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Background: There is clear evidence that the prevalence of primary antibody deficiency (PAD) is higher in patients with recurrent and chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi‐institutional and multidisciplinary evidence‐based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in patients with PAD. Methods: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through August 2022. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. Results: A total of 42 studies were included in this evidence‐based review. These studies were evaluated on incidence of PAD in rhinosinusitis patients, incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence was varied across reviewed domains. Conclusion: Based on the currently available evidence, PAD can occur in up to 50% of patients with recalcitrant CRS. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher‐level studies that compare different treatments in patients with PAD and rhinosinusitis. [ABSTRACT FROM AUTHOR]

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. We systematically synthesized the evidence addressing INCS for CRSwNP. We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] −6.83, 95% confidence interval [CI] −11.94 to −1.71) and exhalation delivery system (EDS) (MD −7.86, 95% CI −14.64 to −1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD −0.31, 95% CI −0.54 to −0.08), spray (MD −0.51, 95% CI −0.61 to −0.41), and EDS (MD −0.35, 95% CI −0.51 to −0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger , and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease. [ABSTRACT FROM AUTHOR]

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P =.02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short‐read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota. [ABSTRACT FROM AUTHOR]

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal "microbiotypes" or "states": the first is Corynebacterium -dominated, the second is Staphylococcus -dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella , and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus , suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future. [ABSTRACT FROM AUTHOR]

Objective: Chronic rhinosinusitis (CRS) has been associated with comorbid depression, yet the prevalence of depression among all patients with CRS is not well described. The Patient Health Questionnaire-9 (PHQ-9), a validated instrument for diagnosing depression, has been used to assess depression in a variety of clinical settings. PHQ-9 scores ≥10 are the threshold for a depression diagnosis. The purpose of this study was to assess the prevalence of depression in a rhinology practice and compare the PHQ-9 with the 22-item Sinonasal Outcome Test (SNOT-22).Study Design: Retrospective chart review.Setting: Tertiary rhinology practice.Subjects and Methods: During the 2-month period ending April 30, 2018, all rhinology patients were asked to complete the PHQ-9 and SNOT-22.Results: Among 216 patients, 46 (21.3%) had a self-reported history of depression, and 39 (18.1%) had a PHQ-9 score ≥10. Of the 39 patients screening positive for depression, 18 (41.9%) had no history of depression. Comparison of PHQ-9 with overall SNOT-22 score had a Pearson's coefficient of 0.632 (P < .005). Logistic regression showed that the highest 2 quintiles of SNOT-22 scores had an odds ratio of 60.6 (95% CI, 9.7-378.3) for a positive depression screen (PHQ-9 score ≥10).Conclusion: Depression rates (estimated by PHQ-9 responses) among rhinology patients are similar to chronic disease populations; depression may be underdiagnosed in rhinology patients. Higher SNOT-22 scores were associated with higher PHQ-9 scores. Further studies are warranted to understand the impact of comorbid conditions of depression and CRS in patient quality of life. [ABSTRACT FROM AUTHOR]

Objective: In the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP), Aspergillus fumigatus (A. fumigatus) can upregulate IL-33 from human sinonasal epithelial cells (SNECs), which then activates innate lymphoid cells causing release of IL-13, an important driver of allergic inflammation. However, the mechanism by which A. fumigatus mediates the induction of IL-33 expression remains to be elucidated. The objectives of this study were to determine the specific fungal component(s) and the receptor responsible for mediating the A. fumigatus induced increase in IL-33 expression in SNECs from patients with CRSwNP.Methods: SNECs from CRSwNP patients were cultured and stimulated with various fungal components in the absence or presence of 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride, an irreversible serine protease inhibitor, or GB83, a reversible protease activated receptor 2 (PAR2) inhibitor. IL-33 expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). PAR2 expression was examined in inflamed mucosa from nonatopic control and CRSwNP patients.Results: Elevation of IL-33 expression in primary SNECs was found in response to fungal protease but not fungal cell wall components. PAR2 expression was elevated in inflamed mucosa from CRSwNP patients in comparison to controls. The A. fumigatus fungal protease-mediated elevation in IL-33 expression by human SNECs was serine protease- and PAR2-dependent.Conclusion: These data suggest that serine protease activity of A. fumigatus is capable of inducing IL-33 expression in CRSwNP SNECs via PAR2, a potential therapeutic target in the treatment of CRSwNP.Level Of Evidence: NA Laryngoscope, 129:2230-2235, 2019. [ABSTRACT FROM AUTHOR]

