Una nueva perspectiva en rinosinusitis: EPOS 2020 / A new perspective on rhinosinusitis: EPOS 2020

Resumen EPOS 2020 (European Position Paper on Rhinosinusitis and Nasal Polyps 2020) es una guía clínica desarrollada por un grupo profesionales expertos en el área rinosinusal de la Sociedad Europea de Rinología, que corresponde a la última actualización de sus versiones anteriores (2005, 2007 y 2012). El objetivo principal del documento es entregar recomendaciones claras basadas en la mejor evidencia disponible y algoritmos de manejo concisos para las patologías de rinosinusitis aguda y crónica tanto en adultos como en pacientes pediátricos. Algunas de las novedades más importantes de esta guía, son: nueva clasificación de rinosinusitis crónica en primarias y secundarias, rinosinusitis crónica en pediatría, nuevos conceptos en cirugía sinusal, entre otros. También enfatiza la importancia de manejo multidisciplinario de la patología, incluyendo el autocuidado del paciente, inclusive promoviendo el uso de medicamentos de venta libre, antes del manejo médico en niveles escalonados de atención. El objetivo de esta revisión es dar a conocer de manera resumida el manejo de rinosinusitis aguda y crónica en adultos propuesta en esta guía.

Abstract EPOS 2020 (European Position Paper on Rhinosinusitis and Nasal Polyps 2020) is a clinical guide developed by a group of professional experts in the rhinosinusal area of the European Society of Rhinology, which corresponds to the latest update of its previous versions (2005, 2007 and 2012). The main objective of the document is to bring clear recommendations based on the best available evidence and concise management algorithms for the pathologies of acute and chronic rhinosinusitis in both adults and pediatric patients. Some of the most important novelties of this guide are: new classification of chronic rhinosinusitis in primary and secondary, chronic rhinosinusitis in pediatrics, new concepts in sinus surgery, among others. It also emphasizes the importance of multidisciplinary management of the pathology, including self-care of the patient, promoting the use of over-the-counter medications, before medical management at tiered levels of care. The objective of this review is to present in a summarized way the management of acute and chronic rhinosinusitis in adults proposed in this guide.

EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.

A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation. OBJECTIVE: This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions. METHODS: The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry. RESULTS: Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro. CONCLUSIONS: This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.

Chronic rhinosinusitis: phenotypes and endotypes.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a broad classification of airway inflammation that affects a significant portion of the population. The current model of delineating patients suffering from CRS is dated and is no longer as simple as the presence of polyps or no polyps. Continued advances in the endotype descriptions of CRS have allowed for new phenotypic descriptions that aid in driving management and research efforts. RECENT FINDINGS: Geographic differences exist between patient presentations, which require a molecular evaluation of the driving forces. Increased understanding of these differences allows for patient-specific treatment decisions. SUMMARY: New descriptions of CRS phenotypes allow for more targeted therapy for patients, particularly to those with difficult to control disease. The previously broad classification of CRS with or without nasal polyps is no longer sufficient at driving these treatment decisions.

Contemporary Classification of Chronic Rhinosinusitis Beyond Polyps vs No Polyps: A Review.

Importance: Chronic rhinosinusitis (CRS) is a broadly defined process that has previously been used to describe many different sinonasal pathologic conditions from odontogenic sinusitis and allergic fungal sinusitis to the more contemporary definition of broad inflammatory airway conditions. Previous classification systems have dichotomized these conditions into CRS with nasal polyps and CRS without nasal polyps. However, clinicians are learning more about the inflammatory subtypes of CRS, which can lead to improved delivery and effectiveness of treatment. Observations: In clinical practice, treatment decisions are often based on observable findings, clinical history, presumed disease, and molecular pathophysiologic characteristics. A proposed classification system is simple and practical. It proposes that the functional anatomical compartments involved create the first level of separation into local and diffuse CRS, which are usually unilateral or bilateral in distribution. Diffuse does not imply "pansinusitis" but simply that the disease is not confined to a known functional anatomical unit. This classification takes into account whether local anatomical factors are associated with pathogenesis. Then the inflammatory endotype dominance is separated into a type 2 skewed inflammation, as this has both causal and treatment implications. The non-type 2 CRS encompasses everything else that is not yet known about inflammation and may change over time. The phenotypes or clinical examples are CRS entities that have been described and how they align with this system. Conclusions and Relevance: Although research continues to further define the subtypes of CRS into phenotypes and endotypes, the proposed classification system of primary CRS by anatomical distribution and endotype dominance allows for a pathway forward.

