Chronic Rhinosinusitis Disease Research Articles

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.

Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor

Introduction: Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied.Methods: 30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6–16y). MRI were evaluated using the CRS-MRI score.Results: After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275–0.999).Conclusions: ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

Chronic Rhinosinusitis and Premorbid Gastrointestinal Tract Diseases: A Population-Based Case-Control Study.

Objectives: The primary aim was to determine the prevalence of gastrointestinal diseases in patients with chronic rhinosinusitis (CRS), utilizing the National Health Insurance Research Database (NHIRD) in Taiwan. Several studies have supported the existence of distinct immune patterns between the Asian and Western populations in CRS patients. Through the population-based case-control study, we could compare the differences between various regions and provide further treatment strategies for subsequent studies in Asian CRS patients. The secondary aim was to assess whether different types of CRS influence the correlation with specific GI diseases. Understanding how different phenotypes or endotypes of CRS may relate to distinct GI disease patterns could provide valuable insights into the underlying mechanisms and potential shared pathways between these conditions. Methods: We use the NHIRD in Taiwan. Newly diagnosed patients with CRS were selected between January 1, 2001 and December 31, 2017 as the case group, and the controls were defined as individuals without a history of CRS. Patients with CRS were divided into two groups: with nasal polyps and without nasal polyps. We also separated GI tract diseases into four groups based on their different pathophysiologies. Results: This study included 356,245 participants (CRS: 71,249 and control: 284,996). The results showed that CRS was significantly associated with some specific GI tract diseases, including acute/chronic hepatitis B, gastroesophageal reflux disease (GERD) with/without esophagitis, achalasia of cardia, peptic/gastrojejunal ulcer, Crohn's disease, and ulcerative colitis. In addition, when CRS was subcategorized into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP), GERD with esophagitis and peptic ulcer were significantly associated with CRSsNP. Conclusions: A significant association between CRS and premorbid GI tract diseases has been identified. Remarkably, GERD with esophagitis and peptic ulcer were significantly associated with CRSsNP. The underlying mechanisms require further investigation and may lead to new treatments for CRS. Researchers can further investigate the mechanisms by referring to our classification method to determine the implications for diagnosis and treatment.

A Comprehensive Epidemiological and Clinical Study of Chronic Rhinosinusitis: First Report from an Iranian Sinusitis Registry Center

Background &amp; Objective: Chronic rhinosinusitis (CRS) is a high prevalent disease throughout the world. The aim of this study was to investigate the epidemiological and clinical characteristics of the CRS patients.&#x0D; Materials &amp; Methods: A total of 241 CRS patients aged 15-70 years were recruited. The prevalence of allergic diseases and its association with CRS, disease severity, and quality of life (QoL) were assessed using GA2LEN and SNOT-22 questionnaires, respectively. Patients' clinical diagnoses and allergic comorbidities were evaluated using paranasal sinus computed tomography (CT), nasal endoscopy, and paraclinical tests (smell identification test, fractional exhaled nitric oxide (FeNO), skin prick test (SPT), pulmonary function test (PFT)).&#x0D; Results: The mean (±SD) age of all participants was 40.1±11.1 years, with a gender distribution of 56% male and 44% female. Nasal polyps (NP) were diagnosed in 42.4% of patients. The total mean SNOT-22 scores and the mean scores of the nasal symptoms category were significantly higher in CRS patients with NP (CRSwNP) compared to CRS without NP (CRSsNP) (OR = 2.3, 95%CI = 9.6–0.55, P = 0.028). Furthermore, there was a significant association between CRSwNP and persistent allergic rhinitis comorbidity (P = 0.006). Finally, a significant association was found between CRSwNP and severe SPT reactivity to Dermatophagoides farina and date palm pollen (P = 0.04 and P &lt; 0.001, respectively).&#x0D; Conclusion: This study suggests that higher SNOT-22 scores may impact QoL in CRSwNP patients. Additionally, a significant association was found between CRS and respiratory allergic diseases.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

Non-Type 2 and Mixed Inflammation in Chronic Rhinosinusitis and Lower Airway Disease.