The allergic airway diseases, including chronic rhinosinusitis (CRS), asthma, allergic bronchopulmonary mycosis (ABPM) and many others, comprise a heterogeneous collection of inflammatory disorders affecting the upper and lower airways and lung parenchyma that represent the most common chronic diseases of humanity. In addition to their shared tissue tropism, the allergic airway diseases are characterized by a distinct pattern of inflammation involving the accumulation of eosinophils, type 2 macrophages, innate lymphoid cells type 2 (ILC2), IgE-secreting B cells, and T helper type 2 (Th2) cells in airway tissues, and the prominent production of type 2 cytokines including interleukin (IL-) 33, IL-4, IL-5, IL-13, and many others. These factors and related inflammatory molecules induce characteristic remodeling and other changes of the airways that include goblet cell metaplasia, enhanced mucus secretion, smooth muscle hypertrophy, tissue swelling and polyp formation that account for the major clinical manifestations of nasal obstruction, headache, hyposmia, cough, shortness of breath, chest pain, wheezing, and, in the most severe cases of lower airway disease, death due to respiratory failure or disseminated, systemic disease. The syndromic nature of the allergic airway diseases that now include many physiological variants or endotypes suggests that distinct endogenous or environmental factors underlie their expression. However, findings from different perspectives now collectively link these disorders to a single infectious source, the fungi, and a molecular pathogenesis that involves the local production of airway proteinases by these organisms. In this review, we discuss the evidence linking fungi and their proteinases to the surprisingly wide variety of chronic airway and systemic disorders and the immune pathogenesis of these conditions as they relate to environmental fungi. We further discuss the important implications these new findings have for the diagnosis and future therapy of these common conditions. [ABSTRACT FROM AUTHOR]

Asthma, chronic rhinosinusitis, and related incurable allergic afflictions of the upper and lower airways are medically important because of their association with the disabling symptom of dyspnea and, at least for asthma, the potential to cause fatal asphyxiation. Extensive research over the past two decades has uncovered both the physiological basis of airway obstruction in asthma and key governing molecular pathways. Exaggerated airway constriction in response to diverse provocative stimuli, termed airway hyperresponsiveness, is mediated through the cytokines interleukin 4 (IL-4) and IL-13 and the transcription factor signal transducer and activator of transcription 6 (STAT6). Overproduction of mucus has long been known to be an essential second component of airway obstruction and is also mediated in part through the IL-4/IL-13/STAT6 pathway. In this review, we discuss a second major signaling pathway which underlies mucus production that is mediated through proteinase-cleaved fibrinogen signaling through Toll-like receptor 4. Unexpectedly, our analysis of human sputum and paranasal sinus fluid indicates that in most cases of severe allergic airway disease, a unique type of airway fungal infection, termed airway mycosis, is pathogenically linked to these conditions. We further discuss how fungal and endogenous proteinases mediate the fibrinogenolysis that is essential to both Toll-like receptor 4 signaling and fibrin deposition that, together with mucus, contribute to airway obstruction. [ABSTRACT FROM AUTHOR]

