Diverse phenotypes and endotypes of fungus balls caused by mixed bacterial colonization in chronic rhinosinusitis

Abstract

Background:The pathogenic roles of fungus and bacteria in chronic rhinosinusitis (CRS) remain unclear. Recently, we described the bacterial ball, which is distinct from the fungus ball, as an unusual phenotype of bacterial infection. In this study, we investigated the clinical, histopathologic, and immunologic characteristics of sinonasal microorganic materials, including fungus ball and bacterial ball. Methods:In this study, we enrolled 80 CRS patients with sinonasal microorganic materials and 10 control subjects who underwent skull base surgery or endoscopic dacryocystorhinostomy and had no signs or symptoms of nasal inflammation. All specimens were stained with hematoxylineosin, Gomori-methenamine-silver, and Gram stain to identify fungal organisms and Gram-positive/negative bacterial colonies. The expression of tumor necrosis factor (TNF)-α; interleukin (IL)-1β; S100A7; S100A8/A9; and short, palate, lung, and nasal epithelial clone 1 (SPLUNC1) were evaluated by enzyme-linked immunosorbent assay using sinus lavage fluid. Results:We histologically classified sinonasal microorganic materials into the following 4 groups: fungus ball (n = 45); bacterial ball (n = 6); mixed ball (formed by a mixture of fungus and bacteria, n = 27); and double ball (formed by separate fungal and bacterial balls, n = 2). Com-pared with the fungus ball, the mixed ball was more frequently detected in immunocompromised patients (p < 0.0001). In addition, TNF-α expression was significantly higher in fungus and mixed balls than in control, whereas the mixed ball showed higher expression of IL-1β compared with the fungus ball. Moreover, the expression of S100A7 and S100A8/A9 protein in the mixed ball was significantly decreased when compared with the fungus ball, whereas there was no significant difference in SPLUNC1 expression between fungus and mixed balls. Conclusion:Our findings suggest that fungal and bacterial interactions are diverse in CRS. Specifically, the mixed ball is prevalent in CRS with an immunocompromised state and it may decrease epithelial barrier function. C 2019 ARS-AAOA, LLC.C hronic rhinosinusitis (CRS) is characterized by inflammation of the mucosa of the nose and paranasal sinuses with a duration of at least 12 consecutive weeks, and is comprised of 2 subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). 1 To date, several heterogeneous factors, including host of Medicine,

Unveiling the Diverse Spectrum of Fungal Rhinosinusitis

“…Contrary to our expectations, fungi exhibit very complex behaviors [6]. Recently, Kim et al [7] reported that fungus balls are a subtype of bioballs, which consist of four phenotypes (fungus ball, bacterial ball, mixed ball, and double ball) [7]. These types appear similar; therefore, it is not possible to discriminate them during endoscopic sinus surgery.…”

Fungus ball of the maxillary sinus: clinical and diagnostic characteristics

“…The most commonly involved fungal agents are Aspergillus species, but many other species of fungi are also reported 1,14,15 . Nevertheless, the pathogenic role of fungal organisms and bacterial colonies, but also their complex interactions in CRS remain unclear 22 .…”

The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases

“…The majority of early work looking at S100A7, also called psoriasin, focused on psoriasis [ 96 , 97 ]. However, several studies suggest that S100A7 may have a role in several respiratory diseases, including lung cancer [ 98 ], asthma [ 99 ], rhinosinusitis [ 100 ], pulmonary complications of systemic sclerosis [ 101 ], and bacterial exacerbations [ 102 ]. S100A7 is a chemotactic protein for CD4+ T cells and neutrophils present in the skin epidermis [ 103 ].…”

“…It also functions as a direct bactericidal protein [ 104 ]. Kim et al demonstrated that levels of S100A7 and S100A8/A9 were reduced in chronic rhinosinusitis (CRS) patients with a mixed ball of bacteria and fungi compared to a fungal ball [ 100 ]. This implies that the barrier function of the nasal epithelial cells is reduced in mixed fungal and bacterial infections thus putting patients at risk of developing an invasive fungal infection.…”