The aim was to discuss the role of non-type 2 inflammation in patients diagnosed with chronic rhinosinusitis (CRS) and comorbid lower airway disease. Medline, Embase, National Institute for Health and Care Excellence, TRIP Database, ProQuest, Clinicaltrials.gov, Cochrane Central Registry of Controlled Trials, Web of Science, government and health organizations, and graduate-level theses. This scoping review followed PRISMA-ScR guidelines. Search strategy was peer-reviewed by medical librarians. Studies were included if they utilized airway sampling, non-type 2 cytokines, and patients with CRS and lower airway disease. Twenty-seven from 7060 articles were included. In patients with CRS and comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and chronic obstructive pulmonary disease (COPD)/bronchiectasis, 60% (n = 12), 33% (n = 2), and 100% (n = 1), respectively, demonstrated mixed or non-type 2 endotypes. Comorbid CRS and asthma produced type 1 (n = 1.5), type 2 (n = 8), type 3 (n = 1), mixed type 1/2 (n = 1), and mixed type 1/2/3 (n = 8.5) endotype shifts. AERD demonstrated type 2 (n = 4), mixed type 2/3 (n = 1), and mixed type 1/2/3 (n = 1) endotype shifts. CRS with COPD or bronchiectasis demonstrated a mixed 1/2 (n = 1) endotype shift. Type 2 disease has been extensively reviewed due to advent biologics targeting type 2 inflammation, but outcomes may be suboptimal due to the presence of non-type 2 inflammation. A proportion of patients with CRS and comorbid lower airway disease demonstrated mixed and non-type 2 endotype shifts. This emphasizes that patients with unified airway disease may have forms of inflammation beyond classical type 2 disease which could inform biologic development. Laryngoscope, 134:1005-1013, 2024.

Geo-climatic risk factors for chronic rhinosinusitis in southwest Iran.

Chronic rhinosinusitis (CRS) is a prevalent and disabling paranasal sinus disease associated with some environmental factors. In this study, we evaluated the effect of geo-climatic factors on CRS in a region of southwest Iran. The study mapped the residency addresses of 232 patients with CRS who lived in Kohgiluyeh and Boyer-Ahmad province and had undergone sinus surgery from 2014 to 2019. The effects of Mean Annual Humidity (MAH), Mean Annual Rainfall (MAR), Mean Annual Temperature (MAT), maximum MAT (maxMAT), minimum MAT (minMAT), Mean Annual Evaporation (MAE), wind, elevation, slope, and land cover were assessed on the occurrence of CRS using Geographical Information System (GIS). Statistical analysis was performed using univariate and multivariate binary logistic regression. Patients came from 55 points including villages, towns, and cities. In univariate analysis, climatic factors including MAT (OR = 0.537), minMAT (OR = 0.764), maxMAT (OR = 0.63), MAR (OR = 0.994), and MAH (OR = 0.626) were significantly related to CRS occurrence. Elevation (OR = 0.999), slope (OR = 0.9), and urban setting (OR = 24.667) were the significant determinants among geographical factors when analyzed independently. The multivariate analysis found maxMAT (OR = 0.5), MAR (OR = 0.994), elevation (OR = 0.998), and urban (OR = 16.8) as significant factors affecting CRS occurrence. The urban setting is the most critical factor affecting CRS disease. Cold and dry areas and low attitude are the other risk factors for CRS in Kohgiluyeh and Boyer-Ahmad province, southwest Iran.

