Empty nose syndrome (ENS) is a rare yet debilitating condition resulting from procedures such as total turbinectomy, submucosal turbinoplasty, and radiofrequency volume reduction [1-3]. Patients with ENS typically experience paradoxical nasal obstruction, dryness, crusting, a sensation of suffocation, excessive airflow, facial pain, and headache [1,4]. The most challenging aspect of this severe condition is its enigmatic pathogenesis, as its occurrence is unpredictable and unrelated to the degree of turbinate volume reduction. Several factors, including altered airflow dynamics, impaired sensory perception of nasal airflow, and psychological predispositions such as anxiety and depression, have been proposed as contributors to ENS development [1].

The nasal cavity serves as both a major source of autonomic afferent stimuli and an autonomic effector organ [5]. Activation of the sympathetic nervous system primarily constricts nasal capacitance vessels, leading to mucosal decongestion and reduced nasal resistance [6]. Conversely, parasympathetic stimulation induces vasodilation of the nasal mucosa and increases secretion and resistance [6]. Given the critical role of normal autonomic nervous system (ANS) function in maintaining nasal physiology, it is reasonable to hypothesize that ANS dysfunction may contribute to ENS, which is characterized by disrupted nasal physiological balance. Recent studies have identified positive correlations between ANS dysfunction and the severity of symptoms in sinonasal diseases such as allergic rhinitis, chronic vasomotor rhinitis, and chronic rhinosinusitis [7-11]. However, no prior study has specifically investigated autonomic dysfunction in patients with ENS, leaving its potential role in ENS pathophysiology unexamined.

The Composite Autonomic Symptom Scale-31 (COMPASS 31) is a validated, user-friendly, self-reported questionnaire that has been widely used to assess ANS dysfunction severity in various clinical conditions outside otorhinolaryngology [7,8,12]. Laboratory tests, such as measurements of blood hormone levels, heart rate variability, and sympathetic skin response, can also assess ANS function [7-9]. However, these tests require specialized interpretation and are often impractical to perform. In contrast, COMPASS 31 provides a standardized and feasible patient-reported measure well-suited for clinical research. Applying this validated instrument to ENS offers a novel approach to quantifying systemic autonomic symptom burden in affected patients.

This study aimed to compare COMPASS 31 scores between patients with ENS and asymptomatic controls and to examine the relationship between ENS-specific symptoms and ANS dysfunction.

We retrospectively recruited patients diagnosed with ENS by a single surgeon at the Department of Otorhinolaryngology of Asan Medical Center, between May 2022 and January 2023.

A total of 26 patients were included in the ENS group. Diagnosis was based on a previous history of turbinate reduction surgery, characteristic nasal symptoms (nasal obstruction, excessive airflow sensation, or nasal crusting), endoscopic or computed tomography confirmation of excessive inferior turbinate resection, and a positive cotton test. The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) was administered to assess patient symptoms. Patients with ENS6Q scores ≥11 were included in the ENS group. Two patients with ENS6Q scores of 10 were also included because their clinical presentation and positive cotton test results were consistent with typical ENS, and both reported symptom improvement after ENS-targeted treatment, validating their inclusion despite slightly subthreshold ENS6Q scores.

The control group comprised 43 asymptomatic individuals recruited from the otorhinolaryngology outpatient clinic. This group included patients with mild nasal septal deviation but no nasal symptoms, individuals seeking cosmetic rhinoplasty without nasal complaints, and otology or laryngology patients with no nasal issues. All control participants underwent nasal endoscopy to confirm the absence of turbinate atrophy, mucosal inflammation, or other sinonasal pathology. Radiologic imaging was not performed for the control group.

Exclusion criteria for both groups included allergic rhinitis, chronic rhinosinusitis, atrophic rhinitis, sinonasal benign tumors, and malignancies. Additionally, patients with hypertension, diabetes mellitus, anxiety, depression, or chronic neurological disorders such as multiple sclerosis or Parkinson’s disease were excluded, as these conditions are known to affect ANS function [7,8,12].

