Subtotal Middle Turbinate Resection in Patients with Chronic Rhinosinusitis with Nasal Polyps is Unlikely to Cause Empty Nose Syndrome: A Multi-Institutional Prospective Study.

BACKGROUND: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores. METHODS: A multi-institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow-up. RESULTS: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow-up was 14.5 ± 2.5 months (range 12.1-22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow-up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively. CONCLUSIONS: Based on prospective multicenter data over 1-2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Associations between chronic rhinosinusitis and the development of non-cystic fibrosis bronchiectasis.

BACKGROUND: Studies have shown an association between chronic rhinosinusitis (CRS) and non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE: We aimed to determine if CRS increases the risk of developing non-CF bronchiectasis. METHODS: A retrospective analysis was conducted utilizing electronic medical records from an academic center. Patients with CRS without bronchiectasis, with at least one chest computed tomography (CT) performed after the diagnosis of CRS, were identified between January 2006 and December 2015. Charts were reviewed until May 2022. The control group was age, sex, and race matched, and included patients without CRS, asthma, or chronic obstructive pulmonary disease (COPD) who had at least one chest CT. Bronchiectasis was identified by chest CT radiology reports. The odds of developing bronchiectasis were analyzed in patients with CRS without asthma or COPD (Cohort 1) and patients with CRS with asthma or COPD (Cohort 2). RESULTS: The odds of developing bronchiectasis were significantly higher in patients with CRS (139/1594, 8.7%) compared to patients in the control group (443/7992 [5.5%], OR 1.63 [1.34-1.99]). Furthermore, the odds of developing bronchiectasis were higher in Cohort 1 (63/863 [7.3%], OR 1.34 [1.02-1.76]) and Cohort 2 (76/731 [10.4%], OR 1.98 [1.53-2.55]) versus the control group. After adjusting for confounding diseases, the association was attenuated in Cohort 1 (OR 1.22 [0.92-1.61]) but remained significant in Cohort 2 (OR 1.78 [1.37-2.31]). CONCLUSIONS: CRS is associated with the future development of non-CF bronchiectasis. Patients with CRS, especially those with asthma or COPD, have a higher likelihood of developing bronchiectasis than patients without CRS.

Single cell RNA sequencing of human eosinophils from nasal polyps reveals eosinophil heterogeneity in chronic rhinosinusitis tissue.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation in the United States, but the actual roles that eosinophils play in CRSwNP remain largely unclear. OBJECTIVE: To reveal the roles and heterogeneity of eosinophils in nasal polyp (NP) tissue, we performed single cell RNA sequencing (scRNA-Seq) analysis of NP tissue. METHODS: Sinonasal tissues (NP and control sinus tissue) and patient matched peripheral blood (PB) samples were obtained from 5 control patients and 5 patients with CRSwNP. Eosinophils were enriched before processing for scRNA-Seq. The gene expression profiles in eosinophils were determined by microwell-based scRNA-Seq technology (BD Rhapsody platform). We predicted the overall function of NP eosinophils by Gene Ontology (geneontology.org) enrichment and pathway analyses and confirmed expression of selected genes by flow cytometry. RESULTS: After filtering out contaminating cells, we detected 5,542 eosinophils from control PB, 3,883 eosinophils from CRSwNP PB, 101 eosinophils from control sinus tissues (not included in further analyses), and 9,727 eosinophils from NPs by scRNA-Seq. We found that 204 genes were downregulated and 354 genes upregulated in NP eosinophils compared to all PB eosinophils (>1.5-fold, Padj < .05). Upregulated genes in NP eosinophils were associated with activation, cytokine-mediated signaling, growth factor activity, NF-κB signaling, and antiapoptotic molecules. NP eosinophils displayed 4 clusters revealing potential heterogeneity of eosinophils in NP tissue. CONCLUSIONS: Elevated eosinophils in NP tissue appear to exist in several subtypes that may play important pathogenic roles in CRSwNP, in part by controlling inflammation and hyperproliferation of other cells.

IL-13 and IL-13-induced periostin levels are specifically decreased in patients following endoscopic sinus surgery for chronic rhinosinusitis.

BACKGROUND: Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. OBJECTIVE: The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. METHODS: MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. RESULTS: A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP level was higher in patients undergoing extensive surgery. CONCLUSION: ESS decreased levels of IL-13 and periostin in the middle meatus. T2 inflammation after ESS was correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes.