Uncontrolled Chronic Rhinosinusitis Research Articles

Chronic rhinosinusitis with nasal polyps-extension of dupilumab treatment intervals

In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24weeks, reducing the dose of dupilumab to once every 4weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended. The course of 29patients with severe CRSwNP, type‑2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4weeks, thereafter up to 6weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany). All patients showed an excellent improvement within the first 3months. The dupilumab application interval was extended to 4weeks after 7-31months (median 13months) and to 6weeks (n = 9) after 17-35months (median 23months). No recurrent polyps or symptoms were subsequently observed. In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to4 and potentially 6weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.

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.

Efficacy of dupilumab in real-life settings: a STROBE study.

Dupilumab, a monoclonal antibody targeting IL-4 and IL-13, has demonstrated its efficacy in several clinical trials. However, to date, real-life data remains limited. The aim of our study was to assess the real-life impact of dupilumab on patients with severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) quality of life. This was a retrospective, monocentric, observational, real-life study, conducted in accordance with the STROBE guidelines. The following parameters were collected before treatment and at 1, 4, and 12 months: Sino-Nasal Outcome Test-22 (SNOT-22), nasal polyp score (NPS), Sniffin' Sticks-16 (SST-16), visual analog scale (VAS) for loss of smell, nasal congestion score (NCS), gustatory VAS, asthma control, oral corticosteroid usage, surgery rates, and occurrence of side effects. The study included 47 patients. SNOT-22 scores decreased from 52.4 ± 24.3 to 12.7 ± 10.5 at 12 months (p < 0.001). NPS decreased from 6.15 ± 1.71 to 1.57 ± 1.40 at 12 months (p < 0.001). SST-16 scores increased from 1.6 ± 2.83 to 9.1 ± 5.4 at 12 months (p < 0.001). NCS decreased from 2.45 ± 0.72 to 0.38 ± 0.63 at 12 months (p < 0.001). Prior to treatment, 72.3% were using oral corticosteroids, compared to 17.0% at 12 months (p < 0.01). Two patients required additional surgery, and 17% reported completely uncontrolled asthma, compared to 0% at 12 months (p < 0.01). Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP.

Difficult-to-treat chronic rhinosinusitis-when thestandard treatment is not effective and biologics are not available

In recent years, significant improvements have been made in the treatment options for uncontrolled chronic rhinosinusitis (CRS) refractory to standard medical and surgical therapy. This is the result of abetter understanding of the pathophysiology and the resulting development of biologicals for CRS with nasal polyps (CRSwNP). However, biologics are not (yet) available for all patients in Europe. Based on the session "Difficult-to-treat CRS, when biologics are not available" at the 29thCongress of the European Rhinologic Society (ERS) 2023 in Sofia, Bulgaria, the treatment options for uncontrolled CRS with the exclusion of biologics will be discussed. The content of the presentations "Is there aplace for antibiotics?" "Indications for revision surgery," "Novel systemic treatment options," "Novel local treatment options," and "Phototherapy for nasal polyps" are outlined and supported by areview of the literature. Various treatment options are available for managing uncontrolled CRS, even if biologic treatments are unavailable. Treatment options for type‑2 (T2)CRS include steroid rinses, repeated short-term oral steroids, steroid-eluting stents, and extended sinus surgery. In the case of nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD), acetylsalicylic acid (ASA) desensitization can be considered. Non-T2 endotypes or CRS without nasal polyps (CRSsNP) may benefit from several weeks of macrolides and xylitol rinses. To accurately assess the efficacy of second-line therapies for treatment of difficult-to-treat CRS within an endotype-specific framework, additional controlled clinical trials are needed that take into account the heterogeneity of CRS endotypes.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) &gt;100 kU/L, a blood eosinophil count (BEC, expressed as ·109 cells / L) ≥0.25, or a tissue eosinophil count ≥10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from ≥0.25 (EPOS2020) to ≥0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.

Patterns of Olfactory Impairment Among Patients with Uncontrolled Chronic Rhinosinusitis.

Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test. A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS. Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS. Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS. 3 Laryngoscope, 134:2341-2348, 2024.

Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 μg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 μg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels &gt;17.0 μg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

Eosinophilia, asthma, NERD and the use of oral corticosteroids predict uncontrolled chronic rhinosinusitis with nasal polyps after surgery.

Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

Type 2 Biomarkers for the Indication and Response to Biologics in CRSwNP.