Advances in biologic therapies for chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis (CRS) is a complex multifactorial inflammatory disease that affects more than ten percent of the adult population globally. CRS represents a large healthcare burden and is associated with significant morbidity. Despite conventional medical and surgical treatments, a subset of patients continue to have poor symptom control due to substantial inflammatory disease persistence. These difficult-to-treat patients represent ideal candidates for biologic therapeutics, which target key inflammatory processes implicated in CRS disease. Biologic agents targeting type 2 inflammation have been shown to reduce disease burden. Phase 3 clinical trials studying the effects of anti-IgE, anti-IL-5/anti-IL-5Rα, and anti-IL-4/IL-13 humanized monoclonal antibodies have shown the efficacy of these therapies to reduce polyp size, the need for revision surgeries, improve daily symptoms, and downregulate inflammatory markers while maintaining an acceptable safety profile. The reductions seen in inflammatory mediators are largely transient following treatment termination and additional investigations are required to discern the long-term effects of biologic use on disease modulation. Specifically, the evidence suggests that these biologics are beneficial for patients with CRSwNPs with comorbid asthma and aspirin exacerbated respiratory disease (AERDBiologics should be used sparingly because of significant cost and accessibility of the treatment. Current guidelines recommend that biologics be reserved for patients with CRSwNP with moderate to severe disease who have failed conventional medical and surgical therapy. Further studies are needed to better endotype patients to optimize biologic use, evaluate long-term effectiveness and compare the relative effectiveness of biologic therapies in these difficult-to-treat patients.

Determinants of physician assessment of chronic rhinosinusitis disease control using EPOS 2020 criteria and the importance of incorporating patient perspectives of disease control.

Herein, we identify CRS manifestations associated with how rhinologists assess CRS control, with a focus on patient perspectives (patient-reported CRS control). Fifteen rhinologists were provided with real-world data from 200 CRS patients. Participating rhinologists first classified patients' CRS control as "controlled", "partly controlled", and "uncontrolled" using 7 CRS manifestations reflecting European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) CRS control criteria (nasal obstruction, drainage, impaired smell, facial pain/pressure, sleep disturbance, use of systemic antibiotics/corticosteroids in past 6 months, and nasal endoscopy findings) and patient-reported CRS control. They then classified patients' CRS control without knowledge of patient-reported CRS control. Inter-rater reliability, and agreement of rhinologist-assessed CRS control with patient-reported CRS control and EPOS guidelines were determined. CRS control classification with and without knowledge of patient-reported CRS control was highly consistent across rhinologists (κw = 0.758). Rhinologist-assessed CRS control agrees with patient-reported CRS control significantly better when rhinologists have knowledge of patient-reported CRS control than not (κw = 0.736 vs. κw = 0.554, p<0.001). Patient-reported CRS control, nasal obstruction, drainage, and endoscopy findings were most greatly associated with rhinologists' assessment of CRS control. Rhinologists' CRS control assessments weakly agreed with EPOS CRS control guidelines with (κw = 0.529) and without (κw = 0.538) patient-reported CRS control. Rhinologists classified CRS as more controlled than EPOS guidelines in almost 50% of cases. This study directly demonstrates the importance of patient-reported CRS control as a dominant influence on rhinologists' CRS control assessment. Knowledge of patient-reported CRS control may better align rhinologists' CRS control assessments and treatment decisions with patients' perspectives. This article is protected by copyright. All rights reserved.

The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease phenotypically classified by the absence (CRSsNP) or presence of nasal polyps (CRSwNP). The latter may also be associated with asthma and hypersensitivity towards non-steroidal anti-inflammatory drugs (NSAID) as a triad termed NSAID-exacerbated respiratory disease (N-ERD). The role of the microbiome in these different disease entities with regard to the underlying inflammatory process and disease burden is yet not fully understood. To address this question, we measured clinical parameters and collected nasal samples (nasal mucosal fluids, microbiome swabs from middle meatus and anterior naris) of patients suffering from CRSsNP (n=20), CRSwNP (n=20) or N-ERD (n=20) as well as from patients without CRS (=disease controls, n=20). Importantly, all subjects refrained from taking local or systemic corticosteroids or immunosuppressants for at least two weeks prior to sampling. The nasal microbiome was analyzed using 16S rRNA gene amplicon sequencing, and levels of 33 inflammatory cytokines were determined in nasal mucosal fluids using the MSD platform. Patients suffering from N-ERD and CRSwNP showed significantly worse smell perception and significantly higher levels of type 2 associated cytokines IL-5, IL-9, Eotaxin and CCL17. Across all 4 patient groups, Corynebacteria and Staphylococci showed the highest relative abundances. Although no significant difference in alpha and beta diversity was observed between the control and the CRS groups, pairwise testing revealed a higher relative abundance of Staphylococci in the middle meatus in N-ERD patients as compared to CRSwNP (p<0.001), CRSsNP (p<0.01) and disease controls (p<0.05) and of Lawsonella in patients suffering from CRSwNP in middle meatus and anterior naris in comparison to CRSsNP (p<0.0001 for both locations) and disease controls (p<0.01 and p<0.0001). Furthermore, we observed a positive correlation of Staphylococci with IL-5 (Pearson r=0.548) and a negative correlation for Corynebacteria and Eotaxin-3 (r=-0.540). Thus, in patients refraining from oral and nasal corticosteroid therapy for at least two weeks known to alter microbiome composition, we did not observe differences in microbiome alpha or beta diversity between various CRS entities and disease controls. However, our data suggest a close association between increased bacterial colonization with Staphylococci and decreased colonization by Corynebacteria as well as increased type 2 inflammation.

Risk of new-onset and prevalent disease in chronic rhinosinusitis: A prospective cohort study.

Chronic rhinosinusitis (CRS) is accompanied by burdensome comorbid conditions. Understanding the relative timing of the onset of these conditions could inform disease prevention, detection, and management. To evaluate the association between CRS and new-onset and prevalent asthma, noncystic fibrosis bronchiectasis (NCFBE), chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease (GERD), and obstructive sleep apnea (OSA). We conducted a prospective cohort study among primary care patients using a detailed medical and symptom questionnaire in 2014 and again in 2020. We used questionnaire and electronic health record (EHR) data to determine CRS status: CRSSE (moderate to severe symptoms with EHR evidence), CRSE (limited symptoms with EHR evidence), CRSS (moderate to severe symptoms without EHR evidence), CRSneg (limited symptoms and no EHR evidence; reference). We evaluated the association between CRS status and new-onset and prevalent disease using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). There were 7847 and 4445 respondents to the 2014 and 2020 questionnaires, respectively. CRSSE (vs CRSneg ) was associated with increased odds of new-onset asthma (OR, 1.74 [CI, 1.09-2.77), NCFBE (OR, 1.87 [CI, 1.12-3.13]), COPD (OR, 1.73 [CI, 1.14-2.68]), GERD (OR, 1.95 [CI, 1.61-2.35]), and OSA (OR, 1.91 [CI, 1.39-2.62]). Similarly, increased odds were observed for associations with the prevalence of these conditions. The findings from the study support further exploration of CRS as a target for the prevention and detection of asthma, NCFBE, COPD, GERD, and OSA.

Multiple reasons underlaying uncontrolled disease in the majority of chronic rhinosinusitis patients.

