Eosinophilic chronic rhinosinusitis is an adult-onset refractory rhinosinusitis, often associated with adult-onset asthma and aspirin intolerance. Patients often present with olfactory disturbances and nasal obstruction, which significantly reduce their quality of life. Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of antineutrophil cytoplasmic antibody-associated vasculitis, characterized by eosinophilia, severe asthma, and systemic vasculitis. EGPA is a systemic disease that involves both ischemic damage to multiple organs and eosinophilic organ damage. Eosinophilic chronic rhinosinusitis and EGPA share a common pathogenesis of eosinophilic inflammation in the airways, and it is sometimes difficult to differentiate between the two diseases, especially in patients who have no obvious evidence of organ damage other than significant rhinosinusitis with eosinophilic inflammation. However, given their differing prognoses, it is important for otorhinolaryngologists to promptly recognize and diagnose these conditions, especially when EGPA is suspected. When treating eosinophilic chronic rhinosinusitis, it is necessary to consider the potential for EGPA and to evaluate the entire body, including comorbidities, to ensure appropriate treatment. This article highlights the key characteristics of both diseases, emphasizing the need forotorhinolaryngologists to be well-informed about EGPA for effective diagnosis and management.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by nasal obstruction, rhinorrhea, postnasal drip, and olfactory dysfunction, all of which significantly impair patients’ quality of life. Eosinophilic chronic rhinosinusitis (ECRS) is often classified as a subset of CRSwNP, with severity determined using criteria established by the JESREC Study. However, severe cases have a recurrence rate exceeding 75% within six years of surgery. For refractory cases that are unresponsive to surgery or oral steroids, the biological agent dupilumab gained insurance approval in 2020, offering new hope for achieving clinical remission. This article reviews the eligibility criteria and treatment evaluation methods for biologics in CRSwNP, as outlined in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020) and EUFOREA guidelines, while also highlighting the key differences in Japanese clinical practices. Although biologics offer a promising treatment option for refractory cases, challenges related to cost and optimal therapy duration remain unresolved.

The advent of immune checkpoint inhibitors (ICIs) has led to dramatic changes in drug therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). ICIs activate cytotoxic T lymphocytes by releasing the inhibitory signals of immune checkpoint molecules that play a role in suppressing excessive immune responses. However, the response rate with ICIs alone is low, and achieving a response takes a relatively long time. Currently, the only drugs approved in Japan for treating R/M SCCHN are the anti-human programmed cell death 1 (PD-1) monoclonal antibodies nivolumab and pembrolizumab. Nivolumab is only approved as a single agent in patients with platinum-refractory R/M SCCHN. In cases where the disease is aggressive or the tumor burden is high, it may be necessary to consider a regimen that includes a cytotoxic anticancer agent or a molecularly targeted agent to achieve a response rate. In addition to the standard EXTREME regimen, regimens for patients with platinum-sensitive R/M SCCHN who have not received chemotherapy include pembrolizumab monotherapy and pembrolizumab plus chemotherapy. Regimen selection is based on the PD ligand 1 combined positive score, which was used as a predictive biomarker of treatment response in the KEYNOTE-048 trial. Even when these ICIs fail, there are cases in clinical practice in which significant tumor shrinkage can be achieved with subsequent drug treatment. In this article, we discuss the appropriate use of these drugs to improve the prognosis of patients with R/M SCCHN.

