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Background: Aspergillus is one of the most common pathogens causing fungal allergy in the respiratory tract. Serum Aspergillus fumigatus- specific immunoglobulin G (Af-sIgG) levels have been used as a biomarker for the diagnosis and treatment response monitoring in airway allergic diseases such as allergic bronchopulmonary aspergillosis and allergic fungal rhinosinusitis. However, its role in common primary chronic rhinosinusitis (CRS) was unclear. Objective: This study aims to evaluate whether serum Af-sIgG level could serve as a biomarker for the disease presentation of primary CRS. Methods: We obtained serum Af-sIgG levels from patients diagnosed as bilateral primary CRS refractory to medical treatment and evaluated the correlations between serum Af-sIgG levels and disease severity in patients with type 2 (T2) and non-T2 CRS. Results: Patients with T2 CRS exhibited significantly higher serum Af-sIgG levels than non-T2 CRS patients. The cut-off value of serum Af-sIgG in T2 CRS was 20.9 mg/L, with an odds ratio of 3.8 (95% CI 1.17-12.20, P =.026). Furthermore, serum Af-sIgG levels were positively correlated with symptom scores evaluated by the Sino-Nasal Outcome Test-22 (SNOT-22) scores in T2 patients (P =.009). While stratified by SNOT-22 total scores, patients with severe disease had higher serum Af-sIgG levels only in T2 CRS (P =.034). In individual domains of SNOT-22 analysis, serum Af-sIgG levels showed a significant correlation with "ear/facial" symptom scores in the T2 group (P <.001). Conclusions: Serum Af-sIgG levels may serve as a supplementary objective biomarker that correlates with identification and subjective measurements of T2 CRS, and may be associated with symptoms arising from Eustachian tube dysfunction. [ABSTRACT FROM AUTHOR]

Background: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years. Objective: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options. Methods: Review article. Results: Fungi-driven respiratory inflammation has been linked to fungal proteinases and toxin activity. In addition, AFRS patients demonstrate a local sinonasal immunodeficiency in antimicrobial peptides and hence limited antifungal activity, along with an exaggerated type 2 inflammatory response, highlighting a possible imbalanced type 1, type 2, and type 3 profile. The elucidation of these dysregulated molecular pathways has highlighted novel potential therapeutic targets. As such, the clinical management of AFRS, which once included surgery and extended courses of oral corticosteroids, is transitioning away from long courses of oral corticosteroids to incorporate novel delivery mechanisms of topical therapeutic targets and biologics for recalcitrant disease. Conclusion: AFRS is an endotype of CRS with nasal polyps (CRSwNP) for which the molecular pathways leading to its inflammatory dysfunction are beginning to be illuminated. In addition to affecting treatment options, these understandings may shape necessary changes to diagnostic criteria and the extrapolated effects of environmental changes on AFRS. More critically, a better appreciation of fungi-driven inflammatory pathways may have implications for the understanding of broader CRS inflammation. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis is a difficult-to-treat disease that is often characterized by recurrent nasal polyp (NP) growth following surgical removal. The disease has been separated into distinct phenotypes based on cellular infiltrate or underlying physiological mechanisms. NPs are composed in part of an inflammatory cellular infiltrate, blood vessels, and a large amount of extracellular matrix (ECM). Despite the recognition of prominent ECM deposition, few studies have examined the components in detail and how they might differ with disease state. Objective: The purpose of this study was to quantitate the expression of ECM components in NPs. Methods: NPs were stained with pico-sirius red to determine total collagen content, and immunofluorescence was used to detect collagen I, collagen III, collagen IV, fibronectin, and laminin. Expression of each was quantitated and analyzed in relation to rhinosinusitis phenotype and separately as a function of polyp eosinophil number. Results: When analyzed by phenotype, collagen I, collagen III, and fibronectin were expressed at the highest levels in noneosinophilic sinus disease. Collagen IV was not different among any groups, and its location was found predominately around vessels. When analyzed as a function of polyp eosinophil number, total collagen and collagen III showed a significant inverse correlation. Conclusions: NP ECM composition differs with disease state with higher expression in cases where eosinophil levels are low. This suggests that in eosinophilic polyps there is a loss of matrix deposition either through break down or a failure to produce the essential components. Understanding these differences may identify new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Allergic fungal rhinosinusitis (AFRS) is characterized by higher revision endoscopic sinus surgery (ESS) rates and unique radiographic features when compared to chronic rhinosinusitis with nasal polyposis (CRSwNP) or chronic rhinosinusitis without nasal polyposis (CRSsNP). Objective: We hypothesized that an increased frequency of concha bullosa in AFRS or other radiographic nuances might allow for accumulation of allergic mucin and contribute to increased ESS revision rates. Methods: A retrospective cohort study was performed. Patient diagnosis (AFRS, CRSwNP, and CRSsNP), basic demographics, and prior ESS rates were collected. Results: A total of 210 consecutive patients were included (AFRS = 70, CRSwNP = 70, and CRSsNP = 70). Pediatric AFRS patients had more unilateral disease (38.1% vs 4.4%; P =.007) and anterior ethmoid skull base erosion (23.8% vs 6.7%; P =.047) than adult AFRS patients. AFRS patients were more likely to be younger (24.9 ± 10.1 years vs 45.6 ± 14.4 years vs 48.7 ± 18.2 years; P <.001), African American (70% vs 14.3% vs 11.4%; P <.001), and have undergone prior ESS (54.3% vs 45.7% vs 31.4%; P =.02) than CRSwNP or CRSsNP patients. Concha bullosa were more prevalent in AFRS patients than CRSwNP or CRSsNP patients across the population (42.9%, 18.6%, and 14.3%; P <.001) and in the setting of no previous surgery (53.1%, 31.6%, and 16.7%; P <.001). Conclusion: In this cohort, pediatric AFRS patients had more unilateral disease and anterior ethmoid skull base erosion. Concha bullosa prevalence was significantly higher in AFRS as compared to those with CRSwNP or CRSsNP, despite prior ESS. Surgeons should consider concha bullosa as a potential anatomical subsite to harbor recurrent or residual disease. [ABSTRACT FROM AUTHOR]

