Factors determining whether diffuse large B-cell lymphoma samples are detected by flow cytometry.

INTRODUCTION: Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. METHODS: Cases with a final diagnosis of DLBCL that were analysed by eight-colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. RESULTS: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B-cell (GCB) and non-GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine-needle aspirates, or between samples from nodal compared to extranodal tissue. CONCLUSION: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight-colour analysis, FCM fails to detect numerous cases of DLBCL.

Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2.

Heterozygous loss-of-function (LOF) mutations in PIK3R1 (encoding phosphatidylinositol 3-kinase [PI3K] regulatory subunits) cause activated PI3Kδ syndrome 2 (APDS2), which has a similar clinical profile to APDS1, caused by heterozygous gain-of-function (GOF) mutations in PIK3CD (encoding the PI3K p110δ catalytic subunit). While several studies have established how PIK3CD GOF leads to immune dysregulation, less is known about how PIK3R1 LOF mutations alter cellular function. By studying a novel CRISPR/Cas9 mouse model and patients' immune cells, we determined how PIK3R1 LOF alters cellular function. We observed some overlap in cellular defects in APDS1 and APDS2, including decreased intrinsic B cell class switching and defective Tfh cell function. However, we also identified unique APDS2 phenotypes including defective expansion and affinity maturation of Pik3r1 LOF B cells following immunization, and decreased survival of Pik3r1 LOF pups. Further, we observed clear differences in the way Pik3r1 LOF and Pik3cd GOF altered signaling. Together these results demonstrate crucial differences between these two genetic etiologies.

CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis.

BACKGROUND: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. OBJECTIVE: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. METHODS: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. RESULTS: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τb = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. CONCLUSIONS: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate.

Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.

Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. METHODS: A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. RESULTS: 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = -8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = -2.37, p = 0.02). CONCLUSION: Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.

Comparison of flow cytometry with other modalities in the diagnosis of myelodysplastic syndrome.

INTRODUCTION: The myelodysplastic syndromes (MDSs) are heterogeneous myeloid malignancies, conventionally diagnosed by cytomorphology and cytogenetics, with an emerging role for flow cytometry. This study compared the performance of a 4-parameter flow cytometry scoring system, the Ogata Score, with other modalities in the diagnosis of MDS. METHODS: Bone marrow aspirate and trephine biopsies from 238 patients performed to assess for possible MDS were analysed, and the flow cytometry score was retrospectively applied. The sensitivity and specificity of the flow cytometry score, the aspirate microscopy, the trephine microscopy with immunohistochemistry, and cytogenetic and molecular results were determined relative to the final diagnosis. RESULTS: The medical records of the 238 patients were reviewed to determine the final clinical diagnosis made at the time of the bone marrow examination. This final diagnosis of MDS, possible MDS or not MDS, was based on clinical features and laboratory tests, including all parameters of the bone marrow investigation, except for the flow cytometry score, which was only determined for this study. The flow cytometry score was 67.4% sensitive and 93.8% specific. Aspirate microscopy had higher sensitivity (83.7%) and similar specificity (92.0%), whereas trephine microscopy had similar sensitivity (66.3%) and specificity (89.4%) to flow cytometry. Although the flow cytometry score had a lower sensitivity than aspirate microscopy, in 18 patients (7.6% of the total) the flow cytometry score was positive for MDS, whereas aspirate microscopy was negative or inconclusive. CONCLUSION: The flow cytometry score and trephine microscopy exhibited reasonable sensitivity and high specificity, and complement aspirate microscopy in the assessment of MDS.

Intrinsic Defects in B Cell Development and Differentiation, T Cell Exhaustion and Altered Unconventional T Cell Generation Characterize Human Adenosine Deaminase Type 2 Deficiency.

