Sinusitis Research Articles

A real-world study to evaluate effectiveness of mepolizumab in treating severe asthma in Taiwan (REMIT).

REMIT is the first real-world study of mepolizumab effectiveness in patients with severe asthma (SA) in Taiwan. The primary objective evaluated changes in clinically significant exacerbations (CSEs; defined as use of oral corticosteroids (OCS) or emergency department (ED) visits and/or hospitalizations) in the 12 months pre- and post-mepolizumab treatment. Secondary objectives assessed changes in the number of CSEs requiring ED visits/hospitalizations and daily maintenance OCS (mOCS) dosage 12 months pre- and post-mepolizumab treatment. Three- and four-component clinical remissions were analyzed based on OCS-free, exacerbation-free, and asthma control (± stability in lung function). REMIT was a retrospective, observational, self-controlled study analyzing patients in Taiwan with SA who were newly prescribed subcutaneous mepolizumab 100 mg Q4W. Data were extracted from records of 15 medical centers in Taiwan for patients indexed between November 1, 2018 and October 31, 2020. A total of 170 patients were included: mean age at index date, 58.7 years; 53.5% female; 100% Chinese; 7.1% with chronic rhinosinusitis with nasal polyps, 1.8% with eosinophilic granulomatosis with polyangiitis, 1.2% with hypereosinophilic syndrome; and 55.7% with blood eosinophil count >300/µL. Pre-treatment, 71.2% had ⩾2 exacerbations, and 28.7% were on mOCS; 75.3% had no prior biologic treatment, and 24.7% had switched from other biologics. Most patients (80.0%) completed ⩾10 mepolizumab doses. Following the first mepolizumab administration (index date), CSEs reduced by 46.0% (rate ratio (RR): 0.545, 95% confidence interval (CI): 0.418-0.710; p < 0.0001) in the 12 months post-index. Exacerbations requiring ED visits/hospitalization reduced by 46.9% (RR: 0.531, 95% CI: 0.349-0.808; p = 0.0031). Median mOCS dose reduced by 100% by end of study and 81.8% of patients discontinued mOCS post-treatment. After 1 year of mepolizumab treatment, 28% and 23% patients achieved three- and four-component clinical remission, respectively. Mepolizumab use in a patient population in Taiwan with SA significantly reduced CSEs and mOCS use in routine clinical practice.

Ventilation tube (grommet) insertion in adult patients with stage III tympanic membrane atelectasis: A case report

Background: Effusion Otitis Media (OME) is a condition where there is an accumulation of fluid in the middle ear without signs of acute infection which can cause hearing loss and complications such as atelectasis. Even though it occurs more often in children, it does not rule out the possibility that OME can occur in adults, although it is less common, OME in adults can cause complaints such as decreased hearing, discomfort or a feeling of fullness in the ears. Management of OME includes conservative treatment with antibiotics, decongestants or topical corticosteroids as well as medic procedures such as installing grommet tubes as well as identifying underlying causative factors such as sinus infections or eustachian outflow disorders. Objective: To report a case of ventilation tube (grommet) insertion in adult patients with stage III tympanic membrane atelectasis Case Report: A 27 year old woman came with complaints of bilateral hearing loss, complaints accompanied by a feeling of fullness in the ears and tinnitus, especially in the left ear. From the results of the otoscopic examination, it was found that the tympanic membrane was retracted and tympanometry showed type B on both ears. Surgical procedure was then carried out for the installation of a ventilation pipe (grommet). Clinical question: How is the management of and adult patients with stage III tympanic membrane atelectasis with ventilation tube (grommet) insertion? Methods: Evidence-based literature study of ventilation tube (grommet) insertion in adult patients with stage III tympanic membrane atelectasis. Result: Grommet tube placement improved hearing in the left ear, with audiometry showing a reduction in hearing threshold from 42 dB to 37 dB. Conclusion: Installation of ventilation tubes (grommets) in adult patients with stage III tympanic membrane atelectasis has proven effective in reducing symptoms such as decreased hearing and a feeling of fullness in the ear and can prevent long-term complications. Grommet tube placement is an effective management option for adult patients with stage III tympanic membrane atelectasis who do not respond to conservative therapy.