Three biologics targeting type 2 inflammation have been approved for the treatment of severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Nevertheless, around 40-60% of patients do not respond well to these biological treatments. Selecting appropriate patients is crucial to improve treatment outcome of biologics. This review summarizes the literature data on type 2 biomarkers, with a specific focus on the indication to biologics for severe CRSwNP. No consensus has been reached on how to define mucosal type 2 inflammation in CRSwNP. Clinical markers (e.g., 22-item Sino-nasal Outcome Test (SNOT-22) score, Lund-Mackay CT score (LMS), ethmoid/maxillary sinus CT score, and CT-radiomics), nasal secretion biomarkers (e.g., eosinophil cationic protein and interleukin-5), blood and nasal cytology eosinophil counts, and nasal swab eosinophil peroxidase activity have been reported to be associated with type 2 inflammation in CRSwNP. The time duration since the last surgery, SNOT-22 score at 1 week of treatment, and baseline serum osteoprotegerin levels might indicate the response to dupilumab. LMS and asthma control test scores were found to have moderate predictive value for acceptable improvement after 24-week treatment of omalizumab. High blood eosinophil levels at baseline were associated with treatment response to mepolizumab and benralizumab. Although several clinical and biological markers might be associated with type 2 inflammation and response to biologics in patients with CRSwNP, their validity requires further investigation. Identifying clinically applicable biomarkers for biologic treatment holds significant promise for advancing personalized approaches to biologics and optimizing treatment outcomes for patients with CRSwNP.

Residual nasal polyp tissue following dupilumab therapy is associated with periostin-associated fibrosis.

Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype. We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration. Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration. Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction.

Biologics in severe uncontrolled chronic rhinosinusitis with nasal polyps: A bicentric experience.

The introduction of biologics in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP) has allowed new therapeutic options and Dupilumab represents the first approved biological agent. Aim of this paper is to provide a multicentric study in a real-life setting of treatment with Dupilumab for severe uncontrolled CRSwNP in Italy. A retrospective data collection was performed from the departments of Otolaryngology of two major health institutions in Rome: San Camillo Forlanini Hospital and Tor Vergata University. Both centres contributed to the study providing information about patients affected by severe uncontrolled CRSwNP and treated with Dupilumab. A total of 83 patients were included in the study (43 males; 40 females; mean age: 55.8 years). Monitoring our patients, we observed improvement in reduction of nasal polyposis and nasal obstruction, respectively measured through NPS and PNIF. Concerning the CRSwNP symptoms and their impact on quality of life, we found an improvement in the olfaction, as measured respectively by SSIT-16 and SNOT-22. Dupilumab has demonstrated broad efficacy in CRSwNP management. Further studies are needed to confirm our results and to establish biomarkers to identify endotypes and predict response to biologics treatment in CRSwNP.

Dupilumab's Impact on Blood Parameters in Nasal Polyposis: 18-Month Follow-Up in Real Life.

Dupilumab represents the first approved biological for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Aim of this paper is to provide a multicentric real-life study about treatment with dupilumab for CRSwNP with a special focus on blood parameters and IgE, IgG, and IgA. A retrospective data collection was jointly conducted at the Otolaryngology departments of San Camillo Forlanini Hospital and University of Rome "La Sapienza" from December 2020 to January 2023. A total of 130 patients were included in the study. Monitoring our patients for 18 months, we observed a reduction in nasal polyposis and an improvement in symptoms and their impact on quality of life. Regarding blood tests, a transient increase in blood eosinophils was found in most cases. Total IgE showed a gradual decrease in values. IgG and IgA also showed a slight reduction of values, while remaining within normal ranges. To the best of our knowledge, this is the first study to evaluate the impact of dupilumab on several blood parameters in patients receiving treatment for CRswNP. Further studies are needed to confirm our results and to understand the underlying immunological mechanisms.

Influence of Prior Endoscopic Sinus Surgery Extent on Dupilumab Effectiveness in CRSwNP Patients.

