[The preliminary application of mNGS in the diagnosis of invasive fungal sinusitis].

Objective: By conducting a retrospective analysis of the clinical data of 14 patients diagnosed with invasive fungal rhinosinusitis (IFRS) confirmed by metagenomics next generation sequencing (mNGS) technology, we aim to explore the rapid diagnosis value of mNGS in IFRS. Methods: The clinical data of 14 IFRS patients admitted to TianJin First Central Hospital were retrospectively analyzed from February 2021 to October 2023. The study cohort comprised 8 males and 6 females, with ages ranging from 14 to 77 years. All patients were diagnosed as IFRS by performing mNGS sequencing technology of nasal sinus lesion biopsy specimens. Clinical data such as laboratory examination, imaging examination, histopathological examination results, treatment plan and prognosis were summarized and analyzed. Results: All 14 patients were diagnosed as IFRS, with mNGS detecting pathogens such as Rhizopus (7 cases), Aspergillus (5 cases), Trichoderma (1 case), and Scedosporium apiospermum (1 case). Follow-up evaluations were conducted for a period ranging from 2 months to 2 years post-treatment. At the end of follow-up, 11 out of 14 IFRS patients achieved a complete cure with no signs of recurrence, while the symptoms of the remaining 3 patients significantly improved with comprehensive treatment. Conclusion: mNGS emerges as a highly effective diagnostic tool for IFRS, providing valuable microbiological evidence for clinical diagnosis and demonstrating promising clinical utility.

Choanephora infundibulifera Rhinosinusitis in Man with Acute Lymphoblastic Leukemia, Tennessee, USA.

Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.

Bacterial and fungal communities in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: Multiple inflammatory mechanisms dynamically interact in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Disruption of the relationship between host and environmental factors on the mucosal surface leads to the development of inflammation. Microorganisms constitute the most important part of environmental factors. METHODS: 28 volunteers (18 CRSwNP patients and 10 healthy individuals) were included in the study. Eight patients were recurrent nasal polyposis cases, and the remaining were primary cases. Swab samples were taken from the middle meatus under endoscopic examination from all participants. After DNA extraction, a library was created with the Swift Amplicon 16S + ITS kit and sequenced with Illumina Miseq. Sequence analysis was performed using QIIME, UNITE v8.2 database for ITS and Silva v138 for 16S rRNA. RESULTS: The predominant bacteria in all groups were Firmicutes, Proteobacteria, Actinobacteria as phyla and Staphylococcus, Corynebacterium, Sphingomonas as genera. Comparison of bacterial communities of CRSwNP patients and control group highlighted Corynebacterium, as the differentiating taxa for control group and Streptococcus, Moraxella, Rothia, Micrococcus, Gemella, and Prevotella for CRSwNP patients. The predominant fungal genus in all groups was Malassezia. Staphylococcus; showed a statistically significant negative correlation with Dolosigranulum. Corynebacterium had a positive correlation with Anaerococcus, and a negative correlation with Neisseria, Prevotella, Fusobacterium and Peptostreptococcus. CONCLUSION: Nasal microbiome of CRSwNP patients shows greater inter-individual variation than the control group. Corynebacterium is less abundant in patients with CRSwNP compared to the control group. Malassezia is the predominant fungus in the nasal cavity and paranasal sinuses and correlates positively with the abundance of Corynebacterium.

Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis.

Staphylococcus aureus mucosal biofilms are associated with recalcitrant chronic rhinosinusitis (CRS). However, S. aureus colonisation of sinus mucosa is frequent in the absence of mucosal inflammation. This questions the relevance of S. aureus biofilms in CRS etiopathogenesis. This study aimed to investigate whether strain-level variation in in vitro-grown S. aureus biofilm properties relates to CRS disease severity, in vitro toxicity, and immune B cell responses in sinonasal tissue from CRS patients and non-CRS controls. S. aureus clinical isolates, tissue samples, and matched clinical datasets were collected from CRS patients with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. B cell responses in tissue samples were characterised by FACS. S. aureus biofilms were established in vitro, followed by measuring their properties of metabolic activity, biomass, colony-forming units, and exoprotein production. S. aureus virulence was evaluated using whole-genome sequencing, mass spectrometry and application of S. aureus biofilm exoproteins to air-liquid interface cultures of primary human nasal epithelial cells (HNEC-ALI). In vitro S. aureus biofilm properties were correlated with increased CRS severity scores, infiltration of antibody-secreting cells and loss of regulatory B cells in tissue samples. Biofilm exoproteins from S. aureus with high biofilm metabolic activity had enriched virulence genes and proteins, and negatively affected the barrier function of HNEC-ALI cultures. These findings support the notion of strain-level variation in S. aureus biofilms to be critical in the pathophysiology of CRS.