Xylometazoline-induced change in aspirated nasal nitric oxide detects obstructed paranasal ostia

The concentrations of nasal nitric oxide (nNO) vary in patients with chronic rhinosinusitis (CRS) supposedly depending upon whether the paranasal ostia are open or obstructed. Our aim was to assess whether nNO levels and their response to topical xylometazoline (a local vasoconstrictor used to alleviate nasal congestion) in patients with CRS differ between those with open or obstructed ostia and if the results were altered by the use of nasal corticosteroids. Sixty-six patients with CRS (43% with nasal polyps) or recurrent acute rhinosinusitis and 23 healthy controls were included. Nasal NO was measured (EcoMedics CLD 88p analyser) before and after two xylometazoline sprays during three consecutive visits: with the medication they were using when they were referred, after 4 weeks of medication pause, and after 4 weeks of using intranasal fluticasone propionate. The relative difference between the nNO before and after dosing of xylometazoline was calculated, and ostial obstruction was evaluated with cone-beam computed tomography at every visit. The nNO measurements were lowest in the patients with CRS and obstructed paranasal ostia. The presence or absence of nasal polyps did not affect the results. Xylometazoline did not significantly affect nNO in the subjects with obstructed ostia, but there was a significant reduction of nNO in those with open ostia. The Xylometazoline-induced change in nNO between the groups with open or obstructed ostia was significantly different at each visit: 'on previous medication' 10% (-5-25) versus -14% (-19 to -9),p= 0.004, 'after medication pause' 6% (-5-17) versus -16% (-23 to -9),p= 0.001 and 'after regular fluticasone spray' 6% (-3-15) versus -9% (-16 to -3),p= 0.04. The native nNO and xylometazoline-induced change in nNO can be used to detect the status of ostial obstruction in patients with CRS irrespective of their topical corticosteroid usage.

Fungal infection among patients with chronic rhinosinusitis who underwent endoscopic sinus surgery

Background: Chronic rhinosinusitis (CRS) involves persistent inflammation of the nasal passages and sinuses, often attributed to Aspergillus species as a primary etiological agent. Effective treatment involves complete eradication of fungal pathogens and restoration of sinus function, commonly achieved through functional endoscopic sinus surgery (FESS). This study aimed to evaluate the clinical and radiological features, assess the prevalence and identify the mycological profile of fungal rhinosinusitis. Methods: This study was a prospective observational analysis involving a cohort of 50 patients treated at the Tirunelveli Medical College between June 2017 and July 2017. Nasal sinus tissues and secretions were collected for mycological and bacteriological analysis. Samples were processed on the same day, with fungal elements identified via KOH mount and cultured on Sabouraud dextrose agar. Bacterial cultures were grown on MacConkey agar and species identification was performed using biochemical tests. Results: Fungal culture results showed that 72% of the patients had a negative culture, while 28% had a positive culture. Among the 50 patients, 36 did not have diabetes or hypertension. All sinuses were involved in 40 patients and 24 had nasal polyps, with bilateral polyps being the most common. The most frequently isolated fungal species was Aspergillus. KOH positivity was strongly correlated with culture positivity, with 9 out of 10 KOH-positive patients also being culture-positive, while KOH negativity was associated with culture negativity in 35 out of 36 patients. Conclusions: CRS significantly affects quality of life, with fungal infections being a notable cause, especially in patients with unilateral sinus involvement. Effective treatment requires endoscopic sinus surgery, followed by antifungal therapy.

