Rank, Matthew A.

BackgroundRevision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes.MethodsRetrospective review of adult CRS patients undergoing ESS with a single surgeon (2010‐2015) was conducted. Outcomes were analyzed by CRS subtypes.ResultsESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin‐exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. At median follow‐up of 28 months (interquartile range [IQR], 10–47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and “all other CRS” 4% at median follow‐up duration of 36, 28, 41, 37, 44, and 26 months, respectively.ConclusionAll CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT‐22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes.

SUMMARYEosinophil peroxidase is an eosinophil-specific, cytoplasmic protein stored in the secondary granules of eosinophils. While eosinophil peroxidase deposition is increased in the esophagus in eosinophilic esophagitis (EOE), its potential role as a peripheral marker is unknown. This study aims to examine the relationship between serum eosinophil peroxidase and esophageal eosinophilia in eosinophilic esophagitis. Prospectively collected serum from 19 subjects with incident EoE prior to treatment and 20 non-EoE controls were tested for serum eosinophil peroxidase, eosinophilic cationic protein, and eosinophil derived neurotoxin using ELISA. Matching esophageal tissue sections were stained and assessed for eosinophil peroxidase deposition using a histopathologic scoring algorithm. Mean peripheral blood absolute eosinophil counts in eosinophilic esophagitis subjects were significantly elevated compared to controls (363 vs. 195 cells/μL,P = 0.008). Absolute median serum eosinophil peroxidase, eosinophil cationic protein, and eosinophil derived neurotoxin did not differ between groups; however, when normalized for absolute eosinophil counts, eosinophilic esophagitis subjects had significantly lower median eosinophil peroxidase levels (2.56 vs. 6.96 ng/mL per eos/μL,P = 0.002, AUC 0.79 (0.64, 0.94 95% CI)). Multivariate analysis demonstrated this relationship persisted after controlling for atopy. Esophageal biopsies from eosinophilic esophagitis subjects demonstrated marked eosinophil peroxidase deposition (median score 46 vs. 0,P < 0.0001). Normalized eosinophil peroxidase levels inversely correlated with esophageal eosinophil density (r = −0.41,P = 0.009). In contrast to marked tissue eosinophil degranulation, circulating eosinophils appear to retain their granule proteins in EoE. Investigations of normalized serum eosinophil peroxidase levels as a biomarker of EoE are ongoing.

Background We previously presented that women with chronic rhinosinusitis (CRS) who elected endoscopic sinus surgery (ESS) have a higher symptom burden than men. Causes of these gender-based differences warranted further study. Objectives To study gender differences in another cohort of adult patients with CRS who underwent ESS and to compare key histopathologic and serologic features Methods Patients with CRS who underwent ESS (from 2011 to 2014) with structured histopathology reports on surgical samples were studied. The 13-item structured histopathology report detailed key metrics of inflammation and the presence of fungal elements. Clinical, 22-item Sino-Nasal Outcome Test (SNOT-22) score, Lund-Mackay computed tomography (CT) score, serologic (immunoglobulin E [IgE] level, absolute eosinophil count) and histopathologic data were compared between male and female patients by using statistical software. Results We studied 130 eligible subjects (mean age, 54.7 years; 49.2% women). Compared with the men, the women had significantly higher preoperative SNOT-22 scores (women, 48.7; men 38.0 [p = 0.004]) but similar CT scores. Serum IgE levels were significantly higher among women versus men (peak, 433.3 versus 190.8 kU/L [p = 0.03]; closest to surgery, 435.0 versus 190.8 kU/L [p = 0.03]). Tissue fungal elements were significantly more prevalent in women versus men (19.0 versus 5.2%; p = 0.02). Up to this point, the analysis was agnostic of clinical details of the subjects. Further analysis was conducted regarding clinical features. Allergic fungal sinusitis (AFS) was found significantly more commonly in the female versus male patients (21.9 versus 9.1%; p = 0.04). Women versus men had a higher prevalence of migraine (19.4 versus 4.6%; p = 0.01) or any primary headache disorders (23.0 versus 6.2%; p = 0.007). Conclusion Women who underwent ESS for CRS had higher SNOT-22 symptom burden. Worsened symptomatology may be secondary to a higher prevalence of primary headache disorders in women. However, surgeons should also be aware that female patients with CRS who seek ESS may have a higher prevalence of severe disease endotypes (more tissue fungal elements, elevated serum IgE levels) and phenotypes.

