Interaction of eosinophilic and neutrophilic inflammation in patients with chronic rhinosinusitis.

PURPOSE OF REVIEW: In the past year, the endotype of chronic rhinosinusitis (CRS) has been studied from a new perspective. Eosinophilic and neutrophilic inflammation are not independent processes in the pathogenesis of CRS. In this review, we will focus on recent research on mixed eosinophilic-neutrophilic inflammation in CRS and discuss the mechanism and potential treatments. RECENT FINDINGS: Traditionally, patients with eosinophilic CRS (ECRS) present with severe clinical manifestations, comorbidities, and a higher recurrence rate. Recent studies have found that approximately 40% of patients with ECRS present with neutrophilic infiltration, while patients with predominantly eosinophilic infiltration along with neutrophilic inflammation present with more complex inflammation, clinical manifestations and exhibit refractory characteristics. SUMMARY: The complex inflammatory profile and refractory clinical characteristics of mixed eosinophilic-neutrophilic inflammation in CRS are current challenges for clinicians. We summarize the features of eosinophilic and neutrophilic inflammation and current studies on the mechanisms of mixed eosinophilic-neutrophilic inflammation and suggest potentially effective therapeutic methods. We hope that this review will help with determining precise treatment options for patients.

Revision surgery versus biologic treatment with omalizumab in recurrent chronic rhinosinusitis with nasal polyps: An analysis of cost-utility and clinical outcomes.

Background: Both revision surgery and omalizumab are recommended therapies for the treatment of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) and can improve patients' clinical symptoms and quality of life (QoL). The aim of this study was to compare the improvement in sinus-related symptoms, QoL, economic cost, and duration cost between treatment with revision-surgery and treatment with omalizumab. Methods: This was a prospective study of patients with recurrent CRSwNP. All patients were asked to complete a 22-item sino-nasal outcome test (SNOT-22), a visual analog scale (VAS), and a 36-item short-form (SF-36) questionnaire at baseline and 6 months after the treatments. Patients were required to document economic costs and duration costs within 6 months and report them at each visit. Results: A total of 44 patients who received the treatment of revision surgery or omalizumab were enrolled in this study. After six months of treatment, the improvements in total SNOT-22 and SF-36 in 8 domains were not different between the 2 treatments. The improvements in rhinologic symptoms, extranasal rhinologic symptoms, and ear/facial symptoms according to the SNOT-22 (P value = 0.0288, 0.0016, and 0.0347, respectively) and the improvements in nasal congestion, loss of smell, and overall symptoms assessed by the VAS (P value = 0.0057, 0.0206, and 0.0122, respectively) were better in the revision surgery group than in the omalizumab group. The economic cost and the total duration cost were obviously lower in the omalizumab group (¥18836 and 1 day) than in the revision surgery group (¥29824 and 23 days). Conclusions: Both revision surgery and omalizumab treatments can improve the clinical symptoms and QoL of patients with recurrent CRSwNP. Patients who underwent revision surgery experienced better improvement in sinus-related symptoms. However, omalizumab treatment clearly showed a benefit in terms of economic cost and duration cost of disease-related care.

[The predicting role of postoperative changes in self-reported symptoms in patients with recurrence eosinophilic chronic sinusitis with nasal polyps].

Objective:To investigate whether changes in postoperative symptoms and signs in patients can predict the recurrence of ECRS after nasal endoscopic sinus surgery. Methods:A total of 70 adult patients with ECRS were enrolled for ESS surgery from June 2020 to March 2022 in a single center. There were 50 males and 20 females, with an average age of （46.9±14.5） years. Follow-up after ESS was at least 52 weeks. Patients undergo peripheral blood tests, CT of the sinuses, olfactory T&T test, visual analogue scale of symptoms（VAS）, and endoscopic scoring. Results:VAS scores and endoscopic scores were analyzed at preoperative and 6th week, 12th week, 24th week and 52th week postoperative. After 12th week postoperatively, there was a clear correlation between symptom scores and endoscopic scores. Moreover, olfactory disorder and nasal discharge were the two most obvious symptoms. There were differences in the expression of multiple preoperative clinical inflammatory indicators between the symptom-controled group and the symptom-uncontrolled group（previous surgical history, concomitant asthma, nasal smear eosinophil, serum EOS%, total IgE, CT score, olfactory score, and symptom score, all with P<0.05）, while there was no difference in baseline endoscopic score（P>0.05）. At 12th week postoperative, the two groups of patients showed significant differences in both symptom scores and endoscopic scores. The symptoms and endoscopic score at the 12th week point of follow-up were used as predictive indicators for recurrence, with sensitivity and specificity of 62.5% and 83.3%, respectively. Conclusion:The changes in postoperative symptom score and endoscopic score in ECRSwNP patients indicated that the recurred ECRS. In the symptom-uncontrolled group, symptomatic and endoscopic scores showed consistent increased scores; In the symptom-controlled group, conflicting results between increased endoscopic scores and stable symptoms suggest that the presence of asymptomatic recurrence must be considered. The changes in symptoms and signs at the 12th week point of follow-up can serve as clinical indicators for preventing disease recurrence.

