Chronic Rhinosinusitis Phenotypes Research Articles

Characterising the allergic fungal rhinosinusitis microenvironment using full-length 16S rRNA gene amplicon sequencing and fungal ITS sequencing.

Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2-mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS. We undertook a cross-sectional study of AFRS patients and non-fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short-read next-generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full-length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT). Thirty-two AFRS and 29 non-fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p = .07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p = .03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p = .005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p = .008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi. A low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia, Aspergillus and Curvularia. While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross-kingdom pathophysiological mechanisms.

Endotypes of Chronic Rhinosinusitis with Primary and Recurring Nasal Polyps in the Latvian Population.

Chronic rhinosinusitis (CRS) is a complex syndrome with various inflammatory mechanisms resulting in different patterns of inflammation that correlate with the clinical phenotypes of CRS. Our aim was to use detected IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, Ki 67, HBD-2, HBD-3, and LL-37 to classify specific inflammatory endotypes in chronic rhinosinusitis with the tissue of nasal polyps (CRSwNP). Samples from 35 individuals with primary and recurrent CRSwNP were taken during surgery. The tissues were stained for the previously mentioned biomarkers immunohistochemically. A hierarchical cluster analysis was performed. The clinical parameters were compared between clusters. Five clusters had significantly different biomarkers between groups. There were no significant differences in the clinical parameters, except for the Lund-Mackay score, which was significantly higher in cluster 4 compared to that of cluster 1 (p = 0.024). Five endotypes of (CRSwNP) are characterized by different combinations of type 1, type 2, and type 3 tissue inflammation patterns. In the Latvian population, endotypes associated with neutrophilic inflammation or a combination of neutrophilic inflammation and type 2 inflammation are predominant. Increased proliferation marker Ki 67 values are not associated with more severe inflammation in the tissue samples of chronic rhinosinusitis with nasal polyps.

Association of mucus eosinophil-derived neurotoxin levels with disease control status in patients with chronic rhinosinusitis.

Identifying the biomarkers for uncontrolled chronic rhinosinusitis (CRS) is important for directing treatment decisions. Eosinophilia has been reported to be involved in the poor disease control of CRS and mucus eosinophil-derived neurotoxin (EDN) is potentially a biomarker of intense eosinophil activation. This study aimed to assess the relationship between mucus EDN levels, disease severity, and degree of CRS control. A total of 150 adult patients with CRS and 25 healthy controls were prospectively enrolled. The nasal mucus and tissue specimens were collected to analyze EDN levels. Disease severity was assessed by Lund-Mackay score and 22-item Sino-Nasal Outcome Test (SNOT-22) score. Five CRS symptom severities during the prior month (nasal blockage, rhinorrhoea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue), use of rescue medications in the last six months, and the presence of diseased mucosa on nasal endoscopy were obtained. Consistent with the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 CRS control criteria, uncontrolled CRS was defined as meeting at least three items. 40% of patients with CRS presented with uncontrolled status. Patients with uncontrolled CRS had significantly higher nasal mucus EDN levels (P = 0.010), percentage of blood eosinophil (P = 0.015), SNOT-22 score (P < 0.001), Lund-Mackay score (P = 0.008), and a more eosinophilic dominant phenotype of CRS (P < 0.001) than patients with controlled CRS. Furthermore, mucus EDN levels were positively correlated with blood eosinophils (r = 0.541, P = 0.005), SNOT-22 score (r = 0.460, P = 0.021), and Lund-Mackay score (r = 0.387, P = 0.039). Mucus EDN levels were the significant parameter related to uncontrolled CRS in multivariable analysis after adjusting for patient demographics and comorbidities (odds ratio = 1.323; P = 0.004). Mucus EDN levels may be a potential biomarker for identifying the CRS control status.

A Novel Model of Staphylococcus aureus-Induced Lymphoplasmacytic Rhinosinusitis in Rats.

