TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

A nasal cell atlas reveals heterogeneity of tuft cells and their role in directing olfactory stem cell proliferation.

The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic, and their relationship to the other specialized epithelial cells is unclear. Here, we establish that the family of MVCs comprises tuft cells and ionocytes in both mice and humans. Integrating analysis of the respiratory and olfactory epithelia, we define the distinct receptor expression of TRPM5+ tuft-MVCs compared with Gɑ-gustducinhigh respiratory tuft cells and characterize a previously undescribed population of glandular DCLK1+ tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we used an integrated single-cell transcriptional and protein analysis. Inhalation of Alternaria induced mucosal epithelial effector molecules including Chil4 and a distinct pathway leading to proliferation of the quiescent olfactory horizontal basal stem cell (HBC) pool, both triggered in the absence of olfactory apoptosis. Alternaria- and ATP-elicited HBC proliferation was dependent on TRPM5+ tuft-MVCs, identifying these specialized epithelial cells as regulators of olfactory stem cell responses. Together, our data provide high-resolution characterization of nasal tuft cell heterogeneity and identify a function of TRPM5+ tuft-MVCs in directing the olfactory mucosal response to allergens.

Not just snot: Local inflammatory profiles in patients with aspirin-exacerbated respiratory disease differ from patients with aspirin-tolerant chronic rhinosinusitis.

KEY POINTS: IL-5, CCL2, and CXCL8 in sinus mucous are higher in patients with AERD relative to aspirin-tolerant patients with CRS These mediators are pleiotropic, leading to widescale inflammatory processes contributing to AERD AERD is not only a T2 disease but heterogeneous: this may explain the refractory nature of AERD.

Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis. OBJECTIVE: We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP. METHODS: NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing. RESULTS: Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes. CONCLUSION: NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP.

Local cytokine levels associate with SNOT-22 and UPSIT scores in chronic rhinosinusitis.

KEY POINTS: Elevated IL-5, IL-13, IL-33, and CCL2 correlate with lower UPSIT scores in CRS and AERD patients. Elevated IL-5, IL-13, TNF-α, CCL2, and CXCL-8 correlate with higher SNOT-22 scores in CRS and AERD patients.

Increased epithelial mTORC1 activity in chronic rhinosinusitis with nasal polyps.

Background: The airway epithelium plays a central role in the pathogenesis of chronic respiratory diseases such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), but the mechanisms by which airway epithelial cells (EpCs) maintain inflammation are poorly understood. Objective: We hypothesized that transcriptomic assessment of sorted airway EpCs across the spectrum of differentiation would allow us to define mechanisms by which EpCs perpetuate airway inflammation. Methods: Ethmoid sinus EpCs from adult patients with CRS were sorted into 3 subsets, bulk RNA sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets from eosinophilic and non-eosinophilic CRSwNP and bulk RNA-seq of EpCs from mild/moderate and severe asthma were assessed. Immunofluorescent staining and ex vivo functional analysis of sinus EpCs were used to validate our findings. Results: Analysis within and across purified EpC subsets revealed an enrichment in glycolytic programming in CRSwNP vs CRSsNP. Correlation analysis identified mammalian target of rapamycin complex 1 (mTORC1) as a potential regulator of the glycolytic program and identified EpC expression of cytokines and wound healing genes as potential sequelae. mTORC1 activity was upregulated in CRSwNP, and ex vivo inhibition demonstrated that mTOR is critical for EpC generation of CXCL8, IL-33, and CXCL2. Across patient samples, the degree of glycolytic activity was associated with T2 inflammation in CRSwNP, and with both T2 and non-T2 inflammation in severe asthma. Conclusions: Together, these findings highlight a metabolic axis required to support epithelial generation of cytokines critical to both chronic T2 and non-T2 inflammation in CRSwNP and asthma.

Optimizing cryopreservation of nasal polyp tissue for cellular functional studies and single-cell RNA sequencing.

KEY POINTS: Mast cell numbers were reduced in samples cryopreserved as whole tissue chunks. Thawed epithelial cells had reduced proliferation rates when preserved as dissociated cell suspensions. The right cryopreservation method to choose may depend on the goals and cell-type focus of the project.

The Impact of Sinonasal Symptoms in Relation to Potentially Life-Threatening Comorbidities.

