Absorbable steroid-eluting sinus implants provide targeted corticosteroid release over a sustained period and are designed to prevent both undesirable adhesion formation and sinus ostia restenosis. Here, we highlight the key evidence of these implants to date and query a group of experts via a Delphi process on the indications and optimal timing for intraoperative or in-office placement of these implants. Six of a total of 12 statements reached consensus and were accepted. Overall, experts largely agree that intraoperative or in-office use of steroid-eluting stents could be considered for patients: (1) who are diabetic or intolerant of oral steroids, (2) undergoing extended frontal sinus surgery, and (3) with recurrent stenosis. Given the lack of expert consensus on other key statements, clinicians should carefully consider these treatment options on a case-by-case basis after shared decision-making.

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Background: Intralymphatic immunotherapy (ILIT) is a potential treatment option for allergic rhinitis (AR). We aimed to determine the efficacy (primary outcomes) and safety (secondary outcomes) of ILIT in treating patients with AR. Methods: An electronic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials CENTRAL (from their inception to December 2020). A random-effects model was used to estimate the pooled prevalence with 95% confidence intervals. This study is registered with PROSPERO (CRD42019126271). Results: We retrieved a total of 285 articles, of which 11 satisfied our inclusion criteria. There were 452 participants with age ranged from 15 to 58 years old. Intralymphatic immunotherapy was given in three doses with intervals of four weeks between doses in 10 trials. One trial gave three and six doses with an interval of two weeks. Both primary and secondary outcomes showed no difference between ILIT and placebo for all trials. There was no difference in the combined symptoms and medication score (SMD -0.51, 95% CI −1.31 to 0.28), symptoms score (SMD −0.27, 95% CI −0.91 to 0.38), medication score (SMD −6.56, 95% CI −21.48 to 8.37), rescue medication (RR 12.32, 95% CI 0.72–211.79) and the overall improvement score (MD −0.07, 95% CI −2.28 to 2.14) between ILIT and placebo. No major adverse events noted. Conclusions: Intralymphatic immunotherapy possibly has a role in the treatment of AR patients. This review found it is safe but not effective, which could be contributed by the high variation amongst the trials. Future trials should involve larger numbers of participants and report standardized administration of ILIT and outcome measures.

Introduction: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. Methods: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). Results: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). Conclusions: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Rhinitis is a common diagnosis with estimates of up to 30% of the Western population suffering from either allergic or nonallergic rhinitis.1 Several medication options exist for rhinitis patients.2 For more accurate diagnosis and consideration of allergy immunotherapy, in vitro or in vivo allergy testing can be done. Procedures such as inferior turbinate reduction/coblation and vidian neurectomy, posterior nasal nerve sectioning, or cryotherapy are also treatment options for refractory cases.2 Work-up during rhinitis consults may include nasal endoscopy and computed tomography (CT) scan, especially when sinusitis is considered in the differential diagnosis.

Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC). Using VH next generation sequencing, we identified an extrafollicular (EF) mucosal IgD+ naïve-like intermediate B cell population with high connectivity to the mucosal IgE ASC. Mucosal IgD+ B cells, express germline epsilon transcripts and predominantly co-express IgM. However, a small but significant fraction co-express IgG or IgA instead which also show connectivity to ASC IgE. Phenotypically, NP IgD+ B cells display an activated profile and molecular evidence of BCR engagement. Transcriptionally, mucosal IgD+ B cells reveal an intermediate profile between naïve B cells and ASC. Single cell IgE ASC analysis demonstrates lower mutational frequencies relative to IgG, IgA, and IgD ASC consistent with IgE ASC derivation from mucosal IgD+ B cell with low mutational load. In conclusion, we describe a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa whereby activated IgD+ naïve B cells locally undergo direct and indirect (through IgG and IgA), IgE class switch.