Chronic rhinosinusitis (CRS) is characterized by sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe CRS phenotypes. Different animal models have been proposed to study the association of CRS and S. aureus. However, current animal models are expensive due to the use of large animals, have high barriers to ethics approval, or require invasive surgical intervention, necessitating a need for a model that can overcome these limitations. This study aimed at establishing a reliable and efficient rat lymphoplasmacytic inflammatory model for rhinosinusitis. Sprague Dawley rats received a daily intranasal application of 20 μL of saline, S. aureus CI-182 exoprotein (250 μg/mL), or exoprotein CI-182 in combination with S. aureus clinical isolate (CI-908 or CI-913) 108 colony-forming unit (CFU)/mL. The rats' sinuses were harvested at 1 and 2 weeks post-intervention. The CFU and histopathologic examination of inflammation were evaluated. S. aureus clinical isolates CI-908 or CI-913 in combination with the exoprotein (CI-182) had higher CFUs and caused persistently higher inflammation at both the 1 and 2-week post-intervention compared to the exoprotein and saline group. The observed inflammatory cell type was lymphoplasmacytic. This study provided evidence that the combination of a S. aureus exoprotein with S. aureus induces inflammation that persists for a minimum of two weeks post-intervention. This model is the first known animal model to create the lymphoplasmacytic inflammation subtype seen in CRS patients. This offers a cost-effective, accessible, non-invasive, and easy-to-replicate model to study the causes and treatment of such inflammation.

Obesity is Associated with Increased Risk of New-Onset Chronic Rhinosinusitis: A United States Population-Based Cohort Study.

The aim of this study was to determine the risk of a new-encounter diagnosis of unspecified chronic rhinosinusitis (CRS), CRS with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 and 2 years following body mass index (BMI) classification of obesity utilizing a large-population-based analytics platform. Retrospective cohort analysis SETTING: The U.S. Collaborative Network within the TriNetX Analytics platform contains deidentified electronic health record (EHR) data of more than 100 million patients and was used to determine the association between obesity and a new encounter diagnosis of 3 CRS phenotypes in this study. After 1:1 propensity score matching, patients with an overweight BMI and obesity were at a higher risk for a new-encounter diagnosis of unspecified CRS and CRSwNP compared to healthy-weight individuals. The obesity cohort had the greatest increased risk of new-onset unspecified CRS with a relative risk of 1.23 (95% CI: 1.20-1.25) and 1.26 (95% CI: 1.24-1.28) 1 and 2 years following BMI classification, respectively. Our study indicates an association between obesity and new-onset unspecified CRS and CRSwNP. With the increasing prevalence of obesity in the United States population, it will be important to understand how obesity-associated CRS may affect treatment response. Future prospective studies are needed to assess causality and define a mechanistic link.

Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry

Chronic rhinosinusitis (CRS) is a persistent nasal and paranasal sinus mucosa inflammation comprising two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drug (NSAID) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. This study investigated levels of 33 different nasal and serum cytokines and phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients (n = 24), additionally examining the influence of comorbid respiratory allergies by mass cytometry. N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels were significantly elevated in allergic subjects, but not in CRS groups. In conclusion, there are distinct immunological features in PBMCs of CRS phenotypes and allergy.

Diverse Endotypes of Chronic Rhinosinusitis and Clinical Implications.

Chronic rhinosinusitis (CRS) is a highly heterogeneous disease characterized by inflammation in the nasal and sinus mucosa. The CRS phenotypes, based on the presence or absence of nasal polyps, are known as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). However, this classification has limitations in fully capturing the mechanisms and clinical manifestations of CRS. To address the heterogeneity of CRS, there has been a growing focus on classifying the condition into distinct endotypes. Endotype classification involves grouping patients based on specific molecular, immunological, and clinical characteristics, allowing for more personalized and targeted treatment approaches.This review delves into the current state of endotype classifications for CRS. It explores the role of geographic factors, microbiome, and subphenotype in shaping different endotypes. Additionally, the review examines how various clinical features are associated with specific endotypes, providing valuable insights into tailoring treatment options for better outcomes and transitions between different endotypes.Overall, this review offers a comprehensive and up-to-date perspective on the intricate realm of CRS endotype classifications. By unraveling the molecular and clinical intricacies, this review lays the foundation for more precise, effective, and individualized treatment strategies in the management of CRS.

