Utility of Serum Interleukine-6 Level in Empty Nose Syndrome.

Objectives: Empty nose syndrome (ENS), a complication resulting from surgical procedures on turbinate tissue, is characterized by paradoxical nasal obstruction with wide nasal airways. Patients with ENS often also experience psychiatric symptoms, and psychiatric disorder detection remains dependent on subjective evaluation. Objective biomarkers for mental status assessment in patients with ENS are unestablished. This study aimed to evaluate the role of serum interleukin-6 (IL-6) levels in the mental status of patients with ENS. Methods: Overall, 35 patients with ENS who underwent endonasal submucosal implantation surgery were prospectively included in the study. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II) were used to assess the physical and psychiatric symptoms of these patients preoperatively, and 3, 6, and 12 months postoperatively. Serum IL-6 levels were analyzed 1 day before surgery. Results: All subjective assessments significantly improved 3 months after surgery and plateaued at 12 months. Patients with higher serum preoperative IL-6 levels tended to experience more severe depression. Regression analysis showed that a preoperative serum IL-6 level > 1.985 pg/mL was significantly correlated with severe depression status in patients with ENS (odds ratio = 9.76, p = 0.020). Conclusions: ENS patients with higher preoperative serum IL-6 levels were more likely to have severe depressive burden. Since more suicidal thoughts or attempts were noted in these patients, timely treatment plan for patients with high levels of serum IL-6 is crucial and may consider psychotherapy after surgical treatment.

Platelet-rich plasma injection for empty nose syndrome: A case report.

Empty nose syndrome (ENS) is a relatively rare disease found in patients who have undergone sinonasal surgery, characterized by excessive reduction of the turbinate, causing intranasal turbulence and loss of receptors within the nasal mucosa. Patients diagnosed with the disease usually experience symptoms including dryness of the nose, nasal pain, paradoxical nasal obstruction, and crusts in the nasal cavity. ENS can be treated with conservative care such as nasal irrigation or nasal moisturizers. Accurate efficacy of surgical treatment of ENS is often difficult to predict and is accompanied by operational obstacles and complications. Platelet-rich plasma (PRP) has recently gained attention as a regenerative therapy in several medical fields. We present two cases of ENS treated by injection of PRP as a simple and less invasive method, and describe its efficacy with nasal endoscopy and subjective questionnaires.

The management of upper airway diseases: an ongoing challenge for the clinician.

Upper airway diseases are widespread in clinical practice. However, some aspects are still debated. The current supplement presents and discusses the most common disorders encountered in daily medical activity. The COVID-19 dramatic pandemic requires an urgent solution. Promising non-pharmacological agents are discussed. Chronic diseases are frequent in childhood, so to know risk factors is useful in their management. Allergic rhinitis and chronic rhinosinusitis should be treated with anti-inflammatory drugs, but complementary compounds should be alternated to preserve health. Empty nose syndrome is a frequent complication of nasal surgery and requires adequate staging and hydrating procedure. Lastly, laryngopharyngeal reflux is an intriguing challenge for the clinician. Alginates represent a safe and effective way to relieve LPR symptoms.

Middle turbinate resection is unlikely to cause empty nose syndrome in first year postoperatively.

PURPOSE: Empty nose syndrome (ENS) is characterized by nasal dryness, crusting, and paradoxical nasal obstruction most commonly after inferior turbinate resection. ENS has also been reported to occur after middle turbinate resection (MTR), and concern for causing ENS is a possible reason surgeons preserve the MT during endoscopic sinus surgery (ESS). The objective was to determine whether MTR during ESS led to ENS. MATERIALS AND METHODS: This was a prospective case series of 95 consecutive patients that underwent bilateral subtotal MTR during ESS with either Draf IIB or Draf III frontal sinusotomies, for chronic rhinosinusitis with or without nasal polyps, and frontal sinus inverted papillomas. Demographic data and postoperative Empty Nose Syndrome 6-item Questionnaire (ENS6Q) scores were obtained. Nasal crusting was also documented on last postoperative nasal endoscopy. RESULTS: Pathologies included chronic rhinosinusitis with nasal polyps (69), without nasal polyps (12), and inverted papillomas (14). Fifty-six patients underwent subtotal MTRs during ESS with Draf IIB, and 39 with Draf III. Mean follow-up was 19.4 months (range 12-49). Mean postoperative ENS6Q score was 2.1. Only 2.1% had ENS6Q scores ≥ 11, and 6.3% had nasal crusting at last follow-up. None of the patients with ENS6Q scores ≥ 11 had nasal crusting at last follow-up. There were no significant differences in outcomes between ages, genders, surgery types, or pathologies. CONCLUSIONS: Patients who underwent bilateral subtotal MTR during ESS were unlikely to develop ENS by at least 1 year postoperatively, based on patients rarely experiencing ENS6Q scores ≥ 11 or persistent nasal crusting.

