+, 3+, or 4+) at Baseline, Month 3, and Month 6. Changes in smear grade and the proportion of participants achieving smear negativity will be evaluated. |
| Change in Mycobacterial Sputum Culture Status Over Time | Baseline, Month 3, and Month 6 | Sputum culture status assessed as positive or negative for nontuberculous mycobacteria using standard mycobacterial culture methods at Baseline, Month 3, and Month 6. Culture conversion is defined as a change from positive at baseline to negative at follow-up assessments. |
| Change in Radiographic Severity Score From Baseline to Month 6 | Baseline and Month 6 | Radiographic Severity Score assessed using a chest radiographic scoring system. Each lung is divided into three areas. The extent of infiltration in each area is scored from 0 to 3, resulting in a total score ranging from 0 to 18. Higher scores indicate more extensive pulmonary disease. |
| Change in Erythrocyte Sedimentation Rate (ESR) From Baseline to Month 6 | Baseline and Month 6 | Erythrocyte sedimentation rate (ESR) will be measured using a standard clinical laboratory assay. Higher values indicate greater systemic inflammation. |
| Change in R5-R20 Measured by Impulse Oscillometry From Baseline to Month 6 | Baseline and Month 6 | R5-R20 measured by impulse oscillometry (IOS). R5 represents total airway resistance and R20 represents central airway resistance. The difference between R5 and R20 (R5-R20) reflects small airway dysfunction. Higher values indicate greater small airway impairment. |
| Change in Post-Bronchodilator FEV1 (% Predicted) From Baseline to Month 6 | Baseline and Month 6 | Post-bronchodilator forced expiratory volume in one second (FEV1), expressed as percent predicted, measured using standardized spirometry according to ATS/ERS recommendations. Higher values indicate better lung function. |
| Anti-NTM Treatment Initiation | Up to Month 6 | Proportion of Participants Requiring Anti-NTM Antibiotic Treatment |
| Adverse Events | Up to Month 6 | Incidence of Adverse Events Related to Hypertonic Saline Inhalation |
| Within-Participant Change in Respiratory Severity Score During Normal Saline and Hypertonic Saline Treatment Periods in the Delayed-Initiation Arm | Baseline to Month 6 | Comparison of RSS change during Months 0-3 while receiving nebulized normal saline and during Months 4-6 while receiving nebulized 3% hypertonic saline in participants assigned to the delayed-initiation arm. |
| Change in Respiratory Severity Score From Month 3 to Month 6 in the Early-Initiation Arm | Month 3 and Month 6 | Evaluation of continued symptom improvement after the initial 3 months of hypertonic saline treatment. |
| Change in Total RSS at Month 6 | Baseline and Month 6 | Total RSS ranges from 0 to 60 and is calculated from six visual analog scales evaluating cough, sputum production, dyspnea, fatigue, sleep disturbance, and overall respiratory symptoms. Higher scores indicate worse symptoms. |
Countries
Taiwan
Contacts
CONTACTSheng-Wei Pan, MD, PhD
CONTACTJia-Yih Feng, MD, PhD
PRINCIPAL_INVESTIGATORSheng-Wei Pan, MD, PhD
Taipei Veterans General Hospital, Taiwan
Outcome results
None listed