Guidelines recommend that the vast majority of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) should have at least one endoscopic sinus surgery (ESS) prior to starting biologics. Because ESS can be performed with a variable extension, the aim of this study would be to evaluate the association between surgical extensiveness, as measured by ACCESS score, and outcomes collected in patients treated with Dupilumab. This is a multicentric retrospective study; patients affected by CRSwNP who were subjected to Dupilumab therapy and who underwent at least one ESS prior to Dupilumab initiation were included. ACCESS score was assigned to each patient's pre-Dupilumab CT scan. Subjective and objective parameters (SNOT-22, NPS, VAS scores, Sniffin' Sticks) were collected before and during the administration of therapy. Statistical correlations between ACCESS scores and clinical outcomes were investigated. A total of 145 patients were included; mean time from last previous ESS was 68.6 months, and on average, patients were subjected to 2.2 surgeries. Many correlations with ACCESS scores were demonstrated: better NPS at all timepoints and subjective scores (30-days SNOT-22, VAS nasal obstruction, and rhinorrhea) were achieved in patients with low ACCESS score (more extensive ESS). On the other hand, significantly worse VAS loss of smell values were demonstrated in patients with lower ACCESS scores. Dupilumab patients subjected to a prior extensive ESS may have reduced size of polyps and improved subjective indicators, together with a decreased chance to recover smell, when compared with patients who underwent a minimal excision. 3 Laryngoscope, 134:1556-1563, 2024.

Biological Treatment for Uncontrolled Chronic Rhinosinusitis with Nasal Polyps: Preliminary Real-World Results from a Tertiary Medical Center.

The efficacy of biological treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) has recently been demonstrated through double-blinded clinical trials. The aim of this study was to provide preliminary real-world experience regarding biological therapy for uncontrolled CRSwNP. The records of patients who received biological treatment in a tertiary medical center between the years 2019 to 2022 were retrospectively reviewed. Patients included in this study were eligible for biological treatment according to the EPOS 2020 criteria. Among patients who had their first follow-up visit <6 months from the treatment initiation, the Sino-Nasal Outcome Test 22 Questionnaire (SNOT-22) score had decreased by 22% (p = 0.01) and the nasal polyp score (NPS) had decreased by 48% (p = 0.05). Among patients who had their first follow-up visit ≥6 months from treatment initiation, the SNOT-22 score had decreased by 40% (p = 0.03) and the NPS had decreased by 39% (p = 0.1). The number of patients who needed systemic steroid treatment had decreased by 68% (p < 0.0001), and the number of patients who needed endoscopic sinus surgery had decreased by 74% (p < 0.0001). These findings correspond with the improvement of clinical symptoms observed in prior randomized clinical trials, thus showing the effectiveness of biologic medications in the treatment of severe CRSwNP in a real-life setting. Although further cohort studies are warranted, our study also suggests evaluating patients at follow-up visits mainly by quality-of-life aspects and investigating longer dosing intervals of dupilumab.

Innovative treatments for severe uncontrolled chronic rhinosinusitis with nasal polyps

ABSTRACT Introduction In recent years, endotypes of chronic rhinosinusitis (CRS) based on the underlying immune mechanisms provided a better understanding of this heterogeneous disease and are frequently applied in diagnosis and treatment. Areas covered In this manuscript, we aim to review novel treatment approaches for this often uncontrolled disease and highlight endotype-driven medical algorithms that could be beneficial in daily clinical practice. Expert opinion With the development of endotyping and the mucosal inflammatory concept, several type 2–targeted biologics and surgical options are nowadays available for treating CRS. However, a better understanding based on clinical trials and real-life experience in daily practice is needed to optimize patient selection, biological drug selection, treatment duration, prediction, and long-term follow-up strategies. Indirect comparison analysis suggested that dupilumab might be the most effective biologic for treating CRS with nasal polyps, but the role and timing of surgery remain unclear. More real-life studies and comparative trials are needed for the optimal integration of biologics into clinical pathways in combination with established treatment approaches such as nasal and oral glucocorticosteroids and adequate surgery to provide long-term perspectives.

Upper Airway Disease in Adults with Cystic Fibrosis in the Era of CFTR Modulators.

