The Role of Fractional Exhaled Nitric Oxide in Diagnosing Asthmatic Type 2 Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. OBJECTIVE: We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma. METHODS: We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund-Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications. RESULTS: FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P < .05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P < .001) and FEV1/FVC (r = -0.324, P = .001). A FeNO level of 27 ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68 ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36 ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%). CONCLUSION: FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment.

Sleep parameter characteristics of patients with OSA who have retropalatal circumferential narrowing and the clinical significance of lateral pharyngeal wall collapse during sleep.

BACKGROUND: The lateral pharyngeal wall (LPW) is a critical anatomic structure in patients with obstructive sleep apnea (OSA). Resolving the retropalatal circumferential (RC) narrowing caused by combination of both LPW collapse and antero-posterior (AP) narrowing holds promise for surgical treatment of OSA. We sought to determine the clinical characteristics and distinctive alterations in sleep parameters of patients with OSA who have RC narrowing and LPW collapse. METHODS: Drug-induced sleep endoscopy (DISE), polysomnography findings, and sleep questionnaires were reviewed retrospectively in patients with OSA. RESULTS: Of the 106 OSA patients examined, 48% showed RC narrowing and 44% showed AP narrowing at the oropharynx level during sleep while 8% of the patients showed only LPW collapse. Patients with RC narrowing with LPW collapse exhibited a higher BMI than those with AP narrowing only. In addition, patients with RC narrowing showed more aggravated sleep parameters including apneic events than patients with AP narrowing alone. The degree of RC narrowing correlated significantly with the severity of OSA as shown by a higher apnea index and lower oxygen desaturations. CONCLUSIONS: Our clinical findings suggest that the presence of RC narrowing with LPW collapse in OSA is closely related to increased apneic and oxygen desaturation events. RC narrowing with LPW collapse may be targets for surgical correction in patients with OSA to improve therapeutic outcomes.

The clinical influence of nasal surgery on PAP compliance and optimal application among OSA subjects uncomfortable with PAP device wear.

This study aimed to evaluate the alteration of PAP compliance after nasal surgery and to determine the optimal indications of nasal surgery in obstructive sleep apnea (OSA) subjects. Among OSA subjects using PAP devices, 29 subjects who underwent septoturbinoplasty due to nasal obstruction were included and their pre- and postoperative medical and PAP records were reviewed retrospectively. Postoperative autoPAP usage data was further assessed by grouping the compliance (the percentage of days with usage ≥ 4 h) data (group 1: the good compliance group; group 2: the poor compliance group). The data showed that 56% of subjects in group 1 complained of nasal obstruction as the only barrier to using a PAP device and about 89% reported experiencing the efficacy of PAP usage. Both the mean and peak average PAP pressures were significantly reduced in group 1 following nasal surgery. Group 2 had multiple subjective problems that interfered with wearing a PAP device and reported a lack of experiencing the efficacy of PAP usage. Preoperative nasal cavity volume values were smaller and absolute blood eosinophil counts were significantly lower in group 1. The current data demonstrate that nasal surgery might increase the compliance of PAP device wear in OSA subjects who complained of only nasal obstruction as a barrier to wearing PAP and who had small nasal cavity volumes combined with allergic inflammation.