Alleviating symptoms of paediatric acute rhinosinusitis and acute otitis media with otorrhea using nasal-spraying Bacillus probiotics: a randomized controlled trial

Acute rhinosinusitis (ARS) in children may be accompanied by acute otitis media (AOM) which is often associated with bacterial co-infections. These conditions are among the primary reasons that children visit hospitals and require antibiotic treatment. This study evaluated the efficacy of the nasal-spraying probiotics (LiveSpo Navax containing 5 billion Bacillus subtilis and B. clausii spores/5 mL) as a supportive treatment for dual ARS and AOM with otorrhea in a randomized, single-blind, controlled clinical trial. Eighty-two patients (41 per group), aged 1 month to 12 years, received standard care along with nasal spraying of either physiological saline (Control group) or LiveSpo Navax (Navax group), administered three times daily over a 7-day follow-up period. A total of sixty-one patients (30–31 per group) completed the trial. The Navax group experienced 68.00% and 96.77% reductions in nasal congestion (by day 3) and rhinorrhea (by day 7), respectively, which were 2.04 and 1.94-fold higher than the Control group, with odds ratios (OR) of 4.31 and 30.00 (p < 0.05). Endoscopic results indicated 8% and 11% higher reductions in nasal mucopurulent discharge and tympanic membrane hyperemia in the Navax group compared to the Control group. By day 3, compared to day 0, the Navax group exhibited > 1200-fold reduction in Streptococcus pneumoniae and ≥ 4-fold reduction in Haemophilus influenzae concentrations (p < 0.05) in both nasopharyngeal and middle ear fluid samples, whereas the Control group showed no significant reductions. Navax treatment reduced IL-6 by 1.35- to 1.74-fold and TNF-α by 1.17- to 1.45-fold, more effectively than the Control group (p < 0.05). These results suggest that nasal-spray Bacillus spore probiotics, with their ability to reduce bacterial load and modulate immune responses, provide a cost-effective and safe solution for alleviating symptoms of both ARS and AOM in children.Trial registration: ClinicalTrials.gov, Identifier NCT05804123 on April 7, 2023.

HMOX1 as a potential drug target for upper and lower airway diseases: insights from multi-omics analysis

Background Oxidative stress is key in inflammatory airway diseases. Heme oxygenase 1 (HMOX1) regulates oxidative stress, but its role in airway diseases needs exploration.MethodsDifferentially expressed genes (DEGs) between healthy nasal mucosa and chronic rhinosinusitis with nasal polyps (CRSwNP) were identified from Gene Expression Omnibus (GEO). Candidate genes were further screened using Gene Set Enrichment Analysis (GSEA) and Random Forest (RF) algorithms. Causal inference between candidate genes and upper and lower airway diseases (CRSwNP, allergic rhinitis (AR), and asthma (AS)) was conducted using bidirectional two-sample Mendelian randomization (TwoSampleMR) analysis. Single-cell RNA sequencing (scRNA-seq) data were used to determine the cellular localization and intercellular interactions of candidate genes. Molecular docking was used to identify potential therapeutic agents.ResultsHMOX1 expression was significantly elevated in CRSwNP. TwoSampleMR analysis indicated a negative causal relationship between HMOX1 exposure and the occurrence of upper and lower airway diseases (CRSwNP [(odds ratio (OR)/95% confidence interval (CI): 0.945/(0.893–0.999), P = 0.044], AR [OR/95% CI: 0.997/(0.994–0.999), P = 0.007], and AS [OR/95% CI: 0.935/(0.895–0.977), P = 0.003]). scRNA-seq data revealed HMOX1 localization in M2 macrophages. Molecular docking identified 15 antioxidants, including Acetylcysteine and Quercetin, that can upregulate HMOX1 expression.ConclusionHMOX1 may have a protective role in the pathogenesis of upper and lower airway diseases (CRSwNP, AR, and AS) by modulating oxidative stress. Antioxidants that increase HMOX1 expression could offer new therapeutic avenues for these diseases.Clinical trialNot applicable.

Orbital emphysema and medial orbital wall fracture after nose-blowing: a case report and review of literature

Nose-blowing is commonly known as the harmless act of expelling nasal mucus by exhaling forcefully through the nose. We report a case of orbital emphysema in a 49-year-old female patient, who suffered from fractures of the medial orbital wall after forcefully blowing her nose. The patient presented to our emergency department with acute right sided periorbital swelling and pain as well as an unremarkable endoscopic examination of the nose. Prior to the event, a common cold with signs of acute sinusitis had been reported. A trauma to the eye was credibly denied, which is consistent with the medical imaging pattern. A CT-scan confirmed the diagnosis and showed air trapped into the orbit as well as multiple fractures of the lamina papyracea with displaced bone fragments. Visual acuity and extraocular muscle motility were intact. The patient was treated conservatively with prophylactic antibiotics and was instructed not to blow her nose. Follow-up examination after seven days showed a complete remission.