The COMPASS 31 consists of 31 items divided into six subdomains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor. Raw scores (ranging from 0–75) were weighted according to established conversion factors to produce final scores ranging from 0–100, with higher scores indicating more severe ANS dysfunction.

The ENS6Q includes six items [13]: dryness, impaired air sensation through the nasal cavities, nasal suffocation, nasal openness, crusting, and nasal burning sensation. Each item is rated from 0 (no problem) to 5 (extremely severe), yielding total scores ranging from 0–30.

All patients in the ENS group completed both the COMPASS 31 and ENS6Q questionnaires, either in paper form or via telephone interview. Control participants completed only the COMPASS 31 questionnaire. The ENS6Q was not administered to the control group, as it specifically evaluates ENS-related symptoms. Because control participants had no nasal complaints or prior nasal surgery, the ENS6Q was deemed clinically irrelevant for this group.

The Institutional Review Board (IRB) of Asan Medical Center approved this study (IRB No. 2023-1027), and the requirement for written informed consent was waived.

In this study, patients with ENS exhibited higher COMPASS 31 scores compared with controls. Among the various ENS symptoms, the severity of crusting showed a positive correlation with total COMPASS 31 scores. These findings suggest a potential role of altered ANS function in ENS pathogenesis, particularly regarding nasal mucosal secretion and crust formation.

The nasal mucosa is richly innervated by multiple neural systems, including the ANS [5,6]. The ANS plays a crucial role in regulating nasal patency and secretion—both of which are commonly impaired in ENS. Consequently, it is plausible that ANS dysfunction contributes to the development of ENS symptoms. Prior research on other nasal disorders has demonstrated associations between ANS dysfunction and conditions such as chronic rhinosinusitis, allergic rhinitis, and vasomotor rhinitis [7-11]. In addition, several psychiatric disorders, including anxiety, depression, and sleep disturbances, have been linked to ANS dysregulation [4,14]. Because patients with ENS often present with both nasal and systemic symptoms, including psychological comorbidities, exploring a potential link between ENS and ANS dysfunction is warranted [4,14-16]. To the best of our knowledge, this is the first study to directly evaluate ANS dysfunction in ENS.

We used the COMPASS 31 questionnaire to assess ANS function in patients with ENS. This tool is simple, time-efficient, and patient-administered, comprising 31 items across six domains. Although COMPASS 31 relies on subjective self-assessment, it remains a practical clinical method for evaluating the degree of ANS dysfunction compared with laboratory-based or in vivo physiological tests [8,12,17,18].

Previous studies have reported elevated COMPASS 31 scores in several medical conditions, including autonomic neuropathy, diabetic polyneuropathy, sinonasal diseases, and chronic rhinosinusitis [7,18,19]. In the present study, the mean total COMPASS 31 score for ENS patients was 19.35, significantly higher than that of the control group (p=0.032, Cohen’s d=0.51). According to Chen et al. [8], patients with chronic rhinosinusitis had a mean COMPASS 31 score of 22.86, a value comparable to that observed in our ENS cohort, suggesting that the degree of ANS dysfunction in ENS may be similar to that seen in other sinonasal disorders. Although the difference in total scores reached statistical significance, the moderate effect size indicates that the clinical significance should be interpreted cautiously.

When comparing the six individual domains of the COMPASS 31, the ENS group did not demonstrate significantly higher scores than controls. This differs from the findings of Chen et al. [7], who reported that orthostatic, secretomotor, and gastrointestinal domain scores significantly improved after surgery in patients with chronic rhinosinusitis.

