Serum Aspergillus fumigatus-Specific IgG as a Complementary Biomarker in Differentiating Endotypes of Chronic Rhinosinusitis: A Study on Its Role and Diagnostic Efficacy in Type 2 Inflammation.

BACKGROUND: Aspergillus is one of the most common pathogens causing fungal allergy in the respiratory tract. Serum Aspergillus fumigatus-specific immunoglobulin G (Af-sIgG) levels have been used as a biomarker for the diagnosis and treatment response monitoring in airway allergic diseases such as allergic bronchopulmonary aspergillosis and allergic fungal rhinosinusitis. However, its role in common primary chronic rhinosinusitis (CRS) was unclear. OBJECTIVE: This study aims to evaluate whether serum Af-sIgG level could serve as a biomarker for the disease presentation of primary CRS. METHODS: We obtained serum Af-sIgG levels from patients diagnosed as bilateral primary CRS refractory to medical treatment and evaluated the correlations between serum Af-sIgG levels and disease severity in patients with type 2 (T2) and non-T2 CRS. RESULTS: Patients with T2 CRS exhibited significantly higher serum Af-sIgG levels than non-T2 CRS patients. The cut-off value of serum Af-sIgG in T2 CRS was 20.9 mg/L, with an odds ratio of 3.8 (95% CI 1.17-12.20, P = .026). Furthermore, serum Af-sIgG levels were positively correlated with symptom scores evaluated by the Sino-Nasal Outcome Test-22 (SNOT-22) scores in T2 patients (P = .009). While stratified by SNOT-22 total scores, patients with severe disease had higher serum Af-sIgG levels only in T2 CRS (P = .034). In individual domains of SNOT-22 analysis, serum Af-sIgG levels showed a significant correlation with "ear/facial" symptom scores in the T2 group (P < .001). CONCLUSIONS: Serum Af-sIgG levels may serve as a supplementary objective biomarker that correlates with identification and subjective measurements of T2 CRS, and may be associated with symptoms arising from Eustachian tube dysfunction.

Risk Factors for Isolated Sphenoid Sinusitis after Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

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.

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.

Patient With Unilateral Nasal Obstruction and a Nasal Mass.

A 65-year-old man presented with a 2-year history of left nasal obstruction and large tumor in the left nasal cavity. What is your diagnosis?

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.

Elevated Serum Aspergillus Fumigatus-Specific Immunoglobulin G in Type 2 Chronic Rhinosinusitis.

Background: Aspergillus fumigatus-specific immunoglobulin G (Af-sIgG) has been applied to diagnose allergic bronchopulmonary aspergillosis, a hypersensitivity reaction to the colonization of the fungus in the lower airways. In the upper airways, it has been reported to be involved in allergic fungal rhinosinusitis and local fungal rhinosinusitis. However, in primary chronic rhinosinusitis (CRS), a more common upper airway disease, the role of Af-sIgG remains unclear. Objective: The aim of our study was to investigate the role of serum Af-sIgG levels in primary CRS patients. Methods: We prospectively recruited patients diagnosed with bilateral primary CRS and patients with nasal septal deviation as the non-CRS group. Patients in the primary CRS group were further classified into two endotypes, including type 2 (T2) and non-T2 groups. Serum samples collected were sent for Af-sIgG analysis. Potential factors and surgical outcomes were analyzed. Results: Forty-eight patients with a diagnosis of primary CRS (including 28 with T2 and 20 with non-T2 CRS) and 22 patients in the non-CRS group were recruited. The T2 CRS group had significantly higher serum Af-sIgG levels than the non-T2 CRS group (odds ratio 10.2 with Af-sIgG more than 27.6 mg/L; p < 0.001). Further multivariate logistic regression showed that the serum Af-sIgG level was the independent factor for early disease recurrence within one year in primary CRS patients. The optimal cutoff value of the serum Af-sIgG level to predict postoperative recurrence was 27.1 mg/L (odds ratio 15.1, p = 0.013). Conclusions: We suggest that the serum Af-sIgG level is a practical marker to detect T2 inflammation and the surgical outcome of primary CRS. By applying this feasible test, we may be able to achieve optimal treatment for every individual with primary CRS. This study may provide physicians with a reference for future clinical applications in dealing with primary CRS.

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.

