Inhaled 3% hypertonic saline is associated with improved symptoms and microbiological stabilisation in antibiotic-naïve nontuberculous mycobacterial lung disease: A prospective study

Background Evidence for hypertonic saline (HS) in nontuberculous mycobacterial lung disease (NTM-LD) remains limited, particularly during watchful waiting when non-antibiotic strategies are needed. We evaluated inhaled 3% HS as a potential adjunct in antibiotic-naïve NTM-LD.Methods In this prospective cohort study, antibiotic-naïve NTM-LD patients were enrolled between September 2024 and December 2025. Patients receiving daily inhaled 3% HS were compared with contemporaneous controls. Symptom burden (visual analog scale, 0–60) and sputum smear status at month 3 were analysed using generalised estimating equations. In vitro experiments assessed HS effects on Mycobacterium abscessus growth and macrophage function, including intracellular bacterial burden, viability, phagocytosis, and pro-inflammatory gene expression.Results Among 45 patients (HS: n = 22; control: n = 23), 3% HS was associated with a significant reduction in symptom burden from baseline (coefficient −4.40, 95% CI −6.43 to −2.37; p < 0.001) and a lower odds of sputum smear positivity at month 3 (odds ratio 0.15, 95% CI 0.03–0.64; p = 0.011) in adjusted analyses. In vitro, HS inhibited extracellular M. abscessus growth in a concentration-dependent manner. Pretreatment of macrophages with 3% HS reduced intracellular M. abscessus burden by 51% (p = 0.021) without impairing viability or phagocytosis, while upregulating pro-inflammatory gene expression, including TNF-α (p = 0.004), IL-6 (p = 0.030), and IL-1β (p = 0.058).Conclusions In antibiotic-naïve NTM-LD, inhaled 3% HS was associated with improved symptom burden and reduced progression to sputum smear positivity. Complementary in vitro findings support both direct antimycobacterial effects and enhanced macrophage-mediated control, supporting HS as a biologically active adjunct during conservative management of NTM-LD.