Biologics in Chronic Rhinosinusitis: Current and Emerging.

Chronic rhinosinusitis (CRS) is categorized phenotypically into CRS with and without nasal polyps (CRSwNP, CRSsNP). Endotyping categorizes the disease based on immune cell activity and inflammatory mechanisms into Type 1, Type 2, and Type 3. The Type 2 endotype is the most researched and associated with asthma, atopic disease, and severe CRSwNP. For patients with poorly controlled CRSwNP, there are 3 approved biologic treatments: omalizumab, dupilumab, and mepolizumab. Many other biologics are being tested in Type 2, non-Type 2, and mixed endotypes in CRSwNP and CRSsNP. These studies will play a significant role in shaping the future of CRS management.

Functions and Clinical Applications of Extracellular Vesicles in TH2 Cell-Mediated Airway Inflammatory Diseases: A Review.

Type 2 airway inflammation (T2AI), driven by type 2 innate lymphoid and CD4+ T helper 2 cells, leads to various diseases and conditions, such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma. Emerging evidence suggests the involvement of extracellular vesicles (EVs) in these diseases. In this review, we describe the immunological T2AI pathogenic mechanisms, outline EV characteristics, and highlight their applications in the diagnosis and treatment of T2AI. An extensive literature search was conducted using appropriate strategies to identify relevant articles from various online databases. EVs in various biological samples showed disease-specific characteristics for chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma, with some demonstrating therapeutic effects against these conditions. However, most studies have been limited to in vitro and animal models, highlighting the need for further clinical research on the diagnostic and therapeutic applications of EVs.

Patient-reported outcome measures for acute rhinosinusitis in adults and children: a systematic review of the quality of existing instruments.

BACKGROUND: Acute rhinosinusitis (ARS) is a self-limiting inflammation of the nose and sinuses caused by viral or bacterial infections that requires primarily symptomatic treatment. Patient-reported outcome measures (PROMs) are suitable tools for the assessment of the effectiveness of remedies for ARS from the patient's perspective in clinical trials and real-world studies. Data regarding the quality of existing PROMs for ARS are limited. PURPOSE: To conduct a systematic review of the quality of existing disease-specific PROMs for use in adults and children with ARS according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, and to derive recommendations for use of the identified instruments in future clinical studies. METHODS: We systematically searched PubMed, Web of Science and Embase for studies reporting on the development and/or validation of PROMs for ARS. We assessed the methodological quality of each included study, evaluated the quality of measurement properties per PROM and study, and graded the evidence. Based on the overall evidence, we derived recommendations for use of the instruments. RESULTS: We identified four studies on three PROMs measuring symptoms of ARS and quality of life in adults (Sinonasal Outcome Test-16, SNOT-16; Measurement of Acute Rhinosinusitis, MARS; Rhinosinusitis Quality-of-Life Assessment, RhinoQoL). For ARS in children, we identified two studies on two PROMs measuring symptoms of ARS (Pediatric Rhinosinusitis Symptom Scale, PRSS; Sinus Symptom Questionnaire, S5). Our assessment of measurement properties indicates that all instruments require further validation before they can be unrestrictedly recommended for use in future research (COSMIN category B). In particular, there were no content validity studies for any of the identified instruments, but also data on other important measurement properties, e.g., structural validity, are lacking. CONCLUSION: Currently, no PROM for ARS in adults and children can be unrestrictedly recommended based on the evaluation of their quality. Further validation is required for all identified PROMs. Content validation involving patients and experts should be given priority. SYSTEMATIC REVIEW REGISTRATION: OSF ( https://doi.org/10.17605/OSF.IO/VAP8U ).

[Possibilities for increasing the effectiveness of treatment of respiratory infections of the upper respiratory tract in children of various age groups]. / Vozmozhnosti povysheniya effektivnosti terapii respiratornykh infektsii verkhnikh dykhatel'nykh putei u detei razlichnykh vozrastnykh grupp.

