Recalcitrant Chronic Rhinosinusitis Research Articles

The role of revision sinus surgery in the initiation of dupilumab therapy: A real-world study of molecular and cellular features.

A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature.

The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.

Increased antibiotic resistance of Pseudomonas aeruginosa isolates from chronic rhinosinusitis patients grown in anaerobic conditions.

In chronic rhinosinusitis (CRS), the congestion and blockage of the nose can cause anaerobic conditions within the sinus cavities which may promote the expression of virulence and antibiotic resistance genes in invading pathogens. Pseudomonas aeruginosa is a facultative anaerobic bacteria and causes severe recalcitrant CRS. In this study, we aimed to evaluate the antimicrobial resistance of P. aeruginosa isolates of CRS patients in planktonic and biofilm form grown in aerobic and anaerobic conditions. P. aeruginosa clinical isolates of CRS patients (n = 25) were grown in planktonic and biofilm form in aerobic and anaerobic conditions. Minimum inhibitory concentrations (MIC) of planktonic forms and minimum biofilm eradication concentrations (MBEC) were determined. Additionally, metabolic activity by fluorescein diacetate assay, biofilm biomass by crystal violet assay and eDNA concentration were assessed in both conditions. P. aeruginosa planktonic cells grown in anaerobic condition exhibited increased gentamicin resistance (p < .01), whereas P. aeruginosa biofilms grown in anaerobic condition displayed significantly increased MBEC values for gentamicin (p < .0001) and levofloxacin (p < .001). The metabolic activity of anaerobic biofilms was significantly higher compared with aerobic biofilms (p < .0001). However, the biofilm biomass of isolates grown in aerobic conditions was higher than anaerobic conditions (p < .5). P. aeruginosa isolates from CRS patients grown in anaerobic conditions showed significantly increased resistance to antibiotics with an increased metabolic activity but decreased biofilm biomass. NA.

Development of a novel self-assessment tool following endoscopic sinus surgery in the management of chronic rhinosinusitis

ObjectiveTo propose a novel quality metric tool for retrospectively examining ESS performed on chronic rhinosinusitis (CRS) patients, ultimately to facilitate clinician self-assessment and optimize care provision within this population. DesignQuality improvement study. SettingMulti-center. ParticipantsObservational, prospective research database of adult patients with medically recalcitrant CRS, presenting to seven North-American academic rhinology centers, who underwent ESS between 2011 and 2021. Participant characteristics, comorbidities, and preoperative study measures were collected. Main outcomes and measuresA simple ratio of preoperative Lund-Mackay (LM) score to the number of sinus regions operated on during the course of ESS was determined for each participant and dichotomized into ratios of >1.0 or <1.0. Results828 study participants with medically recalcitrant CRS met final study inclusion, of which 47.8 % were male with an average age of 49.0 years. Approximately 50.9 % of participants had a history of previous ESS. Overall mean ratio between preoperative LM scores and numbers of surgically addressed sinuses for all patients with CRS (n = 828) was 1.61 (range: 0.00–6.00), with a minority of subjects (n = 108; 13.0 %) found to have ratios below 1.00. Mean ratios between patients who underwent primary ESS versus revision ESS were not statistically different (2.00 [±0.83] vs 1.98 [±0.88]; 0.02 %, 95 % CI -0.10, 0.14; P = 0.76), whereas differences in mean ratios between CRSsNP patients (without nasal polyposis) and CRSwNP patients (with nasal polyposis) were statistically significant (1.78 [±0.93] vs 2.26 [±0.67]; 0.48 %, 95 % CI 0.37, 0.59; P ≤ 0.001). Conclusions and relevanceThis quality metric ratio represents a simple operational means for clinicians to integrate qualitative methodology into self-reflection when evaluating the extent of ESS performed on CRS patients. Its use as a clinical tool for retrospective self-reflection enables the surgeon to identify areas for improvement, assess situational specifics, and hone their craft.

The Interleukin-15 and Interleukin-8 Axis as a Novel Mechanism for Recurrent Chronic Rhinosinusitis with Nasal Polyps.

