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Objectives Chronic rhinosinusitis (CRS) affects approximately 12% of the population and leads to increased health care utilization and indirect costs exceeding $20 billion annually in the United States. The Lund‐Mackay score (LMS) measures radiographic disease severity for CRS but poorly correlates with symptom scores. The association between LMS and health care utilization in CRS patients has not yet been investigated. The study aimed to assess the association between health care utilization and CRS radiographic severity using LMS. Methods CRS patients enrolled in a clinical registry were evaluated. Nasal endoscopy findings and LMS were recorded for patients with sinus CT imaging. Patient symptom scores, demographic characteristics, and health care utilization measures were collected. The relationship between these factors and LMS was examined. Results A total of 556 patients met inclusion criteria. Mean age was 45.3 years, 53.4% were male, and 41.7% had nasal polyps. There was no difference in sex, smoking history, 22‐item Sino‐nasal Outcome Test scores, or past medical history factors between patients with high (≥8, n = 410) and low (

I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is well characterized by type 2 (T2) inflammation characterized by eosinophilia in Western countries. However, the presence and the roles of neutrophils in T2 CRSwNP are poorly understood. OBJECTIVE: To clarify accumulation and inflammatory roles of neutrophils in Western CRSwNP. METHODS: Sinonasal tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS, and neutrophil markers were determined by ELISA. The presence of neutrophils in tissue was determined by flow cytometry. The gene expression profiles in neutrophils were determined by RNA-Sequencing. RESULTS: A neutrophil marker elastase was selectively elevated in nasal polyp (NP) tissue whereas eosinophilic cationic protein (an eosinophil marker) was elevated in both uncinate and NP tissues of CRSwNP patients. NLF myeloperoxidase (another neutrophil marker) was also significantly elevated in CRSwNP compared to control patients. Neutrophil markers were more greatly elevated in CRSwNP patients with recurrent disease. Flow cytometric analysis confirmed that neutrophil numbers were significantly elevated in NPs compared to control tissues. RNA-Sequencing analysis found that 344 genes were >3-fold and significantly elevated in NP neutrophils compared to peripheral blood neutrophils. Gene ontology analysis suggested that elevated genes in NP neutrophils were significantly associated with activation. Results suggest that neutrophils are accumulated in T2 NP tissues and that accumulated neutrophils are highly activated and contribute to inflammation in NPs. CONCLUSIONS: Neutrophils may play a heretofore unrecognized meaningful role in the pathogenesis of CRSwNP in western countries and may be considered to be a potentially important therapeutic target in T2 CRSwNP.

Background Cryoablation of the posterior nasal nerve at the middle meatus has been shown to successfully treat nasal obstruction and symptoms of chronic rhinitis. Cryoablation of both the middle and inferior meatus has not yet been studied. Objectives To evaluate the safety and feasibility of cryoablation of the posterior nasal nerve at both the middle and inferior meatus locations to treat chronic rhinitis. Methods Participants underwent bilateral cryoablation of the posterior nasal nerve at both the middle meatus and inferior meatus and were assessed through 3 months post treatment. The primary endpoint is the change from baseline to 3-month follow-up in the reflective Total Nasal Symptom Score (rTNSS). Other assessments include additional patient-reported outcomes, physician assessment, and independent review and scoring of imaging. Results Thirty participants were enrolled at 3 US centers. There was a significant improvement from baseline in the median rTNSS (–4.0, P Conclusion Cryoablation at both the middle meatus and inferior meatus appears to be a safe and feasible option for treatment of chronic rhinitis. In this feasibility study, there is significant improvement in symptoms post treatment. Adverse events are minor and transient.

Background Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life. Objective The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS). Methods This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups. Results Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR = 2.61 [95% CI = 2.14-3.18]; allergic rhinitis aOR = 1.96 [95% CI = 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR = 1.54 [95% CI = 1.21-1.97]; and autoimmune disease aOR = 1.68 [95% CI = 1.36-2.07]). Antibody deficiency, antibiotic allergy, lower FEV1, radiographic sinus disease severity, nasal polyposis, and systemic corticosteroid use were also associated with frequent AECRS. Conclusion Patients with frequent episodes of AECRS were characterized by a higher prevalence of asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, autoimmune disease, and other allergic and immunologic diseases. These findings identify a high-risk phenotype of patients with CRS for preventive interventions to reduce exacerbation frequency.

Although patients with chronic rhinosinusitis without nasal polyps (CRSsNP) represent a majority of the chronic rhinosinusitis (CRS) population, they have not been completely characterized phenotypically.To perform a comprehensive phenotypic characterization of subjects with CRSsNP, using CRS with nasal polyps (CRSwNP) as a comparator.Patients with a history of CRS with positive sinus computed tomography (18 years old) evaluated in the allergy/immunology or otolaryngology clinics of an academic center between 2002 and 2012 were identified via International Classification of Diseases, Ninth Revision codes. A retrospective chart review was performed on a subset of 507 patients with CRSsNP and 874 with CRSwNP. Characteristics analyzed included demographics, comorbid conditions, and radiologic sinus severity.Of the total CRS population, approximately 82% had CRSsNP and 18% had CRSwNP. Of the 507 patients in the CRSsNP group, 319 (63%) were female compared with 393 of 847 (45%) in the CRSwNP group. The prevalence of atopy was 52% in CRSsNP versus 76% in CRSwNP (P.0001). In CRSsNP, atopic patients had more severe radiographic disease compared with nonatopic patients (P.005). The prevalence of asthma was 36% in CRSsNP versus 56% in CRSwNP (P.0001). Comorbid asthma was not associated with radiographic sinus disease severity in CRSsNP but was associated with severity in CRSwNP (P.0001).The relative prevalence of CRS phenotypes in the western population is approximately 80% CRSsNP and 20% CRSwNP. Patients with CRSsNP were predominantly female, whereas patients with CRSwNP were predominantly male. The prevalence of asthma was higher in our cohort of patients with CRSsNP than previously described. Atopy was associated with more severe radiographic sinonasal disease in CRSsNP, whereas asthma was not associated with radiographic sinonasal disease severity.