Olfactory mucus is nasal mucus that covers the olfactory mucosa located in the uppermost part of the nasal cavity. It is secreted by the Bowman’s glands in the olfactory mucosa. Several functions of olfactory mucus have been postulated, including protection of olfactory nerve tissue, prevention of pathogen invasion into the intracranial space through the nasal cavity, and olfactory perception. Recent advances in molecular biological techniques have permitted insightful analyses of olfactory mucus. In relation to pathology, in experimental animals, degeneration of Bowman’s glands is strongly spatially correlated with age-related degeneration of the olfactory neuroepithelium. Chronic rhinosinusitis is frequently associated with olfactory dysfunction, and the concentration of inflammatory mediators in the olfactory cleft mucus of patients with chronic rhinosinusitis is elevated than in control patients, suggesting roles in pathogenesis. Human olfactory mucus can metabolize odorants, and some of these metabolites have been shown to affect odor perception. This metabolic function is decreased in patients with idiopathic olfactory dysfunction and may be involved in the pathophysiology of olfactory dysfunction. The composition of olfactory mucus differs from that of respiratory mucus, containing high concentrations of lipocalin 15, a lipocalin family member thought to be involved in substance transport. Since there is a correlation between lipocalin 15 distribution in the human olfactory mucosa and that in olfactory receptor neurons, it may be possible to estimate the number of olfactory receptor neurons by quantifying lipocalin 15 in the olfactory mucus. Because olfactory mucus can be sampled minimally invasively in clinical practice, it is hoped that olfactory mucus analyses will lead to the development of objective tests of human olfactory function and new treatments that complement olfactory mucus function.

Background: Dupilumab, prescribed for the treatment of poorly controlled chronic rhinosinusitis with nasal polyps (CRSwNPs), is associated with serious side effects. Notably, eosinophil levels in the peripheral blood may be elevated in some patients. In this study, we examined the detailed characteristics of hypereosinophilia during dupilumab therapy, and developed an algorithm for dupilumab administration.

Materials and Methods: This study included 27 patients with eosinophilic chronic rhinosinusitis (ECRS) that was poorly controlled with existing therapies. Blood tests were conducted at 2 and 24 weeks after dupilumab administration. The criterion for hypereosinophilia was a peripheral blood eosinophil count ≥ 1,500 cells/μl. This study investigated the trends in peripheral blood eosinophil counts associated with dupilumab administration, and the detailed course and response of patients with hypereosinophilia.

Results: Peripheral blood eosinophil counts (mean ± SD) at 2 and 24 weeks after the initiation of dupilumab treatment were 589.2 ± 269.4, 668.6 ± 548.4 and 581.3 ± 418.4, respectively, demonstrating no statistically significant increase; however, hypereosinophilia was observed in 2 patients. One patient developed eosinophilic pneumonia and continued dupilumab treatment with systemic steroid administration.

Conclusion: Eosinophilia (≥1,500 cells/μl) in peripheral blood during dupilumab administration was observed in 2 of 27 patients (7.4%). Based on these results, the present study provides an algorithm for the management of eosinophilia in peripheral blood during dupilumab treatment.

Eosinophilic sinusitis (ES) is often complicated by eosinophilic otitis media (OM), which occurs in approximately 10–15% of sinusitis cases. Recently, biological treatments have been introduced for ES and their indications have expanded to include severe cases. We investigated the effectiveness of biologics on OM in patients with ES who received biological treatment.

Participants: This study included six patients with ES (three men, three women) who received biological treatment and had concurrent OM.

Methods: We examined the age at which OM developed, tympanic membrane findings, presence of bronchial asthma, initial average hearing, average hearing after biological treatment, and history of OM treatment.

Results: The age at onset of OM ranged from 39–70 years (median; 53 years). Tympanic membrane findings showed exudative OM in three cases and chronic OM in three cases. All the patients had concurrent bronchial asthma. Before biological treatment, all patients underwent multiple tympanic membrane incisions and local steroid injections into the tympanic cavity. Of the three patients with chronic OM, one underwent bilateral tympanoplasty, whereas the remaining two experienced spontaneous closure of the tympanic membrane perforations after biological treatment. In the three cases of OM, no fluid was observed post-treatment, and hearing loss improved after biological treatment.

Discussion: This study demonstrated that biological treatment was effective in all cases of ES associated with OM. Because OM often occurs secondary to ES, biological treatment for ES may improve the prognosis of OM.