The prevention of postoperative recurrence after endoscopic sinus surgery (ESS) relies on targeting specific pathological mechanisms according to individuals' immunological profiles. However, essential biomarkers and biological characteristics of difficult-to-treat chronic rhinosinusitis (CRS) patients are not well-defined. The aim of this study was to explore the immunologic profiles of subgroups of CRS patients and determine the specific cytokines responsible for recalcitrant or recurrent CRS with nasal polyposis (rCRSwNP). We used 30 cytokine antibody arrays to determine the key cytokines related to recurrent polypogenesis. Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to assess the levels of these key cytokines in 78 patients. Polymorphonuclear leukocytes (PMNs) isolated from nasal polyps were challenged with specific cytokines to examine the levels of enhanced interleukin (IL)-8 production. Finally, we used immunohistochemistry (IHC) staining to check for the presence and distribution of the biomarkers within nasal polyps. A cytokine antibody array revealed that IL-8, IL-13, IL-15, and IL-20 were significantly higher in the recalcitrant CRSwNP group. Subsequent ELISA screening showed a stepwise increase in tissue IL-8 levels in the CHR, CRSsNP, and CRSwNP groups. PMNs isolated from nine CRSwNP cases all demonstrated enhanced IL-8 production after IL-15 treatment. IHC staining was labeled concurrent IL-8 and IL-15 expression in areas of prominent neutrophil infiltration. Our results suggest that IL-15 within the sinonasal mucosa plays a crucial role in promoting IL-8 secretion by infiltrating PMNs in recalcitrant nasal polyps. In addition, we propose a novel therapeutic strategy targeting the anti-IL-15/IL-8 axis to treat CRS with nasal polyposis.

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.

Timing of Surgery and Outcomes in Chronic Rhinosinusitis: A Narrative Review and Meta-Analysis.

Surgery is often indicated in the treatment of medically recalcitrant chronic rhinosinusitis (CRS). There is conflicting evidence on the impact of timeliness of sinus surgery on the degree of perceived symptom improvement in CRS. The goal of this study was to systematically evaluate the available literature on the relationship between patient wait times for endoscopic sinus surgery (ESS) and postoperative changes in patient-reported outcome measures. Ovid, MEDLINE, CINAHL, and Cochrane Library of Systematic Reviews between January 2000 and September 1, 2023, were searched. A total of 931 studies were independently screened by 2 reviewers. Two studies were included in the meta-analysis, while 4 others were included in a narrative review. Two studies consisting of 1606 patients were included in the meta-analysis. A mean difference in 22-Item Sino-Nasal Outcome Test (SNOT-22) of -0.3 (95% CI = -3.9 to 3.3, I2 = 89%, P < .01 was observed between "long" and "short" groups, while a mean difference in SNOT-22 of -0.1 (95% CI = -2.5 to 2.3, I2 = 80%, P = .03) was observed between "long" and "mid" groups. Patients who receive surgery earlier on their disease process (ie, earlier from the time of diagnosis to eventual surgery) appear to require less access to healthcare resources including prescription medications, thus suggesting better disease control. There is conflicting evidence to conclude whether timing of ESS affects disease-specific measures in patients with CRS. Patients who receive surgery earlier appear to have lower demands on healthcare utilization including visits and prescription use. Our study suggests there is a need for increased access to surgical specialists who manage patients with CRS, and better understanding by primary care specialists in how to manage CRS when specialist access is not available.

Snoring in patients withchronic rhinosinusitis after endoscopic sinus surgery.

In patients with chronic rhinosinusitis (CRS), we assessed quality of life (QOL) of chronic rhinosinusitis (CRS) patients with different self-reported snoring frequencies after endoscopic sinus surgery (ESS), and explored factors associated with pre-ESS snoring and post-ESS snoring reduction. This prospective cohort study was conducted in a tertiary referral center in Chengdu, China. Adult patients withmedically recalcitrant CRS receiving initial ESS were engaged. Self-reported snoring was measured at baseline and 3-year follow-up, along with Sino-Nasal Outcome Test-22 and snoring visual analog scale assessment. Mouth breathing (MB), demographics, behavior, comorbidity factors, and objective CRS severity were considered. In 210 patients who completed this study, 63 (30%) patients reported pre-ESS habitual snoring, and post-operative habitual snoring was observed in 52 (25%) patients. The presence of self-reported snoring was correlated with worse CRS QOL at baseline and 3-year follow-up. Obesity (odds ratio [OR] = 4.30; 95% confidence interval [CI], 1.64-11.28; p < 0.01) and posterior-to-anterior ethmoid sinus ratio greater than one (PE/AE, OR = 0.32; 95% CI, 0.10-0.99; p = 0.05) were associated with pre-ESS snoring in univariable and multivariable analysis. The post-operative reduction of snoring frequency was related with patient age over 65 (OR = 11.55; 95%CI, 1.35-98.79; p = 0.03) and bilateral opacification in the Lund-Mackay system (OR = 8.04; 95%CI, 1.24-51.90; p = 0.03) in multivariable analysis. Pre-operative snoring and MB were associated with increased risk of post-operative snoring (p < 0.01 for each comparison). Post-ESS, self-reported snoring was associated with worse CRS QOL. Obesity and PE/AE > 1 were risk factors of pre-operative snoring. Advanced age and bilateral opacification were associated with greater improvement of snoring after ESS.

S. aureus biofilm metabolic activity correlates positively with patients’ eosinophil frequencies and disease severity in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinus mucosa. Recalcitrant CRS patients are unresponsive to medical and surgical interventions and often present with nasal polyps, tissue eosinophilia, and Staphylococcus aureus dominant mucosal biofilms. However, S. aureus sinonasal mucosal colonisation occurs in the absence of inflammation, questioning the role of S. aureus in CRS pathogenesis. Here, we aimed to investigate the relationship between S. aureus biofilm metabolic activity and virulence genes, innate immune cells, and disease severity in CRS. Biospecimens, including sinonasal tissue and nasal swabs, and clinical datasets, including disease severity scores, were obtained from CRS patients and non-CRS controls. S. aureus isolates were grown into biofilms in vitro, characterised, and sequenced. The patients’ innate immune response was evaluated using flow cytometry. S. aureus was isolated in 6/19 (31.58%) controls and 23/53 (43.40%) CRS patients of 72 recruited patients. We found increased S. aureus biofilm metabolic activity in relation to increased eosinophil cell frequencies and disease severity in recalcitrant CRS cases. Mast cell frequencies were higher in tissue samples of patients carrying S. aureus harbouring lukF.PV, sea, and fnbB genes. Patients with S. aureus harbouring lukF.PV and sdrE genes had more severe disease. This offers insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.

Evaluation and treatment of rhinosinusitis with primary antibody deficiency in adults: Evidence-based review with recommendations.

There is clear evidence that the prevalence of primary antibody deficiency (PAD) is higher in patients with recurrent and chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in patients with PAD. The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through August 2022. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. A total of 42 studies were included in this evidence-based review. These studies were evaluated on incidence of PAD in rhinosinusitis patients, incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence was varied across reviewed domains. Based on the currently available evidence, PAD can occur in up to 50% of patients with recalcitrant CRS. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher-level studies that compare different treatments in patients with PAD and rhinosinusitis.

Risk Factors for Recalcitrant Chronic Rhinosinusitis in Non-Solid and Solid Transplant Recipients.

Transplant patients are high risk for surgery due to their immunocompromised state. There is a paucity of evidence concerning the differences in incidence of chronic rhinosinusitis (CRS) in solid versus non-solid organ transplant. Our aim is to analyze the difference in incidence of CRS requiring endoscopic sinus surgery (ESS) between non-solid and solid transplant populations and determine if certain risk factors are associated with increased incidence of recalcitrant CRS in non-solid versus solid transplants. Retrospective cohort. Multisite tertiary academic center. This is a retrospective chart review of 1303 transplant recipients who were seen in our rhinologic clinic for CRS between 2017 and 2022. A total of 224 patients underwent ESS and were further analyzed for risk factors associated with recalcitrant disease requiring sinus surgery. Subgroup analysis based on solid and non-solid organ transplant was performed. Of the 224 patients in the study, 171/224 (76.3%) had solid transplants while 53/224 (23.6%) had non-solid transplants. 17.19% of all transplant recipients required ESS. The incidence of ESS in non-solid transplants was 28.2% versus 57% in solid transplant. The risk of recalcitrant CRS in solid transplant recipients was almost 1.78 times greater than those with non-solid organ transplant (95% CI, 1.27-2.54, p = 0.0005). Individual factors such as certain immunotherapy drugs, pancytopenia, and rejection appear to correlate with the risk of ESS in both non-solid and solid organ transplant. Risk of ESS was greater in the solid transplant recipients compared to those who received non-solid organ transplant.

Staphylococcus aureus biofilm properties and chronic rhinosinusitis severity scores correlate positively with total CD4+ T-cell frequencies and inversely with its Th1, Th17 and regulatory cell frequencies.