Exploring the Link Between Resilience and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly affects patients' quality of life, impacting both physical and psychological well-being. This study investigated the potential role of resilience in coping with CRSwNP and its relationship to disease severity and cellular proliferation. Methodology Between July 1, 2021, and June 30, 2022, 30 patients diagnosed with CRSwNP were enrolled in a study at Cardiomed Hospital in Cluj-Napoca, Romania. Resilience was assessed using the Connor-Davidson Resilience Scale (CD-RISC), while disease severity was evaluated through patient-reported outcomes (Sino-Nasal Outcome Test (SNOT-22)) and objective measures (Lund-Mackay score). Ki-67 expression was analyzed as a marker of cellular proliferation within nasal polyps. Results No significant correlation was observed between resilience and either SNOT-22 scores or Ki-67 expression. However, a strong positive correlation was found between SNOT-22 scores and Lund-Mackay scores, indicating that patients with more severe symptoms also exhibited greater objective disease burden. In addition, a moderate positive correlation was identified between Ki-67 expression and Lund-Mackay scores, suggesting a potential link between cellular proliferation and disease severity. Conclusion These findings suggest that resilience may not directly influence symptom severity or cellular proliferation in CRSwNP. Further research with larger sample sizes and longitudinal designs is needed to elucidate the complex interplay between resilience, disease pathophysiology, and patient outcomes in CRSwNP. This will ultimately inform the development of more targeted and effective interventions to improve the quality of life for individuals with this chronic condition.

Lipopolysaccharide Causes Acquired CFTR Dysfunction in Murine Nasal Airways.

Cystic fibrosis (CF) is a clinical entity defined by aberrant chloride (Cl-) ion transport causing downstream effects on mucociliary clearance (MCC) in sinonasal epithelia. Inducible deficiencies in transepithelial Cl- transport via CF transmembrane conductance regulator (CFTR) has been theorized to be a driving process in recalcitrant chronic rhinosinusitis (CRS) in patients without CF. We have previously identified that brief exposures to bacterial lipopolysaccharide (LPS) in mammalian cells induces an acquired dysfunction of CFTR in vitro and in vivo. The objective of the current study is to evaluate whether LPS generates a model of acquired CFTR dysfunction murine nasal airways. Basic science. Laboratory. CFTR+/+ murine nasal airways were irrigated with 2 µg/mL LPS or control vehicle twice daily for 1 week and transepithelial Cl- transport assessed with the nasal potential difference (NPD) assay. Histopathologic evaluation included the number of lymphoid aggregates, as well as the epithelial and subepithelial heights. Transepithelial Cl- secretion by NPD was markedly reduced in mice exposed to LPS (in mV, -0.14 ± 7.7 vs control, -6.98 ± 7.15, P < .05), while amiloride-sensitive voltage was preserved (6.38 ± 5.09 vs control, 7.36 ± 2.87, P = .99). Histopathology demonstrated significantly higher lymphoid aggregates per high-power field (2.3 ± 0.9 vs 1.1 ± 0.7, control, P < .01) and increased epithelial height (in µm, 40.88 ± 13.9 vs control, 25.32 ± 6.26, P < .05). Twice daily irrigation with LPS in murine nasal airways over 1 week led to acquired defects in transepithelial Cl- transport. This animal model provides an excellent means to test the contributions of acquired CFTR dysfunction to CRS and test CFTR correctors and potentiators that might improve MCC.

SLAMF8 Disrupts Epithelial Barrier in Chronic Rhinosinusitis with Nasal Polyps via M1 Macrophage Polarization.