Angiogenesis and eosinophilia in the nasal mucosa of patients with different clinical phenotypes of chronic rhinosinusitis

Introduction: Dense inflammatory cell infiltration and vascularization of the nasal mucosa are histological characteristics of chronic rhinosinusitis (CRS). We aimed to evaluate the association between eosinophilia and vascularization in the stroma of mucosal layer/nasal polyps (NP) and clinical parameters in patients with different phenotypes of CRS. Methodology: This cross-sectional study involved 33 patients who had CRS with NP without aspirin sensitivity (CRSwNP), 20 NP patients as a part of aspirin-exacerbated respiratory disease (AERD), and 10 patients who had CRS without NP (CRSsNP), selected for surgery. Control group consisted of 31 subjects without nasal/sinus inflammation, selected for surgery of pneumatized middle turbinate. All patients were clinically scored before surgery for nasal symptoms, quality of life (QoL) outcome and findings from computed tomography scans. NP/nasal mucosa samples of participants were immunohistochemically stained for eosinophil infiltration marker BMK13 and angiogenesis markers CD31 and CD34. Results: AERD patients had the highest level of immunoexpression for BMK13. The strongest staining pattern of CD34 was found in AERD group and the highest expression level for CD31 in CRSwNP group. We found a positive correlation between BMK13, impaired QoL and radiologically evaluated disease extent in patients with CRSwNP. Excepting CRSsNP patients, no correlation was found between the marker of tissue eosinophilia and markers of vascular proliferation. Conclusions: Patients from AERD phenotype have the highest degree of stromal eosinophilic infiltration and endothelial proliferation in comparison to other CRS phenotypes. Eosininophil infiltration marker BMK13 correlates better with the clinical parameters of CRS in comparison to the vascular proliferation markers.

Systematic Review and Meta-analysis: Macrolide in the Treatment of Chronic Rhinosinusitis After Endoscopic Sinus Surgery.

To evaluate the efficacy and safety of macrolide antibiotics therapy in patients with chronic rhinosinusitis (CRS) receiving endoscopic sinus surgery. PubMed, Web of Science, Embase, and Cochrane Library. The electronic databases were comprehensively searched on June 2, 2022, for randomized controlled trials on macrolide antibiotics in the treatment of patients undergoing CRS endoscopic surgery. The primary outcome measures were the sinonasal outcome test (SNOT) score and the visual analog scale (VAS) score. The secondary outcome measures were the nasal endoscopy score (NES), the sinus computed tomography score, and adverse events. A total of 8 studies were included, involving 606 patients who used macrolide for a long time. Meta-analysis showed that no significant difference was observed in SNOT (standardized mean difference [SMD] = -0.13; 95% confidence interval [CI]: -0.38 to 0.13, I2 = 0%) and VAS (SMD = -0.10; 95% CI, -0.88 to 0.68, I2 = 81%) between the macrolide and placebo groups. However, macrolide outperformed the placebo in improving NES (SMD = -0.32; 95% CI, -0.62 to -0.03, I2 = 21%). The use of macrolide did not increase the incidence of adverse events. Long-term use of macrolide after CRS surgery may not significantly improve the quality of life and disease severity of the patients but may play a role in improving postoperative NES in patients with CRS. There is still no sufficient evidence to determine whether the disease phenotype of CRS or the patient's race will affect the efficacy of long-term use of macrolide after CRS.

Bacteriology of Different Phenotypes of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) reduces the health-related quality of life and subsequently causes a tremendous socio-economic impact. Although many studies have been conducted, few have identified a relationship between bacteriological characteristics and different phenotypes or endotypes. Therefore, this study aimed to elucidate the recent trends in bacterial cultures from different types of CRS in the Asian population. This retrospective case-control study recruited patients diagnosed with CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into those with chronic rhinosinusitis with nasal polyps (CRSwNP)/chronic rhinosinusitis without nasal polyps (CRSsNP), eosinophilic chronic rhinosinusitis (eCRS)/non-eosinophilic chronic rhinosinusitis (NECRS), and central compartment atopic disease (CCAD)/lateral-dominant nasal polyp (LDNP) groups. The demographic data and bacteriological characteristics of the groups were analyzed. We included 503 patients, identifying no significant difference between CRSwNP and CRSsNP for several common bacteria in CRS. The number of Staphylococcus epidermidis isolates in culture was significantly higher in the NECRS group (50.46% vs. 32.56%, p = 0.0003) than that in the eCRS group. The number of methicillin-resistant Staphylococcus aureus (MRSA; 8.51% vs. 2.35%, p = 0.0221) positive isolates was significantly higher in the CCAD group than that in the LDNP group. This was the first study in Asia to analyze the relationship between bacteriological characteristics and CCAD. MRSA is significantly higher in the CCAD group than that in the LDNP group. Recognizing the unique microbiology of CRSwNP, eCRS, and CCAD is crucial when selecting antimicrobial therapy to lessen the socio-economic impact. 3 Laryngoscope, 134:1071-1076, 2024.