7 Carney S. Current understanding of the role of eosinophils in CRSwNP and implications for treatment with mepolizumab and benralizumab. The past several years have been extraordinary in the advancement of our understanding of chronic rhinosinusitis with nasal polyps (CRSwNP) and the management options we have to benefit the lives of patients. 8 Tan B. B lineage cells and IgE in allergic rhinitis and CRSwNP and the role of omalizumab treatment. [Extracted from the article]

Objectives We reviewed the phenotyping and endotyping of chronic rhinosinusitis (CRS) and treatment options. Methods We searched PubMed, Google, Google Scholar, and the Proquest Central Database of the Kırıkkale University Library. Results Phenotypes are observable properties of an organism produced by the environment acting upon the genotype, that is, patients with a particular disorder are subgrouped according to common characteristics. Currently, CRS is usually phenotyped as being with (CRSwNP) or without (CRSsNP) nasal polyps. However, this is not immutable as some individuals progress from nonpolyp to polypoid CRS over time. Phenotypes of CRS are also based on inflammatory patterns, generally CRSwNP is eosinophilic, CRSsNP neutrophilic; but there is a spectrum, rather than a clear-cut division into 2 types. An endotype is a subtype of a condition defined by a distinct functional or pathobiological mechanism. Endotypes of CRS can be (1) nontype Th2, (2) moderate type Th2, and (3) severe type Th2 immune reactions, based on cytokines and mediators such as IL4, 5, 13. CRS endotyping can also include a (1) type 2 cytokine-based approach, (2) eosinophil-mediated approach, (3) immunoglobulin E-based approach, and (4) cysteinyl leukotriene-based approach. Subdivisions of CRSwNP can be made into nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergic fungal sinusitis, and eosinophil pauci-granulomatous arteritis by testing. General treatment for all CRS is nasal douching. The place of surgery needs careful reconsideration. Endotype-directed therapies include glucocorticosteroids, antibiotics, aspirin, antifungals, anticytokines, and immunoglobulin replacement. The recognition of united airways and the co-occurrence of CRSwNPs and severe asthma should lead to common endotyping of both upper and lower airways in order to better direct therapy. Conclusion Endotyping can allow for the identification of groups of patients with CRS with a high likelihood of successful treatment, such as patients with a moderate type 2 immune reaction or those with acquired immune deficiency. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s, contrasting articles have advocated and refuted the use of antifungal agents in its management. Although good research shows an interaction of the immune system with fungus in CRS, e.g., allergic fungal sinusitis (AFS), this does not imply that fungi are the cause of CRS or that antifungals will be effective in management. This study was designed to assess the potential advantage of either topical or systemic antifungal therapy in the symptomatic treatment of CRS to aid physicians in making informed decisions about treating patients with CRS. Methods: A systematic review of the literature was performed with meta-analysis. All studies obtained from searches were reviewed and trials meeting the eligibility criteria were selected. CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps or American Academy of Otolaryngology-Head and Neck Surgery criteria. Authors were contacted and original data were used for data analysis. Results: Five studies investigating topical antifungals and one investigating systemic antifungals met the inclusion criteria. All trials were double blinded and randomized. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo. Symptoms scores statistically favored the placebo group for this outcome. Adverse event reporting was higher in the antifungal group. Conclusion: Reported side-effects of antifungal therapies may outweigh any potential benefits of treatment based on this meta-analysis and the authors therefore do not advocate the use antifungal treatment in the management of CRS. [ABSTRACT FROM AUTHOR]