Identifying Residual Psychological Symptoms after Nasal Reconstruction Surgery in Patients with Empty Nose Syndrome.

BACKGROUND: Empty nose syndrome (ENS) is a syndrome of paradoxical nasal obstruction that is thought to be mostly caused by inappropriate turbinate procedures. This study aimed to investigate depression- and anxiety-associated psychological symptoms in patients with ENS before and after surgical reconstruction, and to compare them with those of control subjects. METHODS: Patients with ENS were prospectively enrolled. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item questionnaire (ENS6Q), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) were used to evaluate the participants before and after reconstruction surgery with submucosal Medpor implantation (Stryker, Kalamazoo, MI), as well as control subjects at enrollment. RESULTS: Forty patients with ENS and forty age- and sex-matched controls were recruited. Patients with ENS experienced significant improvement in SNOT-25, ENS6Q, BDI-II, and BAI scores after surgery, but all were significantly greater than those in the control group. Nine patients with ENS (22.5%) had postoperative residual psychological symptoms. Preoperative BDI-II and BAI scores were significant predictors of postoperative residual psychological symptoms. The optimal cut-off value was BDI-II > 28.5 (sensitivity, 77.8%; specificity, 77.4%) in receiver operating characteristic curve analysis. CONCLUSIONS: The nasal and psychological evaluations in patients with ENS significantly improved after nasal reconstruction surgery, but both were significantly greater than those in the control group. Identifying individuals who may experience postoperative residual symptoms and providing a multimodal approach, including surgical reconstruction and psychiatric treatment, are suggested.

Post-irradiation nasal nitric oxide in patients with nasopharyngeal carcinoma.

KEY POINTS: nNO levels decreased at 3 and 6 months and recovered at 12 months after radiotherapy in NPC. nNO may be a feasible biomarker for mucociliary function in post-irradiated NPC patients. Lower nNO levels were associated with more sinonasal burdens in post-irradiated NPC patients.

Microbiome profiling of nasal extracellular vesicles in patients with allergic rhinitis.

Background: Nasal microbiota is crucial for the pathogenesis of allergic rhinitis (AR), which has been reported to be different from that of healthy individuals. However, no study has investigated the microbiota in nasal extracellular vesicles (EVs). We aimed to compare the microbiome composition and diversity in EVs between AR patients and healthy controls (HCs) and reveal the potential metabolic mechanisms in AR. Methods: Eosinophil counts and serum immunoglobulin E (IgE) levels were measured in patients with AR (n = 20) and HCs (n = 19). Nasal EVs were identified using transmission electron microscopy and flow cytometry. 16S rRNA sequencing was used to profile the microbial communities. Alpha and beta diversities were analyzed to determine microbial diversity. Taxonomic abundance was analyzed based on the linear discriminant analysis effect size (LEfSe). Microbial metabolic pathways were characterized using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUst2) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Eosinophils, total serum IgE, and IgE specific to Dermatophagoides were increased in patients with AR. Alpha diversity in nasal EVs from patients with AR was lower than that in HCs. Beta diversity showed microbiome differences between the AR and HCs groups. The microbial abundance was distinct between AR and HCs at different taxonomic levels. Significantly higher levels of the genera Acetobacter, Mycoplasma, Escherichia, and Halomonas were observed in AR patients than in HCs. Conversely, Zoogloea, Streptococcus, Burkholderia, and Pseudomonas were more abundant in the HCs group than in the AR group. Moreover, 35 microbial metabolic pathways recognized in AR patients and HCs, and 25 pathways were more abundant in the AR group. Conclusion: Patients with AR had distinct microbiota characteristics in nasal EVs compared to that in HCs. The metabolic mechanisms of the microbiota that regulate AR development were also different. These findings show that nasal fluid may reflect the specific pattern of microbiome EVs in patients with AR.

Identifying Obstructive Sleep Apnoea in Patients with Empty Nose Syndrome.

Obstructive sleep apnoea (OSA) is characterised by repetitive episodes of upper airway collapse and breathing cessation during sleep. Empty nose syndrome (ENS) is a surgically iatrogenic phenomenon of paradoxical nasal obstruction despite an objectively patent nasal airway. This study aimed to investigate sleep quality and the presence of OSA in ENS patients. Forty-eight ENS patients underwent full-night polysomnography. Total nasal resistance (TNR) was determined using anterior rhinomanometry. Symptoms and quality of life were evaluated by the empty nose syndrome 6-item questionnaire (ENS6Q), Sino-Nasal Outcome Test-22 (SNOT-22), and Epworth Sleepiness Scale questionnaires (ESS). Fourteen, twelve, and fourteen patients had mild, moderate, and severe OSA, respectively. The apnoea-hypopnoea index (AHI) and the lowest SpO2 were 23.8 ± 22.4/h and 85.9 ± 11.1%, respectively. N1, N2, N3 and rapid-eye-movement sleep comprised 30.2 ± 16.9%, 47.3 ± 15.5%, 2.1 ± 5.4%, and 20.0 ± 8.1% of the total sleep time. Body mass index, neck circumference, serum total immunoglobulin E, and ENS6Q score were significantly associated with AHI in the regression analysis. The ENS6Q scores correlated positively with AHI, arousal index, and ESS score, but negatively with TNR. ENS patients showed a high OSA prevalence and significant sleep impairment. The extent of OSA was associated with obesity levels and ENS symptom severity. The ENS6Q scores correlated negatively with nasal resistance, and positively with arousal frequency and daytime sleepiness. The recognition of individuals experiencing marked OSA and provision of appropriate intervention is critical to preventing long-term morbidity and mortality, and improving therapeutic outcomes in ENS patients.

Comparison of SNOT-25 and ENS6Q in evaluating patients with empty nose syndrome.

Objectives: Patients with empty nose syndrome (ENS) experience paradoxical nasal obstruction and various psychological burdens. This study aimed to compare ENS-specific questionnaires of sino-nasal outcome test-25 (SNOT-25) and empty nose syndrome 6-item questionnaire (ENS6Q) in the peri-operative evaluation of ENS. Methods: This was a prospective case series study. Patients with ENS were recruited and evaluated with the SNOT-25, ENS6Q, beck depression inventory-II (BDI-II), and beck anxiety inventory (BAI) before and 6 months after nasal reconstruction surgery. Results: Seventy-four ENS patients were enrolled during the study period. All four evaluations revealed significant improvements after surgery. Pre-operative SNOT-25 scores exhibited a significant correlation with pre-operative ENS6Q (r = 0.682), BDI-II (r = 0.485), and BAI scores (r = 0.608) (p < 0.001), as well as a weak correlation with post-operative SNOT-25 (r = 0.336), BDI-II (r = 0.266), and BAI scores (r = 0.235) (p < 0.05). Additionally, pre-operative ENS6Q scores were significantly correlated with pre-operative BDI-II (r = 0.434), BAI (r = 0.521) (p < 0.001), and post-operative ENS6Q scores (r = 0.262, p < 0.05). However, there was no correlation between pre-operative ENS6Q scores and post-operative BDI-II and BAI scores. Conclusions: Both SNOT-25 and ENS6Q were helpful in evaluating peri-operative symptoms for patients with ENS. Although the ENS6Q score had a good correlation with the BDI-II and BAI scores preoperatively, it was not associated with post-operative BDI-II and BAI scores. Hence, a simultaneous psychological assessment is necessary when evaluating patients using the ENS6Q.Level of Evidence: 2c.

Association between Clinical Factors and Surgical Outcomes for Patients with Persistent Allergic Rhinitis.

Objective: While septoplasty with turbinoplasty is commonly performed for patients with nasal obstruction, no study has addressed its efficacy and related determinants in patients with allergic rhinitis (AR) and various symptoms. This study aimed to identify potential factors associated with surgical outcomes in patients with persistent AR (PAR) who underwent septoplasty with turbinoplasty. Methods: We prospectively recruited patients with PAR and positive allergy test results for surgical treatment. We also collected relevant preoperative laboratory data. The Sinonasal Outcome Test-22 (SNOT-22) survey was administered to all patients one day before and one year after surgery. Results: A total of 128 patients who completed a one-year postoperative follow-up were enrolled. The total SNOT-22 score and five subdomain scores significantly improved postoperatively. We found that women and those with higher preoperative SNOT-22 scores experienced more postoperative improvement and had a greater potential to reach minimal clinically important differences (MCID). A preoperative SNOT-22 score greater than the determined cut-off value of 42.5 had an approximately 6-fold likelihood of MCID achievement. Patients in the nasal obstruction group and non-smokers demonstrated greater postoperative improvement in the sleep subdomain. Conclusions: Women with PAR and those with a preoperative SNOT-22 score above 42.5 were preferable candidates for surgery and expressed greater satisfaction. Notably, rhinologic presentations and non-rhinologic symptoms of PAR patients could benefit from within one year after surgery. Here, we discuss the factors associated with subjective surgical outcomes to help physicians and patients with AR in preoperative consultations.