Objective The recent development of endotypes to categorize disease variants of chronic rhinosinusitis (CRS) reflects an evolving understanding of the various pathophysiologic and pathogenetic mechanisms that contribute to the clinical heterogeneity of CRS manifestations. This review highlights popular endotype-based criteria used to define different CRS with nasal polyposis (CRSwNP) subtypes and further discusses the emerging therapeutic advances for each classificatory approach. Data Sources PubMed literature review. Methods A review of the current literature was conducted to determine present-day uses of immunologic and molecular profiles in the CRSwNP disease spectrum to identify specific endotypes. Results Four distinct but overlapping classification schemes have emerged to define endotypes within the CRSwNP phenotype: 1) type 2 cytokine-based approach, 2) eosinophil-based approach, 3) immunoglobulin (Ig)E-based approach, and 4) cysteinyl based approach. The identification of key inflammatory biomarkers related to these CRSwNP endotypes has broadened the classification of CRS beyond common phenotypic expressions. Furthermore, CRSwNP endotypes may improve the selection of CRSwNP patients who are suitable candidates for biomarker-specific treatment options, such as anti-interleukin-5; anti-IgE; and platelet-directed therapies. Conclusion Chronic rhinosinusitis endotyping with key biomarker patterns of inflammation allows for improved diagnostic and potentially therapeutic classifications of CRSwNP variants. [ABSTRACT FROM AUTHOR]

Background Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. [ABSTRACT FROM AUTHOR]

Objectives: We compared anesthesia with sevoflurane-remifentanil hydrochloride (SR) to total intravenous anesthesia with propofol-remifentanil hydrochloride (PR) in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis in terms of sinonasal mucosal blood flow, the surgical field visualization score, and blood loss. Methods: We performed a double-blinded prospective study at a tertiary care center in 23 adults scheduled to undergo endoscopic sinus surgery for chronic rhinosinusitis. The patients were randomized to receive SR or PR. The sinonasal mucosal blood flow was measured by optical rhinometry. The surgical field visualization score was based on the Boezaart scale. Results: The groups had similar clinical characteristics. During the 60- to 90-minute and 90- to 120-minute operative time windows, the blood flow was significantly greater in the PR group than in the SR group (p = 0.04 and p = 0.03, respectively). The amounts of blood loss in the PR and SR groups were 152.9 ± 161.3 mL and 355.9 ± 393.4 mL, respectively (p = 0.12). The median ratios of the surgical field visualization score to the number of sinuses operated on in the PR and SR groups were 2.1 and 1.8, respectively (p = 0.52). Conclusions: The intraoperative blood flow, as determined by optical rhinometry, was significantly greater with anesthesia with PR than with anesthesia with SR, 1 hour into the procedure; however, this difference did not translate into differences in the amounts of operative blood loss or in the surgical field visualization scores. [ABSTRACT FROM AUTHOR]

Background: The etiology of allergic fungal rhinosinusitis (AFRS) remains controversial. Initially thought to represent an immunoglobulin E (IgE)-mediated hypersensitivity to fungal antigens, additional data have implicated other non-IgE and cellular-mediated pathways. The aim of this study was to characterize T-helper type 1 (Th1) and Th2 immune responses of blood lymphocytes from AFRS patients by fungal antigen stimulation to help differentiate these possible pathways. Methods: Peripheral blood mononuclear cells (PBMCs) isolated from AFRS patients (n = 10) and healthy controls (HCs; n = 11) were exposed to four different fungal extracts (Alternaria, Aspergillus, Cladosporium, and Penicillium) in duplicate. After a 72-hour incubation, the supernatants were analyzed for cytokine levels of three Th1 (interferon [IFN] gamma, interleukin [IL]-2, and tumor necrosis factor alpha) and three Th2 (IL-10, IL-5, and IL-4) cytokines by cytometric bead array flow cytometry. Serum fungal-specific IgE levels were measured by ImmunoCAP (Pharmacia Diagnostics, Kalamazoo, MI). Results: Fungal extracts of Alternaria and Cladosporium stimulated higher levels of IL-5 from PBMCs in AFRS when compared with HCs (p < 0.05). IL-4 was also elevated for Alternaria in AFRS versus HCs (p < 0.05). A skewed Th2 response to fungal antigen exposure was confirmed by an elevated IL-5/IFN-gamma ratio in AFRS subjects (p < 0.05). Initial studies suggest a correlation between percent T-cell activation and IL-5 expression to IgE levels. Fungal antigens stimulated a notable but not statistically significant increase in IL-10 response in HCs. Conclusion: In AFRS patients, fungal antigens stimulated T-cell activation, inducing a predominately Th2 immune response. Healthy controls expressed an inhibitory cytokine IL-10 when exposed to these fungal antigens, possibly serving as a protective response. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion There is clear evidence that prevalence of primary antibody deficiency (PAD) is higher in children with chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi‐institutional and multidisciplinary evidence‐based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in children with PAD.The PubMed, Embase, and Cochrane databases were systematically reviewed from inception through December 2023. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated.A total of 50 studies were included in this evidence‐based review. These studies were evaluated on the incidence of PAD in rhinosinusitis patients, the incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence varied across the reviewed domains.Based on the currently available evidence, the incidence of PAD in children with recalcitrant CRS can be significantly elevated. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher level studies that compare different treatments in children with PAD and rhinosinusitis. [ABSTRACT FROM AUTHOR]