Background: Central compartment atopic disease (CCAD) is a recently described variant of chronic rhinosinusitis with nasal polyp (CRSwNP) associated with inhalant allergy. An association with asthma was noted to be uncommon within our clinical practice. The purpose of this study was to determine allergy and asthma prevalence in CCAD and other CRSwNP subtypes. Methods: A retrospective analysis at a tertiary care institution was performed over the period from 2015 to 2019. CRSwNP was grouped into the following subtypes: allergic fungal rhinosinusitis (AFRS); aspirin-exacerbated respiratory disease (AERD); CCAD; and CRSwNP not otherwise specified (CRSwNP NOS). Patients with sinonasal polyps and concomitant polypoid disease in the central compartment (CRSwNP/CC) were analyzed as a separate cohort for the purpose of this study. Prevalence of allergy and asthma was compared between groups. Results: Three hundred fifty-six patients were included. CRSwNP NOS was the most common subtype (37.1%) and CRSwNP/CC was the least common (3.7%), with other CRS subtypes ranging between 11.5% and 24.2%. Asthma prevalence was highest in AERD (100%) and CRSwNP NOS (37.1%), but substantially lower in AFRS (19.0%) and CCAD (17.1%). Asthma was significantly more common in AERD and CRSwNP NOS when compared with CCAD (p < 0.001 and p = 0.039, respectively). Prevalence of allergy was significantly higher in AFRS (100%), CCAD (97.6%), CRSwNP/CC (84.6%), and AERD (82.6%) when compared with CRSwNP NOS (56.1%) (p < 0.001). Conclusion: CCAD represents a clinically distinct phenotype of CRSwNP with a high prevalence of allergy and low prevalence of asthma. Patients with both CCAD and diffuse sinonasal polyps had an allergy prevalence approaching that of CCAD and an asthma prevalence approaching CRSwNP NOS.

Background: Aspirin-exacerbated respiratory disease (AERD) is the triad of asthma, nasal polyposis, and sensitivity to cyclooxygenase-1 inhibitors. Treatment options include medical management, surgical intervention, and aspirin desensitization (AsaD). Methods: AERD patients were identified using the MarketScan Database from 2009 to 2015. Patients were included using International Classification of Diseases, 9th edition (ICD-9) codes for asthma, nasal polyposis, and drug allergy. Treatments were determined by Current Procedural Terminology (CPT) codes for drug desensitization and endonasal procedures. Geographic trends and timing of interventions between those exposed and not exposed to desensitization were explored. Results: A total of 5628 patients met inclusion criteria for AERD, with mean age 46 years, 60% female; 395 (7%) underwent AsaD and 2171 (39%) underwent sinus surgery. Among patients who were desensitized, 229 (58%) underwent surgery, of whom 201 (88%) had surgery prior to AsaD (median [quartile 1, quartile 3]; 61 days [30, 208] prior to desensitization). For patients undergoing surgery following AsaD (n = 46), surgery was performed a median of 302 (163, 758) days after AsaD. Nineteen patients had multiple surgeries post-AsaD with median time between surgeries being 734 days (312, 1484); 261 patients were not desensitized to aspirin but did undergo multiple surgeries, with the median of the median time between surgeries being 287 days (15, 617), which is shorter than for patients post-AsaD (p < 0.001). Conclusion: A very small percentage of AERD patients undergo AsaD. Patients who had AsaD underwent surgery approximately 2 months prior to AsaD. Patients who underwent AsaD experienced an increased time between surgeries compared to patients who did not undergo AsaD.

Background: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). Methods: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. Results: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. Conclusion: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

Background: Aspirin-exacerbated respiratory disease (AERD) is a recalcitrant inflammatory disorder defined by asthma, nasal polyposis, and sensitivity to cyclooxygenase-1 inhibitors. The timeline and course of disease progression is unclear. Methods: The Truven MarketScan Database, a large American health insurance claims repository, was queried to identify patients meeting criteria for AERD from 2009 to 2015. Included patients had associated International Classification of Diseases, 9th edition (ICD-9) codes consistent with all 3 components of AERD: asthma, nasal polyposis, and drug allergy. Patterns of disease onset and time to progression were analyzed. Results: A total of 5628 patients were identified for study inclusion. Of the 3 components of AERD, 3303 patients (59%) were initially diagnosed with asthma, 1408 (25%) were initially diagnosed with nasal polyps, and 917 (16%) were first diagnosed with drug sensitivity. The most common (36%) sequence of diagnoses was asthma, followed by nasal polyps, followed by drug allergy. The median interval between diagnosis of upper or lower airway involvement (ie, nasal polyps and/or asthma) to recognition of drug sensitivity was 259 days (quartiles Q1 to Q3: 92 to 603 days). In patients with both asthma and nasal polyps diagnoses, the risk of developing drug sensitivity during the study time period was 6%. Conclusion: Upper and lower airway disease is often initially recognized in patients with AERD, whereas drug sensitivity presents month to years later. This delay may be due to the pathophysiology of AERD and disease progression or due to practice patterns in diagnostic testing and coding. Further work is warranted to identify these patients at early stages in their disease progression.