Serum High-Sensitivity C-Reactive Protein Is Associated with Postoperative Psychiatric Status in Patients with Empty Nose Syndrome.

Many patients diagnosed with empty nose syndrome (ENS) later develop mental illness. The literature addressing biomarkers associated with postoperative psychiatric status is limited. This study aimed to assess the association between high-sensitivity C-reactive protein (hs-CRP) and psychiatric status after surgery in ENS. We recruited patients with ENS undergoing endonasal submucosal implantation. Their pre- and postoperative psychiatric status was evaluated using the Beck depression inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). Serum hs-CRP was analyzed one day before and one year after surgery. Of the 43 patients enrolled, all subjective measurements had improved (symptom scores decreased) significantly by the third month postoperatively and remained plateaued till 12 months. Those with preoperative hs-CRP levels > 2.02 mg/L were likely to remain depressive 1 year postoperatively. The regression model showed that a preoperative hs-CRP level > 2.02 mg/L was significantly correlated with postoperative depression in patients with ENS (odds ratio, 19.9). Hs-CRP level seems to be a feasible predictor of surgical outcome regarding improved depression in patients with ENS. Patients with higher preoperative hs-CRP levels should be monitored closely after surgery.

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.

The Role of Phadiatop Tests and Total Immunoglobulin E Levels in Screening Aeroallergens: A Hospital-Based Cohort Study.

BACKGROUND: Screening for the existence of aeroallergens in patients with possible allergic rhinitis using venous blood samples has become more popular, with advantages of increased convenience and less consumption of time. OBJECTIVE: The aim of this study was to investigate the sensitivities and specificities of Phadiatop tests and total immunoglobulin E (IgE) levels in both adults and children. METHODS: This study was conducted prospectively in a tertiary center. The process of recruitment took place from Jan 2015 to Dec 2019, and patients with clinical symptoms that suggested persistent allergic rhinitis were recruited and their serum samples collected. The results of the total IgE and Phadiatop tests as well as the positive items in the ImmunoCAP assay were recorded and analyzed. RESULTS: A total of 9174 cases with complete data were enrolled, including 576 children and 8598 adults. A positive result in the ImmunoCAP assay was considered a positive atopic status towards aeroallergens. While using the total IgE levels to predict positive aeroallergens, the sensitivities and specificities were 65.7% and 85.7%, respectively, for adults and 86.3% and 77.4%, respectively, for children. When we used Phadiatop tests for allergy screening, the sensitivities and specificities was 94.5% and 98.2%, respectively, for the adult group and 98.5% and 96.8%, respectively, for the pediatric group. CONCLUSION: The Phadiatop test had better diagnostic power for aeroallergen detection than the serum total IgE levels, or even the dual test, for both the adult and pediatric groups in this hospital-based study. We suggest that the Phadiatop test is more cost-effective in aeroallergen screening for patients with suspected atopic airway diseases.

Removal of Displaced Dental Implants in the Maxillary Sinus Using Endoscopic Approaches.

With the broad indications for dental implantation, complications rates have increased. Dental implant displacement into the maxillary sinus, although rare, can occur during the restoration of maxillary posterior teeth. We performed a 6-year retrospective review and found 3 cases with displaced implants in the maxillary sinus. Detailed information, including surgical indications and dental implant removal methods, is provided. Dental implants can be dislocated to the maxillary sinus perioperatively or postoperatively. Endoscopic sinus surgery can be performed to remove the implant and restore sinus patency. If the implant is displaced to deeper areas (commonly anterior and inferior) of the maxillary sinus, a prelacrimal recess approach can provide a panoramic view of the maxillary sinus and is a good alternative to the Caldwell-Luc operation in terms of mucosal preservation and postoperative complications.