Summary: Biologics have recently been approved for use in chronic rhinosinusitis with nasal polyps patients. While effective in controlling disease on subjective and objective short‐term outcome measures, limited data suggest that biologics have the potential to be used long term. The current wholesale acquisition costs for biologics are quite high. Widespread, prolonged use of these medications may create a large burden to our healthcare system. Cost‐effectiveness analyses, particularly for specific patient cohorts, are needed to determine appropriate use of these medications. The ethics of patient preference of various treatment options, counseling regarding side effect profiles, and healthcare economics also need to be addressed. [ABSTRACT FROM AUTHOR]

Background: The escalating negative impact of climate change on our environment has the potential to result in significant morbidity of rhinologic diseases. Methods: Evidence based review of examples of rhinologic diseases including allergic and nonallergic rhinitis, chronic rhinosinusitis, and allergic fungal rhinosinusitis was performed. Results: The lower socioeconomic population, including historically oppressed groups, will be disproportionately affected. Conclusions: We need a systematic approach to improve healthcare database infrastructure and funding to promote diverse scientific collaboration to address these healthcare needs. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the sinonasal mucosa consisting of poorly defined subtypes and characterized by variable clinical manifestations, responses to therapy, and underlying pathophysiologies. In the related disorder of asthma, progress has been made in defining disease subtypes on both clinical and pathophysiologic levels, facilitating the development of targeted biologic pharmacotherapy. The potential role of these drugs for the management of CRS will be reviewed. The objective of this work is to highlight the emerging therapeutic targets in CRS in light of evolving treatment options for asthma and enhanced understandings of the clinical manifestations and pathophysiology of CRS. Methods This article is a review of recent studies regarding current and future advances in biomarker-directed therapies in the medical treatment of CRS. Results Various biologic therapies used in the management of asthma have demonstrated clinical promise for CRS, particularly within the CRS with nasal polyposis (CRSwNP) phenotype. Several randomized, double-blind, placebo-controlled studies increasingly support the targeting of immunoglobulin E (IgE) and interleukin (IL)-5 pathways to improve outcome measures in CRSwNP patients. The IL-4/IL-13 pathway and other type 2 inflammatory pathways have also shown potential as targets for CRSwNP, but all pathways require further investigation. Conclusion Recalcitrant CRS in the United States and Europe is most commonly associated with nasal polyposis and a type 2 cytokine skewing in the tissue, resulting in tissue infiltration of eosinophils, mast cells, and basophils. Targeting biomarkers of the associated type 2 pathways may be a practical treatment option for recalcitrant CRSwNP in the future. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of allergic fungal rhinosinusitis (AFRS) is thought to represent an immunological reaction to fungal antigens. Recent studies have implicated superantigens and non-immunoglobulin E (IgE)-mediated mechanisms in the development of AFRS. The objective of this study is to assess the prevalence of Staphylococcus aureus in AFRS vs other subsets of chronic rhinosinusitis with polyps (CRSwNP, also termed non-AFRS). Methods A case series with retrospective review of 19 patients with AFRS and 21 patients with CRSwNP was performed at a tertiary referral center. The diagnosis of AFRS required the presence of defined criteria described by Bent and Kuhn. Bacterial cultures and fungal cultures were analyzed for each group. Results S. aureus was significantly more prevalent in the AFRS group compared with the non-AFRS group (63.2% vs 24.1%, p = 0.005). Conclusion S. aureus has been implicated as a disease modifier in CRSwNP through superantigen-mediated mechanisms. This study demonstrates a higher prevalence of S. aureus in patients with AFRS vs patients with other subsets of CRSwNP (non-AFRS). These results support a potential role for S. aureus in the pathogenesis of AFRS. [ABSTRACT FROM AUTHOR]