Effects of Neutrophil and Eosinophil Extracellular Trap Formation on Refractoriness in Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: This study investigated the clinical implications of neutrophil extracellular trap (NET) formation (NETosis) and eosinophil extracellular trap (EET) formation (EETosis) regarding refractoriness in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). METHODS: Nasal polyp specimens were obtained from 117 patients with CRSwNP who received endoscopic sinus surgery. Disease control status at postoperative 1 year was assessed. Refractory cases were defined as partly controlled or uncontrolled cases according to the EPOS 2020 guidelines. NETosis and EETosis were evaluated through immunofluorescence staining (citrullinated histone H3-human neutrophil elastase and citrullinated histone-galectin-10, respectively) followed by manual counting. The z-score of NET and EET counts was used to define the following four groups: low extracellular trap formation (ETosis), NETosis-predominant, EETosis-predominant, and high-ETosis. RESULTS: The refractory and non-refractory groups showed significant differences in the tissue eosinophil count (P = 0.005) and EET count (P = 0.029). The tissue neutrophil count and the NET/neutrophil ratio were significantly different between the refractory and non-refractory groups of patients with neutrophilic CRS (P = 0.045, 0.031, respectively). Refractoriness significantly differed among the low-ETosis (30.77%), NETosis-predominant (47.83%), EETosis-predominant (56.67%), and high-ETosis (83.33%) groups (P = 0.005). CONCLUSIONS: The results of this study suggest that tissue Eosinophilia and EETosis may play a prognostic role, primarily in CRSwNP and thattissue neutrophilia and NETosis can play as prognostic biomarkers in neutrophilic CRSwNP.

Intranasal inoculation of IFN-λ resolves SARS-CoV-2 lung infection via the rapid reduction of viral burden and improvement of tissue damage.

Introduction: The innate immune responses of upper airway could further our understanding toward antiviral strategies against SARS-CoV-2. We characterize the potential of interferon (IFN)-λ as an innate immune inducer for the rapid clearance of SARS-CoV-2 in the lung and the therapeutic efficacy of intranasal inoculation of IFN-λ to resolve acute lung infection. Methods: Syrian golden hamsters were infected with SARS-CoV-2 and the dynamics of SARS-CoV-2 infection depending on IFN-λ inoculation were tested. Results: SARS-CoV-2-infected Syrian golden hamsters exhibited a significant decrease in body weight and high viral mRNA level at 3 days post-infection (dpi). Although viral replication was reduced completely from 7 dpi, the pathologic findings remained prominent until 14 dpi in the lung of hamsters. The transcription of IFN-λ was significantly induced in response to SARS-CoV-2 infection with the increase of IFN-stimulated genes. Intranasal inoculation of IFN-λ restricted SARS-CoV-2 replication in the lungs of infected completely from 3 dpi with markedly reduction of inflammatory cytokines. The transcriptional phenotypes were altered to the direction of damage repair and tissue remodeling in the lungs of SARS-CoV-2-infected hamsters following intranasal inoculation of IFN-λ, which improved SARS-CoV-2-caused lung damage. Conclusion: Collectively, our findings suggest that IFN-λ might be a potent innate immune inducer in the lung and intranasal inoculation of IFN-λ resolves SARS-CoV-2 infection with rapid viral clearance and improvement of lung damage.

Impact of the COVID-19 and Socioeconomic Status on Access to Care for Otorhinolaryngology Patients.

Since December 2019, COVID-19 has greatly influenced public healthcare systems around the globe in various aspects, including limitation of healthcare accessibility due to lack of both human and financial resources, suspension of clinics, and fear of infection causing healthcare avoidance. The aim of this study was to investigate the impact of COVID-19 on access to healthcare for otorhinolaryngology patients from different socioeconomic status (SES) groups. Otorhinolaryngology patients' disease severity status, diagnosed at the first hospital visit, was investigated during the pre -and post-COVID-19 pandemic era in a single medical center located in Seoul, Korea. An ordinal regression model was used to assess the impact of both SES and the COVID-19 pandemic on otorhinolaryngology diseases. Within the chronic rhinosinusitis group, lower SES was associated with a higher disease severity at the first visit compared to higher SES (OR = 3.25). During the COVID-19 pandemic, while the total number of outpatients was reduced, the severity of these ENT diseases seemed to increase compared to the pre-pandemic severity in every SES group. Our study demonstrates the negative impact a worldwide pandemic can have on healthcare inequity and disease severity, and highlights the importance of re-allocating fundamental resources for those in need during periods of public health crisis.

Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-co-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity.

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects.

Optimal application of soft-palate webbing flap pharyngoplasty combined with nasal surgery for surgical treatment of primary snoring and obstructive sleep apnea.