PURPOSE: Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2. Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodeficiency with viral infections, hypogammaglobulinemia and bone marrow failure. Limited data are available on the phenotype and function of leukocytes from DADA2 patients. The aim of this study was to perform in-depth immunophenotyping and functional analysis of the impact of DADA2 on human lymphocytes. METHODS: In-depth immunophenotyping and functional analyses were performed on ten patients with confirmed DADA2 and compared to heterozygous carriers of pathogenic ADA2 mutations and normal healthy controls. RESULTS: The median age of the patients was 10 years (mean 20.7 years, range 1-44 years). Four out of ten patients were on treatment with steroids and/or etanercept or other immunosuppressives. We confirmed a defect in terminal B cell differentiation in DADA2 and reveal a block in B cell development in the bone marrow at the pro-B to pre-B cell stage. We also show impaired differentiation of CD4+ and CD8+ memory T cells, accelerated exhaustion/senescence, and impaired survival and granzyme production by ADA2 deficient CD8+ T cells. Unconventional T cells (i.e. iNKT, MAIT, Vδ2+ γδT) were diminished whereas pro-inflammatory monocytes and CD56bright immature NK cells were increased. Expression of the IFN-induced lectin SIGLEC1 was increased on all monocyte subsets in DADA2 patients compared to healthy donors. Interestingly, the phenotype and function of lymphocytes from healthy heterozygous carriers were often intermediate to that of healthy donors and ADA2-deficient patients. CONCLUSION: Extended immunophenotyping in DADA2 patients shows a complex immunophenotype. Our findings provide insight into the cellular mechanisms underlying some of the complex and heterogenous clinical features of DADA2. More research is needed to design targeted therapy to prevent viral infections in these patients with excessive inflammation as the overarching phenotype.

SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression.

Sterile α motif domain-containing protein 9-like (SAMD9L) is encoded by a hallmark interferon-induced gene with a role in controlling virus replication that is not well understood. Here, we analyze SAMD9L function from the perspective of human mutations causing neonatal-onset severe autoinflammatory disease. Whole-genome sequencing of two children with leukocytoclastic panniculitis, basal ganglia calcifications, raised blood inflammatory markers, neutrophilia, anemia, thrombocytopaenia, and almost no B cells revealed heterozygous de novo SAMD9L mutations, p.Asn885Thrfs*6 and p.Lys878Serfs*13. These frameshift mutations truncate the SAMD9L protein within a domain a region of homology to the nucleotide-binding and oligomerization domain (NOD) of APAF1, ∼80 amino acids C-terminal to the Walker B motif. Single-cell analysis of human cells expressing green fluorescent protein (GFP)-SAMD9L fusion proteins revealed that enforced expression of wild-type SAMD9L repressed translation of red fluorescent protein messenger RNA and globally repressed endogenous protein translation, cell autonomously and in proportion to the level of GFP-SAMD9L in each cell. The children's truncating mutations dramatically exaggerated translational repression even at low levels of GFP-SAMD9L per cell, as did a missense Arg986Cys mutation reported recurrently as causing ataxia pancytopenia syndrome. Autoinflammatory disease associated with SAMD9L truncating mutations appears to result from an interferon-induced translational repressor whose activity goes unchecked by the loss of C-terminal domains that may normally sense virus infection.

Evaluation of Diffuse Type 2 Dominant or Eosinophilic Chronic Rhinosinusitis With Corticosteroid Irrigation After Surgical Neosinus Cavity Formation.

Importance: Eosinophilic chronic rhinosinusitis (eCRS), contemporarily classified as diffuse type 2 dominant chronic rhinosinusitis (CRS), is characterized by eosinophil-dominant mucosal inflammation. Contemporary management of eCRS as an inflammatory airway condition is multimodal with corticosteroid irrigations after the surgical creation of a neosinus cavity. Objectives: To assess long-term treatment outcomes in patients with primary diffuse type 2 CRS or eCRS receiving multimodal treatment. Design, Setting, and Participants: A prospective cohort study of patients seen in a tertiary rhinology practice recruited from May 2010 to November 2018 was conducted. Follow-up duration was 12 months or more following endoscopic sinus surgery (ESS) with a neosinus cavity formed. Data analysis was performed from August to November 2020. Consecutive adult (≥18 years) patients diagnosed with primary diffuse type 2 dominant CRS or eCRS based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria were included. Type 2 inflammation was defined as more than 10 eosinophils per high-power field obtained from sinus mucosal biopsy and managed with neosinus cavity ESS and ongoing corticosteroid irrigations. Exclusion criteria were less than 12 months of follow-up and secondary CRS. Interventions: Endoscopic sinus surgery with complete removal of intersinus bony partitions to create a neosinus cavity. Nasal irrigation (240 mL) with betamethasone, 1 mg, or budesonide, 1 mg, daily for 3 to 6 months after ESS and tapered to an as-needed basis (minimum, 2-3 per week). Main Outcomes and Measures: Poor control was defined as polyp recurrence (polyp growth in >1 sinus area on a single side), use of long-term systemic therapy (biologic therapy or ≥3 consecutive months of oral corticosteroids), and revision surgery involving polypectomy. The disease in patients with no poor control criteria was defined as well controlled, and the disease in those with 1 or more criteria was considered poorly controlled. Maintenance medical therapy use and patient-reported outcomes based on the 22-item Sinonasal Outcomes Test for preoperative and last follow-up were collected. Results: Of the 222 participants recruited with primary diffuse type 2 dominant CRS or eCRS and minimum of year of follow-up, 126 were men (56.8%). Mean (SD) age was 54.8 (13.6) years, and median (SD) follow-up was 2.2 (2.2) years. Of the 222 patients, 195 (87.8%) had well-controlled disease, 16 (7.2%) had polyp recurrence, 7 (3.2%) continued to receive long-term oral corticosteroid therapy, 5 (2.3%) received biologic therapy, and 8 (3.6%) underwent a revision polypectomy. Clinically meaningful change on the 22-item Sinonasal Outcomes Test and the nasal subdomain score was maintained at the last follow-up in 134 patients (67.0%). Poor disease control was not associated with poor adherence to irrigation use. Conclusions and Relevance: The findings of this cohort study suggest that long-term disease control and reduction in symptom burden in patients with primary diffuse type 2 CRS or eCRS might be achieved when managed as an inflammatory disorder. Maintenance corticosteroid irrigations in the population examined appeared to be successfully self-tapered to disease activity.