Outcomes of olfaction in patients with empty nose syndrome after submucosal implantation.

BACKGROUND: Olfactory dysfunction, such as hyposmia, is a significant symptom of empty nose syndrome (ENS). The efficacy of surgical intervention in olfaction improvements for ENS has not been investigated extensively. OBJECTIVE: The aim of this study was to evaluate changes in olfaction after surgical treatment for ENS. METHODS: This prospective cohort study at a tertiary medical center enrolled patients with ENS indicated for surgical treatment between June 2015 and June 2019. The Sniffin' Sticks 12-items odor identification test (SS-12) and subjective olfaction rating were completed by patients before and after surgery to assess olfaction. RESULTS: A total of 40 patients completed the survey both before and after surgical treatment. Prior to surgery, 25% of the patients had olfactory dysfunction detected by SS-12, whereas 80% of the patients reported a reduction in olfactory function by subjective rating. The degree of olfactory dysfunction by both assessments significantly improved following surgery. The age was a significant predictor of postoperative improvement. CONCLUSION: Surgical treatment is helpful in improving olfaction in patients with ENS who commonly suffer from olfactory dysfunction. Younger patients may benefit more from surgical intervention in aspect of olfaction.

Nasal nitric oxide in relation to psychiatric status of patients with empty nose syndrome.

BACKGROUND: Although cases of empty nose syndrome (ENS) are not very common, the suffering that ENS causes patient is immense and could be very difficult to imagine. Nasal nitric oxide (nNO) is an airway disease biomarker, and its levels increase after endoscopic sinus surgery. The trend of nNO levels in ENS before and after surgical treatment remains unknown. This study aimed to evaluate the role of nNO in ENS. METHODS: Patients with ENS who received surgical implantation and with chronic hypertrophic rhinitis (CHR) who underwent turbinoplasty and completed at least 1 year of follow-up were prospectively enrolled. nNO measurements and subjective assessments [SinoNasal Outcome Test (SNOT)-22, Beck Depression Inventory (BDI)-II, and Beck Anxiety Inventory (BAI)] were performed preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: We enrolled 19 ENS and 12 CHR patients. nNO levels were significantly lower in the ENS than in the CHR patients before surgical treatment (p < 0.001). nNO levels in the ENS patients significantly increased 3 months after implantation and remained plateaued (p = 0.015). BDI-II and BAI scores significantly improved after surgical treatment for the ENS patients but not for the CHR patients; changes in nNO levels correlated well with improvements in BDI-II and BAI scores (p = 0.025 and 0.035, respectively). CONCLUSIONS: nNO significantly increased at third month after surgical treatment and remained plateaued in ENS patients. This increase correlated with improvements in BDI-II and BAI scores. Therefore, nNO may be important in assessing the psychiatric status of empty nose syndrome.

Optimizing Stimulation in a Case of Facial Pain Through "Cross-Talk" of Peripheral and Central Leads: A Case Report.

OBJECTIVES: To describe inter-lead (cross-talk) stimulation between a trigeminal nerve lead and a cervical epidural lead for the treatment of facial pain in a 69-year-old patient with empty nose syndrome. MATERIALS AND METHODS: A trial implant was performed with a peripheral V2 trigeminal lead and a C1-C2 lead in cross-talk configuration. During permanent implant, the V2 lead was placed uneventfully while the central lead could only be advanced to C3-C4. RESULTS: During the trial, pain decreased by 70%. One month after permanent implant, the patient still experienced a 60-70% reduction in pain levels and a decrease from ten to two weekly pain episodes. Nine months post implant, the patient reported complete pain relief (0/10 on a numeric rating scale ranging from 0 to 10) and medications were discontinued. Infrequent exacerbations (3/10) were controlled by increasing stimulation. Three years post implant, the patient continued to have no baseline pain and could easily control exacerbations. CONCLUSION: Cross-talk configuration between a peripheral and a central lead created a more efficient stimulation technique. The resulting paresthesia was superior to that obtained from either lead alone and exceeded the paresthesia obtained from the combination of the two leads when used simultaneously, without an inter-lead configuration.

A 3-year follow-up study after nasal reconstruction surgery in patients with empty nose syndrome.

KEY POINTS: Empty nose syndrome (ENS) is characterized by a patent nasal airway and a sense of nasal obstruction. ENS and psychological symptoms improved after surgery and remained stable for up to three years. Identifying residual disease is necessary for enhancing therapeutic outcomes in ENS patients.