Visual function loss in fungal sphenoid sinusitis: clinical characteristics and outcomes.

Potentially fatal fungal sphenoid sinusitis (FSS) causes visual damage. However, few studies have reported on its visual impairment and prognosis. Five hundred and eleven FSS patients with ocular complications treated at Beijing Tongren Hospital were recruited and clinical features and visual outcomes were determined. Thirty-two of the 511 patients (6%) had visual impairment, with 13 and 19 patients having invasive and noninvasive FSS, respectively. Eighteen patients (56.25%) had diabetes and 2 patient (6.25%) had long-term systemic use of antibiotics (n = 1) and corticosteroids (n = 1). All patients had visual impairment, which was more severe in invasive FSS than in noninvasive FSS. Bony wall defects and sclerosis were observed in 19 patients (59.38%), and 11 patients (34.38%) had microcalcification in their sphenoid sinusitis on computed tomography (CT). After a 5-year follow-up, three patients (9.38%) died. Patients with noninvasive FSS had a higher improvement rate in visual acuity than their counterparts. In the multivariate analysis, sphenoid sinus wall sclerosis on CT was associated with better visual prognosis. FSS can cause vision loss with persistent headaches, particularly in those with diabetes. CT showed the sphenoid sinus wall sclerosis, indicating a better visual prognosis in FSS with visual impairment.

Demographic characteristics and risk factors for invasive fungal sinusitis in the context of COVID-19: A systematic review and meta-analysis.

OBJECTIVES: To identify the demographic characteristics and potential risk factors of invasive fungal sinusitis (IFS) patients with Coronavirus Disease in 2019 (COVID-19). METHODS: Web of Science, Embase, the Cochrane Library, and PubMed were searched from database inception to August 2023 using the combination of medical searching heading terms "invasive fungal sinusitis" and "COVID-19" and their free words. The research protocol was registered on PROSPERO (CRD42023467175). RESULTS: A total of 53 studies were included. The mean age of IFS patients with COVID-19 was 53.72 (95% credible interval [CI]: 51.08, 56.36), with 66% males (95% CI: 0.62, 0.70), and 81% diabetes (95% CI: 0.77, 0.86). The mean time from COVID-19 diagnosis to IFS onset was 19.09 days (95% CI: 16.96, 21.22). The percentage of patients with COVID-19 PCR positivity was 33% (95% CI: 0.21, 0.45). Overall, 71% of patients receiving steroid therapy during COVID-19 infection (95% CI: 0.63, 0.78). The odds ratio of diabetes mellitus, steroid administration, and COVID-19 PCR positivity were 6.09, 2.21, and 1.82, respectively. COVID-19 infection did not affect the IFS stage. CONCLUSION: IFS patients with COVID-19 had an average age of 53.72 years and were predominantly males, with a mean interval of 19.09 days from COVID-19 diagnosis to IFS onset. Diabetes, steroid administration, and COVID-19 PCR positivity were risk factors.

Is maxillary sinusitis and radiographic maxillary sinus opacification associated with an altered microbiology of MRONJ?

OBJECTIVE: Maxillary sinusitis can be a sequela of medication-related osteonecrosis of the jaw (MRONJ). This study aims to characterize the microbiome of maxillary MRONJ with concurrent maxillary sinusitis and radiographic maxillary sinus opacification to determine if there is a relationship between the microbiome of MRONJ and sinus disease. STUDY DESIGN: This retrospective case series was conducted using electronic health records from the University of Pennsylvania and affiliated hospitals. The target population was surgically managed maxillary MRONJ patients. The primary predictor variables were tissue culture results. The primary outcomes were maxillary sinusitis or maxillary sinus opacification. Statistical analysis was performed using chi-squared tests at the 95% confidence interval. RESULTS: Thirty-nine subjects were selected: 25 had sinus opacification and 11 had sinusitis. Resident bacteria were present in 90% of subjects, nonresident bacteria in 74%, and opportunistic organisms in 15%. There were significantly more subjects with chronic sinusitis microbes (79%) than without. There were significantly more gram-positive anaerobes, specifically Propionibacterium, as well as the gram-negative facultative anaerobe, Capnocytophaga, in subjects with concurrent sinusitis. CONCLUSIONS: Maxillary MRONJ with concurrent maxillary sinusitis may be associated with gram-positive anaerobic species, Propionibacterium, and Capnocytophaga colonization. Maxillary MRONJ patients may benefit from sinus evaluation and concurrent surgical intervention.

Chronic Rhinosinusitis-Microbiological Etiology, Potential Genetic Markers, and Diagnosis.

Chronic rhinosinusitis (CRS) is a significant public health problem. Bacterial colonization and impaired mucociliary clearance play a significant role in the inflammatory process. Several inflammatory pathways and host defense elements are altered in CRS, which may contribute to observed differences in the microbiome. To date, researching CRS has been difficult due to limited access to the studied tissue and a lack of available biomarkers. Ongoing scientific research is increasingly based on simple and objective analytical methods, including sensors, detection with PCR, and sequencing. Future research on microbiota and human factors should also include genomics, transcriptomics, and metabolomics approaches. This report analyzes the changes that occur in the paranasal sinuses of people with acute and chronic rhinosinusitis, the composition of the microbiota, the human genetic markers that may shed light on the predisposition to CRS, and the advantages and disadvantages of classical and molecular diagnostic methods, as well as addressing the difficulties of sinusitis treatment.

Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS).

OBJECTIVES: Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma. METHODS: Here, we describe 3 cases of carcinoma mimicking IFS from a single institution. RESULTS: Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality. CONCLUSIONS: We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

Reduced Glycolysis and Cytotoxicity in Staphylococcus aureus Isolates from Chronic Rhinosinusitis as Strategies for Host Adaptation.

Chronic rhinosinusitis (CRS) is a multifactorial infection of the nasal cavity and sinuses. In this study, nasal swabs from control donors (N = 128) and patients with CRS (N = 246) were analysed. Culture methods and metagenomics revealed no obvious differences in the composition of the bacterial communities between the two groups. However, at the functional level, several metabolic pathways were significantly enriched in the CRS group compared to the control group. Pathways such as carbohydrate transport metabolism, ATP synthesis, cofactors and vitamins, photosynthesis and transcription were highly enriched in CRS. In contrast, pathways related to lipid metabolism were more representative in the control microbiome. As S. aureus is one of the main species found in the nasal cavity, staphylococcal isolates from control and CRS samples were analysed by microarray and functional assays. Although no significant genetic differences were detected by microarray, S. aureus from CRS induced less cytotoxicity to lung cells and lower rates of glycolysis in host cells than control isolates. These results suggest the differential modulation of staphylococcal virulence by the environment created by other microorganisms and their interactions with host cells in control and CRS samples. These changes were reflected in the differential expression of cytokines and in the expression of Agr, the most important quorum-sensing regulator of virulence in S. aureus. In addition, the CRS isolates remained stable in their cytotoxicity, whereas the cytotoxic activity of S. aureus isolated from control subjects decreased over time during in vitro passage. These results suggest that host factors influence the virulence of S. aureus and promote its adaptation to the nasal environment during CRS.