Up to 40% of patients with chronic rhinosinusitis (CRS) remain uncontrolled despite guidelines of care being available, with an enormous socio-economic impact. The reasons for uncontrolled disease can be arbitrarily divided into disease-related, diagnosis-related, treatment-related, and patient-related factors. The relative contribution of each factor in uncontrolled CRS remains speculative. This explorative study aimed at determining the factors responsible for uncontrolled CRS in a tertiary care center, thereby identifying the most commons reasons for uncontrolled disease in CRS. Patients with uncontrolled CRS (n = 187) were asked to fill out a questionnaire and underwent a clinical examination at the outpatient clinic of the University Hospital of Leuven, Belgium. Two independent physicians evaluated the (multiple) reason(s) for uncontrolled disease. In uncontrolled CRS, 66% of patients showed two or more reasons for uncontrolled disease according to the physicians' evaluation. Disease-related factors (70%) were most often considered the reason for uncontrolled disease, followed by treatment- (45%), patient- (42%), and diagnosis- (32%) related factors. In case of uncontrolled CRS, the different contributing factors to the uncontrolled nature need to be carefully addressed during diagnostic and therapeutic actions in order to define strategies to improve CRS care. Most uncontrolled CRS patients have multiple reasons contributing to their disease status, with disease-related factors being the most common factor.

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.

ASSOCIATION BETWEEN SMELL LOSS, DISEASE BURDEN, AND DUPILUMAB EFFICACY IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS

<h3>Introduction</h3> This post-hoc analysis investigated the association between baseline smell loss and other aspects of disease in chronic rhinosinusitis with nasal polyps (CRSwNP), and evaluated the effects of dupilumab according to severity of baseline smell loss in the pooled SINUS-24 and SINUS-52 studies (NCT02912468, NCT02898454). <h3>Methods</h3> Nasal polyp score (NPS, 0−8), patient-reported nasal congestion/obstruction (NC, 0−3), and 22-Item Sinonasal Outcome Test (SNOT-22, 0−110) were analyzed according to baseline monthly average patient-reported loss of smell scores (LoS, 0−3) of >1−≤2 (moderate) or >2−≤3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks. <h3>Results</h3> A total of 724 patients were randomized. Baseline LoS was severe in 601 patients (83%) and moderate in 106 patients (15%). At baseline, odds ratios (95% CI) for severe vs moderate LoS were 1.12 (0.96, 1.32) with 1-point increase in NPS, 6.01 (3.95, 9.15) with 1-point increase in NC, 1.03 (1.02, 1.05) with 1-point increase in SNOT-22, and 3.01 (1.97, 4.59) for with vs without prior sinonasal surgery. At Week 24, least squares mean differences (95% CI) dupilumab vs placebo in change from baseline were: NPS −1.90 (−2.56, −1.25) and −1.95 (−2.20, −1.70) in the moderate and severe baseline LoS subgroups, respectively; NC −0.35 (−0.64, −0.06) and −1.00 (−1.13, −0.87); and SNOT-22 −7.52 (−14.55, −0.48) and −21.72 (−24.63, −18.82); all nominal <i>P</i> <0.05 vs placebo. <h3>Conclusion</h3> Increased severity of loss of smell is associated with greater disease burden in CRSwNP. Dupilumab significantly improved outcomes and HRQoL regardless of baseline severity of smell loss.

Measuring control of disease in Chronic Rhinosinusitis; assessing the correlation between SinoNasal Outcome Test-22 and Visual Analogue Scale item scores.

In chronic rhinosinusitis (CRS), aim of treatment is control of disease. EPOS2020 suggests the use of visual analogue scale (VAS) measurements on several symptoms. We aim to determine if individual VAS items can be replaced by widely used SinoNasal Outcome Test-22 (SNOT-22) items when determining control of disease, to avoid using double measurements and to stimulate its use in clinical practice. Analyses were made on correlations between individual SNOT-22 scores and symptom-specific questions from consecutive patients with CRS visiting our tertiary referral rhinologic clinic for the first time. 157 CRS patients were included. Correlations of individual items were strong (r greater than 0.8). Best parity in sensitivity, specificity, positive predicting value, negative predicting value, odds ratio and Receiver Operating Characteristic curves were found in individual item score of VAS greater than 5 and SNOT item-score. This cut off is valid for measuring control of disease, combining several nasal, facial pain and sleep symptoms (controlled, partially controlled and uncontrolled). There is strong correlation between individual items measured as SNOT or VAS. For the definition of CRS disease control, as proposed in EPOS2020, the use of symptoms specific SNOT 23 is predictive of VAS greater than 5.

