Chronic granulomatous invasive fungal sinusitis (CGIFS) is a peculiar disease of the paranasal sinuses due to its rarity, patient subset, and disease course. We describe 7 cases of histopathologically confirmed CGIFS with different treatment plans and varying outcomes. Of particular note was that one of these patients developed allergic fungal rhinosinusitis after complete resolution of his primary invasive disease, a finding that has never been reported in the literature. Another patient had an atypical fungal species ( Aspergillus nidulans) on fungal stain and culture, while one immunodeficient patient had a large intracerebral disease component and died after 2 months of treatment. We also present a review of the pertinent literature investigating this rare disease.

Objective: Modulation of the dysbiotic gut microbiome with “healthy” bacteria via a stool transplant or supplementation is increasingly practiced, however this approach has not been explored in the nasal passages. We wished to verify whether Lactococcus lactis W136 ( L. lactis W136) bacteria could be safely applied via irrigation to the nasal and sinus passages in individuals with chronic rhinosinusitis (CRS) with previous undergone endoscopic sinus surgery, and whether this was accompanied by bacterial community flora modification. Study Design: Prospective open-label pilot trial of safety and feasibility. Setting: Academic tertiary hospital center. Subjects and Methods: Twenty-four patients with CRS refractory to previous medical and surgical therapy received a 14-day course of BID sinus irrigations containing 1.2 × 10 9 CFU live L. lactis W136 . Patients were monitored for safety using questionnaire, sinus endoscopy, otoscopy, UPSIT-40 smell testing, and endoscopically-obtained conventional sinus culture and a swab for 16S microbiome profiling. Results: All 24 patients receiving at least one treatment successfully completed treatment. L. lactis W136 probiotic treatment was safe, with no major adverse events or new infections. Treatment was associated with improvement in sinus symptoms, QOL, and mucosal scores, which remained improved during the subsequent 14-day observation period. Microbiome changes associated with treatment were limited to an increase of the pathobiont Dolosigranulum pigrum , a bacteria identified as potentially beneficial in the upper airways. Subgroup analysis suggested differences in microbiomes and responses for CRSsNP and CRSwNP phenotypes, but these did not attain significance. Conclusion: Intranasal irrigation of live L. lactis W136 bacteria to patients with refractory chronic rhinosinusitis was safe, and was associated with effects on symptoms, mucosal aspect and microbiome composition. Intranasal bacteria may thus find a role as a treatment strategy for CRS. Clinical Trials Registration: www.ClinicalTrials.gov . identifier: NCT04048174.

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Objectives: Identify whether identification of S. aureus on conventional culture is a predictor of success or failure after ESS followed by budesonide nasal irrigations (BUD) in chronic rhinosinusitis (CRS) patients at high risk of recurrence.Methodology: Prospective clinical trial including 116 patients from a tertiary care center at high-risk of disease recurrence following ESS+BUD. Blood samples, microbial swabs, and SNSS/SNOT-22 were taken on the day of surgery (Visit-1) and 4 months postoperatively (Visit-2). Outcomes were evaluated using symptoms and mucosal status as assessed by the Lund-Kennedy endoscopic score.Results: Seventy-five patients (69.4%) attained SNOT-22 MCID or higher. (Mean = 33.4, range 9–75). Objective documentation of recurrence of disease, as defined by combined endoscopic/symptomatic criteria, was noted in 58/116 patients (50%). Revision surgery was associated with a significantly higher rate of disease recurrence (60.0 vs. 28.0%; p < 0.001). Culture for Staphylococcus aureus was associated with disease recurrence, preoperatively and at 4 months post-surgery (p = 0.020; p < 0.001). This was restricted to post-operative cultures in the revision group (10.0 vs. 48.8%; p < 0.001). Other factors associated with poor outcome included intolerance to non-steroidal anti-inflammatory drugs (NSAID) (p = 0.036). Significantly higher Lund-Kennedy scores in the recurrence groups despite similar symptom intensity, emphasizing the importance of considering objective outcome in addition to patient-reported ones.Conclusion: Patients undergoing revision ESS are at high risk of disease recurrence, even when budesonide irrigations are used post operatively. Presence of S. aureus on culture pre-operatively or at 4 months post-ESS is associated with a negative outcome. This suggests that S. aureus negatively influences outcome, possibly via a number of mechanisms, including interactions with the (i) immune system, (ii) regeneration and repair of the sinus epithelium, or (iii) via interference with the sinus microbiome. This suggests that S. aureus may be a simple and inexpensive biomarker for disease severity and indicates a clear need to better appreciate S. aureus on how it contributes mechanistically to disease development and persistence in order to develop targeted therapeutic strategies.

Low CD8+ levels are often identified in CRS patients; however, these patients have disease remarkably similar to those with conventional CRS. This suggests that immune deficiency, whether systemic or locally mediated, is well tolerated and may be present in other forms in CRS. CRS patients with low CD8+ levels may possibly require antibacterial therapies as part of ongoing management.

Background Refractory chronic rhinosinusitis CRS remains a significant burden for patients o en leaving them with few therapeutic options that provide low-morbidity long-term and meaningful symptomatologic and endoscopic disease improvement Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect Our objective was to evaluate the efficacy of low-dose long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations BNIs and endoscopic sinus surgery ESS Methods A double-blind randomized placebo-controlled trial was completed in a single tertiary-care center assessing the addition of mg azithromycin times per week for weeks in adults failing ESS and high-volume BNIs Associated comorbidities as well as symptomatologic microbiologic and serologic values were systematically collected Results A total of patients were enrolled and underwent ESS followed by BNI At the-month post-ESS visit patients showed disease persistence and were randomized to azithromycin or placebo Overall azithromycin when compared with placebo did not show a statistically significant difference in disease clearance vs respectively p = although patients with disease clearance who were on azithromycin showed significantly betteritem Sino-Nasal Outcome Test score improvements than patients on placebo vs − respectively p = In a subgroup analysis excluding aspirin-exacerbated respiratory disease AERD patients azithromycin significantly improved disease clearance when compared with placebo vs respectively p = with a number needed to treat of Conclusion Low-dose azithromycin is a therapeutic option with few side effects Its use can show favorable clinical outcomes in this difficult-to-treat population especially if patients are AERD-negative © 2020 ARS-AAOA, LLC.

Modified CD8A or TAPBP gene function may contribute to the development of refractory CRS via altered MHC1 function and reduction of circulating CD8 lymphocytes. Identification of markers in the CD8A or TAPBP genes via sequencing may offer a basis for genetic testing in CRS.

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