Article Structure
This article is organized into the following sections: Highlights; Clinical Background and Unmet Need; Study Design and Methods; Key Results; Safety and Tolerability; Mechanistic and Clinical Interpretation; Strengths and Limitations; Practice Implications and Research Priorities; Funding and Trial Registration; References.
Highlights
Topical glyceryl trinitrate 0.2% ointment was associated with a statistically significant reduction in total Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) scores, from 17.32 ± 4.34 to 12.52 ± 5.21 (p < 0.001).
Symptom gains were observed across all six ENS6Q domains, with the largest absolute improvement seen in nasal dryness, a hallmark and often highly distressing feature of empty nose syndrome.
Nearly one-third of patients achieved marked improvement, and overall 61.4% reported subjective symptom benefit, suggesting a potentially meaningful conservative treatment option in a disorder with limited nonsurgical therapies.
Adverse effects occurred in 25.0% of patients and were generally mild; headache was the most common complaint and did not significantly shorten treatment duration.
Clinical Background and Unmet Need
Empty nose syndrome (ENS) is an uncommon but potentially severe complication that can follow turbinate volume reduction surgery. Although the nasal cavity may appear anatomically widened, patients often report paradoxical obstruction, dryness, crusting, dyspnea, a sensation of insufficient airflow, and substantial psychologic distress. The syndrome remains challenging for clinicians because its symptoms are often disproportionate to conventional objective measures of nasal patency.
The current diagnostic approach usually integrates a compatible surgical history, endoscopic evidence of altered intranasal anatomy, symptom quantification, and a positive cotton test, in which temporary intranasal placement of cotton improves airflow perception. The ENS6Q has emerged as a practical patient-reported outcome tool and is increasingly used both diagnostically and longitudinally.
Treatment remains difficult. Conservative strategies such as humidification, emollients, saline irrigation, and management of associated anxiety or depression may provide partial relief, but durable symptom control is often elusive. Surgical reconstruction with implants or augmentation procedures is considered for selected patients, yet these interventions require expertise, carry procedural risks, and may not be universally available. In that context, a safe, office-applicable, low-cost topical therapy would be clinically important.
Nitroglycerin is a nitric oxide donor with vasodilatory properties. In the nasal mucosa, a plausible therapeutic rationale is that it may increase mucosal engorgement, restore some degree of tissue bulk, and potentially improve airflow sensation or reduce dryness. However, this concept has had little formal clinical study in ENS. The present report by Ryu, Kang, and Jang therefore addresses a notable therapeutic gap.
Study Design and Methods
This was a preliminary clinical study evaluating the efficacy and safety of topical nitroglycerin ointment in patients with ENS. The report, published in The Laryngoscope on June 5, 2026, enrolled patients diagnosed using a combination of clinical history, nasal endoscopic findings, a positive cotton test, and an ENS6Q score of at least 11.
Eligible participants were instructed to apply Rectogesic (glyceryl trinitrate 0.2%) topically three times daily. The mean age of the study population was 42.09 years, and the male-to-female ratio was 3:1. Based on the percentages provided, the cohort appears to have included 44 patients.
The principal outcome was change in ENS6Q score before and after treatment. The investigators also analyzed change in each of the six questionnaire items, rates of subjective symptom improvement, and adverse events. The abstract does not report a parallel control group, randomization, blinding, or a prespecified comparator, so this should be interpreted as an uncontrolled, early-phase therapeutic evaluation.
Key Results
Overall symptom burden improved significantly
The central finding was a significant reduction in total ENS6Q score from 17.32 ± 4.34 before treatment to 12.52 ± 5.21 after treatment, corresponding to a mean decrease of 4.80 points (p < 0.001). In a condition where baseline symptoms are often chronic and highly disruptive, this magnitude of change is clinically noteworthy, particularly because the investigators relate larger score reductions to the minimal clinically important difference threshold.
The distribution of response is also informative. Sixteen patients, or 36.4%, had moderate improvement defined as a change in ENS6Q of 3 to 6 points. Fifteen patients, or 34.1%, experienced marked improvement with a change greater than 6 points, which exceeded the minimal clinically important difference. Taken together, about 70% of the cohort achieved at least moderate numerical improvement on the study’s main symptom scale.
All symptom domains moved in the same direction
All six ENS6Q items improved significantly after treatment. The largest reduction occurred in nasal dryness, decreasing from 4.16 to 2.86 (p < 0.001). This is an especially relevant observation because dryness is one of the most persistent and treatment-resistant complaints in ENS, and is often closely linked to patient discomfort, disturbed sleep, and repetitive use of saline or moisturizers.
Although the abstract does not list each individual item score in detail, the consistency of improvement across all six domains suggests that the intervention may have influenced more than a single symptom dimension. That pattern is helpful because ENS is a multidimensional syndrome involving airflow perception, sensory disturbance, mucosal symptoms, and global discomfort rather than a single isolated complaint.
Subjective improvement tracked with larger questionnaire gains
Twenty-seven patients, or 61.4%, reported subjective symptom improvement. These patients demonstrated much larger ENS6Q reductions than patients who did not perceive improvement: 7.22 ± 4.99 versus 0.94 ± 2.41, respectively (p < 0.001). This concordance between patient global impression and a validated symptom instrument strengthens the clinical relevance of the quantitative findings.
In practical terms, this means the score changes were not merely statistically significant; they were aligned with the patient’s lived experience of feeling better. For a syndrome that is often underrecognized and difficult to objectify, that alignment matters.
Safety and Tolerability
Eleven patients, representing 25.0% of the cohort, reported adverse effects. Mild headache was the most common event, occurring in six patients and accounting for 54.5% of adverse effects. This is biologically plausible and expected with nitroglycerin exposure, given its vasodilatory mechanism.