Management Patterns in Pediatric Complicated Sinusitis.

OBJECTIVES: Sinusitis is a common pediatric illness that can be complicated by periorbital or intracranial extension. Patients can be managed with antimicrobials alone or in conjunction with surgical intervention. This article examines management patterns and outcomes in pediatric patients presenting with complicated sinusitis. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care pediatric hospital. SUBJECTS AND METHODS: An evaluation of 168 pediatric patients with complicated sinusitis with periorbital complications presenting at a single institution from 2008 to 2018 was performed. Demographics, disease characteristics, in-hospital management, and outcomes were recorded and analyzed. RESULTS: The most common complication was orbital cellulitis, seen in 49% of children. Surgical intervention occurred in 49% of patients, with 36% receiving medical therapy followed by surgery (MTS). Chandler I patients underwent surgical intervention 30% of the time, Chandler II patients 29%, and Chandler III patients 83%. Nineteen percent of initially nonoperative patients started on ampicillin-sulbactam required MTS vs 57% of those started on other antibiotic regimens (P = .01). Twelve percent of initially nonoperative Chandler I to II patients started on ampicillin-sulbactam needed MTS vs 40% started on other antibiotic regimens. Hospital charges for operative patients were $45,056 vs $14,311 for nonoperative patients (P < .01). Hospital charges for patients with surgery followed by medical therapy (SMT) were $45,563 vs $44,393 for MTS (P = .92). CONCLUSION: Nonoperative early stage patients started on ampicillin-sulbactam had a lower risk of MTS. MTS did not cost significantly more than SMT, and there were no significant outcome differences seen.

[Advances in the endotypes of chronic rhinosinusitis].

The pathogenesis of chronic rhinosinusitis（CRS） is complex. There are differences in the clinical manifestations and therapeutic effects of CRS dominated by different causes. At present, there is a lack of uniform classification standards in clinical practice. In this paper, the research progress in the endotype of CRS in recent years was discussed.

Endotypes of chronic rhinosinusitis: Impact on management.

Following the trend in asthma, endotypes for chronic rhinosinusitis with nasal polyps have been established, with type 2 immune reactions representing >80% of nasal polyp cases in Europe and the United States. Endotyping is without doubt useful to predict the natural course of disease, to determine pharmacotherapy and the extent of surgery, and lately also to select patients for treatment with type 2 biologics. However, with the opening of this new era of treatment, limitations of the current possibilities in subgrouping patients also became apparent, as (1) mixed endotypes often can be found and (2) predictions as to the best biologic to be used in an individual patient are not yet possible. Some of the questions to address in the near future are discussed.

A classification of chronic rhinosinusitis with nasal polyps based on structured histopathology.