As many as 30% of AFRS patients exhibit extrasinus expansion into intracranial and orbital compartments without tissue invasion.3 AFRS patients commonly report nasal congestion, thick nasal drainage, and loss of sense of smell, but visual disturbances or facial deformity may result in severe cases.4 AFRS is a challenging CRSwNP subtype to treat given the frequently advanced presentation of disease with extensive, difficult to clear, sticky eosinophilic mucin laden with fungal hyphae. The classic diagnosis of AFRS requires strictly meeting all components of these criteria.8 However, limited reports have suggested that AFRS can progress to an invasive form of fungal sinusitis in certain clinical scenarios.9 As to whether this represents a distinct subtype of AFRS observed in immunocompromised hosts remains unclear. Six of the 32 patients with negative serum fungal-specific IgE had fungal-specific IgE levels within the mucin.13 Although the importance of local IgE reactivity in the absence of systemic IgE elevation is not clear, this phenomenon emphasizes the limits of the current diagnostic criteria for AFRS, especially because these patients would not meet current criteria. [Extracted from the article]

In the last two decades, the development of culture‐independent genomic techniques has facilitated an increased appreciation of the microbiota‐immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial. Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have focused on the bacterial community, mainly highlighting the loss of diversity associated with sinus inflammation. Within the various CRS with nasal polyps (CRSwNP) phenotypes, allergic fungal rhinosinusitis presents an opportunity to investigate the role of fungi in chronic type 2 immune responses as well as the antifungal immune pathways designed to prevent invasive fungal diseases. In this review, we examine the spectrum of fungi‐associated sinus diseases highlighting the interaction between fungal species and host immune status on disease presentation. With a focus on fungi and type 2 immune response, we highlight the current knowledge and its limitations of the sinus mycobiota along with cellular interactions and activated molecular pathways linked to fungi. [ABSTRACT FROM AUTHOR]

I. Executive Summary: Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS. [ABSTRACT FROM AUTHOR]

Background: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness. Methods: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients. Results: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice. Conclusion: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long‐term effects of biologics. [ABSTRACT FROM AUTHOR]