Chronic rhinosinusitis (CRS) represents chronic inflammation of the sinus mucosa characterised by dysfunction of the sinuses' natural defence mechanisms and induction of different inflammatory pathways ranging from a Th1 to a Th2 predominant polarisation. Recalcitrant CRS is associated with Staphylococcus aureus dominant mucosal biofilms; however, S. aureus colonisation of the sinonasal mucosa has also been observed in healthy individuals challenging the significance of S. aureus in CRS pathogenesis. We aimed to investigate the relationship between CRS key inflammatory markers, S. aureus biofilm properties/virulence genes and the severity of the disease. Tissue samples were collected during endoscopic sinus surgery from the ethmoid sinuses of CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls (n = 59). CD3+ T-cell subset frequencies and key inflammatory markers of CD4+ helper T cells were determined using FACS analysis. Sinonasal S. aureus clinical isolates were isolated (n = 26), sequenced and grown into biofilm in vitro, followed by determining their properties, including metabolic activity, biomass, colony-forming units and exoprotein production. Disease severity was assessed using Lund-Mackay radiologic scores, Lund-Kennedy endoscopic scores and SNOT22 quality of life scores. Our results showed that S. aureus biofilm properties and CRS severity scores correlated positively with total CD4+ T-cell frequencies but looking into CD4+ T-cell subsets showed an inverse correlation with Th1 and Th17 cell frequencies. CD4+ T-cell frequencies were higher in patients harbouring lukF.PV-positive S. aureus while its regulatory and Th17 cell subset frequencies were lower in patients carrying sea- and sarT/U-positive S. aureus. Recalcitrant CRS is characterised by increased S. aureus biofilm properties in relation to increased total CD4+ helper T-cell frequencies and reduced frequencies of its Th1, Th17 and regulatory T-cell subsets. These findings offer insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.

Epithelial innate immune response to Pseudomonas aeruginosa-derived flagellin in chronic rhinosinusitis.

Pseudomonas aeruginosa is a common colonizing pathogen in the upper respiratory tract and is associated with recalcitrant chronic rhinosinusitis (CRS). Herein we sought to characterize the effect of P. aeruginosa-derived flagellin on human sinonasal epithelial cell (HSNEC) immune responses and determine whether these pathways are disrupted in CRS. Air-liquid interface cultures were established from CRS and healthy control donors. Cells were incubated with P. aeruginosa-derived flagellin for 24hours and transcriptional changes were assessed using whole transcriptome RNA sequencing. Apical and basolateral secretion of the pro-inflammatory cytokines in interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were measured after stimulation by lipopolysaccharide or flagellin and responses were compared between CRS and healthy control patients. HSNECs were weakly responsive to lipopolysaccharide, whereas flagellin stimulated a profound innate immune response dominated by TNF-α, IL-1β, and IL-17 signaling and activation of the IL-17C/IL-23 axis. CRS-derived HNSECs showed an altered innate immune response to flagellin, characterized by a profound increase in TNF-α secretion coupled with reduced IL-6 secretion. Flagellin activates a potent innate immune response in HSNECs characterized by pro-inflammatory mediators and cytokines/chemokines associated with neutrophilic inflammation. HSNECs from CRS patients have a dysregulated innate immune response to flagellin characterized by an imbalance between IL-6 and TNF-α secretion.

Frontal sinus stenting in endoscopic sinus surgery: the 10-year Oxford experience.

Frontal sinus stents have been introduced to reduce frontal sinus re-stenosis after surgery and to improve outcomes. This study was a retrospective analysis of 19 patients who had endoscopic sinus surgery with approach to the frontal sinus and insertion of a soft sinus stent. The frontal recess was patent in 78.9 per cent and stenosed in 21.1 per cent of patients; no completely closed recesses were observed. Mean follow up was 20.7 months, and time period of stenting was 9.8 months on average; complications were observed in 47.4 per cent of the patients, with post-operative sinonasal infection being the most common. In the authors' experience, indications for frontal sinus stenting include recalcitrant chronic rhinosinusitis after multiple functional endoscopic sinus surgeries (especially in chronic rhinosinusitis with nasal polyps), patients with history of important craniofacial surgery or trauma, and recurrent mucoceles. The stent was overall well tolerated as only minor complications were observed. Close clinical follow up is mandatory.

Tissue eosinophilia and computed tomography features in paediatric chronic rhinosinusitis with nasal polyps requiring revision surgery.