[Clinical treatment options oriented to the endotype of chronic rhinosinusitis].

Chronic rhinosinusitis（CRS） is an inflammatory disease involving the mucosa of the nasal and paranasal sinuses for more than 12 weeks and can be classified as CRS with nasal polyp（CRSwNP） and CRS without nasal polyp（CRSsNP） depending on the phenotype. Clinical treatments reveal significant differences in disease prognosis and improvement in quality of life in patients with the same clinical phenotype. Inflammatory cells infiltration and inflammatory mediators are important factors driving CRS endotypes. In particular, CRS with predominantly eosinophilic infiltration and type 2 CRS present severe clinical symptoms, comorbidities, and high recurrence rates. CRS endotype-oriented treatment methods may better contribute to improving patient prognosis and quality of life. This article summarizes the current progress of CRS endotype research and reviews the endotype-oriented treatment options.

Bacterial diversity and community characteristics of the sinus and dental regions in adults with odontogenic sinusitis.

BACKGROUND: The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion samples were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted tooth extraction patients. DNA was extracted, and 16S rRNA sequencing was performed to explore the characteristics and structure of the microbiome in the sinuses and dental regions of OS patients. RESULTS: The alpha diversity of the oral and nasal microbiomes in OS patients was higher than that in controls. Principal coordinate analysis (PCoA) showed that oral samples clustered separately from nasal samples, and the beta diversity of oral and nasal samples in OS patients was higher than that in controls. The dominant phylum was Bacteroidetes in OS patients and Firmicutes in controls in both the oral and nasal cavity. The dominant genera in the oral microbiome and nasal microbiome of OS patients were similar, including Fusobacterium, Porphyromonas and Prevotella. Co-occurrence network analysis showed decreased microbial connectivity in the oral mucosa and nasal secretion samples of OS patients. CONCLUSIONS: Odontogenic infection promotes structural and functional disorders of the nasal microbiome in OS. The interaction of dominant pathogens in the nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS.

Precision medicine in chronic rhinosinusitis - using endotype and endotype-driven therapeutic options.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a heterogeneous disease, and its complex pathophysiological characteristics pose a challenge to its clinical treatment. CRS is distinguished not only by clinical phenotype but also by endotype characteristics, which are divided into type 2 CRS and non-type 2 CRS. AREAS COVERED: In this review, we summarize and discuss current studies that depict the mechanisms and endotypes of CRS. In particular, inflammatory cells and the microbiome play a role in the pathophysiology of CRS. We also listed some of the biomarkers described in recent studies that may serve as a theoretical foundation for additional investigations. We have summarized the advantages and disadvantages of existing treatments and listed the available biological treatments for CRS in detail. EXPERT OPINION: Endotype-driven therapeutic options face many challenges because of the complexity of the disease. Glucocorticoids, nasal endoscopic surgery, and biological therapy are the main treatments used in clinical practice, but they have limitations. This review provides advice on the clinical management and treatment options for patients with different endotypes, which will be more conducive to improving the quality of life and reducing the financial burden on patients.

A prospective single-arm study on the efficacy and safety of short-course oral corticosteroids followed by topical corticosteroids in patients with severe chronic rhinosinusitis with nasal polyps.

