Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations.

BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. OBJECTIVE: Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). METHODS: We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. RESULTS: Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. CONCLUSION: NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.

Predictors of Visual Acuity and Usefulness of a Treatment Algorithm in Rhinogenous Optic Neuritis.

Rhinogenous optic neuritis, which causes neuropathy associated with visual dysfunction, greatly reduces patient quality of life and requires suitable early treatment. This study aimed to analyze visual outcome predictors in patients with rhinogenous optic neuritis and to develop and investigate the usefulness of an algorithm to facilitate early treatment. Prospective and retrospective investigations were conducted at the Department of Otorhinolaryngology. The visual outcomes after sinus surgery of 24 of 53 patients suspected of having rhinogenous optic neuritis were analyzed. Furthermore, the usefulness of the treatment algorithm was evaluated in 27 of these 53 patients. Data from 24 patients who underwent surgery were included in a multiple regression analysis to investigate the associations between visual outcomes and concomitant symptoms and the time from symptom onset to surgery. The mean time from the initial examination to a request for otorhinolaryngological examination to assess the usefulness of the treatment algorithm was compared in 27 patients who did not undergo an initial otorhinolaryngological examination. Visual acuity improved in 23 participants who underwent surgery. Multivariate analysis identified the time from onset to surgery and headache as significant predictors of postoperative visual acuity. The mean time from the initial examination to a request for otorhinolaryngological examination was significantly shorter after the algorithm was introduced (1.13 days, 8 patients; P = .008). Early surgical treatment is essential to avoid further postoperative visual acuity decreases in patients with rhinogenous optic neuritis. Patients who experience headache may have poorer postoperative outcomes.

Postoperative evaluation of olfactory dysfunction in eosinophilic chronic rhinosinusitis - comparison of histopathological and clinical findings.

Background: Olfactory dysfunction in eosinophilic chronic rhinosinusitis (ECRS) is poorly understood. Objective: To compare olfactory mucosal injury due to eosinophil infiltration in ECRS with postoperative olfactory function. Methods: Seventeen ECRS patients (ECRS group) and 18 bilateral rhinosinusitis (non-ECRS group) patients were compared. At 3 and 12 months post-endoscopic sinus surgery (ESS), all patients were evaluated for subjective symptoms (nasal obstruction, nasal discharge and olfactory dysfunction), endoscopic nasal findings, CT score and T&T olfactometer recognition threshold test. The eosinophil count, OMP-positive cells and epithelial erosion in olfactory mucosa collected during ESS were compared with the postoperative olfactory function. Results: The non-ECRS group showed significant improvement in all clinical findings at 3 and 12 months, but the ECRS group showed worsening of the olfactory dysfunction symptoms and T&T olfactometer recognition threshold at 12 months because of recurrence of sinusitis. The groups differed significantly in the ΔT&T value (i.e. pre-ESS T&T recognition threshold - post-ESS T&T recognition threshold) at both 3 and 12 months, and the degree of olfactory improvement differed. Histologically, the ECRS group showed significantly more eosinophils, fewer OMP-positive cells and greater epithelial erosion than the non-ECRS group. Conclusions: Eosinophilic inflammation was thought to cause olfactory mucosal injury/dysfunction.