Rat nasal mucosa-derived ectodermal mesenchymal stem cells: A new therapeutic option for chronic rhinosinusitis.

OBJECTIVE: To investigate the effect of nasal mucosa-derived ectodermal mesenchymal stem cells (NM-EMSCs) on the inflammatory state of rats with chronic rhinosinusitis (CRS) and the underlying therapeutic mechanism. METHODS: NM-EMSCs were isolated and extracted to construct a rat model of CRS. Fifteen Sprague‒Dawley (SD) rats were randomly divided into three groups: CK + NS group rats were injected locally with saline in the nasal mucosa; CRS + NS group rats were injected locally with saline in the nasal mucosa; and CRS + EMSCs group rats were injected locally with NM-EMSCs in the nasal mucosa. One rat from the CRS + EMSCs group was randomly euthanized at 2, 4, and 6 days after injection, and the nasal mucosa tissues were collected for HE staining, Masson's trichrome staining, and periodic acid-Schiff staining. RESULTS: NM-EMSCs specifically expressing CD73, CD105, and CD90 were successfully isolated from the nasal mucosa of rats and were able to differentiate into adipocytes, osteoblasts, and chondrocytes. After saline and NM-EMSC injection, compared with those in the blank control CK + NS group, the nasal mucosa in the CRS + NS and CRS + EMSC groups exhibited obvious thickening, a large amount of inflammatory cell infiltration, and increased collagen and mucin distribution. Four days post-NM-EMSC injection, the thickening of the nasal mucosa in the CRS group was gradually alleviated, the inflammatory cell infiltration gradually decreased, and the distribution of collagen and mucin and the collagen-positive area gradually decreased. Moreover, only a small number of inflammatory cells were visible, and the distribution of mucins was limited to 6 days post-NM-EMSC injection. CONCLUSION: NM-EMSCs effectively attenuated inflammation in the nasal mucosa of CRS model rats.

Respiratory Aspects of Primary Ciliary Dyskinesia.

This review article explores the respiratory aspects of primary ciliary dyskinesia (PCD), a rare, heterogenous, genetic disorder characterized by impaired motile ciliary function. It discusses the clinical diagnosis and management strategies for PCD-related respiratory disease, including chronic sinusitis, otitis media with effusion, recurrent pneumonia, and bronchiectasis. The review emphasizes the need for a multidisciplinary approach to optimize care and clinical trials to improve outcomes in individuals with PCD, highlighting the importance of accurate diagnosis.

Pediatric sinusitis: complications and management in the emergency department.

Upper respiratory infections are some of the most common reasons for pediatric patients to present to the emergency department. A small percentage of these viral infections can evolve into acute bacterial sinusitis (ABS), which can be further complicated by the development of orbital, intracranial, and osseous complications. Differentiating between viral upper respiratory infections and ABS and identifying cases of ABS that require antibiotics can pose a challenge. This issue highlights the patterns of illness that are most consistent with ABS, based on the most current clinical practice guidelines. Additionally, this issue reviews clinical features that should raise suspicion for complicated disease and provides associated diagnostic and management pearls.

Endotype and Phenotype Related Postoperative Effects of Bacterial Lysate in Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes. METHODS: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators. RESULTS: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months. CONCLUSION: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5.

Does Managing Patients With Chronic Rhinosinusitis Improve Their Depression Score? Prospective Study.