Doxycycline may be more clinically effective in type 2 chronic rhinosinusitis nasal polyp comorbid with asthma

Objective Chronic rhinosinusitis with nasal polyp (CRSwNP) is one of the major phenotypes of chronic rhinosinusitis (CRS) with a high symptom burden. Doxycycline can be used as add-on therapy in CRSwNP. We aimed to evaluate short-term efficacy of oral doxycycline on visual analog scale (VAS) and SNOT-22 (Sino-nasal outcome test) score for CRSwNP. Methods Visual analog score (VAS) for nasal symptoms and total SNOT-22 scores of 28 patients who applied with the diagnosis of CRSwNP and received 100 mg doxycycline for 21 days were analyzed in this retrospective cohort study. Doxycycline efficacy was also evaluated in subgroups determined according to asthma, presence of atopy, total IgE and eosinophil levels. Results After 21-day doxycycline treatment, there was a significant improvement in VAS score for post-nasal drip, nasal discharge, nasal congestion, and sneeze, and total SNOT-22 score (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). No significant improvement was observed in VAS score for the loss of smell (p = 0.18). In the asthmatic subgroup, there were significant improvements in all VAS scores and total SNOT-22 score after doxycycline. In the non-asthmatic subgroup, there was no significant change in any of the VAS scores, but total SNOT-22 score was significantly improved (42 [21–78] vs. 18 [9–33]; p = 0.043). Improvement in VAS score for loss of smell is significant in only some subgroups like asthmatic patients, non-atopic patients, and patients with eosinophil >300 cell/µL. Conclusions Doxycycline can be considered as an add-on treatment for symptom control in patients especially with CRSwNP comorbid with asthma.

Inflammatory characteristics of central compartment atopic disease.

Central compartment atopic disease (CCAD) is an emerging phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP) characterized by prominent central nasal inflammatory changes. This study compares the inflammatory characteristics of CCAD relative to other phenotypes of CRSwNP. A cross-sectional analysis of data from a prospective clinical study was performed on patients with CRSwNP who were undergoing endoscopic sinus surgery (ESS). Patients with CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and non-typed CRSwNP (CRSwNP NOS) were included and mucus cytokine levels and demographic data were analyzed for each group. Chi-squared/Mann-Whitney U tests and partial least squares discriminant analysis (PLS-DA) were performed for comparison and classification. A total of 253 patients were analyzed (CRSwNP, n=137; AFRS, n=50; AERD, n=42; CCAD, n=24). Patients with CCAD were the least likely to have comorbid asthma (p=0.0004). The incidence of allergic rhinitis in CCAD patients did not vary significantly compared to patients with AFRS and AERD, but was higher compared to patients with CRSwNP NOS (p=0.04). On univariate analysis, CCAD was characterized by less inflammatory burden, with reduced levels of interleukin 6 (IL-6), IL-8, interferon gamma (IFN-γ), and eotaxin relative to other groups and significantly lower type 2 cytokines (IL-5, IL-13) relative to both AERD and AFRS. These findings were supported by multivariate PLS-DA, which clustered CCAD patients into a relatively homogenous low-inflammatory cytokine profile. CCAD has unique endotypic features compared to other patients with CRSwNP. The lower inflammatory burden may be reflective of a less severe variant of CRSwNP.

Therapeutic Strategies to Prevent the Recurrence of Nasal Polyps after Surgical Treatment: An Update and In Vitro Study on Growth Inhibition of Fibroblasts.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine-acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine-acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence.

Functional Alteration and Differential Expression of the Bitter Taste Receptor T2R38 in Human Paranasal Sinus in Patients with Chronic Rhinosinusitis.