AIMS: In chronic rhinosinusitis with nasal polyps (CRSwNP), tools based on objective evidence, such as histopathology, are needed to assist clinical decision-making. The main aim of this exploratory investigation was to determine whether structured histopathology could be used to classify CRSwNP in homogeneous histological clusters. METHODS AND RESULTS: A cohort of 135 CRSwNP patients was assessed, on the basis of clinicopathological features: allergic fungal rhinosinusitis (17 patients); non-steroidal anti-inflammatory drug-exacerbated respiratory disease (19 patients); intrinsic asthma (18 patients); extrinsic asthma (21 patients); allergy (21 patients); histologically eosinophilic (22 patients); and histologically non-eosinophilic (17 patients). For structured histopathology, we considered: the degree of inflammation; eosinophil count; eosinophil aggregates; neutrophil infiltration; goblet cell hyperplasia; basement membrane thickening; fibrosis; hyperplastic/papillary changes; squamous metaplasia; mucosal ulceration; and subepithelial oedema. Cluster analysis identified four distinct sets of cases. On discriminant analysis, the global error rate was 1.48%, and the stratified error rates were 4.34%, 0%, 0%, and 0% for clusters 1, 2, 3 and 4, respectively. Cluster 1 was characterised by infrequent fibrosis (<4.5% of cases). Cluster 2 mainly featured neutrophil infiltration in 100% of cases, hyperplastic/papillary changes in 70% of cases, and fibrosis in 65% of cases. Cluster 3 showed fibrosis in 100% of cases. Cluster 4 showed hyperplastic/papillary changes in 100% of cases, and fibrosis in 92% of cases. CONCLUSIONS: This study shows that cluster analysis can identify different histotypes among CRSwNP patients. The next step will be to investigate, in a larger series, the clinical (e.g. prognostic) implications of identifying such homogeneous clusters of patients with CRSwNP on the basis of their structured histopathology.

Inflammation and Endotyping in Chronic Rhinosinusitis-A Paradigm Shift.

Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory condition of the paranasal sinuses and nasal passage. It is characterized as inflammation of the sinonasal passage, presenting with two or more symptoms (nasal blockage, secretions, facial pain and headaches) for more than 12 weeks consecutively. The disease is phenotypically differentiated based on the presence of nasal polyps; CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Traditionally, CRSwNP has been associated with a type 2 inflammatory profile, while CRSsNP has been associated with a type 1 inflammatory profile. Extensive work in characterizing the inflammatory profiles of CRS patients has challenged this dichotomy, with great variation both between and within populations described. Recent efforts of endotyping CRS based on underlying pathophysiology have further highlighted the heterogeneity of the disease, revealing mixed inflammatory profiles coordinated by a number of inflammatory cell types. This review will highlight the current understanding of inflammation in CRS, and discuss the importance and impact of refining this understanding in the development of appropriate treatment options for CRS sufferers.

[Classification of chronic rhinosinusitis with nasal polyps based on eosinophilic inflammation].

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disorder characterized by chronic sinonasal mucosal inflammation. CRSwNP can be subdivided into two types based on eosinophilic inflammation: eosinophilic CRSwNP (Eos CRSwNP) and non-eosinophilic CRSwNP (Non-Eos CRSwNP). Eos CRSwNP and Non-Eos CRSwNP demonstrate distinct clinical manifestations, treatment outcomes, and cellular and immunopathologic characteristics. However, currently, there is no unified and generally accepted standard to define the Eos CRSwNP. The aim of this review is to compare the advantages and disadvantages of current methods used to classify Eos CRSwNP, in order to lay foundation for further study.

Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant subgroups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenotypic subgrouping approach. The underlying drivers of these distinct microbial clusters were also investigated, together with associations with epithelial barrier integrity. Sinus biopsy specimens were collected from CRS patients (n = 23) and disease controls (n = 8). The expression of 42 tight junction genes was evaluated using quantitative PCR together with microbiota analysis and immunohistochemistry for measuring mucosal integrity and inflammation. CRS patients clustered into two distinct microbial subgroups using probabilistic modelling Dirichlet (DC) multinomial mixtures. DC1 exhibited significantly reduced bacterial diversity and increased dispersion and was dominated by Pseudomonas, Haemophilus, and Achromobacter DC2 had significantly elevated B cells and incidences of nasal polyps and higher numbers of Anaerococcus, Megasphaera, Prevotella, Atopobium, and Propionibacterium In addition, each DC exhibited distinct tight junction gene and protein expression profiles compared with those of controls. Stratifying CRS patients based on clinical phenotypic subtypes (absence or presence of nasal polyps [CRSsNP or CRSwNP, respectively] or with cystic fibrosis [CRSwCF]) accounted for a larger proportion of the variation in the microbial data set than with DC groupings. However, no significant differences between CRSsNP and CRSwNP cohorts were observed for inflammatory markers, beta-dispersion, and alpha-diversity measures. In conclusion, both approaches used for stratifying CRS patients had benefits and pitfalls, but DC clustering provided greater resolution when studying tight junction impairment. Future studies in CRS should give careful consideration to the patient subtyping approach used.IMPORTANCE Chronic rhinosinusitis (CRS) is a major human health problem that significantly reduces quality of life. While various microbes have been implicated, there is no clear understanding of the role they play in CRS pathogenesis. Another equally important observation made for CRS patients is that the epithelial barrier in the sinonasal cavity is defective. Finding a robust approach to subtype CRS patients would be the first step toward unravelling the pathogenesis of this heterogeneous condition. Previous work has explored stratification based on the clinical presentation of the disease (with or without polyps), inflammatory markers, pathology, or microbial composition. Comparisons between the different stratification approaches used in these studies have not been possible due to the different cohorts, analytical methods, or sample sites used. In this study, two approaches for subtyping CRS patients were compared, and the underlying drivers of the heterogeneity in CRS were also explored.