Background The role of microbiota in sinonasal inflammation can be further understood by targeted sampling of healthy and diseased subjects. We compared the microbiota of the middle meatus (MM) and inferior meatus (IM) in healthy, allergic rhinitis (AR), and chronic rhinosinusitis (CRS) subjects to characterize intrasubject, intersubject, and intergroup differences. Methods Subjects were recruited in the office, and characterized into healthy, AR, and CRS groups. Endoscopically‐guided swab samples were obtained from the MM and IM bilaterally. Bacterial microbiota were characterized by sequencing the V3‐V4 region of the 16S ribosomal RNA (rRNA) gene. Results Intersubject microbiome analyses were conducted in 65 subjects: 8 healthy, 11 AR, and 46 CRS (25 CRS with nasal polyps [CRSwNP]; 21 CRS without nasal polyps [CRSsNP]). Intrasubject analyses were conducted for 48 individuals (4 controls, 11 AR, 8 CRSwNP, and 15 CRSwNP). There was considerable intersubject microbiota variability, but intrasubject profiles were similar ( p = 0.001, nonparametric t test). Intrasubject bacterial diversity was significantly reduced in MM of CRSsNP subjects compared to IM samples ( p = 0.022, nonparametric t test). CRSsNP MM samples were enriched in Streptococcus , Haemophilus , and Fusobacterium spp. but exhibited loss of diversity compared to healthy, CRSwNP, and AR subject‐samples ( p < 0.05; nonparametric t test). CRSwNP patients were enriched in Staphylococcus , Alloiococcus , and Corynebacterium spp. Conclusion This study presents the sinonasal microbiome profile in one of the larger populations of non‐CRS and CRS subjects, and is the first office‐based cohort in the literature. In contrast to healthy, AR, and CRSwNP subjects, CRSsNP MM samples exhibited decreased microbiome diversity and anaerobic enrichment. CRSsNP MM samples had reduced diversity compared to same‐subject IM samples, a novel finding.

Background Endotyping chronic rhinosinusitis (CRS) through simplified cytokine assays may help direct individualized therapy such as corticosteroids, antibiotics, or biologics. We performed an unsupervised network analysis to endotype CRS and control subjects using a commercially available cytokine‐chemokine immunoassay. Methods A 41‐plex cytokine‐chemokine array along with major basic protein (MBP) assay was performed on sinonasal surgical tissue of 32 adults. Subjects were defined as non‐CRS controls (n = 6), CRS with nasal polyps (CRSwNP; n = 13), and CRS without nasal polyps (CRSsNP; n = 13). Unsupervised network modeling was performed to reveal association cytokine‐chemokine (“analyte”) clusters and “subject” groups. Results Network mapping and unsupervised clustering revealed 3 analyte clusters and 3 subject groups. Analyte cluster‐1 was composed of T helper 1 (Th1)/Th17 type markers, analyte cluster‐2 Th2 markers, and analyte cluster‐3 chemokines (CC) and growth factors (GF). Subject group‐1 was devoid of CRSwNP, had fewer asthmatics, and was associated most strongly with analyte cluster‐3 (CC/GF) ( p < 0.001). Subject group‐2 was characterized with the most asthmatics (86%) and CRSwNP (100%) patients, and was associated with analyte cluster‐2 (Th2; p < 0.001). Subject group‐3 was associated with both analyte cluster‐1 (Th1/Th17) and analyte cluster‐3 (CC/GF) ( p < 0.001), and had the highest proportion of CRSsNP patients (62.5%). Tissue levels of MBP, eosinophilia, and computed tomography (CT) scores were significantly higher in subject group‐2 vs other groups ( p ≤ 0.05). Conclusion An unbiased network‐mapping approach using a commercially available immunoassay kit reveals 3 distinct tissue cytokine‐chemokine signatures that endotype CRS patients and controls. These signatures are prominent even in a limited number of patients, and may help formulate individualized therapy and optimize outcomes.