Chronic rhinosinusitis (CRS) is prevalent in people with cystic fibrosis (PwCF) and is often refractory to treatments. Uncontrolled CRS might negatively impact the lower airways and the quality of life. The aim of this study is to evaluate the burden of cystic fibrosis (CF)-related CRS in the era of CF transmembrane conductance regulator (CFTR) modulators. Adult PwCF were asked to fill in a questionnaire on sinonasal complaints, they underwent a nasal endoscopy, bacteriological sampling, and a CT scan. Afterwards, these outcome measures were compared between patients treated with and without modulators. In the 122 included patients, CRS was present in 83%. CFTR modulators were prescribed in 48% of the patients, with a median of 10 months since the start of the treatment. Subjectively, the median SNOT-22 score was 16/110. Objectively, a median Lund-Kennedy score of 6/12 and modified Lund-Mackay score of 10/24 were observed. No correlation could be found between SNOT-22 score and other outcome measures including endoscopy and radiology. Altogether, 21% of the patients had controlled disease. When comparing patients treated with and without modulators, significantly lower CT scores (p=0.0018) and less bacterial colonization (p=0.0082) were observed in patients receiving modulators. CF-CRS is highly prevalent in our cohort and only the minority of PwCF has a well-controlled disease. A multidisciplinary ENT-pneumology clinic would be beneficial, as there is a high discrepancy between patient-reported symptoms and the extent of the disease. CFTR modulators are promising, as lower CT scores and less bacterial colonization were observed in the modulator group. Level 3 Laryngoscope, 133:2898-2909, 2023.

Treatment Strategy of Uncontrolled Chronic Rhinosinusitis with Nasal Polyps: A Review of Recent Evidence

Chronic rhinosinusitis (CRS) is recognized as a heterogeneous disease with a wide range of clinical features, resulting in significant morbidity and cost to the healthcare system. While the phenotypic classification is determined by the presence or absence of nasal polyps and comorbidities, the endotype classification has been established based on molecular biomarkers or specific mechanisms. Research on CRS has now developed based on information based on three major endotypes: types 1, 2, and 3. Recently, biological therapies targeting type 2 inflammation have been clinically expanded and may be applied to other inflammatory endotypes in the future. The purpose of this review is to discuss the treatment options according to the type of CRS and summarize recent studies on new therapeutic approaches for patients with uncontrolled CRS with nasal polyps.

Dupilumab for chronic rhinosinusitis with nasal polyps: real-life retrospective 12-month effectiveness data.

Dupilumab, an IL-4/13 receptor inhibitor, is approved for the treatment of uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). We evaluated the effectiveness and safety of dupilumab for CRSwNP based on retrospective 12-month follow-up data of 41 patients. We analysed nasal endoscopy scores, patient-reported outcome measures (PROMs), 12-item SniffinSticks odor identification test (SSIT-12), total serum IgE, serum Eosinophilic Cationic Protein (ECP), and total blood eosinophil count (BEC). We performed statistical analysis using non-parametric ANOVA-type models and Spearman's correlation. At month 1, endoscopy scores, PROMs and SSIT-12 showed meaningful improvements that were maintained until month 12. Initial elevations in both median ECP and BECs returned to near baseline levels by month 12. The percentage of patients withBEC ≤ 0.6 remained increased at month 12 (42.1%) compared to baseline (19.5%). Total serum IgE levels decreased progressively and correlated with nasal polyp scores at month 12. "Adequate response" was reached in 86.8% of our cohort. Our data suggest that dupilumab is effective for the treatment of CRSwNP. The potential for short- and long-term BEC elevations in some CRSwNP patients should be carefully monitored.

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.

Extending the use of the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire in a cross-sectional study: Patients with chronic rhinosinusitis versus healthy controls.

There are several instruments to assess health-related quality of life (HRQoL) in chronic rhinosinusitis (CRS). Unfortunately, none of them evaluates all three health domains (physical, social and psychological) important to assess the overall well-being of the patient. The Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q) does assess all these elements. Initially, the EES-Q is validated to evaluate the impact of endoscopic endonasal surgery (EES) on HRQoL. The aim of this study is to assess whether EES-Q outcomes differ in patients with CRS compared with healthy individuals. Therefore, extending the use of the EES-Q for all CRS patients. Cross-sectional study. Tertiary referral hospital. One hundred patients with uncontrolled CRS (50% with nasal polyps) scheduled to receive EES. The questionnaire was completed preoperatively. Healthy control subjects (n= 100) without any history of sinusitis or a known current medical treatment at a hospital were included. Mann-Whitney U test was performed to identify differences in EES-Q scores (domain scores and EES-Q score). The median EES-Q score in CRS patients (33.8) was significantly higher (p< 0.001) than in the control group (10.4). As well as the physical (52.5 vs. 16.4, p< 0.001), psychological (13.8 vs. 5.0, p< 0.001) and social (37.5 vs. 2.5, p< 0.001) domain scores. With this study, we are extending the use of the EES-Q. It indicates that the EES-Q can be a valuable clinical tool to assess multidimensional HRQoL in all patients with CRS.