BACKGROUND: To assess the risk of depression in patients with chronic rhinosinusitis (CRS) in a tertiary care center and the effect of treatment on depression scores. METHODS: This prospective cohort study was conducted at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between November 2021 and June 2022 and included adult patients (≥14 years) with CRS. The validated Arabic or English Sinonasal Outcome Test (SNOT-22) and Patient Health Questionnaire-9 (PHQ-9) were used before treatment and 3 to 6 months after surgery and maximal medical treatment. PHQ-9 scores were compared at baseline and follow-up visits. The relationship between changes in SNOT-22 and PHQ-9 scores were assessed using Spearman's correlation and simple linear regression. RESULTS: Overall, 38 participants with a mean ± SD age of 32.7 ± 12 years were enrolled. CRS with nasal polyps (55.26%) was the most frequently seen condition, followed by allergic fungal CRS (31.58%) and CRS without nasal polyps (13.16%). Six patients (15.7%) had PHQ-9 scores ≥10, indicating they had major depressive disorder. PHQ-9 and SNOT-22 scores improved significantly after treatment (3.7 ± 5.8 vs 6.5 ± 6.9 pretreatment, P = .001; 20.7 ± 20.5 vs 45.6 ± 28.9 pretreatment, P < .0001, respectively). Mean ± SD change in PHQ-9 and SNOT-22 scores was -2.7 ± 7 and -24.9 ± 29.8, respectively. SNOT-22 and PHQ-9 scores were positively correlated (r = .522, P < .001). PHQ-9 score change was significantly associated with SNOT-22 score change (ß = .178, 95% confidence interval 0.12-0.23, P < .0001). CONCLUSION: CRS affects the quality of life and psychological well-being of patients. Patient-centered care with maximal medical and surgical treatment help overcome its deleterious consequences.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Characteristics and management of pediatric medial subperiosteal orbital abscesses.

INTRODUCTION: Subperiosteal orbital abscesses (SPOA) are the most common suppurative complications of acute bacterial sinusitis. Medial SPOAs arise from infection of the ipsilateral ethmoid sinus and favor initial conservative management reserving surgical drainage for patients who do not demonstrate clinical improvement. No standard algorithm defining medical versus surgical treatment of medial SPOAs exist in the pediatric population. OBJECTIVES: To identify a size cutoff for medial SPOAs to predict the likelihood for surgical drainage. METHODS: This is a retrospective review of patients with medial SPOAs at a tertiary care center from 2003 to 2017. Diagnosis of SPOA was based on radiographic findings. Variables included are patient demographics, antibiotic therapy, surgical intervention, and length of stay. RESULTS: 82 patients with a medial SPOA were included with an average age at presentation of 6.27 (range 0-15) years were included in this study. 62 patients were male (75.6 %), and 20 were female (24.4 %). The average abscess length was 16.1 mm, range 4.5-30.7 mm. The average abscess width was 4.17 mm, range 1.5-14.6 mm. The odds ratio for surgical treatment with every 1 mm increase in abscess width was 1.89 (95CI:1.33-2.69, p < 0.001). Abscesses over 3.6 mm width were 6.65 times more likely to undergo surgical drainage than those less than 3.6 mm (OR:6.65, 95CI:2.52-17.54, p < 0.001). The average(SD) length of stay was 5.4(3.0) days for patients who underwent surgery and 4.0(0.9) days for patients treated with conservative measures, p < 0.001. CONCLUSION: Medial SPOAs greater than 3.6 mm were more likely to undergo surgical drainage; however there was no difference in the likelihood of drainage between anteriorly and posteriorly based medial abscesses. These findings help further characterize the landscape of pediatric subperiosteal abscesses that are managed with surgical drainage.

[Modern management of chronic rhinosinusitis]. / Modernes Management der chronischen Rhinosinusitis.

Chronic rhinosinusitis is a common disease. Due to the significant reduction of the quality of life, possible serious complications and economic consequences, a sufficient therapy is essential. With the entry of biologics into the treatment of chronic rhinosinusitis, relevant innovations have emerged in recent years. This article is aimed at providing an up-to-date overview of the conservative and surgical treatment options for chronic rhinosinusitis.

[Current diagnostics and therapy in chronic rhinosinusitis]. / Aktuelle Diagnostik und Therapie der chronischen Rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis is a prevalent condition with significant implications for both patients and society at large. The diagnostic and treatment approaches are primarily guided by the EPOS2020 guidelines in Europe, which increasingly delve into the molecular -mechanism of the disease and its resulting phenotypes. In recent years, biologics have emerged as a promising option, in particular for cases that are refractory to conventional therapies. However, the management landscape has become more intricate, necessitating consideration and potential concurrent treatment of comorbidities. Moreover, the utilization of biologics is accompanied by substantial costs, warranting personalized assessment for each patient. Hence, the establishment of specialized boards comprising clinicians from diverse disciplines to collaborate on treatment recommendations is imperative.