Background Ear symptoms are common among patients presenting to a rhinology clinic. Validated inventories are available for patient quality-of-life in sinonasal disease and Eustachian tube dysfunction (ETD). This study sought to determine the extent of ETD symptoms, using validated metrics, in a large population of patients presenting to a tertiary rhinology clinic. Methods Seven-item Eustachian Tube Dysfunction Questionnaires (ETDQ-7) and 22-item Sino-Nasal Outcome Tests (SNOT-22) were prospectively collected from 492 patients treated in a tertiary rhinology clinic. Patient diagnoses were retrospectively determined from the medical record. Correlation between reported SNOT-22 and ETDQ-7 scores were analyzed, in addition to the number of patients meeting the criterion score for ETD. Results A total of 213 patients reported mean ETDQ-7 scores >2.1, consistent with a diagnosis of ETD. Overall SNOT-22 scores were strongly correlated with ETDQ-7 scores ( r = 0.679, p < 0.001). The SNOT-22 ear subdomain was very strongly correlated with the ETDQ-7 score ( r = 0.847, p < 0.001), while there was a moderate correlation with the SNOT-22 rhinologic subdomain ( r = 0.486, p < 0.001). Patients with allergic fungal sinusitis had decreased ETDQ-7 scores compared to patients with other rhinologic diagnoses ( p = 0.010). Conclusion Symptoms of ETD are common in patients treated in a rhinology clinic, with 43.3% of patients reporting symptom scores consistent with a formal diagnosis of ETD. Increased SNOT-22 scores are correlated with increased ETDQ-7 scores, even when only the SNOT-22 rhinologic subdomain is considered. Patients presenting for treatment of rhinologic symptoms likely have an increased prevalence of otologic symptoms and ETD. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) and asthma describe inflammation of the upper and lower airway, respectively. Not surprisingly, the prevalence of CRS and asthma has been linked, with up to 50% asthma prevalence in CRS with nasal polyposis (CRSwNP) patients. However, these prevalence rates do not address subtypes of CRSwNP including allergic fungal rhinosinusitis (AFRS). This study sets out to objectively determine asthma prevalence in CRS subtypes prospectively. Methods A prospective prevalence study of adult CRS patients was conducted over a 1-year period at a tertiary care center. Patients were grouped into CRSwNP, CRS without nasal polyposis (CRSsNP), or AFRS. Patients were administered the Asthma Screening Questionnaire (ASQ) and asthma was confirmed by pulmonary function testing (PFT) if positive on the ASQ. Chi square analysis was performed to compare the asthma prevalence among the CRS subtypes. Results A total of 410 patients (age 48.1 ± 16.4; 53.5% male) were included. Of these, 178 (43.4%) had CRSwNP, 166 (40.5%) had CRSsNP, and 66 (16.1%) met criteria for AFRS. Analysis revealed that 48.3% of CRSwNP patients, 16.5% of CRSsNP patients, and 23.6% of AFRS patients had asthma confirmed by PFTs. Chi square analysis showed a significant difference in asthma prevalence between CRSwNP and AFRS ( p = 0.0016) and CRSwNP and CRSsNP ( p = 0.0000), but no significant difference between CRSsNP and AFRS ( p = 0.2380). Conclusion There is a significant difference in the prevalence of asthma between CRSwNP and AFRS, suggesting a fundamental distinction in their etiologies despite similar immunologic profiles. Further efforts to delineate these biological disparities are underway. [ABSTRACT FROM AUTHOR]

Background: Initial attention on the pathophysiology of chronic rhinosinusitis (CRS) has focused on eosinophils. Other immune cells such as mast cells (MCs) have been identified and appear to be elevated in CRS with nasal polyp (NP) patients. MCs are commonly linked to immunoglobulin E (IgE)-mediated inflammatory changes characterized by elevated T helper 2 cytokines. Although atopy is a common comorbid condition with CRS, the objective of this study was to determine if elevated MCs are linked primarily to atopic status in CRS patients and to understand the significance of MCs in the pathophysiology of CRS. Methods: Ethmoid sinonasal mucosa from patients undergoing endoscopic sinus surgery was harvested from 3 groups: healthy control (HC), CRS without NP (CRSsNP), and CRS with NP (CRSwNP) and analyzed by flow cytometry to quantify CD117+/CD203c+ MCs and CRTH2+ CD4+ T cells. Relative expression of prostaglandin D2 synthase in ethmoid mucosa was determined by quantitative real-time polymerase chain reaction (PCR). Results: MCs were significantly elevated in CRSwNP patients as compared to CRSsNP patients and HCs. This elevation was not solely dependent on the presence of IgE-mediated hypersensitivity. Relative expression of prostaglandin D2 synthase was also increased in CRSwNP patients along with an associated presence of a CRTH2+ memory CD4+ T cell population. Conclusion: Elevated percentages of MCs are found in the sinonasal mucosa of CRSwNP patients, regardless of atopic status. Secreted by MCs, elevated prostaglandin D2 may play a role in the recruitment of CRTH2+ cells to the inflamed mucosa of CRSwNP patients © 2012 ARS-AAOA, LLC. [ABSTRACT FROM AUTHOR]