Prognostic role of blood eosinophil and basophil levels in allergic fungal rhinosinusitis (AFRS).

PURPOSE: 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. MATERIALS AND 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.

Are allergic fungal rhinosinusitis and allergic bronchopulmonary aspergillosis lifelong conditions?

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.

Role of preoperative versus postoperative itraconazole in allergic fungal rhinosinusitis.

Antifungals used as adjuvant to surgery in AFRS (Allergic Fungal Rhinosinusitis) have shown varying success in delaying recurrences. Itraconazole has been used both as preoperative and postoperative adjuvant. This study investigates the role of itraconazole in AFRS and compares its role between preoperative and postoperative administration of the drug. Patients were randomly divided into groups as: Group 1 (n = 25), received 4 weeks itraconazole in the preoperative period and operated subsequently, Group 2 (n = 25), received 4 weeks itraconazole in the postoperative period, Group 3 (n = 50), matched patients of AFRS, who didn't receive itraconazole. All the groups received oral steroids in tapering doses staring from 1 mg/kg for 6 weeks in the postoperative period. Symptomatic (SNOT 20), radiologic (Lund Mackay, LM) scores and endoscopic (Kupferberg's NE Grades) were noted. Primary postoperative follow-up was for 24 weeks with routine CT scans and nasal endoscopies, followed by which all the patients were followed with nasal endoscopies only with CT scans when required. Both preoperative and postoperative itraconazole showed significant improvement in the SNOT, LM, and Kupferberg's grades in the follow-up period. Preoperative itraconazole therapy showed significantly better results compared to postoperative itraconazole therapy though the recurrence rates were similar in both groups. Itraconazole is a better preoperative adjunct in AFRS than postoperative.

Allergic Fungal Airway Disease.

Fungi are ubiquitous and form their own kingdom. Up to 80 genera of fungi have been linked to type I allergic disease, and yet, commercial reagents to test for sensitization are available for relatively few species. In terms of asthma, it is important to distinguish between species unable to grow at body temperature and those that can (thermotolerant) and thereby have the potential to colonize the respiratory tract. The former, which include the commonly studied Alternaria and Cladosporium genera, can act as aeroallergens whose clinical effects are predictably related to exposure levels. In contrast, thermotolerant species, which include fungi from the Candida, Aspergillus, and Penicillium genera, can cause a persistent allergenic stimulus independent of their airborne concentrations. Moreover, their ability to germinate in the airways provides a more diverse allergenic stimulus, and may result in noninvasive infection, which enhances inflammation. The close association between IgE sensitization to thermotolerant filamentous fungi and fixed airflow obstruction, bronchiectasis, and lung fibrosis suggests a much more tissue-damaging process than that seen with aeroallergens. This review provides an overview of fungal allergens and the patterns of clinical disease associated with exposure. It clarifies the various terminologies associated with fungal allergy in asthma and makes the case for a new term (allergic fungal airway disease) to include all people with asthma at risk of developing lung damage as a result of their fungal allergy. Lastly, it discusses the management of fungirelated asthma.

Exploring the immunopathology of type 2 inflammatory airway diseases.

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.

The Role of Serum Galactomannan Assay as a Potential Surrogate Biomarker for Fungal Microinvasion in Allergic Fungal Rhinosinusitis.

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.

Neutrophil Lymphocyte Ratio: A Predictor of Disease Severity in Nasal Polyposis and Allergic Fungal Rhinosinusitis.

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).

Successful Use of Dupilumab as a Salvage Therapy for Recalcitrant Allergic Fungal Rhinosinusitis: A Case Report.

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.

Production of medium-chain fatty acids by co-fermentation of antibiotic fermentation residue with fallen Ginkgo leaves.

The co-fermentation of antibiotic fermentation residues (AFRs) and fallen Ginkgo leaves at C/N ratios of 10-60 was conducted for medium-chain fatty acids (MCFA) production. It was found that a proper C/N ratio could largely promote the MCFA accumulation. Group with C/N ratio of 50 exhibited highest MCFA production of 133.14 mmol C/L, which was 42 %-121 % higher than the other groups. Through the co-fermentation, substrate condition was optimized with rich micro-nutrients in AFRs and abundant polysaccharides in Ginkgo leaves, the hydrolysis of leaves was promoted by the active microbes in AFRs, and the predominance of CE microbes was also stimulated with the dilution of AFRs. The increased C/N ratio significantly affected the SCFA producers like genus Escherichia Shigella and Proteiniphilum, and enriched CE microbes like genus Romboutsia, Eubacterium and Clostridium_sensu_stricto_12. Functional enzymes analysis showed that both reverse ß oxidation and fatty acid biosynthesis pathways were strengthened with the increased C/N ratio.