OBJECTIVE: While general health may be influenced by sinonasal symptoms, their effects may be overshadowed by comorbid states which may be more serious. To assess the validity of this postulate, we measured the extent to which sinonasal symptoms and concurrent conditions influenced general health. STUDY DESIGN: Observational outcomes study. SETTING: Academic medical center, community care sites. METHODS: Adults with sinonasal symptoms completed the 22-item Sinonasal Outcome Test, along with the Patient-Reported Outcomes Measurement Information System global health short form. Comorbidities were categorized with the Deyo modification of the Charlson comorbidity index. Multivariate regression analyses were utilized to determine the relative impact of sinonasal symptoms and concurrent comorbid conditions on general health. RESULTS: Data from 219 consecutive patients demonstrated that sinonasal symptoms were associated with significantly diminished general physical (ß = -1.431, p < .001), mental (ß = -1.000, p < .001), overall (ß = -1.026, p < .001), and social health (ß = -0.872, p = .003), regardless of the presence of potentially life-threatening comorbid conditions. Comorbid conditions included cardiovascular disease, chronic obstructive pulmonary disease, connective tissue disease, peptic ulcer, diabetes mellitus, and hepatic disease. The effect of sinonasal symptoms was neither subsumed nor overshadowed by the effects of comorbid states. Nasal, ear, sleep, and psychological domain scores were also associated with general physical, mental, and global health while adjusting for the impact of comorbidities. CONCLUSION: Sinonasal symptoms have a substantial effect on general health which is not subsumed by the presence of potentially life-threatening concurrent comorbidities. These data may help support the importance of funding and resource allocation for conditions causing sinonasal symptoms.

Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal cells (BCs). Recent studies have identified transcriptionally distinct BCs, but the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown. OBJECTIVE: We sought to determine the role of T2 cytokines in regulating airway BCs. METHODS: Single-cell and bulk RNA sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of inhibitors of IL-4R signaling. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and regeneration. RESULTS: Two subsets of BCs were found in human and murine respiratory mucosa distinguished by the expression of basal cell adhesion molecule (BCAM). BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. In the sinonasal mucosa, BCAMhi BCs expressing TSLP, IL33, CCL26, and the canonical BC transcription factor TP63 are increased in patients with CRSwNP. In cultured BCs, IL-4/IL-13 increases the expression of BCAM and TP63 through an insulin receptor substrate-dependent signaling pathway that is increased in CRSwNP. CONCLUSIONS: These findings establish BCAM as a marker of airway stem cells among the BC pool and demonstrate that airway epithelial remodeling in T2 inflammation extends beyond goblet cell metaplasia to the support of a BC stem state poised to perpetuate inflammation.

The Sinonasal Outcome Test-22 or European Position Paper: Which Is More Indicative of Imaging Results?

OBJECTIVE: The 22-item Sinonasal Outcome Test (SNOT-22) is a trusted measure of symptom severity in chronic rhinosinusitis. The European Position Paper on Rhinosinusitis (EPOS) provides widely accepted diagnostic criteria, which include sinonasal symptoms, their duration, and imaging results. Our objective was to compare these approaches to assessing symptoms to determine if either was more indicative of radiologic findings, to support decisions in telehealth. STUDY DESIGN: Observational outcomes study. SETTING: Tertiary care center. METHODS: In total, 162 consecutive patients provided a structured sinonasal history, completed the SNOT-22, and underwent sinus computed tomography (CT) within 1 month. SNOT-22 scores, EPOS-defined symptom sets, and Lund-Mackay results were assessed. To facilitate direct comparisons, we performed stepwise evaluations of sinonasal symptoms alone and combined with duration. The discriminatory capacity for imaging results was determined through areas under the receiver operating characteristic curves (ROC-AUC) for dichotomous outcomes and ordinal regression for multilevel outcomes. RESULTS: In ROC-AUC analyses, SNOT-22 and EPOS-defined symptoms had similar discriminatory capacity for Lund-Mackay scores, regardless of duration. Within ordinal regression analyses, SNOT-22 nasal scores were significantly associated with Lund-Mackay scores, while EPOS-defined nasal symptoms were not statistically significantly related. CONCLUSIONS: SNOT-22 nasal scores and EPOS-defined nasal symptoms may have similar associations with imaging results when assessed via ROC-AUC, while SNOT-22 may have more association within ordinal data. Understanding the implications of discrete patterns of symptoms may confer benefit, particularly when in-person and fiberoptic exams are limited.

Aspirin-Exacerbated Respiratory Disease: Association Between Patient-Reported Sinus and Asthma Morbidity.

