Highlights
- Intranasal saline alone resolved symptoms in nearly 30% of children with obstructive sleep-disordered breathing (OSDB) during a 6-week run-in period.
- In children with persistent symptoms after the initial run-in, no clinical or statistical difference was found between intranasal mometasone furoate and continued saline treatment.
- Cumulative conservative management with saline led to a total symptom resolution rate of approximately 50% over 12 weeks.
- Current evidence suggests that a 3-month trial of intranasal saline should be recommended before escalating to specialist referral or surgical intervention.
Disease Burden and Clinical Context
Obstructive sleep-disordered breathing (OSDB) is a prevalent condition in the pediatric population, ranging from primary snoring to obstructive sleep apnea (OSA). It is characterized by partial or complete upper airway obstruction during sleep, which disrupts normal ventilation and sleep patterns. Left untreated, OSDB is associated with significant comorbidities, including neurocognitive impairment, behavioral issues such as ADHD-like symptoms, cardiovascular strain, and impaired quality of life. For decades, the gold-standard treatment for moderate-to-severe OSDB has been adenotonsillectomy. However, surgery carries inherent risks, including post-operative hemorrhage, pain, and the costs associated with anesthesia and hospitalization.
Given these challenges, there has been a growing interest in medical alternatives. Intranasal steroids (INS) have long been the pharmacological mainstay for mild-to-moderate OSDB, based on the hypothesis that they reduce lymphoid tissue inflammation (adenoid hypertrophy) and nasal mucosal edema. However, the comparative efficacy of INS versus simple saline irrigation—and the potential for saline to act as a therapeutic agent rather than a mere placebo—has remained a subject of clinical debate. The MIST+ randomized clinical trial was designed to address this uncertainty and provide high-level evidence to guide primary care and specialist practice.
Study Design and Methodology
The MIST+ (Mometasone for Intranasal Symptoms Treatment) trial was a double-blind, placebo-controlled, randomized clinical trial conducted at two major specialist pediatric centers in Australia. The study targeted children aged 3 to 12 years who were referred to specialist waitlists for symptoms of OSDB. The trial utilized a unique two-stage design to isolate the effects of saline irrigation from the effects of corticosteroid treatment.
In the first phase, all 150 recruited children underwent a 6-week “run-in” period during which they received once-daily intranasal saline. Following this period, children were reassessed using the Sleep-Disordered Breathing (SDB) score, a validated tool for measuring symptom severity. Children whose symptoms resolved during the saline run-in (defined as an SDB score less than -1) were monitored but not randomized. Those with persistent symptoms (SDB score ≥-1) proceeded to the second phase.
In the second phase, 93 children were randomized in a 1:1 ratio to receive either intranasal mometasone furoate (50 µg once daily) or to continue the intranasal saline regimen for an additional 6 weeks. The primary outcome was symptom resolution (SDB score < -1) at the 12-week mark. Secondary outcomes included changes in behavior (measured via the Strengths and Difficulties Questionnaire), quality of life (OSA-18 tool), and parental perception of the need for surgical intervention.
Key Findings and Results
The results of the MIST+ trial challenge the conventional reliance on intranasal steroids as the superior medical treatment for OSDB. Out of the 139 children who completed the initial 6-week saline run-in, 41 children (29.5%) experienced total symptom resolution. This finding suggests that nearly one-third of children referred for specialist care for OSDB may improve with simple saline hygiene alone.
Among the 93 children with persistent symptoms who entered the randomized phase, the rates of symptom resolution were remarkably similar between the two groups. In the intranasal steroid (INS) group, 35.6% (95% CI, 22.9%-50.6%) achieved resolution, while in the saline group, 36.4% (95% CI, 23.5%-51.6%) achieved resolution. The risk difference was a negligible -0.9% (95% CI, -20.7% to 19.0%; P = .93), indicating no evidence of a clinically significant benefit of mometasone over saline.
Furthermore, secondary outcomes, including behavioral scores and quality-of-life metrics, showed no significant differences between the groups. Importantly, parental perception of the need for surgery did not differ between those using steroids and those using saline. Subgroup analyses, which looked at factors such as the presence of allergies or the degree of tonsillar hypertrophy, failed to identify any specific phenotype that was more likely to respond to steroids than to saline. When viewing the trial as a whole, approximately 50% of the original cohort achieved symptom resolution after 12 weeks of conservative intranasal management.
Clinical Interpretation and Expert Commentary
The MIST+ trial provides a critical piece of evidence for the “watchful waiting” approach supplemented by nasal hygiene. The high response rate to saline irrigation—both in the run-in and the randomized phase—suggests several physiological mechanisms may be at play. Saline may improve OSDB symptoms by clearing inflammatory mediators, reducing mucosal crusting, and improving mucociliary clearance, thereby decreasing upper airway resistance. This “washout effect” appears to be just as potent as the anti-inflammatory effect of corticosteroids in this specific population.
From a health policy perspective, these findings are significant. If half of the children referred for OSDB can be managed successfully in a primary care setting with saline, the burden on pediatric ENT waitlists and surgical theaters could be drastically reduced. Clinicians should consider that many cases of pediatric OSDB may be transient or highly responsive to non-pharmacological interventions. The trial also highlights the importance of the placebo or “care” effect in pediatric trials; the structured daily routine of administering a nasal spray may itself lead to perceived or actual improvements in sleep hygiene and parental reporting.
However, it is essential to note the study’s limitations. The trial focused on symptomatic resolution rather than objective polysomnography (PSG) data. While the SDB score is a validated clinical tool, PSG remains the objective standard for diagnosing OSA severity. Additionally, the study duration was 12 weeks; long-term follow-up is necessary to determine if these improvements are sustained or if symptoms recur once the saline treatment is discontinued.
Conclusion and Practice Implications
The MIST+ randomized clinical trial demonstrates that intranasal saline is a highly effective, low-cost, and safe first-line treatment for children with sleep-disordered breathing. Because intranasal steroids offered no additional benefit over saline, the routine prescription of corticosteroids as an initial medical management strategy for OSDB should be reconsidered.
Based on these results, a 3-month trial of intranasal saline is an appropriate first-line recommendation for children presenting with OSDB symptoms. This approach allows for the resolution of symptoms in approximately 50% of cases, potentially sparing thousands of children from unnecessary specialist referrals and surgical procedures. For those whose symptoms persist beyond 12 weeks of saline therapy, further investigation via polysomnography or consultation with an otolaryngologist remains the appropriate next step.
Funding and Registration
This study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia. The trial is registered at ClinicalTrials.gov with the identifier NCT05382494.
References
1. Nixon GM, Anderson D, Baker A, et al. Intranasal Treatments for Children With Sleep-Disordered Breathing: The MIST+ Randomized Clinical Trial. JAMA Pediatr. 2026;180(1):e255717. doi:10.1001/jamapediatrics.2025.5717.
2. Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012;130(3):576-584.
3. Kedem AS, et al. Intranasal steroids for pediatric obstructive sleep apnea: A meta-analysis. Otolaryngol Head Neck Surg. 2020;162(1):18-27.