The bitter taste receptors (T2Rs) expressed in human sinonasal mucosae are known to elicit innate immune responses involving the release of nitric oxide (NO). We investigated the expression and distribution of two T2Rs, T2R14 and T2R38, in patients with chronic rhinosinusitis (CRS) and correlated the results with fractional exhaled NO (FeNO) levels and genotype of the T2R38 gene (TAS2R38). Using the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, we identified CRS patients as either eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 56) patients and compared these groups with 51 non-CRS subjects. Mucosal specimens from the ethmoid sinus, nasal polyps, and inferior turbinate were collected from all subjects, together with blood samples, for RT-PCR analysis, immunostaining, and single nucleotide polymorphism (SNP) typing. We observed significant downregulation of T2R38 mRNA levels in the ethmoid mucosa of non-ECRS patients and in the nasal polyps of ECRS patients. No significant differences in T2R14 or T2R38 mRNA levels were found among the inferior turbinate mucosae of the three groups. Positive T2R38 immunoreactivity was localized mainly in epithelial ciliated cells, whereas secretary goblet cells generally showed lack of staining. The patients in the non-ECRS group showed significantly lower oral and nasal FeNO levels compared with the control group. There was a trend towards higher CRS prevalence in the PAV/AVI and AVI/AVI genotype groups as compared to the PAV/PAV group. Our findings reveal complex but important roles of T2R38 function in ciliated cells associated with specific CRS phenotypes, suggesting the T2R38 pathway as a potential therapeutic target for promotion of endogenous defense mechanisms.

Phenotypes of Chronic Rhinosinusitis and Peripheral Blood Leukocytes Parameters in Elderly Patients.

Background and Objectives: Chronic rhinosinusitis (CRS) is a common disease that can be differentiated into two phenotypes, with or without polyps (CRSwNP) or CRSsNP), which may be unilateral (UNIL) or bilateral (BIL). CRS may have an impact on absolute neutrophils and lymphocytes count in peripheral blood. The aim of the study was to investigate whether the incidence of a specific CRS phenotype changes with age and to compare the values of neutrophils, lymphocytes and neutrophil-to-lymphocyte ratio in the peripheral blood between groups of patients below and above 65 years of age with different CRS phenotypes. Material and Methods: A total of 235 patients aged 65 and over were examined, including 140 (59.6%) males. The group of patients &lt;65 years of age comprised 160 subjects, including 103 (64.4%) males. In both groups, the sequence of frequency of particular phenotypes was similar: the most common phenotype was bilateral CRSwNP followed by CRSsNP BIL, CRSsNP UNIL, and finally, CRSwNP UNIL. Direct comparisons between determined phenotype in both groups of different ages revealed that, in the group ≥65 years, CRSwNP BIL occurred significantly more often than in the group &lt;65 years of age. In fact, in the &lt;65 group, bilateral CRSsNP was more common. The absolute neutrophils and lymphocytes counts were significantly higher in the whole group of patients with CRS ≥65 years of age and absolute number of neutrophils was higher in ≥65 years of age group with bilateral CRSsNP. Conclusions: The higher number of neutrophils in the whole ≥65 years of age group and in older patients with bilateral CRSsNP may indicate that CRS, despite of phenotype, may be an important source of infection that requires surgical treatment in elderly patients as well.

Pleiomorphism of the cytokine profile in nasal polyp tissue depending on the phenotype of chronic rhinosinusitis with nasal polyps

To compare inflammation response in patients with different phenotypes of CRSwNP according to level secretion of the key cytokines in nasal polyp tissue. 292 patients with CRSwNP were divided into four phenotypes: group 1 - CRSwNP without respiratory allergy (RA) and without BA; group 2a - CRSwNP+ AR with aBA; group 2b - CRSwNP+AR without aBA; group 3 - CRSwNP+nBA. Control group (n=36) included patients with hypertrophic rhinitis without atopy or BA. Using multiplex assay we defined the level of IL-1β, IL-4, IL-5, IL-6, IL-13, IFN-γ, TGF-β1, TGF-β2, TGF-β3 in nasal polyp tissue. The evaluation of cytokines levels in nasal polyps in different CRSwNP phenotypes showed a pleiotropy of different cytokine secretion depending on different comorbid pathology. In control group we estimated the lowest levels of all detected cytokines in comparison with other CRS groups. High levels of local proteins IL-5 and IL-13 and low levels of all isoform of TGF-β characterized CRSwNP without RA and BA. The combination of CRSwNP with AR showed high levels of proinflammatory cytokines IL-6 and IL-1β, and high levels of TGF-β1 and TGF-β2. The combination of CRSwNP with aBA estimated low levels of proinflammatory cytokines IL-1β, IFN-γ; in case of CRS+nBA we determined the highest levels of TGF-β1, TGF-β2 and TGF-β3 in nasal polyp tissue. Each CRSwNP phenotype is characterized by different mechanism of local inflammation. This underlies the necessity to diagnose BA and respiratory allergy among these patients. The evaluation of local cytokine profile in different CRSwNP phenotypes can help to determine the target anticytokine therapy for patients who has low efficacy of basic corticosteroid therapy.