BACKGROUND: The association between sinonasal and pulmonary symptoms in aspirin-exacerbated respiratory disease is not fully established. OBJECTIVE: To characterize sinonasal and asthma symptomatology, and to determine whether reported sinonasal symptoms predict asthma severity. METHODS: Prospectively collected data from an aspirin-exacerbated respiratory disease registry cohort were included from 2013 to 2018. Sinonasal symptomatology measured by Sino-Nasal Outcomes Test (SNOT) 22-item total scores was used as the predictor variable, with Asthma Control Test (ACT) scores and percent predicted FEV1 (FEV1% predicted) as primary outcomes. All instances of paired data on the same date were used. ACT score was also evaluated with FEV1% predicted as the outcome. Mixed effects regression was completed. RESULTS: From 1065 aspirin-exacerbated respiratory disease registry subjects (mean age, 48.1 ± 12.8 years; 68.0% females, 29.8% males), mean SNOT-22 score was 42.3 ± 24.12 (n = 1307 observations from 869 subjects), mean ACT score was 19.4 ± 5.2 (n = 1511 observations from 931 subjects), and mean FEV1% predicted was 82.8 ± 19.6 (n = 777 observations from 307 subjects). SNOT-22 score significantly predicted ACT scores (P < .0001, 1185 paired observations from 845 subjects) and FEV1% predicted (P = .018, 485 observations from 246 subjects). Any 10-point increase in SNOT-22 score was associated with a 0.87-point decrease in ACT score and a 0.75% decrease in FEV1% predicted. Any 1-point increase in ACT score was associated with a 1.0% increase in FEV1% predicted (P < .0001, 616 observations from 269 subjects). The most severe SNOT-22 symptoms were sense of smell/taste and blockage/congestion of nose. CONCLUSIONS: SNOT-22 scores significantly predict ACT scores and FEV1% predicted, and ACT scores significantly predict FEV1% predicted. This study demonstrates an association between patient-reported rhinosinusitis and asthma symptom severity and subjective and objective measures of asthma severity.

Sinonasal Outcome Scores and Imaging: A Concurrent Assessment of Factors Influencing Their Association.

OBJECTIVE: The overall discriminatory ability of validated instrument scores for computed tomography (CT) findings of chronic rhinosinusitis has limitations and may be modified by multiple factors. To support optimal methods for assessment, we studied which factors could influence this relationship, including the concurrent impact of multiple discrete CT scoring mechanisms, colocalized imaging findings, and nasal comorbid conditions. STUDY DESIGN: Observational outcomes study. SETTING: Academic medical center. METHODS: Patients with sinonasal complaints who completed the 22-item Sinonasal Outcome Test (SNOT-22) and underwent CT were included. Multivariate ordinal regression was utilized to assess associations. CT data were quantified with the Lund-Mackay system, Zinreich system, and a direct measure of maximal mucosal thickness. The impact of incidental findings (mucous retention cysts, periapical dental disease) and nasal comorbid conditions was also assessed. RESULTS: A total of 233 patients were included. SNOT-22 nasal scores were significantly associated with CT results when those with incidental findings were excluded, regardless of the radiologic scoring mechanism utilized: Lund-Mackay regression coefficient, 0.321 (P = .046); Zinreich, 0.340 (P = .033); and maximum mucosal thickness, 0.316 (P = .040). This relationship subsided when incidental findings were present. SNOT-22 overall scores, sleep scores, and psychological domain scores had no significant association with imaging results, regardless of radiologic scoring system utilized. Nasal comorbid conditions had inconsistent associations. CONCLUSIONS: SNOT-22 nasal domain scores were associated with all 3 radiologic scoring systems when incidental findings were absent but not when they were present. Delineating the presence or absence of these colocalized findings affected the relationship between SNOT-22 scores and radiological results, beyond other concurrent factors.

AHNS endocrine surgery section consensus statement on nasopharyngolaryngoscopy and clinic reopening during COVID-19: How to get back to optimal safe care.

This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID-19 pandemic. The aim is to provide evidence-based recommendations defining the risks of COVID-19 in clinic, the importance of pre-visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.

Aspirin-exacerbated respiratory disease: A review.

