Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease\'s pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

We conducted this study to determine if serum galactomannan (GM) can be used as a marker to implicate the invasiveness of allergic fungal rhinosinusitis (AFRS), and correlate this value with the aggressiveness of disease documented via computed tomography (CT). All paranasal CT scans done for AFRS patients prospectively over a five-year period (2015-2019) were included. An indigenous 20-point score was used to document the extent of bone erosion seen on CT, wherein a higher score meant a greater extent of bone erosion. It was then correlated with serum GM scores. The median CT scores of galactomannan-positive (GM+) patients were compared with the median CT scores of galactomannan-negative (GM-) patients 3 using Mann-Whitney U test. The patients were divided into five groups based on the extent of disease-No bone erosion, erosion of only sinus wall/orbit, 3 erosion of orbit and skull base, erosion of only skull base and lateral extension of disease into infratemporal fossa (ITF). Subgroup analysis was conducted over mean GM values in these groups using ANOVA test. p-value < 0.05 was considered significant. Statistical analysis was performed using SPSS version 25.0. A total of 92 patients were included (56 males, 36 females). No statistically significant difference was found (p-value = 0.42) between the CT scores of galactomannan-positive (GM+) group and galactomannan-negative (GM-) group. The mean GM scores amongst the five sub-groups did not show a statistically significant difference. Serum galactomannan values correlate poorly with aggressiveness of disease quantified on non-contrast CT of paranasal sinuses.

To evaluate Neutrophil Lymphocyte ratio (NLR) as a predictor of disease severity in Nasal Polyposis and Allergic Fungal Rhinosinusitis (AFRS). This was a prospective non-randomized interventional study. Disease severity was graded based on endoscopic and CT scoring. Patients were given pre-operative oral steroids for two weeks and taken up for surgery. The pre-treatment neutrophil lymphocyte ratios were calculated from the differential leucocyte counts and compared with the disease severity and post-operative values. In the interventional arms, the disease severity correlated with the NLR. The mean pre-treatment NLR showed a statistically significant change after the intervention at eight weeks. The NLR normalized in patients with nasal polyposis and continued to be higher in patients with AFRS. NLR correlated to the disease severity and showed a linear correlation with the extent of the disease. NLR could be a potential cost-effective marker for disease severity and prognostication. Level of Evidence: Individual Cohort Study (2b).

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) which is distinguished by the presence of eosinophilic mucin, type 1 hypersensitivity reaction resulting from fungi residing within the sinus, and characteristic imaging findings of the paranasal sinuses. Surgical intervention, sinonasal irrigations, and topical and systemic medications are commonly used to reduce the fungal load and antigenic stimulation. Despite the advancement of medical and surgical management of AFRS, a high recurrence rate is still a significant concern. The proper treatment for refractory AFRS remains controversial. Herein, we discuss the use of dupilumab for controlling refractory AFRS. We report a case of a 33-year-old female patient known to have had AFRS for 16 years. Due to the recurring nature of her illness, 16 functional endoscopic sinus surgeries (FESS) have been done to control her symptoms. The last operation was done in our institution; evidence for cure was insufficient with the persistence of symptoms. After a consensus decision with the multidisciplinary management team, she was an appropriate candidate for therapy with dupilumab. After six months of using the medication, magnificent improvement and control of symptoms were noted, and post-treatment CT scans illustrated excellent progression from previous scans. AFRS could be an extremely debilitating disease with significant impairment of quality of life even when standard therapy and extensive surgical interventions are implemented. Dupilumab can be an excellent option as a salvage therapy for recalcitrant AFRS with significant improvement in patients\' quality of life and resolution of symptoms.

OBJECTIVE: The diagnostic criteria of allergic fungal rhinosinusitis focus on characteristic clinical, radiographic, histopathologic findings and immunologic characteristics of the disease. None of these are useful for a prompt outpatient diagnosis of the condition. No clear endoscopic signs (pathognomonic) of polyps in allergic fungal rhinosinusitis are mentioned in the literature.
OBJECTIVE: The objective of this study is to describe and evaluate the sensitivity and specificity of an endoscopic sign the intrapolypoidal white particles for the diagnosis of allergic fungal rhinosinusitis in outpatient setting.
METHODS: In a descriptive, cross-sectional study, 46 chronic rhinosinusitis patients were examined by endoscope in the outpatient clinic. The endoscopic images of the nasal polypi were captured preoperatively. During endoscopic surgery, a sample of nasal polypi was taken for fungal staining and culture. Results of histopathology were compared to the impression of rhinologist on the images of nasal polypi captured preoperatively.
RESULTS: The most common endoscopic features were the expansion of sinus (24, 52.2%) and intrapolypoidal white particles (50%). Intrapolypoidal white particles were calculated to have 85.71% sensitivity, 65.63% specificity, 52.17% positive predictive value, 91.3% negative predictive value and 71.74% diagnostic accuracy.
CONCLUSIONS: This study offers a new endoscopic sign, intrapolypoidal white particles for diagnosing allergic fungal rhinosinusitis.