Discordance of chronic rhinosinusitis disease control between EPOS guidelines and patient perspectives identifies utility of patient-rated control assessment.

The objective of this study was to determine concordance of patient-reported chronic rhinosinusitis (CRS) disease control with CRS disease control assessed according to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. In 421 participants, CRS disease control was determined using EPOS criteria which include the burden of 5 symptoms measured on a binary scale, use of rescue medications in the prior 6 months and presence of diseased mucosa on nasal endoscopy. Symptom severity was also assessed using a visual analogue scale (VAS). Participants rated their CRS disease control as "controlled","partly controlled" or "uncontrolled". Patient-reported and EPOS-based CRS disease control ratings agreed for 49.6% of participants. Amongst cases of disagreement, EPOS guidelines assessed worse CRS disease control relative to 92.9% of patients. Facial pain/pressure and impaired sense of smell distinctly associated with patient agreement with EPOS guidelines on having "uncontrolled" CRS. Higher VAS symptom scores were associated with worse patient-reported CRS disease control (i.e., agreeing with EPOS guidelines). Removal of the nasal endoscopy criterion improved agreement between patients' and EPOS control assessments, and replacement of this criterion with patient-reported control further aligned EPOS guidelines with patient perspectives. EPOS guidelines regularly assess worse CRS control than assessed by patients. The lack of more gradated symptom severity criteria and inclusion of nasal endoscopy may contribute to discordance of EPOS guidelines with patient-reported CRS control. Replacement of nasal endoscopy findings with a measure of patient-reported CRS disease control better aligns EPOS CRS disease control guidelines with patients' perspectives.

Levels of eicosanoids in nasal secretions associated with nasal polyp severity in chronic rhinosinusitis

Severe nasal polyposis and mucosal inflammation, in patients with chronic rhinosinusitis (CRS) may include a dysregulated eicosanoid profile, but a clinical role for eicosanoids in CRS with nasal polyps (NP; CRSwNP) remains to be elucidated. This study focused on assessing levels and clinical implications of inflammatory mediators in nasal secretions and urine from patients with different NP severity or Aspirin Exacerbated Respiratory Disease (AERD). Levels of leukotrienes E4 and B4, prostaglandins D2 and E2 as well as 15(S)-hydroxyeicosatetraenoic acid were measured with enzyme immunoassays and cytokines with magnetic bead immunoassays. Patients with CRSwNP were subdivided based on NP score; CRSwNP-low (NP score ≤ 4, n = 11) or CRSwNP-high (NP score ≥ 5, n = 32) and compared to CRS without polyps (CRSsNP, n = 12), CRSwNP-AERD (n = 11) and individuals without CRS (n = 25). Smell test score, fractional exhaled nitric oxide (FeNO), blood eosinophils and Sinonasal outcome test-22 were assessed as clinical markers. Leukotriene E4, prostaglandin D2 and 15(S)-hydroxyeicosatetraenoic acid in nasal secretions correlated with NP score. Nasal leukotriene E4 also correlated with FeNO and smell test score, with highest levels found in CRSwNP-AERD. Levels of prostaglandin D2 in nasal secretion as well as urinary levels of the prostaglandin D2 metabolite 11β-prostaglandin F2α differed between CRSNP-high and CRSwNP-low. Urinary 11β-prostaglandin F2α was associated with asthma comorbidity whereas a similar association with prostaglandin D2 in nasal secretions was not observed. In conclusion, subdividing patients based on NP severity in combination with analysis of eicosanoids in non-invasively collected nasal secretions, may have clinical implications when assessing CRS disease severity.

Disease control in chronic rhinosinusitis: a qualitative study of patient perspectives.

