Efficacy of Endoscopic Posterior Nasal Neurectomy in Treating Eosinophilic Chronic Rhinosinusitis

<b><i>Objectives:</i></b> Recent guidelines have revealed that eosinophilic chronic rhinosinusitis (ECRS) exhibits a strong tendency for recurrence after surgery and impairs quality of life. Neuropeptides play an important neuroimmunological role. The aim of this study was to determine the efficacy of posterior nasal neurectomy (PNN) for the treatment of ECRS by inhibiting type 2 cytokine expression. <b><i>Methods:</i></b> Forty-six patients were divided into group A and group B according to a random number table. Group A underwent conventional functional endoscopic sinusitis surgery (FESS) combined with PNN, and group B underwent conventional FESS alone. The subjective and objective symptoms included a 10-cm visual analog scale (VAS), 22-item SinoNasal Outcome Test (SNOT-22) score, nasal speculum Lund-Kennedy score, and paranasal sinus computed tomography (CT) Lund-Mackay score at the 1-year postoperative follow-up. <b><i>Results:</i></b> Postoperative VAS (10.33 ± 2.18 vs. 8.38 ± 2.11, <i>p</i> &#x3c; 0.01) and Lund-Kennedy score (1.95 ± 1.32 vs. 3.14 ± 1.35, <i>p</i> &#x3c; 0.01) were significantly improved. The rhinorrhea score (1.76 ± 0.83 vs. 2.90 ± 1.14, <i>p</i> &#x3c; 0.001) in the VAS and the discharge (0.43 ± 0.51, vs. 0.95 ± 0.67, <i>p</i> &#x3c; 0.01) and edema (0.57 ± 0.60 vs. 0.95 ± 0.59, <i>p</i> &#x3c; 0.05) scores in the Lund-Kennedy score were observed to have improved significantly in group A compared with those in group B. <b><i>Conclusions:</i></b> FESS combined with PNN suppresses edema symptoms, which might significantly decrease the surgical recurrence rate of ECRS in the long term.

IL13 May Play an Important Role in Developing Eosinophilic Chronic Rhinosinusitis and Eosinophilic Otitis Media with Severe Asthma

A woman in her 50s was a super responder to benralizumab administered for the treatment of severe bronchial asthma (BA) with eosinophilic chronic rhinosinusitis with nasal polyp (ECRS) and eosinophilic otitis media (EOM). She exhibited the gradual exacerbation of ECRS/EOM despite good control of BA approximately 1 year after benralizumab initiation. Therefore, the treatment was switched to dupilumab, and the condition of the paranasal sinuses and middle ear greatly improved with the best control of her asthma. The patient reported that her physical condition was the best of her life. However, she developed a pulmonary opacity on chest computed tomography after 6 months. Histological examination of the lung parenchyma and cell differentiation of the bronchoalveolar lavage fluid indicated atypical chronic eosinophilic pneumonia, and treatment was switched to mepolizumab. Similarly to the period of benralizumab treatment, exacerbation of ECRS/EOM reduced her quality of life approximately 10 months after the administration of mepolizumab. Dupilumab was again introduced as a replacement for mepolizumab. The clinical course and consideration of the interaction between inflammatory cells led us to speculate that interleukin-13 could play a key role in the development of ECRS/EOM with severe BA.

Effect of Dupilumab on Depression in Asthma with Eosinophilic Chronic Rhinosinusitis in the Japanese Population

<b><i>Introduction:</i></b> Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). <b><i>Methods:</i></b> The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. <b><i>Results:</i></b> Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. <b><i>Discussion/Conclusion:</i></b> Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

S100A8 Enhances IL-1β Production from Nasal Epithelial Cells in Eosinophilic Chronic Rhinosinusitis

Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. Our data demonstrate that S100A8 results in production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis

Background: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. Methodology: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). Results: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. Conclusions: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Therapeutic indications for sinonasal topical steroid treatment and its effects on eosinophilic chronic rhinosinusitis after endoscopic sinus surgery

Objective This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. Method Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. Results Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). Conclusion These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.

Achieving the best method to classify Eosinophilic Chronic Rhinosinusitis: a systematic review

Background: Chronic Rhinosinusitis is currently classified into eosinophilic and non-eosinophilic, according to the histologic quantification of the number of eosinophils in nasal mucosa biopsy. There is a lack of unanimous histopathologic criteria and methodology for this classification and no consensus regarding a cut-off point for Eosinophils per High power field. Methodology: A systematic electronic search was performed on BVS, PUBMED, PUBMED PMC, SCOPUS, WEB OF SCIENCE, EMBASE, COCHRANE and PROQUEST databases looking for studies that reported a cut point for classification of Eosinophilic Chronic Rhinosinusitis (eCRS), and data concerning methodology of classification was extracted. Results: We identified 142 studies that reported 29 different cut-off values for classification of eCRS, and different methods of histologic analysis. Out of these studies 13 reported their own methodology to establish the cut-off point, and used different reference standards as polyp recurrence, asthma and allergy, immunocytochemistry, quality of life index, standard deviation of the control population and cluster analysis. Conclusions: Further studies are needed to determine a precise cut-off point, especially international multicentered cluster analysis. Moreover, methodologic standardization of biopsy and analysis is needed to certify comparable results. Multiple biopsy sites, densest cellular infiltration area examination and oral steroids restriction at least four weeks before sampling are advisable.

Effects of Endoscopic Sinus Surgery for Eosinophilic Chronic Rhinosinusitis on Respiratory Functions and FeNO Production in the Lower Respiratory Tract

Objective: To confirm the relevance of upper and lower airway inflammation in eosinophilic chronic rhinosinusitis (ECRS), the effects of endoscopic sinus surgery (ESS) on lower airway functions and inflammation need to be examined in ECRS patients. Methods: Chronic rhinosinusitis patients with nasal polyps (25 non-ECRS, 28 ECRS) were enrolled. The 12 patients in the ECRS group had comorbid asthma, in contrast to none in the non-ECRS group. We divided ECRS patients into 2 groups of ECRS with and without asthma. Clinical markers, including fraction of exhaled nitric oxide (FeNO), respiratory functions, and the Asthma Control Test (ACT) questionnaire, were investigated before and after ESS. Results: The FeNO levels in the ECRS with asthma group decreased after ESS. The mean FeNO levels in this group were 56.3 ppb before ESS and 24.9, 25.1, 25.0, and 15.5 ppb 1, 2, 3, and 4 months, respectively, after ESS. The mean forced expiratory rates in 1 second before and after ESS were 67.6% and 73.0%, respectively. The mean maximal expiratory flow rates at 50% of the vital capacity before and after ESS were 45.8% and 58.0%, respectively. Significant differences were observed in respiratory functions before and after ESS. The mean ACT scores in the ECRS with asthma group before and after ESS were 17.5 and 23.5, respectively. The ACT scores were significantly higher after than before ESS. Conclusions: The present results indicate that ECRS and bronchial asthma are common eosinophilic airway inflammatory diseases, and ESS for eosinophilic sinusitis may improve lower airway function.