COVID-19 Clinical Phenotypes: Presentation and Temporal Progression of Disease in a Cohort of Hospitalized Adults in Georgia, United States.

BACKGROUND: The epidemiological features and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) have been described; however, the temporal progression and medical complications of disease among hospitalized patients require further study. Detailed descriptions of the natural history of COVID-19 among hospitalized patients are paramount to optimize health care resource utilization, and the detection of different clinical phenotypes may allow tailored clinical management strategies. METHODS: This was a retrospective cohort study of 305 adult patients hospitalized with COVID-19 in 8 academic and community hospitals. Patient characteristics included demographics, comorbidities, medication use, medical complications, intensive care utilization, and longitudinal vital sign and laboratory test values. We examined laboratory and vital sign trends by mortality status and length of stay. To identify clinical phenotypes, we calculated Gower's dissimilarity matrix between each patient's clinical characteristics and clustered similar patients using the partitioning around medoids algorithm. RESULTS: One phenotype of 6 identified was characterized by high mortality (49%), older age, male sex, elevated inflammatory markers, high prevalence of cardiovascular disease, and shock. Patients with this severe phenotype had significantly elevated peak C-reactive protein creatinine, D-dimer, and white blood cell count and lower minimum lymphocyte count compared with other phenotypes (P < .01, all comparisons). CONCLUSIONS: Among a cohort of hospitalized adults, we identified a severe phenotype of COVID-19 based on the characteristics of its clinical course and poor prognosis. These findings need to be validated in other cohorts, as improved understanding of clinical phenotypes and risk factors for their development could help inform prognosis and tailored clinical management for COVID-19.

Intraocular solitary extramedullary plasmacytoma presenting as unilateral anterior and intermediate uveitis preceded by refractory glaucoma.

BACKGROUND: Solitary extramedullary plasmacytoma (SEP) is a localised proliferation of monoclonal plasma cells involving soft tissue with no or minimal bone marrow involvement and no other systemic evidence of multiple myeloma. Intraocular involvement is exceedingly rare. CASE PRESENTATION: We report a 78-year-old man who was referred with glaucoma in the right eye. He subsequently developed anterior chamber (AC) inflammation and refractory glaucoma then dense vitritis. A vitrectomy was performed with the biopsy revealing numerous plasma cells with atypical findings. In conjunction with the flow cytometry results, and a systemic work up excluding multiple myeloma, a diagnosis of SEP was made. The patient was treated with ocular external beam radiotherapy with resolution of the intraocular inflammation and control of the intraocular pressure. He remains well with no local recurrence and no development of multiple myeloma over a follow up period of 2.5 years. CONCLUSIONS: This is the first case report of SEP presenting as intraocular inflammation without a uveal tract mass.

Genetic Medicine for Hearing Loss: OTOF as Exemplar.