Endoscopic sinus surgery (ESS) is an effective and safe treatment modality for medically recalcitrant chronic rhinosinusitis (CRS) in the paediatric population, especially in older children or those with nasal polyposis (CRSwNP). We aimed to elucidate the inflammatory pattern and clinical characteristics of CRSwNP related to revision surgery after ESS in a paediatric population. We retrospectively enrolled 146 patients with bilateral CRSwNP. Twenty-two patients had recurrent nasal polyps that required revision surgery. The clinical characteristics, computed tomography (CT) features, tissue eosinophil count, and immunoactivity of signature cytokines in the two groups were analysed. Tissue eosinophil infiltration and immunoreactivity of eosinophilic cationic protein and IL-5 in the sinus mucosa were higher in patients that required revision surgery. The revision surgery group was significantly younger and had positive aeroallergen test results, higher total Lund-Mackay scores, and ethmoid/maxillary sinus ratio on CT images than those without revision surgery. A nomogram was developed to predict the probability of the requirement of revision surgery according to the logistic regression analysis results. We developed a nomogram model using clinical characteristics, tissue eosinophilia, and CT features for the preoperative identification of patients vulnerable to revision surgery in paediatric CRSwNP. This could help clinicians predict the probability of recurrence and perform intensive postoperative adjunct therapy and follow-up.

Association between laryngopharyngeal reflux, gastroesophageal reflux and recalcitrant chronic rhinosinusitis: A systematic review.

To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). PubMed, Cochrane Library and Scopus. Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies. A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo- and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls. Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events.

Minimal Radiographic Mucosal Thickness or Opacification Criterion for Sinus-Specific Endoscopic Sinus Surgery for Chronic Rhinosinusitis.

Primary chronic rhinosinusitis (CRS) is typically a diffuse process and the extent of endoscopic sinus surgery (ESS) performed for medically recalcitrant CRS is impacted by many factors. However, some third-party payors have implemented policies to authorize coverage for ESS in a sinus-by-sinus manner based on a minimal measurement of millimeters of mucosal thickening or sinus opacification in the corresponding sinus that is being surgically addressed. Our objective was to determine whether such policies are based on scientific evidence that in patients with medically recalcitrant CRS, a minimum measurement of mucosal thickening or sinus opacification is a predictor of CRS in that sinus or improved outcomes after ESS on a sinus-by-sinus basis. Medline, Embase, Scopus, and Web of Science databases, from inception through May 2022. A systematic review was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. We identified 6070 abstracts which were screened and from which 112 studies ultimately underwent a full-text review. From these studies, we found that none investigated (or provided evidence of) whether any minimal degree of radiographic mucosal thickening or sinus opacification predicted CRS or better outcomes after ESS in a sinus-specific manner. We were unable to find evidence supporting a minimum millimeter measurement of mucosal thickening or sinus opacification as predictors of CRS or better post-ESS outcomes in a sinus-specific manner in patients with medically recalcitrant CRS. The extent of ESS for CRS should be determined through personalized medical decision-making that considers all patient-specific factors.

Risk Factors for Recalcitrant Chronic Rhinosinusitis in Organ Transplant Recipients.

Studies suggest that transplant patients are at risk for chronic rhinosinusitis (CRS). However, there is limited information in the literature regarding frequency and reasons for failure of adequate medical therapy. We aim to determine the risk factors associated with the development of medically recalcitrant CRS requiring endoscopic sinus surgery (ESS). Retrospective cohort. Mayo Clinic. This is a retrospective chart review of 925 transplant recipients seen at Mayo Clinic between 2017 and 2022. (1) a rhinologic consultation after transplant and (2) clinical diagnosis of CRS. A total of 549 patients met the inclusion criteria and were divided based on the need for ESS versus successful treatment with medical therapy. Univariate and logistic regression analyses were performed to identify risk factors and predictive variables related to failure of medical therapy. Of the 549 patients, 201/549 (37%) had medically recalcitrant disease requiring ESS, while 348/549 (63%) were successfully treated with medical therapy Based on logistic regression, patients with recurrent acute rhinosinusitis in the pretransplant period were 8.68 more likely to have a recalcitrant disease (95% confidence interval, 3.72-20.28, p < 0.0001). Some of the largest determinants of medical therapy failure in the posttransplant period were CRS with nasal polyps, odontogenic CRS, and noninvasive fungal sinusitis. The presence of neutropenia, aplastic anemia, and living transplant were also associated with medically recalcitrant CRS requiring ESS. Our predictive model identifies with high accuracy the patients who may be at risk of developing recalcitrant CRS in the organ transplant population.