Recent studies show that M1 macrophages accumulate predominantly in non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP). However, the precise mechanisms regulating M1 macrophages and their impact on the epithelial barrier remain unclear. We aim to investigate the expression and regulatory role of SLAMF8, a molecule exclusively expressed in myeloid cells, in M1 macrophage polarization and its potential contribution to neCRSwNP development. We evaluated SLAMF8 expression and its correlation with clinical variables using real-time quantitative polymerase chain reaction and Western blot in sinonasal mucosa samples from CRSwNP and control subjects. Immunofluorescence staining confirmed the co-expression of SLAMF8 with macrophages. After SLAMF8 knockdown, we explored the influence on macrophage M1 polarization and the effect on epithelial-mesenchymal transition (EMT) process and tight junction integrity in epithelial cells through an indirect co-culture system of M1 macrophages with human nasal epithelial cells. SLAMF8 was highly expressed on M1 macrophages in polyp tissues, notably in neCRSwNP, and correlated with disease severity indices only in neCRSwNP. SLAMF8 knockdown in THP-1 cells reduced M1 macrophage markers (CD86, iNOS, and NLRP3) and decreased secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Co-culture with M1 macrophage supernatant after SLAMF8 knockdown enhanced epithelial viability, reduced EMT and apoptosis, and upregulated tight junction markers Occludin and Claudin-4 in nasal epithelial cells. SLAMF8 elevation correlates with the EMT, epithelial tight junction and disease severity in neCRSwNP. The SLAMF8 upregulation promotes M1 macrophage polarization, by which facilitates EMT and impairs nasal epithelial barrier function. SLAMF8 may represent a novel therapeutic target for neCRSwNP.

Migraine diagnosis in patients with sinus headache symptoms: a cross-sectional study at Khartoum ENT Hospital

BackgroundSinus headache is the most common diagnosis reported by patients with migraine who received a non-migraine diagnosis. Thus, the aim of this study was to determine the prevalence of migraine among patients present with sinus headache to Khartoum ENT Hospital.ObjectiveTo study the prevalence of migraine (using IHS criteria) among patients present with sinus headache at Khartoum ENT Hospital.MethodsThis is a cross-sectional hospital-based study conducted at Khartoum ENT Hospital in the period between July 2022 to February 2023 including all patients with self-reported or physician diagnosed “sinus headache”, without a suspected secondary cause of headache. Diagnosis of migraine was made using the IHS criteria.Data was collected by the researcher, entered and analyzed using SPSS.ResultsThis study included 197 patients with a mean age of 33 ± 10 years, and female predominance 129 (65. 5%). The most common presentation was nasal blockage 178 (90.4%), flowed by facial pain 87 (44.7%), and nasal discharge 42 (21.3%). Autonomic symptoms included lacrimation 71 (36%), conjunctival injection 20 (10%), and eyelid edema 6 (3%), and 26 (13%) had positive family history of migraine. The prevalence of migraine was 67 (34%); 40 (20%) without aura and 27 (14%) with aura. Migraine was significantly associated with autonomic symptoms, and family history of migraine, and poor response to NSAIDs and nasal sprays compared to non-migraine headache (P-value < 0.05).ConclusionMigraine is not uncommon as 34% of patients with self-reported or physician diagnosed sinus headache meet the International Headache Society (IHS) criteria of Migraine. Migraine was associated with autonomic symptoms and a positive family history of migraine. The presence of good response among those who used antimigraine medications may aid the diagnosis of migraine.

Efficacy and Safety of Dupilumab Across Different Th2-Type-Mediated Diseases: A Real-Life Preliminary Experience

Background: Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4/IL-13 pathway, is able to dampen T helper (Th)2-mediated inflammation in several conditions characterized by this particular type of phlogosis. The aim of this study was to review the efficacy and safety of dupilumab treatment in conditions underpinned by Th2-type inflammation in a cohort of real-world patients referred to our outpatient clinic. Methods: Data from all patients with atopic dermatitis, chronic rhinosinusitis with nasal polyps, asthma, and other Th2-type-mediated inflammatory conditions treated with dupilumab were retrospectively reviewed. Results: Twenty-two patients were included in the study: 14 with atopic dermatitis, 5 with chronic rhinosinusitis with nasal polyps, 2 with asthma, and 1 with prurigo nodularis; some of the patients had more than one atopic condition. A complete response was observed in 13 out of 22 patients (59.1%); when partial responses were included in the analysis, the overall response rate was 86.4%. No adverse events were recorded, either locally or systemically. Total IgE levels dropped in all patients, in some cases reaching values close to those typically observed in nonatopic subjects. When eosinophilia was present at baseline, this also normalized during dupilumab treatment. Conclusions: Dupilumab was safe and effective across multiple conditions driven by Th2-type chronic inflammation; effective interference with the Th2-type pathway was inferred by the progressive reduction in serum total IgE levels, which reached the normal range in a fraction of patients, and by the reduction in peripheral blood eosinophil counts. Further studies in different Th2-mediated diseases are warranted.