The article discusses the experience of complex therapy of rhinitis and sinusitis in children of various age groups, confirming the effectiveness of the combined effects of local thermotherapy, pulsed red light and low-frequency magnetic field. This combination of physical factors has an anti-inflammatory, decongestant, stimulating local cellular activity effect and helps to increase the effectiveness and reduce the overall treatment time for these diseases. The purpose of the study is to evaluate the effectiveness of the combined use of heat, red spectrum phototherapy and magnetic field in the treatment of children with rhinitis and sinusitis. Materials and methods. The observation included 30 children with rhinitis and 40 children with sinusitis aged 2-18 years, receiving combined physiotherapy procedures as part of the main treatment. Results and its discussion. The positive effect of the combined effects of thermotherapy, pulsed light radiation in the red range and low-frequency magnetic field on clinical symptoms and functional indicators of nasal breathing in children with rhinitis and sinusitis has been confirmed. Conclusions. The use of a course of procedures combined with the effects of local thermotherapy, pulsed red light and low-frequency magnetic field against the background of the main treatment helps to increase the effectiveness of the treatment of respiratory infections of the upper respiratory tract in children of various age groups.

Optogenetics Neuromodulation of the Nose.

Recently developed optogenetic technology, which allows high-fidelity control of neuronal activity, has been applied to investigate the neural circuits underlying sensory processing and behavior. The nasal cavity is innervated by the olfactory nerve and trigeminal nerve, which are closely related to common symptoms of rhinitis, such as impairment of smell, itching, and sneezing. The olfactory system has an amazing ability to distinguish thousands of odorant molecules at trace levels. However, there are many issues in olfactory sensing mechanisms that need to be addressed. Optogenetics offers a novel technical approach to solve this dilemma. Therefore, we review the recent advances in olfactory optogenetics to clarify the mechanisms of chemical sensing, which may help identify the mechanism of dysfunction and suggest possible treatments for impaired smell. Additionally, in rhinitis patients, alterations in the other nerve (trigeminal nerve) that innervates the nasal cavity can lead to hyperresponsiveness to various nociceptive stimuli and central sensitization, causing frequent and persistent itching and sneezing. In the last several years, the application of optogenetics in regulating nociceptive receptors, which are distributed in sensory nerve endings, and amino acid receptors, which are distributed in vital brain regions, to alleviate overreaction to nociceptive stimuli, has gained significant attention. Therefore, we focus on the progress in optogenetics and its application in neuromodulation of nociceptive stimuli and discuss the potential clinical translation for treating rhinitis in the future.

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.

Patient-Reported Outcome Measures in Rhinitis and Chronic Rhinosinusitis.

Patient-reported outcome measures (PROMs) are valuable in the assessment and management of rhinitis and chronic rhinosinusitis (CRS). They measure outcomes that may include symptoms, disease control, well-being, and health-related quality of life (QOL). PROMs for rhinitis and rhinosinusitis are often used before and after an intervention, for example, medication, therapeutic procedure, or, in allergic rhinitis (AR), allergen immunotherapy. Although widely used in clinical trials for AR and conjunctivitis, symptom score PROMs are less validated than disease control or QOL measures. The best validated PROM for AR is the Rhinitis Quality of Life Questionnaire, but there is no universally accepted criterion standard for symptom and disease control PROMs. For CRS, at least 15 different criteria have been used to assess disease control in clinical studies, but what CRS disease control means and how it should be measured are concepts in evolution. The most used QOL measure for CRS is the 22-item Sinonasal Outcome Test. The use of PROMs to support clinical decisions and for shared decision-making for rhinitis and rhinosinusitis still has many challenges, including the selection of the preferred instrument, when and how to administer, the impact of comorbidities, and questionnaire fatigue for both patient and provider.

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.

Assessing the quality of artificial intelligence-generated patient counseling for rhinosinusitis.

KEY POINTS: GPT-4 generated moderate quality information in response to questions regarding sinusitis and surgery. GPT-4 generated significantly higher quality responses to questions regarding treatment of sinusitis. Future studies exploring quality of GPT responses should seek to limit bias and use validated instruments.