Background: The appropriate surgical approach to the severely diseased maxillary sinus is still debatable. Some advocate creating a wide maxillary antrostomy to allow for increased ventilation and improved delivery of postoperative medication. Others, however, recommend more aggressive surgery with complete clearance of all diseased tissue. The aim of this study was to evaluate the outcome of canine fossa puncture and canine fossa trephine (CFT) for the severely diseased maxillary sinus. Methods: A retrospective chart review was performed on 97 patients who underwent a CFT as a part of endoscopic sinus surgery or modified Lothrop procedure. Outcomes were measured in terms of the maxillary sinus endoscopy grade at last follow-up and need for revision surgery. Two groups were formed: those who experienced recurrence of disease and those who were disease free at last follow-up. A comparison was made between the two groups and differences were noted. Results: A CFT was performed in 97 patients with nasal polyposis (NP) who had an average number of 2.38 previous sinus surgeries. At an average follow-up of 27.8 months, 80 of the patients were disease free. In 17 patients disease recurred, and 11 of those required revision surgery with a CFT. Those patients who had recurrence of disease tended to be more allergic, have higher Lund-Mackay score, and had an increased number of prior sinus surgeries. In addition, allergic fungal sinusitis was associated with a poorer prognosis after CFT. Conclusion: CFT allows for complete clearance of all gross disease in the maxillary sinus. CFT decreases the chance of disease recurrence in patients with severe NP. [ABSTRACT FROM AUTHOR]

Background: Allergic fungal sinusitis (AFS) is considered a different disease from other polypoid chronic rhinosinusitis diseases (CRS) with eosinophilic mucus (EM) termed eosinophilic mucus chronic rhinosinusitis (EMCRS). To substantiate this, studies on cellular responses to fungi and sinus mucosal inflammatory cell populations in AFS and other EMCRS diseases are required. This study was designed to examine polyp inflammatory cell populations and peripheral blood fungal-specific T-cell responses in AFS, other EMCRS subgroups (defined later), and polypoid CRS without EM. Methods: A prospective study was performed. Clinical characteristics, including CRS symptoms, sinus computed tomography (CT) scans, allergy status, intraoperative endoscopy, presence of EM, and fungal culture results were used to define patient groups. Polyps and peripheral blood were examined for populations of eosinophils, lymphocytes (CD4+, CD8+ T cells, natural killer cells, and B cells), and neutrophils using immunohistochemistry, cytospin preparations and flow cytometry. Fungal-specific peripheral blood lymphocyte proliferation was examined in AFS patients, other EMCRS patients, CRS patients, and controls. Results: There was no significant difference in the percentage of cell populations and fungal-specific lymphocyte proliferation between AFS and other EMCRS diseases. However, AFS and other EMCRS polyps had a higher percentage of eosinophils and CD8+ T cells whereas CRS polyps had higher CD4+ T cells. Fungal-specific lymphocyte proliferation was significantly greater in AFS and other EMCRS patients regardless of fungal allergy, whereas in CRS and controls, higher proliferation was observed in fungal-allergic individuals. Conclusion: These findings question the basis for differentiating AFS from other EMCRS diseases based on fungal allergy and fungi in EM. Fungal-specific cellular response was present in AFS and other EMCRS diseases, different from that associated with fungal allergy, suggesting a nonallergic fungal immune response. Increased CD8+ T cells in EMCRS polyps signify a different type of inflammation to CRS that may be driven by CD8+ T cells. [ABSTRACT FROM AUTHOR]