Central Compartment Atopic Disease and Its Surgical Outcomes: Olfactory Changes and Technical Notes.

Central compartment atopic disease (CCAD) is a recent, novel phenotype of chronic rhinosinusitis. Only a few studies have assessed olfactory function in patients with CCAD. We aimed to investigate olfactory function changes after functional endoscopic sinus surgery (FESS) in patients with CCAD and proposed some surgical techniques to enhance the postoperative olfactory outcomes in such patients. A retrospective cohort study. We collected data from 23 patients (8 men and 15 women) with CCAD who underwent FESS performed by a surgeon in Taiwan, between June 2018 and December 2021. The demographic data, olfactory function, and serum and tissue eosinophil percentages of the included patients were analyzed. The Top International Biotech Smell Identification Test (TIBSIT; Top International Biotech, Taipei, Taiwan) was used to assess olfactory function. Of the 23 patients, most (95%) showed a positive reaction to aeroallergens, and 2 patients (8.7%) had asthma. Ten patients (43.5%) had peripheral eosinophilia, and 9 (39%) had eosinophilic nasal polyps. Moreover, the patients presented with variable olfactory dysfunction; the mean preoperative TIBSIT (pr-TIBSIT) score was 12.8 ± 2.3 (range: 0-43), whereas the mean postoperative TIBSIT (po-TIBSIT) score was 29.2 ± 1.9 (range: 16-44). The po-TIBSIT score was significantly better than the pre-TIBSIT score (paired t test, P < .0001). The improvement in olfactory function was not significantly correlated with the patients' age, serum eosinophil percentages, and nasal polyp eosinophil counts. Our findings indicate that CCAD is significantly associated with olfactory dysfunction and that FESS can effectively improve olfactory function. To optimize postoperative olfactory outcomes, precise removal of polyps from the olfactory cleft without damaging the neuroepithelium is recommended. Our study provides valuable insights into the management of CCAD patients undergoing FESS and can guide surgical decision-making to achieve optimal olfactory function outcomes.

Endoscopic sinus surgery outcomes in patients with chronic rhinosinusitis and immunoglobulin deficiencies

BackgroundPatients with chronic rhinosinusitis (CRS) and immunoglobulin deficiencies (ID) have more recalcitrant sinonasal disease and a subset of these patients undergo surgical management for their CRS. However, there is a paucity of literature on the surgical outcomes in this patient population and appropriate treatment algorithms for CRS in patients with ID. The objective of this study was to better elucidate the outcomes of endoscopic sinus surgery (ESS) in patients with ID in terms of disease-specific quality-of-life scores and the need for revision surgery.MethodsA case–control study was performed comparing adult patients with ID and healthy controls that had undergone ESS for CRS. Patients were matched based on age, sex, CRS phenotype, and preoperative Lund-Mackay score. The revision surgery rates, time to revision surgery, and changes in sinonasal outcome tests (SNOT-22) were evaluated.ResultsThirteen patients with CRS and ID were matched to 26 control patients with CRS. The revision surgery rate for cases and controls was 31% and 12%, respectively, but there was no statistical difference (p > 0.05). There was a clinically meaningful reduction in SNOT-22 scores in both groups from the preoperative to postoperative period [mean of 12 points in patients with ID (p = 0.323) and 25 points in controls (p < 0.001)], however, there was again no significant difference between cases and controls (p > 0.05).ConclusionOur data suggests that patients with ID have clinically meaningful improvement in SNOT-22 scores after ESS but may have higher revision rates than immunocompetent patients with CRS. ID are rare disease entities, thus most attempts at studying this cohort would be limited by sample size. Further homogenous data on immunoglobulin deficient patients is required for future meta-analysis to better understand the impact of ESS in patients with ID.

Relationship of chronic rhinosinusitis with Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis.