Safety and efficacy of cryotherapy on chronic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Chronic rhinitis is when the nasal passages become inflamed and irritated, causing symptoms like nasal congestion, runny nose, sneezing, and postnasal drip that last for at least 12 weeks. While various medical treatments are available for chronic rhinitis, studies have shown that patients often do not comply with the treatment or report that it is ineffective. Cryotherapy for the nasal mucosa is a surgical option that has shown promise for these patients, with acceptable side effects. AIM: Our goal is to evaluate the existing literature regarding the effectiveness and safety of cryotherapy as a treatment for chronic rhinitis. METHODS: We searched four electronic databases for relevant studies. Data were extracted from the included studies after screening procedures. Using the random effect model, we calculated the pooled mean difference (MD) for our continuous outcomes and pooled proportions for categorical outcomes. The I2 test was used to detect heterogenicity. Randomized controlled trials (RCTs) were assessed for methodological quality using the Cochrane risk of bias assessment tool 2, while observational studies and single-arm studies were assessed using the National Institutes of Health's tools. RESULTS: Our study comprised 21 studies; eighteen were eligible for analysis, with 1663 patients with chronic rhinitis. All of our assessed outcomes showed improvement with cryotherapy from their baseline status. Our pooled MDs for Total Nasal Symptom Score (rTNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Nasal Obstruction Symptom Evaluation (NOSE) scores were as follows: ( - 3.58, 95% CI [ - 3.80, - 3.37], p < 0.001), ( - 1.48, 95% CI [ - 1.68, - 1.27], p < 0.001), and ( - 26.65, 95% CI [ - 33.98, - 19.31], p < 0.001), respectively. Regarding nasal obstruction and rhinorrhea, cryotherapy showed effectiveness in 61% and 52% of patients in the complete relief subgroup and 26% and 34% in the < 50%-relief subgroup, respectively. CONCLUSION: We observed significant improvement in our measured outcomes as rTNSS, RQLQ, and NOSE scores compared to the baseline state, demonstrating the cryotherapy's efficacy. This improvement was consistent in all subsequent follow-up periods. However, we need more high-quality RCTs for stronger evidence to be generalized.

Clinical effectiveness of focused ultrasound combined with plasma radiofrequency ablation technique in the treatment of persistent strain rhinitis.

Examine the effects of focused ultrasound in combination with plasma radiofrequency ablation technology on the physiological stability and postoperative recovery of persistent strain rhinitis. For a control experiment, 90 patients with persistent strain rhinitis were chosen and split into two groups: the control group (CG) and the experimental group (EG). The CG used conventional radiofrequency ablation technology, while the EG used focused ultrasound technology combined with radiofrequency ablation technology to treat persistent strain rhinitis. Between the EG and the CG, compare and contrast the recovery of nasal symptoms, nasal signs, postoperative discomfort, and postoperative respiratory status. One quarter after surgery, there was a substantial difference in physical sign ratings between the EG and the CG, and a particularly significant difference was seen after six months of treatment. One year following surgery, there was a statistical difference between the EG and the CG in the comparison of effective rates at various intervals, with a P value of .013. At 6 months following surgery, the MTT times in the EG and CG for the comparison of nasal function were 12.63 2.65 and 17.68 2.84, respectively, with statistically significant differences. The difference between the EG and the CG in the MTR comparison is statistically significant. In the comparison of NNO values between the EG and the CG after different treatment times. The nitric oxide value of the EG patients decreased over time, with statistical significance one month after surgery and one year after surgery. It is evident from the comparison of various symptom efficacy rates that the EG has a higher treatment effectiveness rate than the CG, and the total treatment effect difference following surgery has statistical significance. Indicators for PONV, PA, directional ability, respiratory recovery, and olfactory recovery performed better in the EG than in the CG, and the differences were statistically significant. Focused ultrasound and plasma radiofrequency ablation technology have a good therapeutic impact in the treatment of persistent strain rhinitis and can significantly reduce MTT. This technology can effectively improve symptoms such as nasal congestion, nasal flow, and headache in patients, and the therapeutic effect is long-lasting. The hospitalization time after treatment is significantly shortened.

Spending, utilization, and coverage for chronic rhinosinusitis with nasal polyposis therapies among Medicare Advantage beneficiaries.

KEY POINTS: CRSwNP-specific mean total annual spending ranged from $5,837 (EDS-FLU) to $28,058 (dupilumab). Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery. While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS-FLU.

Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

[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.

[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.