Background: Oral itraconazole is an antifungal that has been shown to be of benefit to patients with allergic bronchopulmonary aspergillus (ABPA). It is hypothesized that itraconazole may similarly benefit patients with allergic fungal sinusitis (AFS), a disease similar to ABPA. This study was designed to evaluate the therapeutic response of itraconazole in patients with refractory chronic fungal sinusitis who have failed maximal medical and surgical therapy. Methods: A retrospective chart review was performed of 23 patients with AFS and nonallergic eosinophilic fungal sinusitis treated with oral itraconazole. Charts were reviewed for patient demographics, comorbidities, allergies, fungal cultures, type of surgery performed, and amount of oral steroids used before and after itraconazole. All patients were given a 6-month dose of itraconazole (100 mg b.i.d.) when recurrence developed after surgery. Time to next recurrence, change in oral steroid use, and outcomes were noted. Liver function tests were taken at monthly intervals while on itraconazole. Results: Twenty-three patients, 13 men and 10 women, were started on oral itraconazole for recurrent fungal sinusitis. Nineteen patients responded to the medication with a decrease in symptoms and fungal mucin/polyps on endoscopy. Three patients had to stop because of elevated liver enzymes. In the remaining 16 patients a decrease in oral steroid use was noted. In addition, 11 of the 16 patients are disease free to date at a mean follow-up of 15.7 months. No permanent complications occurred from the use of the medication. Conclusion: Oral itraconazole may be of benefit to those patients with recalcitrant fungal sinusitis who have failed maximal medical and surgical therapy. Itraconazole may prolong the time to next recurrence and may enable the patient to significantly decrease or stop oral steroids. [ABSTRACT FROM AUTHOR]

Objective: To investigate bony erosion patterns in allergic fungal sinusitis (AFS) and to determine whether the extent of erosion correlates with demographics and preoperative clinical parameters. Study Design: Retrospective review of prospectively collected data. Methods: Seventy-four patients with a histopathologic diagnosis of AFS were identified. Preoperative computed tomographies (CT) were reviewed to determine sites with bony erosion. The 20-item Sinonasal Outcomes Test (SNOT-20) scores, endoscopy scores, and Lund-Mackay CT scores were compared between patients with and without bony erosion. Patients with bony erosion were further classified based on the extent of erosion. Statistical analysis was performed by using the Student's t-test and the χ2 test of independence. Results: Of the 74 patients, 39 (52.7%) had bony erosion and 35 (47.3%) did not. Bony erosion was found to be associated with younger age (27.5 versus 36.0 years; p = 0.011) and African American race (p = 0.041). Preoperative CT scores correlated with the presence and extent of bony erosion (p = 0.010). Sex, race, number of previous surgeries, SNOT-20 scores, and endoscopy scores did not correlate significantly. Conclusion: Younger age and African American race were found to significantly correlate with bony erosion in AFS, which indicated that a more severe inflammatory response was mounted in these patient groups. As expected, higher Lund-Mackay scores correlated with the severity of erosion. The lack of correlation with SNOT-20 scores indicated the insidious nature of this destructive disease. The level of evidence is 4. [ABSTRACT FROM AUTHOR]