Eight months of integrated yoga, hydrotherapy and acupuncture on serum IgE levels and symptoms severity of a patient with chronic allergic rhinosinusitis: A case report.

A 27-year-old man with Allergic rhino sinusitis presented to our hospital in July 2020 with complaints of continuous sneezing, coughing while rising from bed for half an hour, and the same complaints repeated in the afternoon for half an hour, as well as a continuous dry cough for half an hour in the evening. He also had complaints of itching and skin rashes, particularly in his limbs. He underwent yoga (45 minutes, 5-6 days a week) including Jalaneti (a yogic cleansing technique, i.e. nasal irrigation with warm salt water for twice a week), hydrotherapy (enema using neem leaves paste mixed with water and steam bath on first day, followed by facial steam on alternate days) and Acupuncture (one session a week) for 8 months. Results showed a reduction in immunoglobulin E (IgE) levels and symptom severity suggesting that integrated yoga, hydrotherapy, and acupuncture are effective in the management of chronic allergic rhinosinusitis. All treatments were well tolerated without adverse effects. Though the result is encouraging, further studies are required with a larger sample size.

Pädiatrische Rhinologie. / Pädiatrische Rhinologie.

The following review article highlights key topics in pediatric rhinology that are currently the focus in research and at conferences as well as in the interdisciplinary discussion between otorhinolaryngologists and pediatricians. In particular, congenital malformations such as choanal atresia or nasal dermoid cysts are discussed, followed by statements on the current procedures for sinogenic orbital complications as well as on the diagnosis and therapy of chronic rhinosinusitis in children. Furthermore, updates on the role of the ENT specialist in the care for children with cystic fibrosis and primary ciliary dyskinesia are provided.

[Clinical observation of the course of eosinophilic otitis media against the background of biological therapy of chronic polypous rhinosinusitis]. / Klinicheskoe nablyudenie techeniya eozinofil'nogo srednego otita na fone provedeniya biologicheskoi terapii khronicheskogo polipoznogo rinosinusita.

Eosinophilic otitis media (EoOM) is a variant of exudative otitis media characterized by a persistent persistent course, the presence of a very viscous effusion in the tympanic cavity, comorbidally associated with chronic polypous rhinosinusitis and bronchial asthma. The disease is characterized by a persistent progressive course, which can lead to a gradual decrease in hearing up to complete deafness. Conservative treatment methods for EoOM include local and systemic administration of glucocorticosteroids. Encouraging data on the effectiveness of biological therapy have appeared in recent publications. The above clinical observation examines the course of EoOM in a patient who received biological therapy with dupilamab.

[Chronic rhinosinusitis with nasal polyposis : A retrospective analysis of therapeutic approaches in 463 patients]. / Chronische Rhinosinusitis mit Polyposis nasi : Retrospektive Analyse des therapeutischen Vorgehens bei 463 Patienten.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, the treatment of which has undergone significant changes in recent years. In addition to surgical approaches, topical and systemic steroids, and adaptive acetylsalicylic acid (ASA) desensitization, three specific antibodies have complemented the therapeutic portfolio since 2019. METHODS: A retrospective evaluation of all patients who presented as outpatients for the first time due to CRSwNP in 2007 and 2008 (collective A) and 2017 and 2018 (collective B) was performed, up to and including June 2023. RESULTS: The clinical courses of 463 patients (mean age 49.1 years, range 5-82 years; 65.9% male) were included in the analysis. Conservative treatment with nasal corticosteroids started before initial presentation was more frequent in collective B (collective A 43.9% vs. collective B 72.2%). In 278 of the 463 patients (60%; A: 62%, B: 58%), at least one operation on the nasal sinuses had been performed after initial presentation; in 101 of these patients (36.3%) recurrent polyposis (within mean follow-up of 2.4 years) required further treatment. The indication for ASA provocation/desensitization was applied less frequently in collective B, also due to a high discontinuation rate (at least 38%) of the maintenance therapy. Of the total cohort, 16 patients (3.5%; A: n = 8, B: n = 8) were meanwhile switched to antibody therapy at recurrence. CONCLUSION: A step-by-step guideline-orientated approach is recommended in the treatment of CRSwNP. Systemic antibodies as an add-on to nasal corticosteroids are a relatively new therapeutic option for treatment-refractory CRSwNP, which reduces the indication for ASA desensitization, which is associated with a relatively high incidence of side effects and poor compliance.