Millions of people worldwide have disabling hearing loss because one of their genes generates an incorrect version of some specific protein the ear requires for hearing. In many of these cases, delivering the correct version of the gene to a specific target cell within the inner ear has the potential to restore cochlear function to enable high-acuity physiologic hearing. Purpose: In this review, we outline our strategy for the development of genetic medicines with the potential to treat hearing loss. We will use the example of otoferlin gene (OTOF)-mediated hearing loss, a sensorineural hearing loss due to autosomal recessive mutations of the OTOF gene.

Predictors at Admission of Mechanical Ventilation and Death in an Observational Cohort of Adults Hospitalized With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. METHODS: We conducted a retrospective observational cohort investigation of 297 adults admitted to 8 academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for predictors of invasive mechanical ventilation (IMV) and death. RESULTS: Compared with age <45 years, ages 65-74 years and ≥75 years were predictors of IMV (aORs, 3.12 [95% CI, 1.47-6.60] and 2.79 [95% CI, 1.23-6.33], respectively) and the strongest predictors for death (aORs, 12.92 [95% CI, 3.26-51.25] and 18.06 [95% CI, 4.43-73.63], respectively). Comorbidities associated with death (aORs, 2.4-3.8; P < .05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Prehospital use vs nonuse of angiotensin receptor blockers (aOR, 2.02 [95% CI, 1.03-3.96]) and dihydropyridine calcium channel blockers (aOR, 1.91 [95% CI, 1.03-3.55]) were associated with death. CONCLUSIONS: After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.

Demographics, comorbidities and outcomes in hospitalized Covid-19 patients in rural southwest Georgia.

BACKGROUND: There is limited data on outcomes in patients with coronavirus disease 2019 (Covid-19) in rural United States (US). This study aimed to describe the demographics, and outcomes of hospitalized Covid-19 patients in rural Southwest Georgia. METHODS: Using electronic medical records, we analyzed data from all hospitalized Covid-19 patients who either died or survived to discharge between 2 March 2020 and 6 May 2020. RESULTS: Of the 522 patients, 92 died in hospital (17.6%). Median age was 63 years, 58% were females, and 87% African-Americans. Hypertension (79.7%), obesity (66.5%) and diabetes mellitus (42.3%) were the most common comorbidities. Males had higher overall mortality compared to females (23 v 13.8%). Immunosuppression [odds ratio (OR) 3.6; (confidence interval (CI): 1.52-8.47, p=.003)], hypertension (OR 3.36; CI:1.3-8.6, p=.01), age ≥65 years (OR 3.1; CI:1.7-5.6, p<.001) and morbid obesity (OR 2.29; CI:1.11-4.69, p=.02), were independent predictors of in-hospital mortality. Female gender was an independent predictor of decreased in-hospital mortality. Mortality in intubated patients was 67%. Mortality was 8.9% in <50 years, compared to 20% in ≥50 years. CONCLUSIONS: Immunosuppression, hypertension, age ≥ 65 years and morbid obesity were independent predictors of mortality, whereas female gender was protective for mortality in hospitalized Covid-19 patients in rural Southwest Georgia. KEY MESSAGES Patients hospitalized with Covid-19 in rural US have higher comorbidity burden. Immunosuppression, hypertension, age ≥ 65 years and morbid obesity are independent predictors of increased mortality. Female gender is an independent predictor of reduced mortality.

Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020.

SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged ≥65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation† (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.

Topography of polyp recurrence in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo-sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy. This study aims to determine, in patients with polyp recurrence, the most common sinuses involved. METHODS: A prospective case-series was conducted on consecutive adult (≥18 years) post-FESS eCRS patients followed for a minimum of 12 months. All patients had a neo-sinus cavity created surgically and used corticosteroid irrigations daily for 3-6 months, then tapered to disease control. Sinus cavities were assessed by endoscopy on last follow-up. Polyp recurrence was defined as a score of 5 or 6 in the MLMES in ≥3 sinus cavities. Patient-reported outcomes based on SNOT22 and NSS, frequency of corticosteroid irrigations, and courses of systemic antibiotics and corticosteroid were collected. The pattern of sinus involvement was analyzed. RESULT: A total of 342 sinus cavities were assessed (mean ± standard deviation, 54.9 ± 13.4 years, 43.2% female). Polyp recurrence occurred in 4.3% (6.4% of patients, n = 7 unilateral) of sinus cavities. Frontal and ethmoid sinus cavities were most affected in those with polyp recurrence, compared to the maxilla and sphenoid (100% vs 100% vs 53% vs 53%, p < 0.01). Although those patients with polyp recurrence utilized more systemic corticosteroids courses per year (0.4 ± 0.4 vs 0.1 ± 0.3, p < 0.01), the use of corticosteroid irrigations was similar (% >4/week; 66.7% vs 48.9%, p = 0.13). Prior surgery was more common in patients with polyp recurrence (86.7% vs 53.5%, p = 0.01). CONCLUSION: The frontal and ethmoid sinuses were most affected in those patients with polyp recurrence. Whether the disease is more active in this location or topical therapy has limited access requires further evaluation.