Importantly, the presence of adverse effects did not significantly affect treatment duration. That finding suggests the tolerability profile was manageable in most cases, although the abstract does not provide details on severity grading, discontinuation rates, blood pressure effects, or whether any patients required dose adjustment. Clinicians considering off-label use would still need to counsel patients regarding headache, dizziness, and possible hypotension, particularly in those taking other vasodilators or phosphodiesterase-5 inhibitors.
Mechanistic and Clinical Interpretation
Why might topical nitroglycerin help ENS? The most plausible explanation is local vasodilation with transient mucosal engorgement. Patients with ENS have lost turbinate tissue and, with it, some of the normal aerodynamic, humidification, and sensory functions of the nasal cavity. Even a modest increase in residual mucosal fullness could alter airflow distribution and wall contact, reducing the uncomfortable mismatch between objectively open anatomy and subjectively inadequate airflow.
Improvement in dryness is also mechanistically credible. By increasing blood flow and mucosal turgor, topical nitroglycerin may help counter a desiccated intranasal environment, at least temporarily. Whether this effect meaningfully restores the complex neurosensory abnormalities believed to contribute to ENS is less certain. The syndrome likely involves not only altered anatomy but also disruption of trigeminal airflow sensing and central symptom perception. Therefore, nitroglycerin should be viewed as a potentially helpful symptomatic therapy rather than a definitive pathophysiologic correction.
From a translational standpoint, this study is attractive because it tests a readily available medication in a condition with limited treatment options. If future trials confirm benefit, topical nitroglycerin could become a step in conservative management before or alongside consideration of reconstructive surgery.
Strengths and Limitations
Strengths
The study addresses a genuine unmet need in rhinology. Diagnostic inclusion criteria appear clinically sensible and fairly stringent, combining history, endoscopy, cotton test positivity, and a symptom threshold on ENS6Q. The use of a validated disease-specific questionnaire improves interpretability, and the reporting of both scale-based and subjective outcomes is helpful. Safety data, while limited, are also clinically relevant because nitroglycerin is known to have characteristic side effects.
Limitations
The main limitation is the absence of a control group. ENS symptoms can fluctuate, and placebo effects may be substantial in symptom-driven disorders, especially when a topical treatment is used repeatedly and patients are monitored closely. Without randomization or blinding, one cannot separate pharmacologic benefit from expectancy effects or regression to the mean.
The sample size was modest, and the abstract does not specify treatment duration in detail, long-term follow-up, adherence verification, or objective physiologic measurements such as acoustic rhinometry, computational fluid dynamics, mucosal imaging, or validated psychologic assessments. It is also unclear whether concomitant therapies such as saline, moisturizers, or psychiatric medications were standardized.
Generalizability is another issue. ENS is heterogeneous with respect to surgical history, residual turbinate anatomy, psychiatric comorbidity, and symptom phenotype. It remains uncertain which patients are most likely to respond. For example, patients with predominant dryness may derive greater benefit than those whose dominant complaint is dyspnea or panic-related air hunger.
Finally, because nitroglycerin can cause headache and other systemic vasodilatory effects, the optimal dosing frequency, application technique, and lowest effective dose remain to be established.
Practice Implications and Research Priorities
This study does not establish a new standard of care, but it does provide an actionable signal. For clinicians managing highly symptomatic ENS, topical glyceryl trinitrate may represent a reasonable investigational conservative option in carefully selected patients, particularly when dryness is prominent and surgical intervention is not desired or not yet indicated.
Any real-world use should be individualized. Patients should be screened for contraindications to nitrates, counseled about headache and dizziness, and monitored for tolerability. Because the treatment is off-label in this setting, shared decision-making is essential. It should also be framed as adjunctive rather than curative, integrated with humidification strategies, nasal care, and when needed, psychologic support.
The next research steps are straightforward. A randomized, placebo-controlled trial is needed, ideally with standardized background therapy, predefined responder analyses, and longer follow-up. Future studies should also explore whether cotton test responsiveness predicts nitroglycerin benefit, whether objective changes in mucosal thickness or airflow patterns can be measured, and whether specific ENS phenotypes respond differently. Comparative studies against other conservative therapies would also be valuable.
Funding and Trial Registration
The abstract as provided does not report a funding source. No ClinicalTrials.gov registration number is listed in the citation information supplied. Readers should consult the full published article for any additional disclosures, funding statements, or protocol registration details.
Conclusion
Ryu and colleagues present encouraging preliminary evidence that topical nitroglycerin ointment may improve symptoms of empty nose syndrome, including a significant reduction in total ENS6Q score and notable relief of nasal dryness. The safety profile appears acceptable, with mostly mild adverse effects such as headache. Although the uncontrolled design prevents firm efficacy conclusions, the findings are clinically intriguing in a condition where nonsurgical therapies remain limited. For otolaryngologists, this study opens a plausible and testable avenue for conservative ENS management, while underscoring the need for controlled trials to define efficacy, durability, and optimal patient selection.
References
1. Ryu SS, Kang S, Jang YJ. Clinical Efficacy of Topical Nitroglycerin Ointment for Patients With Empty Nose Syndrome. The Laryngoscope. 2026-06-05. PMID: 42248804.
2. Velasquez N, Thamboo A, Habib AR, Huang Z, Nayak JV. The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q): a validated 6-item questionnaire as a diagnostic aid for empty nose syndrome patients. International Forum of Allergy & Rhinology. 2017;7(1):64-71.
3. Sozansky J, Houser SM. Pathophysiology of empty nose syndrome. The Laryngoscope. 2015;125(1):70-74.