The definition of disease control in chronic rhinosinusitis (CRS) is an active area of study. However, investigations have not engaged CRS patients in how they think about disease control. This study seeks to understand the patient perspective on CRS disease control. Qualitative phenomenological study using constant comparative methodology was applied. The research team conducted 10, one-on-one interviews with CRS patients ranging from 22 to 55 minutes in length. The content of the interview protocol was determined through iterative discussion amongst all authors. Two authors served as coders to identify recurrent themes. Themes were analyzed for meaning and conclusions were summarized. Three recurring themes determined from patients were that (1) use of the terminology control adequately represents this phenomenon, (2) components of control could be classified into four main themes relating to CRS symptomatology, exacerbation of comorbid disease, quality of life and acute exacerbations of CRS, and (3) when patients deem their CRS is uncontrolled they are more willing to escalate their treatment to include escalating their daily maintenance regimen, seeking otolaryngology referral, taking rescue medication or undergoing endoscopic sinus surgery. CRS patients consider their daily symptoms, the severity and frequency of CRS exacerbations, impact on quality of life as well as exacerbation of comorbid disease when thinking about their disease control. Disease control is a goal of treatment for patients and uncontrolled disease motivates patients to seek further treatment. Physicians should explore all components of CRS control when considering disease status and need for further treatment.

Chronic Rhinosinusitis and the Increased Incidence of Atopic Dermatitis.

Chronic rhinosinusitis (CRS) is often associated with other comorbidities due to chronic inflammation. However, no population-based, longitudinal study has investigated the relationship between CRS and chronic skin inflammation. To investigate the potential relationship between CRS and chronic skin inflammatory diseases, such as atopic dermatitis (AD), vitiligo, and psoriasis. A total of 5638 patients with CRS and 11 276 without CRS as a comparison group, were included from the Korean National Health Insurance Service database from 2002-2013. A propensity score matching (1:2) was performed using the nearest neighbor matching method, sociodemographic factors, and enrollment year. The Cox proportional hazards model was used to analyze the hazard ratio of CRS for AD, vitiligo, and psoriasis. Results from this study showed that patients with CRS had no significant risk of the subsequent development of vitiligo or psoriasis compared to patients without CRS. However, we found a significantly higher incidence of AD in CRS patients than in those without CRS. The incidence of AD was 63.59 per 1000 person-years in the CRS group and 45.38 per 1000 person-years in the comparison group. Additionally, young and middle-aged CRS patients were independently associated with a higher incidence of subsequent AD events, but we could not find a significantly higher incidence of AD events in the elderly group. Our findings suggest there are no significant differences in the overall risk of vitiligo and psoriasis events in patients with CRS; however, we detected a higher risk of AD in young and middle-aged CRS patients. Therefore, clinicians should consider the risk of developing AD in specific patients who are newly diagnosed with CRS.

Environmental air pollution and chronic rhinosinusitis: A systematic review.

ObjectiveChronic rhinosinusitis (CRS) is a highly prevalent and burdensome disease. The pathophysiology is not fully elucidated, but environmental pollutants have been suggested to impact the inflammatory component of the disease process. This review aims to summarize the role of environmental pollution in CRS onset and disease severity.MethodsA systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were queried in August 2021. Original articles reporting on air pollution exposure in CRS were included. Other forms of sinonasal disease were excluded.ResultsLiterature search produced 11,983 articles, of which 10 met inclusion criteria. Outcomes evaluated included incidence/prevalence, disease severity, quality of life, and histopathologic/microbial changes. Air pollutant exposure was associated with higher odds of CRS, particularly with particulate matter (PM) exposure. Increasing air pollution exposure was also associated with worsened disease severity and detectable histopathologic changes. Impact on quality of life was less clear.ConclusionAir pollution (particularly PM) is correlated with CRS incidence/prevalence and disease severity, with evidence of histopathologic changes in CRS tissue samples. Further research is warranted to better understand the mechanisms by which air pollution components may cause CRS and type 2 inflammation.Level of Evidence3a