The ENS group showed significantly higher prevalence rates of changes in general body sweating (23.1% vs. 2.3%, p=0.006, Cohen’s h=0.698), excessively dry mouth (38.5% vs. 14.0%, p=0.019, Cohen’s h=0.572), and urinary incontinence (34.6% vs. 9.3%, p=0.009, Cohen’s h=0.638) than the control group. Similarly, Chen et al. [8] reported that chronic rhinosinusitis patients had a higher prevalence of excessively dry mouth (70.8%), though the frequencies of changes in body sweating and urinary incontinence were lower (20.3% and 12.3%, respectively). While the total COMPASS 31 score provides a validated summary of autonomic symptom burden, it is important to note that subdomains such as orthostatic intolerance, gastrointestinal, and bladder function may not directly reflect nasal physiology or ENS-related mechanisms. Nevertheless, the elevated prevalence of symptoms such as abnormal sweating and dry mouth in ENS patients may suggest a broader systemic dysregulation rather than a purely localized nasal condition.

The ENS6Q, a validated six-item tool encompassing dryness, impaired air sensation through the nasal cavities, nasal suffocation, nasal openness, crusting, and nasal burning, is used to both diagnose ENS and assess its severity [13,20]. In our study, nasal dryness was the most bothersome symptom (mean score 3.79). To evaluate the relationship between ENS symptom severity and ANS dysfunction, we analyzed correlations between total ENS6Q and COMPASS 31 scores. No significant correlation was found between the two total scores, suggesting the complex and multifactorial nature of ENS symptomatology. However, among individual ENS6Q items, the crusting symptom showed a significant positive correlation with the total COMPASS 31 score (p=0.012, r²=0.381). Increased crusting in ENS is typically due to excessive airflow through the nasal cavity following turbinate volume reduction, and this finding may indicate that patients with greater ANS dysfunction are more prone to crusting due to impaired regulation of mucosal gland secretion. Additionally, two patients with ENS6Q scores of 10 were included because they displayed characteristic ENS features and positive cotton test results, and both improved following ENS-directed medical treatment. Their inclusion was therefore clinically justified and unlikely to have affected the overall results.

Overall, these findings suggest that ENS symptom manifestation and ANS dysfunction may be closely interconnected. However, because causality cannot be established within the scope of this study, it remains possible that chronic nasal symptoms and mucosal alterations associated with ENS may secondarily induce ANS dysfunction. Thus, the relationship between ENS and ANS dysregulation may be bidirectional and requires further exploration through longitudinal or interventional studies.

Although our results revealed significantly higher total COMPASS 31 scores and a greater prevalence of certain autonomic symptoms in the ENS group, most individual autonomic domains did not differ significantly between the two groups. Therefore, the current findings do not conclusively support the hypothesis that ANS dysfunction directly contributes to ENS pathogenesis. Furthermore, some autonomic symptoms, such as urinary incontinence, may reflect potential selection bias rather than a true ENS-specific association.

This study has several limitations. First, it relied exclusively on subjective, questionnaire-based assessments (ENS6Q and COMPASS 31) to evaluate ENS symptoms and ANS dysfunction. The lack of objective autonomic testing methods—such as heart rate variability, sympathetic skin response, or pupillary light reflex—precludes confirmation of physiological ANS dysfunction and limits the ability to infer causality between ANS impairment and ENS. Second, the relatively small sample size in both groups may restrict the generalizability of the findings. Third, although the control group did not undergo radiologic imaging, all control participants underwent nasal endoscopy, which confirmed the absence of pathology; nonetheless, the possibility of undetected abnormalities cannot be completely excluded. Fourth, various clinical factors—including age, sex, and medical history—can influence ANS function. Although patients with conditions known to affect ANS activity (e.g., hypertension, diabetes mellitus, psychological disorders, and chronic neurological diseases) were excluded, and no significant age or sex differences were observed between groups, other unmeasured factors may still have affected the results. Future studies incorporating objective ANS function testing and longitudinal assessments, including pre- and post-treatment comparisons, are needed to clarify whether ANS dysfunction plays a causal role in ENS pathogenesis.

In conclusion, patients with ENS demonstrated higher total COMPASS 31 scores compared with controls, and nasal crusting scores showed a positive correlation with autonomic symptom burden. These findings suggest potential involvement of ANS dysfunction in ENS pathophysiology, particularly in the regulation of nasal mucosal secretion.