A Systematic Review and Meta-Analysis of Management Options for Empty Nose Syndrome: A Proposed Management Algorithm.

OBJECTIVE: Empty nose syndrome (ENS) is an acquired condition characterized by paradoxical nasal obstruction and sensation of nasal dryness often accompanied by psychological disorders such as depression or anxiety, typically occurring after the loss of inferior turbinate tissue or volume in the setting of prior sinonasal surgery. This review aims to identify and evaluate the reported management options. DATA SOURCES: PubMed, Scopus, and Web of Science. REVIEW METHODS: The terms "empty nose syndrome" OR "atrophic rhinitis" were used in a systematic search of original articles since the year 1990, yielding 1432 individual studies. These were screened on the Covidence platform for inclusion if any intervention was reported for the treatment of ENS. A pooled analysis of standardized mean differences (SMDs) combined with a random effects model was employed to report outcomes in Empty Nose 6-Item Questionnaire (ENS6Q), Sino-Nasal Outcome Test (SNOT), anxiety, and depression scores. RESULTS: A total of 35 articles were included, comprising 957 individual ENS patients. Surgical interventions mostly in the form of meatus augmentation implants accounted for 26 out of the 36 articles. The remaining ten articles included medical and psychological management options. SMD in SNOT, ENS6Q, anxiety, and depression scores were reported and demonstrated statistically significant improvements in follow-up periods of up to 1 year. All articles reported favorable outcomes following their chosen interventions. CONCLUSION: There is a paucity of evidence on the management of ENS and an absence of randomized controlled trials. Surgical intervention appears to be the current mainstay of treatment, but there is a potential role for psychological and medical management.

Use of bovine-derived collagen matrix in the surgical treatment of empty nose syndrome.

KEY POINTS: Bovine-derived collagen matrix (BDCM) is a safe augmentation material in patients with empty nose syndrome. BDCM augmentation results in clinically and statistically significant improvement in nasal symptoms. Improvements in nasal symptoms with BDCM augmentation may be durable and can be seen up to 2 years postoperative.

Subtotal Middle Turbinate Resection in Patients with Chronic Rhinosinusitis with Nasal Polyps is Unlikely to Cause Empty Nose Syndrome: A Multi-Institutional Prospective Study.

BACKGROUND: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores. METHODS: A multi-institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow-up. RESULTS: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow-up was 14.5 ± 2.5 months (range 12.1-22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow-up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively. CONCLUSIONS: Based on prospective multicenter data over 1-2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Computed Tomographic Evaluations in Patients with Empty Nose Syndrome.

OBJECTIVE: We aimed to evaluate computed tomography (CT) images of patients with empty nose syndrome (ENS), investigate the impact of reconstruction surgery on sinus inflammation, and identify the optimal airspace diameter after surgery. METHODS: We conducted a retrospective case series analysis, identifying and enrolling patients with ENS with perioperative CT findings. The clinical characteristics of the participants were collected, and the modified Lund-Mackay (mLM) CT scores were determined. The anterior airspace diameter was evaluated by measuring the distance between the septum and the lateral nasal wall on the coronal plane at the level of the nasolacrimal duct. RESULTS: Twenty patients with ENS and perioperative CT images were enrolled. The mean total mLM CT score and all subsite scores showed no significant changes after surgery. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) score, Sino-nasal Outcome Test-25 (SNOT-25) score, sleep symptoms domain, psychological domain, and empty nose symptoms domain were significantly associated with anterior airspace diameter in the regression analysis. CONCLUSION: There was no significant difference in sinus inflammation between preoperative and postoperative CT evaluations. The anterior airspace diameters were significantly associated with ENS6Q and SNOT-25 scores. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2105-2110, 2024.

Evaluation of Post-Intervention Outcomes in Patients with Empty Nose Syndrome.