P0516 Chronic Rhinosinusitis and Inflammatory Bowel Disease: discovering the gut-lung axis- preliminary results from a single-center pilot study

Abstract Background Inflammatory Bowel Diseases (IBD) are multifactorial and debilitating diseases that significantly impact patients’ quality of life. As it is known, they involve an altered immune system. For this reason, patients with IBD have an increased risk of developing other chronic immune disorders, including chronic rhinosinusitis (CRS). The coexistence of these two conditions can undoubtedly affect patients’ life and disease history. This study aims to define the prevalence of CRS in IBD patients and assess how it affects their quality of life. Methods We conducted a prospective, observational, monocentric pilot study. in which we enrolled consecutive IBD under biological therapy. We collected clinical, demographic, and disease history data. Four questionnaires were administered to the patients: the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), EuroQol 5 Dimension 5 Level (EQ-5D-5L), the Short-Form- 36 (SF-36), and the SNOT-22 questionnaire to identify subjective symptoms of CRS. According to the SNOT-22 score, patients were divided into two groups: patients without/mild CRS (group 1, SNOT-22 &amp;lt;30 points) and patients with moderate/severe CRS (group 2, SNOT-22&amp;gt;30 points). Results We enrolled 50 IBD patients, of which 48% were affected by ulcerative colitis (UC) and 52% were affected by Crohn’s Disease (CD). Among them, 42% (n=21) of patients were naive to biological therapy, while 48% had failed at least two lines of biological therapy. We observed no statistically significant differences in the mean values of the score of SNOT-22 between naive and multi-failure patients (30.1 and 28.5, respectively, p=0.76). Dividing patients based on the SNOT-22 score, 42% were part of group 1 (absent or mild CRS), and 58% were part of group 2 (moderate/severe CRS).CD patients of group 2 had a significantly higher disease activity, defined according to the Harvey-Bradshaw Index (HBI), compared to group 1 (mean value of 2.3 vs 0.48, p=0.008).We did not observe statistically significant differences in Full Mayo Score between group 1 and group 2 UC patients. The median VAS EQ-5D-5L was compared between Groups 1 and 2 showing a lower score in patients with moderate/severe CRS (66.6 vs. 81.3, p = 0.0019). Conclusion CRS is frequent in IBD patients. Those with both conditions have reduced quality of life, more severe symptoms, and worse disease characteristics than those without CRS. Level of some cytokines can induce alterations of gastrointestinal motility in gastrointestinal disorders, due to increased intestinal barrier damage. However, our findings are preliminary, and further studies, clinical evaluations, and specialized laboratory investigations are needed to better understand the gut-lung axis.

Real-world effectiveness of mepolizumab in Japanese asthma patients with diverse backgrounds: Improvements in rhinosinusitis imaging (J-Real-Mepo).