Nasal mucosal brushing as a diagnostic method for allergic rhinitis.

Background: Allergen specific immunoglobulin E (spIgE) in the nasal mucosa is a biomarker for local allergic rhinitis. Inferior turbinate tissue biopsy is a sensitive method to detect nasal spIgE but is invasive. Nasal brushing is a relatively noninvasive method to detect nasal spIgE that may be of comparable diagnostic utility. Objective: To assess the performance of nasal brushing to obtain a nasal spIgE sample compared with an inferior turbinate tissue biopsy among patients who underwent turbinate surgery. Methods: A diagnostic cross-sectional study that involved participants who were undergoing turbinate surgery was performed. Nasal brushing, inferior turbinate tissue biopsy, blood collection, and skin-prick test (SPT) were performed perioperatively and tested for house-dust allergens. A receiver operating curve was used to assess the performance of the nasal brushings to obtain nasal spIgE samples compared with the inferior turbinate tissue biopsy. The diagnostic utility of nasal brushings of spIgE compared with serum spIgE testing and SPT was also assessed. Results: A total of 157 patients (41.61 ± 14.83 years; 37.6% women) were included. Nasal brushing was an excellent method to sample for nasal spIgE compared with inferior turbinate tissue biopsy (Area under curve (AUC) 0.87 [95% confidence interval {CI}, 0.81-0.93], p < 0.01). Positive house-dust allergen spIgE results of nasal brushings was defined as > 0.1 kUA/L. Nasal brushings for spIgE sampling was also able to predict the presence of serum spIgE (AUC 0.93 [95% CI, 0.89-0.97], p < 0.01) and SPT (AUC 0.80 [95% CI, 0.72-0.87], p < 0.01). Conclusion: Nasal brushing constituted an easy and relatively noninvasive method to sample nasal epithelium. This sampling technique was comparable with an inferior turbinate tissue biopsy and may be developed as a diagnostic tool for the diagnosis of local allergic rhinitis.

Atopy in chronic rhinosinusitis: impact on quality of life outcomes.

BACKGROUND: Chronic rhinosinusitis (CRS), in particular with nasal polyps (CRSwNP), has been linked with skewed T-helper 2 and immunoglobulin E (IgE)-mediated allergic responses. The role of atopy in CRS, however, remains unclear. Correlations between immunological allergic markers and patient-reported outcomes measures (PROMs) were investigated. METHODS: A cross-sectional study of adult patients with CRS undergoing endoscopic sinus surgery was conducted. Immunological allergic markers included automated immunoassay testing for serum-specific IgE to common allergens (house dust mite, grass, mold, animal epithelia) and total IgE. PROMs were assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22). Patients were defined as atopic based on either a positive specific IgE or elevated total IgE (>160 kU/L). RESULTS: A total of 446 patients (45.7% female, age 49.05 ± 14.96 years) were recruited, of which 42.8% had asthma, 51.6% had CRSwNP, and 63.0% had eosinophilic CRS. Positive allergen sensitization was detected in 52.9% patients. Total IgE levels were elevated in 28.0% with mean IgE level of 161 ± 269 kU/L. Atopy was associated with younger age at the time of surgery, CRSwNP, asthma, and eosinophilic CRS (eCRS). Atopy was also associated with increased severity in nasal symptom score (13.1 ± 6.4 vs 11.9 ± 6.0, p = 0.04), as well as worse scores in the loss of smell/taste (χ2 (1) = 5.97, p = 0.02) and need to blow nose (χ2 (1) = 4.26, p = 0.04) questions in the CRS population. In the CRSwNP population, there was no significant association between atopy and PROMs. CONCLUSION: Comorbid atopy in CRS is associated with additional symptom burden, reflected mainly within the nasal symptom quality of life markers. Atopy assessment in CRS is important to ensure appropriate and successful treatment of the disease.