Reduced Proliferative Capacity and Defense against Staphylococcus aureus in Human Nasal Mucosal Epithelium Lacking ZNF365.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nose characterized by barrier disruption and environmental susceptibility, and the deletion of ZNF365 may be a factor inducing these manifestations. However, there is no study on the mechanism of action between CRSwNP and ZNF365. Therefore, this study focuses on the effect of the zinc finger protein ZNF365 on the proliferation of nasal mucosal epithelial cells and their defense against Staphylococcus aureus (S. aureus). METHODS: Immunohistochemistry and Western blot were applied to verify the changes of ZNF365 expression in nasal polyp tissues and control tissues, as well as in primary epithelial cells. ZNF365 was knocked down in human nasal mucosa epithelial cell line (HNEpc), and the proliferation, migration, and transdifferentiation of epithelium were observed by immunofluorescence, QPCR, CCK8, and cell scratch assay. The changes of mesenchymal markers and TLR4-MAPK-NF-κB pathway were also observed after the addition of S. aureus. RESULTS: ZNF365 expression was reduced in NP tissues and primary nasal mucosal epithelial cells compared to controls. Knockdown of ZNF365 in HNEpc resulted in decreased proliferation and migration ability of epithelial cells and abnormal epithelial differentiation (decreased expression of tight junction proteins). S. aureus stimulation further inhibited epithelial cell proliferation and migration, while elevated markers of epithelial-mesenchymal transition and inflammatory responses occurred. CONCLUSION: ZNF365 is instrumental in maintaining the proliferative capacity of nasal mucosal epithelial cells and defending against the invasion of S. aureus. The findings suggest that ZNF365 may participate in the development of CRSwNP.

Microbiome analyses in chronic rhinosinusitis.

In this edition of Rhinology we feature the work of Connell and colleagues from Australia on chronic rhinosinusitis that describes an interesting new pipeline to characterize the bacterial composition of microbiota. We are constantly exposed to a multitude of micro-organisms in the environment and our immune system has the important task discerning and fighting off potential threats. In most people the immune system is doing its job properly and prevents anything untoward from happening. On occasion, a microbe slips by the first (innate) level of defense and we might suffer from an infection. This then activates the second layer of (the adaptive) defense tasked to clear this infection. Sometimes the immune system gets its wrong and starts a full-out defense against something harmless, and an allergy is born. The task of the immune system of doing what is right is even more difficult than it might seem at first sight. In addition to these incidental potential threats, our mucosal surfaces are lined with commensal bacteria which contributes to the complexity of our environment. This collection of bacteria or microbiome has become a major focus of research, as the composition of this microbiome seems related to the health state of the individual. Originally the relationship between the gut microbiome and the development of asthma and allergy was the main focus. In recent years, the focus has been broadened to include the microbiome of the upper and lower airways. In addition to allergy, our field has also been given more and more attention to studying the microbiome in chronic rhinosinusitis.

[Advances in next-generation sequencing technology to analyze the microbiome of patients with chronic sinusitis].

Chronic rhinosinusitis （CRS） is a chronic inflammatory disease of the sinus mucosa, and the pathogenesis of CRS has not been fully elucidated, and the impact of dysbiosis of the microbiome in the nasal cavity and even in the gut on the pathogenesis of CRS remains controversial. Next-generation sequencing technology, a culture-independent high-throughput sequencing method, contributes to a comprehensive understanding of the CRS microbiome. This article reviews the progress of research on the relevance of bacteria and other microorganisms to CRS and the microbial characteristics of the sinus and intestinal tract of patients with CRS, introduces next-generation sequencing technologies for the study of the CRS microbiome, and discusses the therapeutic prospects of CRS and the possibility of probiotic therapy.

Gut microbiota and chronic rhinosinusitis: a two-sample Mendelian randomization study.