SinoNasal Microbiota Transfer to treat recalcitrant chronic rhinosinusitis: A case series.

KEY POINTS: SinoNasal Microbiota Transfer (SNMT) was safe with immediate benefit in all recipients, with sustained improvement in two of three recipients for up to 180 days. The addition of antimicrobial photodynamic therapy worsened chronic rhinosinusitis. These promising SNMT results warrant further study of safety and efficacy.

[Acute and chronic rhinosinusitis age characteristics]. / Vozrastnye osobennosti techeniya ostrogo i khronicheskogo rinosinusita.

Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and treatment. At the same rhinosinusitis is one of the most common in otorhinolaryngology's practice, both in children and adults. The of adults paranasal sinuses (PNS) anatomy differs from children's PNS anatomy. Although ostiomeatal complex occlusion is recognized as a major cause of poor ventilation and drainage of the adult paranasal sinuses, it does not have a strong effect on pediatric rhinosinusitis, but adenoids play a key role. Adenoids are bacteria and biofilms reservoirs that cause chronic refractory rhinosinusitis regardless of pharyngeal tonsil size. The prevalence of chronic rhinosinusitis (CRS) is lower in children than in adults. Diagnosis of children's rhinosinusitis is more difficult because nasal cavity endoscopic examination is performed rarely due to the occasional need of general anesthesia during the procedure. Moreover, it's necessary to take into account prevailing etiological role of viruses in ARS at children's age and chronic adenoiditis often accompanies pediatric CRS, which requires attention prescribing medical therapy as the basis of rhinosinusitis treatment. The DysheLORz based on Pelargonium sidoides roots is highly effective and safe for children's and adults ARS and CRS treatment, both as monotherapy and in combination with topical steroids and antibiotics. This herbal medicine immunomodulatory effect is mediated mainly by stimulating the production of TNF-α, IL-1, IL-12 and IFN-γ. It activates macrophages and improves their phagocytic activity. IL-12, together with TNF-α, enhances NK and cytotoxic CD8+ lymphocytes' activity against infected cells. IL-12 effect on Th1 lymphocytes maturation provides a link between innate and adaptive immunity. This is also increasing MCP-1, IP-10 and MIP-1ß chemokines synthesis and decreasing MIP-1α, ENA-78, GROα and IL-8 production in PNS and nasal mucosa. This leads to decrease of neutrophils chemotaxis to the inflammation site, and decline of serine proteases concentration (neutrophils main enzymes), that increases mucous membrane epithelial barrier permeability, reducing bacterial infections risk. Additionally, Pelargonium sidoides increases epithelial cells beating cilia frequency and inhibits hemagglutinin and neuraminidase present on influenza virus surface. The drug increases antimicrobial peptides production as defensins, human neutrophil peptides (HNP) and bactericidal permeability-increasing protein (BPI), which is also important for rapid inflammation regression in rhinosinusitis. It causes bacterial adhesion to epithelial cells inhibition, phagocytosis stimulation, nitric oxide (NO) release and oxidative burst. The medicine had a direct effect on Streptococcus pneumoniae, Staphylococcus aureus, Neisseria, Moraxella catarrhalis and Haemophilus influenza. Based on these data, it is possible to explain the high effectiveness and safety of the drugs based on Pelargonium sidoides in ENT organs inflammation treatment, for both adults and children over 1 year old.

[Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study]. / Biologikatherapie bei schwer erkrankten Patienten mit "NSAID-exacerbated respiratory disease" und stattgehabter ASS­Desaktivierung : Ergebnisse einer multizentrischen Studie.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type­2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B­SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.