Chronic rhinosinusitis patients display an aberrant immune cell localization with enhanced S aureus biofilm metabolic activity and biomass

<h3>Background</h3> Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinus mucosa associated with dysfunction of the sinuses' natural defense mechanism and induction of different inflammatory clusters. Severe recalcitrant CRS is unresponsive to medical and surgical interventions and often has <i>Staphylococcus aureus</i>–dominant mucosal biofilms. <h3>Objectives</h3> This study aimed to characterize <i>in vitro</i> grown <i>S aureus</i> biofilm properties in relation to inflammation and CRS severity. The spatial pattern of inflammatory cells in patients' sinonasal tissue was also examined. <h3>Methods</h3> <i>S aureus</i> isolated from the nasal swabs of patients with CRS with nasal polyps (CRSwNP), those with CRS without nasal polyps, and controls (n = 72) were grown into biofilm <i>in vitro</i>, and their metabolic activity, biomass, colony-forming units, and exoprotein production were quantified. <i>S aureus</i> virulence genes were evaluated using whole-genome sequencing. Patients' matched sinonasal tissue blocks (n = 57) were analyzed using Opal multiplex immunostaining, and their disease severity was determined using the Lund-Mackay computed tomography score. Correlations among <i>S aureus</i> biofilm properties, the frequency and localization of key immune cells in corresponding sinonasal mucosa, and the disease severity were investigated. <h3>Results</h3> Increased infiltration of CD3⁺, CD68⁺, CD20⁺, and CD138⁺ cells was observed in tissue of patients with CRSwNP compared to tissue from controls. CD3⁺, CD138⁺, and MBP⁺ cells diffused deeper into the tissue in CRSwNP but clustered close to the epithelium in controls. This study also found CRSwNP–derived <i>S aureus</i> biofilms showed thicker biomass, higher colony-forming units, and higher exoprotein production than those from controls did (<i>P</i> < .05). <i>S aureus</i> biofilm properties, inflammatory cell numbers, and CRS severity scores were positively correlated. <h3>Conclusions</h3> These findings support the notion of an aberrant immunolocalization of key immune cells in CRSwNP with a critical role of <i>S aureus</i> biofilms in CRS etiopathogenesis.

Outcomes of Non-Mucosa Sparing Endoscopic Sinus Surgery (Partial Reboot) in Refractory Chronic Rhinosinusitis with Nasal Polyposis: An Academic Hospital Experience.

The reboot approach could be an effective treatment option to lower recurrence rates (RRs) in recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The purpose of this study was to investigate RR, recurrence-free survival (RFS), quality of life (QoL) improvement, and oral corticosteroid (OCS) intake in pluri-operated CRSwNP patients treated with partial reboot surgery. A consecutive sample of patients with recalcitrant CRSwNP, ineligible for monoclonal antibodies, underwent partial reboot surgery. The 22-item SinoNasal Outcome Test (SNOT-22), Visual Analogue Scales (VAS) scores, OCS intake, and endoscopic Nasal Polyp Score (NPS) were collected pre and postoperatively. The main outcomes were RR and RFS, and comparison of disease-free time with previous endoscopic surgeries. Thirty pluri-operated patients were enrolled. Before the reboot, all had experienced disease recurrence at a mean recurrence time of 8.08 ± 2.83 months after surgery. After reboot, 7 (23.3%) had recurrence at a mean time of 16.67 ± 3.07 months (p=0.02); none needed additional revision surgery till time of data collection. RR at 12, 18, and 24 months follow-up resulted significantly lower for reboot than other previous surgeries (p=0.010, p=0.002, p=0.016, respectively); RFS difference resulted significant (log-rank test=4.16; p=0.04). Differences between pre-and post-operative total and single-items scores of SNOT-22 were significant (p=0.001), as well as VAS scores (p=0.001). Before the reboot, 21 patients (70%) took ≥2 OCS courses per year; at the latest follow-up visit, none had taken any course of OCS after reboot. The reboot approach showed lower RR, longer RFS, improved QoL, and zeroing of OCS uptake. Larger samples and longer follow-up studies are needed to assess long-term efficacy and safety of this procedure. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2022. Laryngoscope, 133:1584-1589, 2023.