OBJECTIVES: To conduct a systematic review and meta-analysis of published articles to assess the impact of inferior turbinate/meatus augmentation in patients diagnosed with empty nose syndrome (ENS). DATA SOURCES: PubMed, Cochrane database, Embase, Web of Science, SCOPUS, and Google Scholar. REVIEW METHODS: Six databases were searched to December 2022. We retrieved studies evaluating improvements in refractory ENS-related symptoms based on various patient-reported outcome measures after inferior turbinate/meatus augmentation. RESULTS: As a result of meta-analysis, Sinonasal Outcome Test, Empty Nose Syndrome 6-Item Questionnaire (ENS6Q), and depression scores were measured at 1 week; 1, 3, and 6 months; and later than 12 months after intervention for patients with ENS. All scores revealed significant symptom improvement. By reference to the minimal clinically important difference of the ENS6Q (6.25), inferior turbinate/meatus augmentation relieved the nasal symptoms of ENS in the long term. Although the improvements in anxiety scores at 1 week (0.4133 [-0.3366; 1.1633], 0.00, I2 = NA) and 1 month (0.4525 [-0.0529; 0.9579], I2 = 0.0%) were not statistically significant, the scores differed significantly at 3 months (0.7351 [0.4143; 1.0559], I2 = 28.4%), 6 months (0.8297 [0.6256; 1.0337], I2 = 37.2%), and longer than 12 months (0.7969 [0.4768; 1.1170], I2 = 0.0%). CONCLUSION: These data and analysis suggest that performing inferior turbinate/meatus augmentation on ENS patients may improve not only nasal symptom scores but also accompanying psychological problems such as anxiety and depression. Laryngoscope, 134:2005-2011, 2024.

Application of a Novel 3D-Printed Nasal Plug as a Conservative Treatment for Empty Nose Syndrome.

OBJECTIVE: Empty nose syndrome (ENS) is commonly treated by surgery, albeit with limited success. Herein, we introduce our experience of applying a newly developed "3D-printed nasal plug" as an alternative conservative treatment modality. METHODS: This retrospective study included 20 patients (14 males, 6 females; mean age 46.5 ± 13.5 years) with ENS who underwent the application of the 3D-printed nasal plug at Asan Medical Center between June 2022 and May 2023. Symptom improvement was assessed by Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) before and after applying the nasal plug. Clinical results, such as duration and frequency of plug use, discomfort, and level of satisfaction, were investigated. RESULTS: The mean follow-up duration was 40.3 ± 24.2 weeks. The average duration of nasal plug usage was 10.8 h per day and 5.3 days a week. The ENS6Q scores improved from 19.6 ± 4.6 to 6.8 ± 5.1 (mean reduction 12.8 ± 5.9) after 30 minutes of wearing. Symptom "nose feelings too open" was improved most by a score of 3.0 ± 1.5 (p < 0.001). Thirteen patients (65.0%) reported that the effectiveness of the plug, initially confirmed at the first wearing, was well maintained during the entire follow-up. Four patients (20.0%) wore the nasal plug uninterruptedly throughout the week, whereas nine patients (45.0%) wore it intermittently as needed. Frequently reported complaints with plug usage were 'displacement of the plug' and 'cosmetic concerns' about the visible hook portion. CONCLUSION: A 3D-designed nasal plug can be a useful conservative treatment option for ENS patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3935-3940, 2024.

Functional Exercise Capacity and Perceived Exertion in Patients with Empty Nose Syndrome.

Empty nose syndrome (ENS) is a complex condition characterized by symptoms such as dyspnea, nasal discomfort, and emotional challenges. This study aimed to evaluate functional exercise capacity and perceived exertion in patients with ENS. Patients with ENS who presented with a range of severe symptoms were prospectively enrolled. Pulmonary function was evaluated using spirometry, and functional exercise capacity was measured via the 6 min walk test (6-MWT). Perceived exertion was quantified using the Borg scale, and cardiopulmonary function was evaluated by monitoring peripheral oxygen saturation (SpO2). These parameters were assessed before and after nasal reconstruction surgery. A total of 44 patients with ENS were enrolled and classified into mild-to-moderate (n = 20) and severe (n = 24) symptom groups. Spirometry results showed no significant differences before and after surgery in the entire cohort. Perceived exertion showed significant postoperative improvement (p = 0.006). The severe ENS symptom group experienced significant improvement in SpO2 (p = 0.013) and perceived exertion (p = 0.002) at the end of the 6-MWT after surgery. Surgical intervention significantly enhanced functional exercise capacity (p = 0.038) in patients with mild-to-moderate ENS symptoms. Surgical reconstruction positively affected perceived exertion and SpO2 at the end of the 6-MWT in patients with ENS. The severity of ENS symptoms, as assessed by SNOT-25 scores, influenced these outcomes. These findings underscore the potential benefits of surgical intervention for enhancing exercise tolerance and respiratory efficiency.

The Serpentine Sign: A Reliable Endoscopic and Radiographic Finding in Empty Nose Syndrome.