OBJECTIVES: Aspirin-exacerbated respiratory disease (AERD) is a chronic respiratory condition characterized by a triad of symptoms: asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory reaction to aspirin and other cyclooxygenase-1 inhibitors, also known as nonsteroidal anti-inflammatory drugs. The objective of this review is to provide otolaryngologists with an overview of the pathophysiology, diagnosis, and treatment of this under-recognized condition. DATA SOURCES AND METHODS: Foundational papers on AERD were reviewed, focusing on the clinical otolaryngology and allergy/immunology literature and other high impact journals or trials. RESULTS: AERD results from increased production of pro-inflammatory leukotrienes and a decrease in production of anti-inflammatory prostaglandins associated with the dysregulation of multiple enzymes influencing eicosanoid metabolism. Diagnosis hinges on a high index of suspicion, careful history, and confirmatory testing for all three elements. Treatments include endoscopic sinus surgery; topical, inhaled, or oral corticosteroids; aspirin desensitization; leukotriene modifying drugs; and the new class of biologics such as dupilumab. CONCLUSION: AERD is an under-recognized disease associated with substantial patient-reported morbidity. We expect rapid progress in the pathophysiological understanding of this disease and available treatments in the coming decades. LEVEL OF EVIDENCE: 5.

Endoscopic management of lateral sphenoid cerebrospinal fluid leaks: Identifying a radiographic parameter for surgical planning.

OBJECTIVE: Repair of cerebrospinal fluid (CSF) leaks of the lateral recess of the sphenoid (LRS) sinus can be challenging to accomplish via an endoscopic transphenoidal approach. The endoscopic transpterygoid approach can improve surgical access to the lateral recess but requires more extensive surgical dissection. We review our experience with LRS CSF leak repair via both techniques to determine whether preoperative radiologic data can help predict the most appropriate surgical approach. METHODS: Electronic medical records of patients with LRS CSF leaks were retrospectively reviewed at a single tertiary referral center. Radiographic measurements from preoperative computed tomography images were reviewed. RESULTS: Twenty-two LRS CSF leaks were identified. The transphenoidal and transpterygoid approach were used in 6 (27.3%) and 16 (72.7%) cases, respectively.The mean vidian canal to foramen rotundum angle of the repairs accessed transphenoidally as compared to the transptyergoid approach were not significantly different (41.93° ±10.91, 40.72° ±19.49, respectively; P = .63). However, the mean volume of the LRS accessed by the transpterygoid approach was significantly greater compared to those accessed through the transphenoidal approach (0.97 cm3 ± 0.48, 0.39 cm3 ± 0.40, respectively; P = .04). A LRS volume of 0.400 cm3 or greater predicted the use of the transpterygoid approach with 93.3% sensitivity and 60.0% specificity. CONCLUSION: This study demonstrated that LRS CSF leaks that necessitated repair by the transpterygoid approach, rather than transphenoidal approach, were in the context of significantly larger lateral recess. Assessment of the LRS volume is a quantifiable parameter to aid in preoperative surgical planning. LEVEL OF EVIDENCE: Level 4.

Psychological Status as an Effect Modifier of the Association Between Sinonasal Instrument and Imaging Results.

OBJECTIVE: To determine whether psychological status is an effect modifier of the previously observed low discriminatory capacity of Sinonasal Outcome Test-22 (SNOT-22) scores for Lund-Mackay computed tomography (CT) results. STUDY DESIGN: Observational outcomes study. SETTING: Tertiary care center. SUBJECTS AND METHODS: We assessed patients presenting with chronic sinonasal complaints who underwent CT of the sinuses within 1 month of completing the SNOT-22 instrument. SNOT-22 overall and domain scores were calculated, as were Lund-Mackay CT scores. The discriminatory capacity of SNOT-22 scores for CT results was determined using the receiver-operator characteristic area under the curve (ROC-AUC). Patient-Reported Outcome Measurement Information System (PROMIS) mental health T-scores were assessed, and stratified analyses were used to test for effect modification by psychological status. RESULTS: In stratified analyses, patients with better PROMIS mental health scores had SNOT-22 overall (ROC-AUC 0.96) and nasal domain scores (ROC-AUC 0.97-0.98) that were highly discriminatory for Lund-Mackay scores, while those with worse mental health scores did not (ROC-AUC 0.42-0.55, P < .007). Patients with better SNOT-22 psychological domain scores also had nasal scores that discriminated among CT results significantly better than those with worse psychological domain scores (ROC-AUC 0.65-0.69 and 0.34-0.35, respectively, P < .013). CONCLUSIONS: Psychological status is an effect modifier of the relationship between SNOT-22 and Lund-Mackay scores. SNOT-22 scores were discriminatory for Lund-Mackay CT results in patients with better psychological status, while they were nondiscriminatory in those with worse psychological status. When assessing the relationship between subjective and objective measures of chronic rhinosinusitis, accounting for effect modification may have practical utility.