BACKGROUND: The nasal cavity and gut are interconnected, both housing a rich natural microbiome. Gut microbiota may interact with nasal microbiota and contribute to the development of chronic rhinosinusitis (CRS). However, the specific role of gut microbiota in CRS has not been fully investigated. Therefore, we conducted a two-sample Mendelian randomization study to reveal the potential genetic causal effect of gut microbiota on CRS. METHODS: We performed a two-sample Mendelian Randomization (MR) analysis using aggregated data from genome-wide association studies (GWAS) on gut microbiota and CRS. The primary method used to assess the causal relationship between gut microbiota and CRS was the inverse variance weighting (IVW) method. In addition, sensitivity analyses were conducted to evaluate the robustness of the MR results, including heterogeneity, pleiotropy, and leave-one-out tests. RESULTS: Genetically predicted twelve gut microbiota, including class Coriobacteriia, class Methanobacteria, family Coriobacteriaceae, family Methanobacteriaceae, family Pasteurellaceae, genus Haemophilus, genus Ruminococcus torques group, genus Subdoligranulum, order Coriobacteriales, order Methanobacteriales, order Pasteurellales, and phylum Proteobacteria, demonstrated a potential inhibitory effect on CRS risk (P < 0.05). In addition, four gut microbiota, including family Streptococcaceae, genus Clostridium innocuum group, genus Oscillospira, and genus Ruminococcaceae NK4A214 group, exhibited a causal role in increasing CRS risk (P < 0.05). Sensitivity analyses showed no evidence of heterogeneity or pleiotropy (P > 0.05). CONCLUSIONS: This study reveals the causal relationship between specific gut microbiota and CRS, which provides a new direction and theoretical foundation for the future development of interventions and prevention and treatment strategies for CRS.

Enhanced phylogenetic insights into the microbiome of chronic rhinosinusitis through the novel application of long read 16S rRNA gene amplicon sequencing.

INTRODUCTION: 16S rRNA next generation sequencing (NGS) has been the de facto standard of microbiome profiling. A limitation of this technology is the inability to accurately assign taxonomy to a species order. Long read 16S sequencing platforms, including Oxford Nanopore Technologies (ONT), have the potential to overcome this limitation. The paranasal sinuses are an ideal niche to apply this technology, being a low biomass environment where bacteria are implicated in disease propagation. Characterising the microbiome to a species order may offer new pathophysiological insights. METHODOLOGY: Cohort series comparing ONT and NGS biological conclusions. Swabs obtained endoscopically from the middle meatus of 61 CRSwNP patients underwent DNA extraction, amplification and dual sequencing (Illumina Miseq (NGS) and ONT GridION). Agreement, relative abundance, prevalence, and culture correlations were compared. RESULTS: Mean microbiome agreement between sequencers was 61.4%. Mean abundance correlations were strongest at a familial/genus order and declined at a species order where NGS lacked resolution. The most significant discrepancies applied to Corynebacterium and Cutibacterium, which were estimated in lower abundance by ONT. ONT accurately identified 84.2% of cultured species, which was significantly higher than NGS. CONCLUSIONS: ONT demonstrated superior resolution and culture correlations to NGS, but underestimated core sinonasal taxa. Future application and optimisation of this technology can advance our understanding of the sinonasal microenvironment.

Temperature influences commensal-pathogen dynamics in a nasal epithelial cell co-culture model.

Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses, and microbial dysbiosis associated with CRS is thought to be a key driver of host inflammation that contributes to disease progression. Staphylococcus aureus is a common upper respiratory tract (URT) pathobiont associated with higher carriage rates in CRS populations, where S. aureus-secreted toxins can be identified in CRS tissues. Although many genera of bacteria colonize the URT, few account for the majority of sequencing reads. These include S. aureus and several species belonging to the genus Corynebacterium, including Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum, which are observed at high relative abundance in the healthy URT. Studies have examined bacterial interactions between major microbionts of the URT and S. aureus, but few have done so in the context of a healthy versus diseased URT environment. Here, we examine the role of temperature in commensal, pathogen, and epithelial dynamics using an air-liquid interface cell culture model mimicking the nasal epithelial environment. Healthy URT temperatures change from the nares to the nasopharynx and are increased during disease. Temperatures representative of the healthy URT increase persistence and aggregate formation of commensal C. propinquum and C. pseudodiphtheriticum, reduce S. aureus growth, and lower epithelial cytotoxicity compared to higher temperatures correlating with the diseased CRS sinus. Dual-species colonization revealed species-specific interactions between Corynebacterium species and S. aureus dependent on temperature. Our findings suggest URT mucosal temperature plays a significant role in mediating polymicrobial and host-bacterial interactions that may exacerbate microbial dysbiosis in chronic URT diseases.IMPORTANCEChronic rhinosinusitis is a complex inflammatory disease with a significant healthcare burden. Although presence of S. aureus and microbial dysbiosis are considered mediators of inflammation in CRS, no studies have examined the influence of temperature on S. aureus interactions with the nasal epithelium and the dominant genus of the healthy URT, Corynebacterium. Interactions between Corynebacterium species and S. aureus have been documented in several studies, but none to date have examined how environmental changes in the URT may alter their interactions with the epithelium or each other. This study utilizes a polarized epithelial cell culture model at air-liquid interface to study the colonization and spatial dynamics of S. aureus and clinical isolates of Corynebacterium from people with CRS to characterize the role temperature has in single- and dual-species dynamics on the nasal epithelium.