Up to 50% of patients with chronic rhinosinusitis (CRS) have comorbid asthma, and we have reported that a subset of CRS patients who have nasal polyps (CRSwNP) have elevated autoantigen-specific antibodies within their nasal polyps (NP). While increases in the prevalence and/or severity of both asthma and autoimmunity in women are well characterized, it is not known whether CRSwNP is more severe or frequent in women than men. We sought to determine whether CRSwNP demonstrated sex-specific differences in frequency and/or severity. Using a retrospectively collected database of tertiary care patients (n = 1393), we evaluated the distribution of sex in patients with CRSwNP with or without comorbid asthma or aspirin hypersensitivity. We further compared the severity of sinus disease between men and women with CRSwNP. Although women comprised 55% of CRS patients without NP (CRSsNP), a significantly smaller proportion of CRSwNP patients were female (38%, P

CRSsNP is a heterogenous disease but type 2 inflammation in CRSsNP was more common than type 1 inflammation among patients in Chicago, Illinois. Distinct therapeutic strategies may be needed depending on the type of inflammation found in CRSsNP.

Ongoing sensory input is critical for shaping internal representations of the external world. Conversely, a lack of sensory input can profoundly perturb the formation of these representations. The olfactory system is particularly vulnerable to sensory deprivation, due to the widespread prevalence of allergic, viral, and chronic rhinosinusitis, but how the brain encodes and maintains odor information under such circumstances remains poorly understood. Here we combined functional magnetic resonance imaging (fMRI) with multivariate (pattern-based) analyses and psychophysical approaches to show that a seven-day period of olfactory deprivation induces reversible changes in odor-evoked fMRI activity in piriform cortex and orbitofrontal cortex (OFC). Notably, multivoxel ensemble codes of odor quality in OFC became decorrelated following deprivation, and the magnitude of these changes predicted subsequent olfactory perceptual plasticity. Our findings suggest that transient changes in these key olfactory brain regions are instrumental in sustaining odor perception integrity in the wake of disrupted sensory input.

The objectives of the study were to determine the prevalence of chronic rhinosinusitis (CRS) overall and its 2 phenotypic variants, CRS with and without polyposis (NP), in patients with chronic inflammatory comorbidities including autoimmune disorders, inflammatory bowel disease, and atopic dermatitis. These findings were compared with data in patients with asthma. Patients with hypertension were also used as a reference group to estimate the incidence of CRS in a group with regular medical follow-up.A retrospective, cross-sectional query of a large tertiary care electronic medical record database was performed.Electronic medical record database prevalence of CRS in patients with hypertension was 4.4%. The prevalence of CRS was 18% in asthma (P.0001), 7% in atopic dermatitis, 3.5% in inflammatory bowel disease, and ranged from 1.4% to 5.9% in autoimmune disorders. The frequency of CRS patients exhibiting the NP phenotype was similarly low in patients with autoimmune disease and hypertension, but was significantly greater in patients with asthma (P.0001), inflammatory bowel disease (P = .033), and atopic dermatitis (P = .049),These findings suggest similar prevalence of overall CRS in patients with autoimmune disease and inflammatory bowel disease, and background rates as estimated by observations in hypertension patients. Inflammatory bowel disease and atopic dermatitis patients with CRS exhibit some skewing toward the NP phenotype, as do asthmatics, where this association is well known.

Background Genetic studies on chronic inflammatory diseases have resulted in an emphasis on the epithelial interface with the environment and the genes that influence this interaction. This study examines the expression of key epithelial genes implicated in the pathogenesis of other inflammatory disorders for their role in chronic rhinosinusitis (CRS). Methods Epithelial cells were collected from the inferior turbinate, middle turbinate, and/or uncinate from 62 subjects undergoing sinonasal surgery. Patient groups included 21 CRS patients with nasal polyposis, 23 CRS patients without nasal polyposis, and 18 controls. Samples were analyzed for S100A7, S100A8, S100A9, SLC9A3R1, G-protein-coupled receptor for asthma, and serine protease inhibitor kazal type 5 (SPINK5) by quantitative real-time polymerase chain reaction. Immunohistochemistry (IHC) was performed to analyze expression of SPINK5 lympho epithelial kazal-type inhibitor (LEKTI) in sinonasal samples. Results Expression of S100A7 and S100A8 was significantly decreased in CRS with and without nasal polyps when compared with controls. S100A9 expression was significantly decreased in CRS without nasal polyps, and SPINK5 expression was significantly decreased in CRS with nasal polyps. SPINK5 (LEKTI) protein was detected in sinonasal tissue and was significantly decreased in polyp samples using IHC. Conclusion This study shows marked reductions in the level of expression of several genes involved in epithelial barrier maintenance and repair in the inflammatory state of CRS.