OBJECTIVE: Empty nose syndrome (ENS) is a relatively uncommon disease that greatly impacts the quality of life and presents diagnostic challenges. We sought to identify objective clinical findings unique to patients with ENS, and in doing so identified compensatory mucosal hypertrophy in an alternating, undulating swelling on endoscopy and coronal computerized tomography (CT) that we have termed the "Serpentine Sign." Here, we investigated whether this radiographic finding is a reliable manifestation in ENS patients. METHODS: Retrospective review was undertaken to identify ENS patients with past turbinoplasty, an ENS6Q score of at least 11/30, and symptomatic improvement with the cotton placement test. Control patients without complaints of ENS symptoms (ENS6Q < 11) were identified for comparison. ENS and control patients had coronal CT imaging available to evaluate for the Serpentine Sign, as well as ENS6Q scores, and histologic analysis of nasal tissue. RESULTS: 34 ENS and 74 control patients were evaluated for the presence of the Serpentine Sign. Of the 34 patients with ENS, 18 exhibited this radiographic finding on CT imaging (52.9%) compared to 0 of the 74 control patients (p < 0.0001). Further analysis demonstrated that ENS patients with the Serpentine Sign had lower median scores on ENS6Q than ENS patients without (17.5 vs. 22, p = 0.033). Histology revealed disorganized subepithelium rich in seromucinous glands similar to the nasal septum swell body. CONCLUSION: The "Serpentine Sign" is a unique presentation of hypertrophic change to the nasal septum soft tissue that is specific to ENS patients and may serve as a reliable radiographic and endoscopic finding in diagnosis. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1089-1095, 2024.

Evaluation of sinonasal-related quality of life of 49 patients undergoing endoscopic skull base surgery.

OBJECTIVE: This study aimed to evaluate the sinonasal-related Quality of Life (QoL) in patients undergoing endoscopic skull base surgery. METHODS: A retrospective study was performed, including patients with benign and malignant tumors at a single institution. Each patient completed the 22-Item Sino-Nasal Outcome Test (SNOT-22) and the Empty Nose Syndrome 6 Item Questionnaires (ENS6Q) to assess their perceived QoL at least 2-months after treatment. RESULTS: Forty-nine patients were enrolled in this study. The average score was 25.1 (Stander Deviation [SD] 14.99) for SNOT-22 and 6.51 (SD=5.58) for ENS6Q. Analysis of the overall results for the SNOT-22 showed that olfactory damage was the most serious syndrome. The most frequently reported high-severity sub-domains in SNOT-22 were nasal symptoms and sleep symptoms. Nasal crusting was the most severe item in ENS6Q according to the report. Nine patients (18.4%) had a score higher than 10.5 which indicates the high risk of Empty Nose Syndrome (ENS). SNOT-22 score was related to the history of radiotherapy (p< 0.05), while the ENS6Q score was not. CONCLUSIONS: The possibility of patients suffering from ENS after nasal endoscopic skull base surgery is at a low level, although the nasal cavity structure is damaged to varying degrees. Meanwhile, patients undergoing endoscopic skull base surgery were likely to suffer nasal problems and sleep disorders. Patients who had received radiotherapy have a worse QoL than those without a history of radiotherapy. LEVEL OF EVIDENCE: Level 3.

Morphology, Not Only Volume: A Study on Empty Nose Syndrome and Inferior Turbinates.

OBJECTIVES: Empty nose syndrome (ENS) is an underdiagnosed but burdensome clinical condition. Studies that have addressed the impact of remnant inferior turbinate volume (ITV) on ENS are scarce. We aimed to evaluate the impact of ITV and phenotyping on the severity and presentation of ENS. METHODS: All the enrolled patients underwent the following subjective assessments: the ENS 6-Item Questionnaire (ENS6Q), Sino-Nasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). The ITV was obtained from finely cut (1-mm-thick slices) sino-nasal computed tomography scan images and analyzed using ImageJ. The correlation between ITV, subjective measurements, and morphology of inferior turbinates was evaluated. ENS was categorized as torpedo type (balanced tissue volume) or pistol type (posterior dominance) based on the morphology. RESULTS: Overall, 54 patients met the inclusion criteria. The ITV was positively correlated with the ENS6Q score and domain of ENS symptoms in SNOT-25. Neither BDI-II nor BAI scores had a significant correlation with ITV. Based on their morphological classification, the torpedo type exhibited diverse manifestations in the SNOT-25 analysis in response to changes in ITV, while the pistol type demonstrated an elevated rhinologic symptom burden and ENS-specific symptoms as their ITV increased. Nasal resistance did not correlate with the ITV in either type of ENS. CONCLUSIONS: Symptoms were paradoxically worse in ENS patients with greater remnant ITV, and distinct morphological phenotypes in the nasal cavities may result in different presentations. Further investigation into the correlation between remnant inferior turbinates and nerve function is warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3060-3066, 2024.