Compartmental Endoscopic Surgical Anatomy of the Inferior Intraconal Orbital Space.

Objectives This study aims to define the endoscopic anatomy of inferior intraconal space, in terms of its neurovascular structures and relationship to fixed anatomic landmarks. Design A cadaveric anatomical study was conducted. Setting This study was conducted at an academic cranial base center. Participants Cadaveric subjects have been investigated. Main Outcome Measures After dissection of the inferior intraconal space, the number and position of ophthalmic artery (OA) and oculomotor nerve (OMN) branches to the inferior rectus muscle (IRM) were quantified relative to the fixed landmark of the posterior maxillary wall. The point where the OMN branch to the inferior oblique muscle (IOM) crossed the lateral IRM margin was quantified. Results A total of 18 OA branches were identified with a mean ± standard deviation of 2.6 ± 0.53 branches. The mean distance of the OA branch insertion from the posterior maxillary wall was 7.11 ± 5.65 mm. The average number of OMN branches to the IRM was 1.63 ± 0.74 with a mean insertion distance of 1.88 ± 1.89 mm. The OMN branch to the IOM crossed the lateral IRM margin 5.38 ± 5.42 mm from the posterior maxillary wall. Conclusions This cadaveric study quantifies the variability of two critical neurovascular structures salient to endoscopic approaches to the inferior intraconal space, the OMN, and OA contributions to the IRM. Knowledge of the interrelationship between these structures is essential in safe technique for dissection.

Utility of intraoperative computed tomography for cochlear implantation in patients with difficult anatomy.

OBJECTIVE AND IMPORTANCE: To describe cases that illustrate the utility of intraoperative computed tomography (CT) in cochlear implantation of patients with difficult temporal bone anatomy. CLINICAL PRESENTATION: A 2-year-old male with congenital X-linked stapes gusher syndrome and a 2-year-old female with enlarged vestibular aqueduct underwent successful cochlear implantation with the help of intraoperative CT. In the latter case, the initial intraoperative C-arm fluoroscopy suggested malposition of the electrode, however, was not able to provide details for adjustments. In both cases, intraoperative CT changed the insertion technique of the operating surgeon and allowed for improved electrode positioning. A 47-year-old female with polyostotic fibrous dysplasia and a 55-year-old male with post-meningitis near-total cochlear obliteration underwent successful cochlear implantation with confirmation of electrode position with intraoperative CT. In the former case, the image-guided navigation system was also implemented. Finally, a 72-year-old female underwent cochlear implantation during which intraoperative C-arm fluoroscopy suggested intra-cochlear insertion. However, postoperative CT showed the electrode extending into the internal auditory canal (IAC), illustrating the limitations of C-arm fluoroscopy. INTERVENTION: Intraoperative CT imaging and image-guided navigation system. CONCLUSION: When faced with challenging temporal bone anatomy, intraoperative CT can provide critical details of the patient's microanatomy that allows for improved localization of the electrode and adjustments in operative techniques for successful cochlear implantation.

Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis.

Objective Periostin is an extracellular matrix protein that is elevated in the sinonasal tissues of patients with chronic rhinosinusitis (CRS). The purpose of this study was to determine whether serum periostin could serve as a molecular biomarker of nasal polyp burden in sinonasal disease. Study Design Prospective cohort study. Setting Academic medical center. Subjects and Methods Serum periostin levels were measured by ELISA on blood samples collected from patients undergoing sinus surgery for CRS (n = 71), further stratified by phenotype as defined by nasal polyps and asthma. Results were compared with assays performed on control subjects (n = 62). Results Mean serum periostin levels were markedly elevated in patients with CRS versus controls (66.1 ng/mL [95% CI, 51.6-80.6] vs 38.7 ng/mL [95% CI, 34.4-42.9], respectively, P = .004). In addition, mean periostin levels were significantly higher in CRS patients with nasal polyps as compared with those without polyps (94.8 ng/mL [95% CI, 67.3-122.4] vs 41.1 ng/mL [95% CI, 35.2-47.0], respectively, P < .001). Periostin levels did not correlate with sex ( P = .473), smoking history ( P = .748), aspirin-exacerbated respiratory disease status ( P = .136), oral steroid use within 1 month of surgery ( P = .281), use of topical steroid nasal spray ( P = .864), or number of prior sinus operations ( P = .973). Conclusion Serum periostin appears to be a novel molecular biomarker for the presence of nasal polyps and may serve as an indicator of CRS endotypes.