Nasal lavage microbiome, but not nasal swab microbiome, correlates with sinonasal inflammation in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterized by highly viscous mucus obstructing the lower and upper airways, chronic neutrophil inflammation and infection resulting not only in lung destruction but also in paranasal sinus involvement. The pathogenesis of CF-associated chronic rhinosinusitis (CRS) is still not well understood, and it remains unclear how the microbiome in the upper airways (UAW) influences paranasal sinus inflammation. METHODS: In a cross-sectional study in pediatric patients with CF under stable disease conditions, we examined the microbiome in relation to inflammation by comparing nasal swabs (NS) and nasal lavage (NL) as two UAW sampling methods. The microbiota structure of both NS and NL was determined by 16S rRNA gene amplicon sequencing. In addition, pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, TNF-α) and proteases (SLPI, TIMP-1, NE/A1-AT complex) as well as neutrophil elastase activity were measured in NL. RESULTS: Simultaneous NS and NL samples were collected from 36 patients with CF (age range: 7 - 19 years). The microbiome of NS samples was shown to be significantly lower in α-diversity and evenness compared to NL samples. NS samples were particularly found to be colonized with Staphylococcus species. NL microbiome was shown to correlate much better with the sinonasal inflammation status than NS microbiome. Especially the detection of Moraxella in NL was associated with increased inflammatory response. CONCLUSION: Our results show that the NL microbiome reflects sinonasal inflammation better than NS and support NL as a promising tool for simultaneous assessment of the UAW microbiome and inflammation in children with CF.

Sinonasal microbiome and inflammatory profiles in fungal ball and chronic rhinosinusitis.

OBJECTIVE: Fungal balls (FB) are the main form of non-invasive fungal rhinosinusitis found in immunocompetent hosts. Bacterial coinfection affects clinical symptoms. We investigated the sinonasal microbiome and inflammatory profiles in FB and chronic rhinosinusitis (CRS) patients. METHODS: Thirty-three participants were prospectively recruited. Nasal swab samples and sinonasal tissues were collected from controls, and FB and CRS patients. DNA extraction and microbiome analysis using V3-V4 region 16S rRNA sequencing were performed. Inflammatory cytokine levels in the sinonasal tissues, blood eosinophil counts, and serum total IgE were measured. RESULTS: No significant differences were observed in species richness or evenness measures. The phylogenetic tree demonstrated that the FB samples were different from the controls. The sinus bacteria composition differed among the groups. At the phylum level, Firmicutes in FB were significantly depleted compared with those in CRS, while Proteobacteria were more enriched in FB than that in controls and CRS. At the genus level, in FB, Staphylococcus and Corynebacterium were significantly decreased compared to those in the controls. The prevalence of Haemophilus was the highest in FB. Blood eosinophil counts and IL-5 and periostin levels in the sinonasal tissue of the FB group were significantly lower than those in the CRS group. CONCLUSIONS: FB patients had different microbiome compositions and fewer type 2 inflammatory profiles than CRS patients did. However, whether these findings cause FB or result from bacterial and/or fungal infection remains unclear. Further studies are needed to reveal how these differences occur and affect the development of FB and clinical symptoms.

Optimization of diagnostic and procedural codes to identify patients with acute invasive fungal sinusitis.

KEY POINTS: Acute invasive fungal sinusitis (IFS) is a rare disease with high mortality There is no designated International Classification of Diseases code for IFS We propose a novel method to identify IFS using optimized codes complemented by medications.