BACKGROUND: Excessive collapse of the soft palate and lateral pharyngeal wall narrowing are established causes of loud snoring and sleep apnea in subjects with obstructive sleep apnea (OSA). Therefore, delicate surgical techniques are needed to reshape the soft palate and create sufficient tension in the lateral pharyngeal wall. This study aimed to determine the therapeutic outcome and favorable indications of soft-palate webbing flap pharyngoplasty in subjects with OSA and primary snoring. METHODS: A total of 174 subjects who underwent soft-palate webbing flap pharyngoplasty combined with uvulopalatal flap and septoturbinoplasty from August 2015 to February 2020 were included in this study. Medical records, including pre- and postoperative sleep parameters, were retrospectively reviewed. The primary outcome measure was the degree of improvement in AHI after surgery. Other outcomes were differences in surgical response rates, subjective visual analog score (VAS) for snoring, sleep quality, and complications. RESULTS: Polysomnographic results showed that apnea-hypopnea index (AHI) scores were significantly reduced from 39.6 ± 6.1 to 22.9 ± 3.6 following soft-palate webbing flap pharyngoplasty in 59 subjects, and overall success and response rates of this technique were analyzed with 71%. We found that the successful outcomes were observed in 50% of mild (n = 12) and 56% of moderate (n = 16) subjects with OSA subjects due to lateral pharyngeal wall collapse. The success rate of soft-palate webbing flap pharyngoplasty was relatively higher in subjects with mild and moderate OSA than those with severe OSA. Additionally, the mean VAS snoring scale was 4.7 and subjects' primary snoring intensity significantly improved to 2.9 after soft-palate webbing flap pharyngoplasty. Subjective symptoms such as daytime sleepiness and sleep quality also showed improvement. Most complications were found to be minimal and improved by 1 month after the operation. CONCLUSION: Our data demonstrate that soft-palate webbing flap pharyngoplasty is an effective treatment for OSA and primary snoring and may be a promising technique to reduce lateral pharyngeal wall collapse.

Endotype-related recurrence pattern of chronic rhinosinusitis in revision functional endoscopic sinus surgery.

OBJECTIVE: The recurrence of chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS) is influenced by various factors, potentially including the endotype based on the molecular pathophysiology of CRS. This study investigated differences in the recurrence pattern of CRS by endotype after primary FESS. METHODS: This retrospective study enrolled patients who had undergone revision FESS for recurrent CRS. Based on their clinical diagnosis, the patients were divided into two endotype groups: recurrent eosinophilic CRS (rECRS) and recurrent non-eosinophilic CRS (rNECRS). We compared and analyzed preoperative computed tomography (CT) findings, including typical anatomical findings of recurred CRS such as lateralized middle turbinate and retained uncinate process, the sinus where recurrence took place, and previous surgical completeness of the sinuses, between the rECRS and rNECRS groups. RESULTS: In total, 142 patients were enrolled (48 rECRS, 94 rNECRS). No significant difference was found in the typical anatomic findings of recurrent CRS between the rECRS and rNECRS groups. The rates of the completeness of previous surgeries was significantly higher in rECRS than in rNECRS(P=.031). Despite the completeness of previous surgeries, the recurrence rate of frontal and ethmoidal sinuses was higher in the rECRS than rNECRS(P=.012, P<.001, respectively). In subgroup analysis according to the severity of ECRS, the number of involved sinuses and the rates of CRS recurrence and surgical completeness in frontal and anterior ethmoidal sinuses increased with ECRS severity. CONCLUSIONS: CT findings of revision FESS cases differed by CRS endotype. The rECRS group showed higher recurrence in the frontal and ethmoidal sinuses despite a higher surgical completeness rate. Incomplete surgery was more often found in the rNECRS group.

Feasibility of Surgical Treatment for Laryngomalacia Using the Spontaneous Respiration Technique.

