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.

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.

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.

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.

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.

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.

Mucosal Thickening Occurs in Contralateral Paranasal Sinuses following Sinonasal Malignancy Treatment.

Objective To investigate the incidence and degree of contralateral sinus disease following treatment of sinonasal malignancy (SNM) using radiological findings as an outcome measure. Study Design Retrospective case series. Setting Tertiary referral academic center. Participants Patients with SNM treated with surgical and adjuvant radiotherapy with or without concurrent chemotherapy. Main Outcome Measures Pre- and posttreatment computed tomography and magnetic resonance imaging scans, Lund-Mackay (LM) score, date of diagnosis, chemotherapy, and dosage of radiation therapy (RT). Results There was a significant difference between pre- and posttreatment LM scores ( p < 0.001) of the contralateral paranasal sinuses. There was no statistical significance between the change in pre- and posttreatment LM scores and patient age, gender, chemotherapy, RT dosage, and time lapse between diagnosis and when we performed this study in the univariate and the multivariable analyses. Conclusions Following treatment of SNM with surgical resection and RT, there was a significant increase in incidence and degree of mucosal thickening of the contralateral sinus by LM grading that persisted after the completion of treatment. This indicates the need for long-term follow-up to monitor for chronic rhinosinusitis as a delayed complication following treatment of SNM.

Factors influencing the need for endoscopic sinus surgery in adult patients with cystic fibrosis.

BACKGROUND: Risk factors in adult patients with cystic fibrosis (CF) associated with surgical intervention have not been delineated. OBJECTIVE: To identify characteristics of adult patients with CF and with chronic rhinosinusitis that predict surgical intervention with endoscopic sinus surgery (ESS). METHODS: Patients were identified in a tertiary sinus center by the International Classification of Diseases, Ninth Revision codes 277.00-277.03, which represent CF. Charts were reviewed for the CF transmembrane conductance regulator (CFTR) gene mutation, Lund-Mackay score (LMS), the 22-item Sino-Nasal Outcome Test (SNOT-22) score, previous ESS, and occurrence of ESS after presentation. The Fisher exact test was used to test frequency of events between the groups, and the Mann Whitney U test and the t-test were used to compare means among LMS, SNOT-22, and age. The Cox proportional hazard analysis was used to calculate hazard ratios (HR) for the impact of LMS, SNOT-22 score, previous ESS, and CFTR gene mutation status on the occurrence of ESS after presentation. RESULTS: One hundred and fifteen patients met the inclusion criteria for the study. Patients with a history of surgery more often underwent ESS after presentation (p ≤ 0.01). The LMS and the SNOT-22 score were not significantly different between the groups of previous ESS and no previous ESS (p = 0.23 and p = 0.28, respectively). A severe mutation genotype was predictive of ESS after presentation (p = 0.03). SNOT-22 scores did not differ between the severe and mild groups (36.0 and 32.4, respectively; p = 0.57), but the mean LMS was significantly higher in the severe mutation group (12.5 and 9.7; p ≤ 0.01). Univariate Cox proportional hazard analysis revealed an increased occurrence of ESS for patients with severe mutations (HR, 3.6; p ≤ 0.01) or a history of ESS (HR, 2.3; p ≤ 0.01). CONCLUSION: The occurrence of ESS in adult patients with CF was predicted by previous ESS intervention as well as the severity of CFTR mutation.

General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis.

OBJECTIVE: Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. STUDY DESIGN: Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. METHODS: Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis-related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. RESULTS: Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. CONCLUSION: Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. LEVEL OF EVIDENCE: 3b. Laryngoscope, 2016 127:296-302, 2017.

The Impact of Angiotensin-Modulating Antihypertensives on Time Interval to Revision Surgery for Nasal Polyps.

OBJECTIVE/HYPOTHESIS: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to suppress expression of periostin, a matricellular protein that is markedly elevated in nasal polyp tissue. The purpose of this study was to determine whether use of these antihypertensive agents affects the time to revision sinus surgery in patients with polyp regrowth. STUDY DESIGN: Case series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS: Records were reviewed for 330 patients who underwent ≥2 operations for chronic sinusitis with nasal polyps from April 1987 through August 2015. The time between surgical interventions was compared with patient demographics and clinical characteristics, including use of ACEIs and ARBs. RESULTS: Sixty patients were taking ACEIs or ARBs during the study period, of which 32 had concurrent asthma. The mean interval between polyp operations was 61.0 ± 45.2 months (range, 2-228.6 months). Among patients with asthma (n = 197), the mean time to revision surgery was prolonged by >2 years for those taking ACEIs or ARBs (81.0 vs 54.5 months, P = .006). A similar impact on time to revision surgery was not observed for nonasthmatics taking these medications (61.0 vs 65.2 months, P = .655). CONCLUSION: Use of ACEIs and ARBs is associated with an increased time to revision sinus surgery among patients with concurrent nasal polyps and asthma. A possible mechanism of this observed effect is suppression of periostin expression through inhibition of the angiotensin pathway.

Transnasal endoscopic medial maxillary sinus wall transposition with preservation of structures.

OBJECTIVES/HYPOTHESIS: To evaluate the increase in access to the maxillary sinus (MS) with transnasal endoscopic medial maxillary sinus wall transposition (TEMMT), while preserving major structures of the nasal cavity. STUDY DESIGN: The study was divided into three parts: anatomical, radiographic, and case series. METHODS: Three cadaveric dissections (total of six sides) confirmed the feasibility of the TEMMT approach. Radiographic measurements using maxillofacial computed tomography scans were taken to assess the maximal antrostomy. The TEMMT approach was performed on six consecutive patients with benign MS disease. RESULTS: The cadaveric measurements were consistent with the radiographic measurements, which confirmed the maximum access to the MS. The radiographic measurements ranged from 14.4 to 39.1 mm in the anteroposterior dimension, 8.2 to 23.7 mm in the superior-inferior dimension, and 36° to 98° in the angle between the medial and anterior wall of the MS. In the patient series, five patients presented with an odontogenic cyst, and one patient had an antrochoanal polyp in the MS. The TEMMT approach provided excellent access and adequate resection, as well as preservation of the nasolacrimal duct and inferior turbinate. Finally, the mucosal flap was sufficient to cover the inferior meatal antrostomy. CONCLUSIONS: TEMMT provides excellent access into the MS, especially the floor and anterior wall, without the morbidities of the Caldwell-Luc or medial maxillectomy approach. In addition, the transposition of the inferior turbinate and the mucosal flap provides coverage of the medial wall with preservation of the inferior meatus, inferior turbinate, and nasolacrimal duct for patients with benign MS disease. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1504-1509, 2016.