Although randomized controlled trials (RCT) have demonstrated the efficacy of mepolizumab for asthma, they have excluded certain patient subgroups. To bridge the gap between RCT and real-world practice, the effectiveness of mepolizumab in a diverse population, including those potentially excluded from RCT, was assessed. Its effects on imaging findings and symptoms of chronic rhinosinusitis (CRS) with asthma were also assessed. This retrospective observational study of patients in Japan (J-Real-Mepo: UMIN000045021) evaluated multiple endpoints and analyzed the relationship between clinical background and treatment outcomes. Mepolizumab significantly reduced exacerbations, improved Asthma Control Test (ACT) scores, and forced expiratory volume in 1s, and reduced oral corticosteroid (OCS) dose, regardless of patient characteristics, including age, body mass index, smoking history, and comorbidities. Regarding RCT exclusion criteria, 29.4% of patients had no history of exacerbations. Although 25.4% of these patients required continuous OCS, the OCS dose was reduced similar to those with a history of exacerbations. Disease control and mepolizumab effectiveness in patients with a smoking history ≥10 pack-years was similar to that of never-smokers. Patients with eosinophil counts <150/μL had lower ACT scores and higher OCS use compared with patients with eosinophilia and comparable effectiveness regarding exacerbation and OCS reduction. Significant improvements in Lund-Mackay scores and CRS symptoms were observed. Mepolizumab effectiveness was demonstrated in a broad range of patients including those with RCT exclusion criteria, who had significant disease or OCS burden. These findings may explain the consistent results between RCT and real-world studies of mepolizumab.

ORL : what's new in 2024

This article highlights recent advancements in otorhinolaryngology. It reviews innovations in managing sudden sensory-neural hearing loss through low-dose glucocorticoid treatments and explores pediatric audiology breakthroughs, particularly gene therapy for DFNB9 deafness. In speech pathology and oncology, a new minimally invasive robotic surgical approach enhances organ preservation for head and neck cancers. Rhinology advancements include biological therapies for chronic rhinosinusitis with polyps. Together, these developments expand therapeutic options, significantly improving patient quality of life in the ORL field.

Diversity and Evolution of the Mobilome Associated with Antibiotic Resistance Genes in Streptococcus anginosus.

Streptococcus anginosus is an important cause of pyogenic infections, bacteremia, and chronic maxillary sinusitis. Mobile genetic elements (MGEs) play a key role in lateral gene transfer, resulting in broad transfer of antibiotic resistance genes (ARGs). However, studies on ARG-associated MGEs in S. anginosus are still rare. To fill this gap, we used sequencing data from 11 clinical S. anginosus to characterize their mobilome diversity through comparative analysis. We found 47 well-characterized MGEs, including 23 putative integrative and conjugative elements (ICEs), 16 prophages/integrative mobilizable elements, and 8 composites. They were inserted into 16 positions, 4 of which were hot spots. A comprehensive analysis revealed that ARG-associated ICEs belong to four groups as follows: single serine integrases (ICESan49.2), tyrosine integrases (ICESan26.2), triple serine integrase ICEs (ICESan195.1), and a putative transposon integrase (ICESan49.1), all of which were similar to ICEs/transposons widely distributed among other streptococci. The eight composites were composed of multiple ICEs or transposons through successive accretion events (tandem or/and internal integration). In conclusion, we found that S. anginosus accumulates a variety of ARG-associated ICE/composites that may enable S. anginosus to serve as an ARG-associated MGE repository for other streptococci. The analysis of composites here provides a paradigm to further study mobilome evolution.

Variations in Ciliary Beat Frequency Based on Chronic Rhinosinusitis Endotype and Phenotype.

Chronic rhinosinusitis (CRS) is traditionally classified into CRS with or without nasal polyps and more recently into eosinophilic and non-eosinophilic endotypes. Limited research exists on the relationship between CRS subtype and mucociliary function. This study compares ciliary beat frequency (CBF) across CRS subtypes. To investigate CBF across different CRS subtypes and validate spectrally encoded interferometric microscopy (SEIM) against phase contrast microscopy (PCM) for measuring CBF. Sinonasal mucosa from endoscopic endonasal surgery cases were imaged ex vivo at physiologic temperature with PCM and SEIM. CBF measurements were compared between disease states (control vs chronic rhinosinusitis with nasal polyps (CRSwNP) vs chronic rhinosinusitis without nasal polyps (CRSsNP) and control vs eosinophilic chronic rhinosinusitis vs noneosinophilic chronic rhinosinusitis), as well as between PCM and SEIM. CRSwNP mucosa (5.77 ± 0.12 Hz) had significantly lower CBF compared to control (6.23 ± 0.11 Hz; p=0.001). Both eosinophilic rhinosinusitis (5.74 ± 0.16 Hz; p=0.005) and noneosinophilic CRS mucosa (6.00 ± 0.08 Hz; p=0.03) had significantly lower ciliary beat frequency compared to control (6.28 ± 0.11 Hz). There was no significant difference between PCM (7.65 ± 0.60 Hz) and SEIM (7.64 ± 0.51 Hz) as a means of evaluating CBF (p=0.36). Among CRS subtypes, eosinophilic, noneosinophilic, and CRSwNP are associated with lower ciliary beat frequency when compared to healthy controls. SEIM may have value in measuring ciliary beat frequency.