Several studies have demonstrated the association between chronic rhinosinusitis (CRS) and autoimmune diseases. However, there are few long-term longitudinal studies on this relationship. Therefore, we investigated the association between CRS and the risk of a subgroup of autoimmune disease using a representative nationwide cohort sample. We investigated the association between CRS and autoimmune diseases, including Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis. A total of 15,130 CRS patients and 30,260 patients without CRS were enrolled after 1:2 propensity score matching. A Cox proportional hazards model was used to analyse the hazard ratio (HR) of CRS for autoimmune disease. The incidence of Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis was 0.55, 0.10, and 0.48 per 1000 person-years, respectively. Among autoimmune diseases, the risk of Sjogren's syndrome in CRS patients was significantly increased to an adjusted HR (aHR) of 1.70, whereas we could not detect any significant risk of developing systemic lupus erythematosus or ankylosing spondylitis. In the subgroup analysis according to CRS phenotype, the adjusted HR of developing Sjogren's syndrome was greater in CRS patients without nasal polyps) than in CRS patients with nasal polyps. Our study suggests that CRS without nasal polyps is associated with an increased incidence of Sjogren's syndrome diagnosis compared to CRS without nasal polyps. Additionally, there was no association between CRS and systemic lupus erythematosus or ankylosing spondylitis, regardless of CRS phenotype.

DYNAMICS OF CLINICAL SYMPTOMS UNDER THE INFLUENCE OF ENDOTYPE-ORIENTED PHARMACOTHERAPY OF CHRONIC RHINOSINUSITIS WITH NASAL POLYPOSIS

Chronic rhinosinusitis (CRS) is a clinical syndrome including several clinical phenotypes and endotypes with differences in pathophysiology. Chronic rhinosinusitis with nasal polyposis (NP) is the most severe CRS phenotype associated with treatment resistance and frequent recurrence after surgery. Among patients with CRS with NP, up to 96% have radiological changes that demonstrate damage to the paranasal sinuses and indicate a diffuse lesion. Pharmacotherapy based on endotyping using aminocapronic acid (ACA) competitively inhibits plasminogen and plasmin formation, inhibits C3a and C5a, which can affect the pathophysiological mechanisms of polypus growth, is promising.&#x0D; The aim of the study: to evaluate the clinical effectiveness of the additional appointment of ACA in comparison with patients receiving standard therapy of CRS with NP according to clinical recommendations.&#x0D; Material and methods. The study included 120 outpatients, divided into two groups: the main (n-60) and the control (n-60) ones. The main group (n-60) included 35 (58.3%) men and 25 (41.7%) women, the control group (n-60) included 32 (53.3%) men and 28 (46.7%) of women. The average age of the main group was 45.8 years; the control group was 47.0 years. Patients were prescribed basic treatment, but patients in the main group were additionally prescribed aminocapronic acid (ACA). The evaluation of the treatment effectiveness was based on the analysis of the dynamics of clinical symptoms: rhinorrhea, postnasal drip, nasal congestion, reduced sense of smell according to the SNOT 22 scale (from 0 to 5 points for each symptom) at V2 (5±1), V3 (10±1), V4 (20±1) and V5 (30±1) compared to V0, as well as the presence of indications for surgical treatment were determined at V3.&#x0D; Results. The use of aminocapronic acid in CRS with NP contributes to a reliable reduction in the severity of the main clinical symptoms (rhinorrhea, postnasal drip, nasal congestion, reduced sense of smell) at V2 and V3 in comparison with patients of the control group. This provided a statistically significant difference at 25% in the reduction of operated patients: 56.7% in the main group versus 81.7% in the control group (p&lt;0.05). Conservative treatment was continued for 43.3% of patients in the main group and for 18.3% of patients in the control group (p&lt;0.05). Such a difference in the dynamic of symptoms regression can be explained by the peculiarities of the biological action of ACA, which can influence the pathophysiological features that characterize the endotype of diffuse eosinophilic CRS with NP. After the removal of the operated patients, the groups did not differ significantly differ in the dynamics of the regression of rhinorrhea, postnasal drip, nasal congestion, decreased sense of smell at V4 and V5 (p&gt;0.05). Differences in the results of treatment are attributed to the clinical effects of ACA, since the group characteristics of the patients were commensurable.&#x0D; Conclusions:&#x0D; &#x0D; the use of ACA in addition to the basic therapy in patients suffering from CRS with NP contributes to a significant reduction in the severity of the main clinical symptoms in the first 10 days of treatment compared to patients in the control group;&#x0D; the positive dynamics of clinical symptoms correlates with a reliable, at 25%, reduction in the number of surgical interventions.&#x0D;