Allergic Fungal Rhinosinusitis: The Role and Expectations of Biologics.

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.

The Evaluation of the Sensitivity and Specificity of a New Endoscopic Diagnostic Sign of Allergic Fungal Rhinosinusitis: Intrapolypoidal White Particles.

PURPOSE: 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. METHODOLOGY: 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. CONCLUSION: This study offers a new endoscopic sign, intrapolypoidal white particles for diagnosing allergic fungal rhinosinusitis.

Failure of facet replacement system with metal-on-metal bearing surface and subsequent discovery of cobalt allergy: report of 2 cases.

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.

Current understanding of allergic fungal rhinosinusitis.

Studying the pathophysiology of allergic fungal rhinosinusitis (AFRS) has proved challenging. While this clinical entity is easily distinguishable based on the clinical criteria set forth by Bent and Kuhn twenty-five years ago, studies examining type 2 inflammatory profiles in AFRS can make it seem more alike other CRS subtypes than it is different. Still, evolving research seems to clearly delineate this subtype from others in CRS. This review will critically evaluate the evolution of research examining the pathophysiology of AFRS and will conclude with a summary of the special considerations in the management of this fascinating disease.

Emerging and legacy flame retardants in indoor dust from East China.

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.

The spectrum of allergic fungal diseases of the upper and lower airways.

Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease.

Fungal rhino sinusitisin in tehran, iran.

BACKGROUND: Fungal rhino sinusitis (FRS) is an important infection of para nasal sinuses, which encompasses two main categories; invasive and noninvasive forms according to histopathological findings. Aspergillus spp are the most common species isolated from noninvasive form, while Mucorales are more frequently isolates from acute infections. METHODS: Four hundred fifty patients suspected to fungal rhino sinusitis were investigated in a cross-sectional prospective study from June 2009 to Sep 2013. All patients under went endoscopic sinus surgery of the middle meatus. Tissue biopsies were investigated for culture, histopathology and molecular examination. RESULTS: Totally, 87 patients were diagnosed with fungal rhinosinusitis. A. flavus was the most common etiological agent of chronic invasive form (CIFRS), allergic fungal rhino sinusitis (AFRS) and fungus ball (FB), while Rhizopus oryze (26.7%) was the most common cause of infection in acute invasive fungal rhino sinusitis (AIFR). However, a few rare species such as Shyzophyllum commune and Fusarium proliferatum were also isolated. CONCLUSION: Diabetes is the most important predisposing factor for patients with acute invasive form of sinusitis and the most involved sinuses were unilateral multiple sinuses and maxillary sinus.

Medical management of allergic fungal rhinosinusitis following endoscopic sinus surgery: an evidence-based review and recommendations.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a subset of polypoid chronic rhinosinusitis that is characterized by the presence of eosinophilic mucin with fungal hyphae within the sinuses and a Type I hypersensitivity to fungi. The treatment of AFRS usually involves surgery in combination with medical therapies to keep the disease in a dormant state. However, what constitutes an optimal medical regimen is still controversial. Hence, the purpose of this article is to provide an evidence-based approach for the medical management of AFRS. METHODS: A systemic review of the literature on the medical management of AFRS was performed using Medline, EMBASE, and Cochrane Review Databases up to March 15, 2013. The inclusion criteria were as follows: patients >18 years old; AFRS as defined by Bent and Kuhn; post-sinus surgery; studies with a clearly defined end point to evaluate the effectiveness of medical therapy in postoperative AFRS patients. RESULTS: This review identified and assessed 6 medical modalities for AFRS in the literature: oral steroids; topical steroids; oral antifungals; topical antifungals; immunotherapy; and leukotriene modulators. CONCLUSION: Based on available evidence in the literature, postoperative systemic and standard topical nasal steroids are recommended in the medical management of AFRS. Nonstandard topical nasal steroids, oral antifungals, and immunotherapy are options in cases of refractory AFRS. No recommendations can be provided for topical antifungals and leukotriene modulators due to insufficient clinical research reported in the literature.