OBJECTIVE: Allergic fungal rhinosinusitis (AFRS) forms a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) that is mainly characterized by eosinophilic nasal polyps, allergic mucin detected in the sinuses at surgery, and specific features on computerized tomography. Which biological markers predict disease recurrence in AFRS is still not clear, and the role of blood inflammatory cells in predicting recurrent polyps after surgery has yet to be investigated. The aim of this study was to newly investigate the prognostic role (in terms of recurrence rate) of preoperative blood eosinophil and basophil levels in AFRS.
METHODS: A consecutive series of 17 adult patients who underwent endoscopic sinus surgery for AFRS was retrospectively assessed.
RESULTS: Sinonasal polyps recurred in 7 of 17 patients. Considering the whole cohort, a significant positive correlation emerged between blood eosinophil and basophil counts, but not between blood and tissue eosinophil counts. Statistical analysis found significantly higher blood eosinophil and basophil levels in AFRS patients who relapsed than in those who did not.
CONCLUSIONS: Considering the current difficulty of identifying more effective, personalized approaches to postoperative disease management in AFRS, our preliminary data support the impression that blood eosinophil and basophil levels warrant testing in further prospective and larger (preferably multi-institutional) investigations as part of the preoperative work-up for patients with AFRS in order to administer dedicated postoperative medical treatments for patients at higher risk of relapse.

The aim of this study was to report on 2 patients in whom metal-on-metal (MOM) facet replacements failed, with subsequent positive findings on allergy testing. Motion-preserving devices have been used with limited success when instrumentation is indicated in the mobile spine. MOM-bearing surfaces in orthopedics were developed to increase implant longevity, yet have been associated with numerous adverse outcomes, including local tissue reactions, pseudotumors, metallosis, and the need for revision surgery. Five patients with spinal stenosis and low-grade spondylolisthesis were randomized to undergo facet replacement surgery with the ACADIA facet replacement system at the authors\' institution. Two patients experienced a return of neurological symptoms after a pain-free interval (< 2 years) with development of local tissue reaction and positive findings on allergy testing to cobalt, the metal in the MOM-bearing surface. Both patients underwent successful removal of the implant and revision to titanium posterior spinal fusion and interbody fusion without further complication. Motion-preserving devices have been designed and trialed for specific indications in the mobile spine. Given the adverse results from MOM devices in hip arthroplasty and now the early reports with MOM facet replacements, caution is warranted when moving forward with any MOM joint-bearing surface. Both patients presented here had an unusual tissue reaction locally and subsequent positive allergy testing results to cobalt. These 2 patients appear to have developed a delayed hypersensitivity reaction to the metal, likely from fine debris at the MOM interface.

To understand human exposure to dust-associated flame retardants in the biggest metropolitan area (city of Shanghai) of East China, our study determined a suite of legacy and emerging flame retardants in dust from dwellings, cars, and university computer labs. The results exhibited a consistent dominance of organophosphate flame retardants (OPFRs) over polybrominated diphenyl ethers (PBDEs) and other alternative flame retardants (AFRs) regardless of microenvironments. In addition to OPFRs, some alternative flame retardants, such as decabromodiphenyl ethane (DBDPE), 2-ethylhexyltetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)-3,4,5,6-tetrabromobenzoate (BEH-TEBP), and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), were also frequently detected. Among them, DBDPE exhibited concentrations comparable to those of PBDEs. Comparison with international studies indicated that concentrations of ∑PBDEs (0.2-12.3 μg/g dry weight or dw) and ∑OPFRs (3.8-165.5 μg/g dw) from Shanghai dwellings (bedroom and living room) were generally in the middle of concentration ranges reported worldwide, whereas elevated DBDPE concentrations (0.1-9.5 μg/g dw) was observed compared with most other countries or regions. OPFR compositions in house dust from this study also differed from those from many other countries. This suggested inter-regional differences in market demands on the quantities and types of flame retardants. Human intake estimation suggested elevated exposure for toddlers when compared with adults, although the daily intake estimations of individual flame retardants were generally 2-4 orders of magnitude lower than the reference doses. The findings from this preliminary study developed a baseline for future evaluation of the sources and fate of emerging flame retardants and related human exposure risks in East China.

Aspergillus fumigatus can cause several allergic disorders including Aspergillus-sensitized asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergic fungal rhinosinusitis (AFRS). ABPA is an immunological pulmonary disorder caused by allergic reactions mounted against antigens of A. fumigatus colonizing the airways of patients with asthma (and cystic fibrosis). Allergic bronchopulmonary mycosis is an allergic fungal airway disease caused by thermotolerant fungi other than A. fumigatus On the other hand, AFRS is a type of chronic rhinosinusitis that is also a result of hypersensitivity reactions to the presence of fungi that become resident in the sinuses. The pathogenesis of ABPA and AFRS share several common features, and in fact, AFRS can be considered as the upper airway counterpart of ABPA. Despite sharing similar immunopathogenetic features, the simultaneous occurrence of the two disorders is uncommon. Due to the lacuna in understanding of the causative mechanisms, and deficiencies in the diagnosis and treatment, these disorders unfortunately are lifelong illnesses. This review provides an overview of the pathogenesis, diagnosis, and long-term outcomes of both these disorders.