BACKGROUND: Little evidence exists regarding an integrated multidimensional evaluation methodology to analyze the within-patient effects of medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to use an integrated evaluation model to analyze the effects of short-course oral corticosteroid (OCS) followed by intranasal corticosteroid spray (INCS) therapy in patients with severe CRSwNP. METHODS: In all, 32 patients with severe CRSwNP received oral methylprednisolone for three weeks followed by intranasal budesonide spray for nine weeks in this prospective single-arm study. An evaluation model integrating the concepts of the core outcome set (COS), clinical control and minimum clinically important difference (MCID) was longitudinally evaluated. RESULTS: All uncontrolled patients at baseline showed similar progressive improvements from baseline and more than 1 MCID response across core outcomes during the OCS period, with severe CRSwNP being partly controlled in 31 (96.9%) patients and uncontrolled in 1 (3.1%) patient at 3 weeks. During the subsequent INCS period, 14 (43.8%) patients gradually deteriorated to an uncontrolled status at 12 weeks, whereas 18 (56.2%) exhibited partly controlled CRSwNP until 12 weeks. CONCLUSIONS: In more than half of the patients, severe CRSwNP was partly controlled with the initial OCS followed by INCS therapy. An integrated evaluation model was used to facilitate the comprehensive evaluation of within-patient response, especially in patients with different responses to the same treatment. TRIAL REGISTRATION: ChiCTR1900024287.

Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors.

BACKGROUND: Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. OBJECTIVE: We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. METHODS: Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. RESULTS: Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. CONCLUSION: Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.

Clinical effectiveness and potential predictability of omalizumab in patients with difficult-to-treat chronic rhinosinusitis with nasal polyps and asthma based on the noninvasive markers - A real-life prospective study.

Background: Clinical studies on the effectiveness of omalizumab in patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are scarce in China. Moreover, identifying potential biomarkers predicting its efficacy remains a great challenge. Methods: In this prospective trial, all enrolled patients underwent endoscopic examination, computed tomography, blood tests, etc, and they completed a 22-item sino-nasal outcome test (SNOT-22), visual analogue scale (VAS), and asthma control test (ACT) evaluation, at baseline and after 24-week omalizumab therapy. Results: Twenty-two patients were finally recruited. Their VAS scores were significantly better including nasal congestion, anterior rhinorrhea, postnasal drip, and loss of smell (P < 0.01). Seventeen patients reported a reduction in SNOT-22 scores of ≥8.9 and 19 patients achieved ACT scores >20. The median change in the Lund-MacKay score (LMS) was 6. Both the Lund-Kennedy score (LKS) and nasal polyp score showed significant improvement (P < 0.01). Only 3 parameters in the pulmonary function test showed evident amelioration (P < 0.05). The eosinophilic CRSwNP and the male subgroups showed better improvements in subjective and objective evaluation. A receiver operating characteristic curve indicated a cutoff value of 17.5 and 16.5 in LMS had the moderate predictive value (AUC = 0.706) for the decline in the SNOT-22 (more than 8.9 points) and reduction in anterior rhinorrhea VAS (more than 2 cm), respectively. A cutoff value of 18.5 in ACT could provide the moderate predictive value (AUC = 0.771) for the reduction of loss of smell VAS (more than 2 cm). Conclusions: The beneficial effectiveness of omalizumab in the patients with difficult-to-treat CRSwNP and asthma was confirmed. ECRSwNP and male patients were more likely to have positive responses. The multiple cutoff values for the LMS and ACT may serve as useful predictors for improvement acceptable to difficult-to-treat CRSwNP patients.

Recent advances in the diagnosis of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is a disorder with high prevalence worldwide. Identification of clinically relevant allergens is the key step for the diagnosis, allergen avoidance and allergen specific immunotherapy for AR. Areas covered: With the new findings of mechanisms of AR and the development of technology, much progress has been achieved in the diagnosis of AR recently. We review the recent advances about local IgE, in vivo and in vitro tests, cytological diagnosis and nitric oxide (NO) in the diagnosis of AR. Expert commentary: AR is traditionally diagnosed with the combined evaluation of history and allergen sensitization by in vivo skin prick tests and in vitro allergen specific IgE in serum, to confirm the correlation between clinical history and potential allergens. Nasal provocation test and local IgE measurement can be used to diagnose local AR. Allergen microarray has the ability to detect more potential allergens. Basophil activation and mast cell activation tests can be used in allergen diagnosis and to modify the response to immunotherapy, while cytological diagnosis is useful in the differential diagnosis of AR and non-AR. Nasal NO has been confirmed to be an optimal biomarker to discriminate between AR and non-AR.