Endotypes of Chronic Rhinosinusitis Across Ancestry and Geographic Regions.

PURPOSE OF REVIEW: Preliminary studies have suggested differences in endotypes of chronic rhinosinusitis (CRS) across ancestry/ethnic groups. Eosinophilic CRS (ECRS) is the predominant subtype for Western/European ancestry CRS patients and non-eosinophilic CRS (nECRS) for Asian patients. This review aims to re-analyze CRS endotypes across ancestry populations using one consistent criteria to existing data. RECENT FINDINGS: Although tissue eosinophilia is the most commonly used criterion for ECRS, various cut-off points are suggested. Surrogate markers have been extensively studied. Sixty-six cohorts with study criteria were included with a total of 8557 patients. Raw data from 11 studies 544 patients were re-analyzed using number of tissue eosinophils. At lower cut-off values of ≥ 5 and ≥ 10 cells/HPF, most patients of Asian and Western/European ancestry were classified as ECRS without difference. In contrast, at cut-off points of ≥ 70 and ≥ 120 cells/HPF, the majority of both groups became reclassified as nECRS. After applying one consistent criteria to existing data, differences across ancestry and geographic populations in endotypes of CRS were no longer evident.

Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention.

BACKGROUND: Chronic rhinosinusitis (CRS) is a diverse clinical syndrome with a heterogeneous pathophysiology. Early attempts to identify CRS endotypes and biomarkers have largely relied on analysis of surgically obtained tissue, thus limiting their practical utility. This study examined the ability of mucus T helper 2 (Th2) biomarkers to predict CRS disease severity and clinical characteristics. METHODS: CRS (n = 90) and healthy control subjects (n = 17) were prospectively enrolled prior to surgical intervention and mucus levels of interleukin (IL)-4, IL-5, and IL-13 were determined using a multiplex cytometric bead assay. Data for relevant cytokines was then scaled, normalized, and later combined to develop standardized metrics indicative of Th2-associated inflammation. Th2-high and Th2-low subgroups were consequently identified and validated against factors associated with disease severity and clinical outcomes. RESULTS: Mucus levels of IL-5 and IL-13 were elevated in CRS subjects compared to controls, while no significant difference was noted for IL-4. IL-5 and IL-13 high CRS were associated with worse objective measures of disease severity and greater rates of revision surgery. Similar relationships were noted for both cytokines when CRS with nasal polyps (CRSwNP) patients were analyzed separately. Th2-high CRS and Th2-low CRS were then categorized using a scaled IL-5/IL-13 metric. Th2-high CRS was characterized by an increased number of subjects with nasal polyps and comorbid asthma, and worse symptom and computed tomography (CT) scores. CONCLUSION: The Th2-associated cytokines, IL-5 and IL-13, are detectable in sinonasal mucus and their levels can be used to define Th2-high and Th2-low CRS. Identification of Th2-high and Th2-low endotypes using mucus-based biomarkers could facilitate stratification of CRS subgroups and guide personalized therapies.

Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype.

BACKGROUND: Revision 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. METHODS: Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes. RESULTS: ESS 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. CONCLUSION: All 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.