OBJECTIVES: In this study, we review our institutional experience with pediatric laryngomalacia (LM) and report our experiences of patients undergoing supraglottoplasty using the spontaneous respiration using intravenous anesthesia and high-flow nasal oxygen (STRIVE Hi) technique. METHODS: The medical records of 29 children with LM who visited Seoul National University Hospital between January 2017 and March 2019 were retrospectively reviewed. Surgical management was performed using the STRIVE Hi technique. Intraoperative findings and postoperative surgical outcomes, including complications and changes in symptoms and weight, were analyzed. RESULTS: Of the total study population of 29 subjects, 20 (68.9%) were female. The patients were divided according to the Onley classification as follows: type I (n=13, 44.8%), II (n=10, 34.5%), and III (n=6, 20.7%). Twenty-five patients (86.2%) had comorbidities. Seventeen patients (58.6%) underwent microlaryngobronchoscopy under STRIVE Hi anesthesia. Four patients with several desaturation events required rescue oxygenation by intermittent intubation and mask bagging during the STRIVE Hi technique. However, the procedure was completed in all patients without any severe adverse effects. Overall, 15 children (51.7%) underwent supraglottoplasty, of whom 14 (93.3%) showed symptom improvement, and their postoperative weight percentile significantly increased (P=0.026). One patient required tracheostomy immediately after supraglottoplasty due to associated neurological disease. CONCLUSION: The STRIVE Hi technique is feasible for supraglottoplasty in LM patients, while type III LM patients with micrognathia or glossoptosis may have a higher risk of requiring rescue oxygenation during the STRIVE Hi technique.

Clinical Characteristics Other Than Intralesional Hyperdensity May Increase the Preoperative Diagnostic Accuracy of Maxillary Sinus Fungal Ball.

OBJECTIVES: This study aimed to evaluate the clinical characteristics of maxillary sinus fungus ball (MFB) to increase the preoperative diagnostic accuracy. METHODS: A retrospective review of 247 patients who underwent endoscopic sinus surgery for unilateral maxillary sinusitis from January 2015 to December 2017 at a single institution was performed. Patients with pathologically proven MFB were compared to those with unilateral chronic maxillary sinusitis (CMS). Patient demographics and computed tomography (CT) findings were evaluated. The CT features were categorized as intralesional hyperdensity (calcification), the irregular lobulated protruding lesion (fuzzy appearance), maxillary sinus full haziness without mass effect, maxillary sinus full haziness with mass effect, and others. A regression tree analysis was performed. RESULTS: In total, 247 patients were analyzed; among them, 179 (72.5%) had MFB and 68 (27.5%) had CMS. MFB showed predominance in older individuals. Among the radiological features, intralesional hyperdensity was most commonly associated with MFB. The presence of a fuzzy appearance or full opacity with mass effect was also associated with MFB. The highest area under the curve was noted with the regression tree analysis based on the model, which included the presence of intralesional hyperdensity, demographic data (age), and presence of fuzzy appearance or maxillary sinus full haziness with mass effect in case of absence of intralesional hyperdensity (0.904). CONCLUSION: A simple algorithm to optimize the preoperative diagnosis of MFB was developed. Physicians should be aware of such findings in the management of patients presenting with unilateral CMS.

Direct look from a predator shortens the risk-assessment time by prey.

Decision making process is an important component of information use by animals and has already been studied in natural situations. Decision making takes time, which is expressed as a cost in evolutionary explanations of decision making abilities of animals. However, the duration of information assessment and decision making process has not been measured in a natural situation. Here, we use responses of wild magpies (Pica pica) to predictably approaching humans to demonstrate that, regardless of whether the bird perceived high (decided to fly away) or low (resumed foraging) threat level, the bird assessed the situation faster when approaching humans looked directly at it than when the humans were not directly looking at it. This indicates that prey is able to extract more information about the predator's intentions and to respond sooner when the predator is continuously ("intently") looking at the prey. The results generally illustrate how an increase of information available to an individual leads to a shorter assessment and decision making process, confirming one of central tenets of psychology of information use in a wild bird species in its natural habitat.