Advancing the research on management of global airway disease: insights from a post hoc analysis.

Chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) frequently coexist, forming a complex multimorbid condition often referred to as "global airway disease." This concept reflects shared pathophysiological mechanisms of eosinophilic inflammation and underscores the need for integrated treatment strategies targeting both upper and lower airway manifestations (1). The burden of severe CRSwNP, asthma, and N-ERD is substantial, particularly in terms of reduced quality of life, recurrent exacerbations, revision endoscopic sinus surgeries (ESS), and healthcare utilization (2). Biologics represent a significant advancement in the treatment of global airway diseases.

Clinical Spectrum of Orbital Cellulitis: Case Series From Subperiosteal Abscess to Life-Threatening Cavernous Sinus Thrombosis

Background: Orbital cellulitis encompasses a range of orbital infections with varying severity. This case series highlights the diverse clinical presentations, management strategies, and outcomes of orbital cellulitis, emphasizing the importance of prompt diagnosis and treatment. Case presentation: We present two cases of orbital cellulitis with contrasting presentations. The first case involved a 16-year-old male with acute rhinosinusitis who developed severe orbital cellulitis complicated by cavernous sinus thrombosis (CST), requiring aggressive medical and surgical interventions. The second case involved a 2-month-old female with a subperiosteal abscess secondary to ethmoid and maxillary sinusitis, who responded well to medical management alone. Conclusion: Orbital cellulitis presents a wide spectrum of clinical scenarios, ranging from localized infections to life-threatening intracranial involvement. Early recognition, appropriate imaging, and timely intervention are crucial for optimizing outcomes. While CST necessitates aggressive measures, subperiosteal abscesses can often be managed medically, particularly in young children.

IL-25 Enhances B Cell Responses in Type 2 Inflammation Through IL-17RB Receptor.

Alarmin cytokine IL-25 promotes type 2 inflammatory responses in disorders such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and known targets include ILC2 and Th2 cells. However, other cellular targets for IL-25 remain poorly defined. To investigate induction and expression of IL-25 receptor (IL-17RB) by B cells and evaluate responsiveness of IL-17RB-expressing B cells to IL-25 invitro. IL-17RB expression, regulation and function on B cells were evaluated in peripheral blood-derived B cells by flow cytometry and RT-PCR, including in response to IgE-inducing stimuli (anti-CD40 mAb and IL-4). Single-cell RNA sequencing was used to compare IL-17RB+ and IL-17RB-activated peripheral blood-derived B cells. To evaluate B cell IL-17RB expression within type 2 inflamed tissue, B cells were compared from nasal polyps, control turbinate tissue and matched peripheral blood. Activation of B cells with anti-CD40 and IL-4 increased IL-17RB expression at both protein and mRNA level, which was further upregulated by IL-25. B cells induced to express IL-17RB responded to IL-25 with enhanced antibody production. Single-cell RNA-sequencing showed that IL17RB+ activated B cells expressed higher levels of IGHE, CCL17 and CCL22 compared to IL17RB- B cells. B cells from nasal polyp tissue expressed higher levels of surface IL-17RB compared with control tissue, correlating with patient-reported CRSwNP severity (SNOT-22). Peripheral blood B cells activated under IgE-inducing conditions express surface IL-17RB, and tissue IL-17RB+ B cells are increased in type 2 inflammation. IL-17RB+ cells have a distinct transcriptional profile and respond to IL-25 with enhanced antibody production, highlighting the IL-25/IL-17RB pathway as a potential therapeutic target for CRSwNP and other type 2 inflammatory disorders.