Acquired Immunity in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a prevalent disease that is associated with significant costs and quality of life impairments. Currently, patients are classified into subgroups based on clinical characteristics, most often the presence or absence of nasal polyps. However, despite medical and surgical treatment, many of these patients continue to have symptoms. Recent efforts have focused on gaining a more complete understanding of the inflammatory mechanisms that drive pathogenesis in CRS, and it is becoming clear that the inflammatory processes in CRS are quite complex. As our understanding of these complex phenotypes improves, it may become possible to classify patients into endotypes based on unique inflammatory patterns within the sinus mucosa. This information may also lead to the identification of appropriate targeted therapies for different endotypes. This review will discuss our current understanding of endotypes in CRS along with the unique adaptive immune responses that may contribute to these different endotypes and, finally, some potential targeted therapeutics for the next generation of CRS treatment strategies.

Translation and validation of the Rhinosinusitis Disability Index for use in Nigeria.

The Rhinosinusitis Disability Index (RSDI) is a validated and reliable measure of severity of chronic rhinosinusitis. The objective of this study was to translate and validate the instrument for use in Nigeria. This is a methodological study. 71 patients with chronic rhinosinusitis attending two Otolaryngology clinics in Lagos, Nigeria. Using standardized methods and trained translators, the RSDI was translated to vernacular (Yoruba language) and back-translated to culturally appropriate English. Data analysis comprised of assessment of the item quality, content validity and internal consistency of the back-translated Rhinosinusitis Disability Index (bRSDI), and correlation to the original RSDI. Content validity (floor and ceiling effects) showed 0% floor and ceiling effects for the total scores, 0% ceiling effects for all domains and floor effect for physical domain, and 9.9 and 8.5% floor effects for functional and emotional domains, respectively. The mean item-own correlation for physical domain was 0.54 ± 0.08, 0.72 ± 0.08 for functional domain and 0.74 ± 0.07 for emotional domain. All domain item-own correlations were higher than item-other domain correlations. The total Cronbach's alpha was 0.936 and was higher than 0.70 for all the domains representing good internal consistency. Pearson correlation analysis showed strong correlation of RSDI to bRSDI (total score 0.881; p = 0.000, and domain subscores-physical: 0.788; p = 0.000, functional: 0.830; p = 0.000, and emotional: 0.888; p = 0.000). The back-translated Rhinosinusitis Disability Index shows good face and content validity with good internal consistency while correlating linearly and significantly with the original Rhinosinusitis Disability Index and is recommended for use in Nigeria.

Association between computed tomography findings and clinical symptoms in chronic rhinosinusitis with and without nasal polyps.

Objective of this study was to test whether there is a difference between chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps in the association of extent of disease on CT scans with symptom severity and health-related quality-of-life (HRQL) impairment. Data sets from 271 chronic rhinosinusitis (CRS) patients who completed the Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scores were subjected to principal component analysis (PCA) to identify a symptom components related to CRS. After controlling for demographics, medical therapy, and comorbidities, the association between symptom components/items excluded from PCA and Lund-Mackay score (LMS) was evaluated. No association was found between the total SNOT-22 score and LMS in CRS patients. There was an independent association between a higher "nasal" symptom component derived from SNOT-22 PCA and LMS in patients with CRSwNP (p < 0.001), but not in CRSsNP patients, with a statistically significant difference between two patient subsets (p = 0.003). In patients with CRSsNP, higher (worse) SNOT-22 "facial pain" was associated with lower LMS (p = 0.022), although the estimated change in LMS was modest. Considering VAS PCA components, higher "nasal" symptoms were associated with higher LMS in CRSwNP patients (p < 0.001) but not in CRSsNP, with a statistically significant difference between CRS groups (p = 0.024). A higher "pain" PCA component was associated with lower LMS in CRSsNP patients (p = 0.019). This study found significant differences in the relationship between symptom burden and CT scores between CRS phenotypes and no association between HRQL impairment and CT scores.

Unsupervised network mapping of commercially available immunoassay yields three distinct chronic rhinosinusitis endotypes.

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.