Background Women electing endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) report higher symptom burden but have lower computed tomography (CT) scores. Gender‐specific analysis of outcomes from ESS therefore merits further study. The objective of this work was to study gender‐specific differences in outcomes from ESS for CRS by analyzing preoperative and postoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Methods Data from adult CRS patients electing ESS (2011‐2013) were retrospectively collected. SNOT‐22 total, rhinologic/nonrhinologic subdomain, and individual item scores were analyzed for gender‐specific differences. Results Two hundred and forty‐eight patients met study criteria (mean age 55.4 years; 49.6% female). Preoperatively, mean Lund‐Mackay CT score was 11.1; average total SNOT‐22 score was 41.9. Compared to men, women had lower CT score (10.2 vs 12.0; p = 0.004) but higher total SNOT‐22 score (44.7 vs 39.1; p = 0.02). Both genders showed significant improvement in total SNOT‐22 scores at 3, 6, 12, and 24 months following ESS ( p < 0.001), with largely similar slopes of improvement. The greatest improvement occurred at 3 months (SNOT‐22 decreased by 25.4 points), with stable improvement after 12 months (SNOT‐22 decreased by 21.3 points). Higher total SNOT‐22 scores in females were noted preoperatively and until 6 months post‐ESS; these were driven by rhinologic and nonrhinologic‐otolaryngic subdomain items. No gender differences in anxiety/depression prevalence or psychological subdomain scores were noted preoperatively or postoperatively. Conclusion Both male and female CRS patients showed significant and durable symptom relief following ESS. Women reported higher symptom burden prior to surgery, and in the early postoperative period. However, after 1‐year post‐ESS, both genders showed similar symptom scores. The trend and magnitude of improvement were similar in both genders.

BackgroundThe objective of this work was to describe the association between baseline clinical characteristics and attendance at follow‐up visits after endoscopic sinus surgery (ESS).MethodsA retrospective review of chronic rhinosinusitis (CRS) patients electing ESS at a tertiary‐care center (2011‐2013) was conducted. Baseline characteristics were studied for association with clinic attendance at 3, 6, 12, and 24 months post‐ESS.ResultsWe identified 268 patients. Significant decline occurred in the number of patients following up after ESS (3 months: 246 patients [92%]; 6 months: 145 [54%]; 12 months: 94 [35%]; and 24 months: 90 [34%]). Older patients were more likely to follow up at 3 months (mean age 55.7 vs 48.4 years, p = 0.04) and 6 months (57.5 vs 52.3 years; p = 0.01) post‐ESS. Those with higher preoperative sinus computed tomography (CT) (Lund‐Mackay) scores were more likely to follow at 6 months (11.8 vs 10.3, p = 0.01), 12 months (12.6 vs 10.3, p < 0.001), and 24 months (12.2 vs 10.5, p = 0.01). At 12 months having asthma (p = 0.03), previous ESS (p = 0.04), nasal polyps (p < 0.0001), allergic fungal sinusitis (AFS) (p = 0.002), and granulomatosis with polyangiitis (GPA) (p = 0.01) were associated with clinic attendance. At 24 months asthma status (p = 0.003), previous ESS (p = 0.002), AFS (p = 0.04), GPA (p = 0.001), and aspirin‐exacerbated respiratory disease (AERD) (p = 0.006) were associated with higher attendance. Geographical proximity did not impact attendance.ConclusionThe sharpest decline in patient follow‐up occurred between 3–6 months after ESS. Higher preoperative sinus CT scores, previous ESS, presence of asthma, and diagnosis of recalcitrant CRS subtype (nasal polyps, AERD, AFS, GPA) were factors associated with increased long‐term attendance.