[Blood eosinophilia in patients with severe bronchial asthma and chronic polypous rhinosinusitis treated with dupilumab: A review].

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics. METHODS AND ANALYSIS: The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample. TRIAL REGISTRATION: NCT05228041/DRI_2021/0030.

Butyrate inhibits type 2 inflammation in eosinophilic chronic rhinosinusitis.

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.

Antibiotics for Acute Sinusitis in Children: A Meta-Analysis.

CONTEXT: Acute sinusitis is one of the leading causes of antibiotic prescriptions in children. No recent systematic reviews have examined the efficacy of antibiotics compared with placebo. OBJECTIVE: We sought to determine if antibiotics are superior to placebo in the treatment of acute sinusitis in children. DATA SOURCES: Medline and Embase were searched from their origin to July 2023. STUDY SELECTION: We considered randomized placebo-controlled studies focusing on the treatment of acute sinusitis. In all studies, symptoms were present for <4 weeks and subjects were <18 years of age. DATA EXTRACTION: Two authors independently extracted the data. We pooled data primarily using fixed-effects models. RESULTS: Analysis of 6 included studies showed that antibiotic treatment reduced the rate of treatment failure by 41% (with a risk ratio of 0.59; 95% confidence interval 0.49-0.72) compared with placebo. There was substantial heterogeneity between the studies (I2 = 69.7%), which decreased substantially when the 1 study with a high risk of bias was removed (I2 = 26.9%). Children treated with antibiotics were 1.6 times more likely to have diarrhea than those who were not treated with antibiotics (risk ratio = 1.62, 95% confidence interval 1.04-2.51). LIMITATIONS: A small number of studies were eligible for inclusion. Included studies differed in their methodology. CONCLUSIONS: In children with clinically diagnosed acute sinusitis, antibiotics significantly reduced the rate of treatment failure compared with placebo. However, given the favorable natural history of sinusitis, our results could also support close observation without immediate antibiotic treatment.

Varicella mimicking complications of acute rhinosinusitis in an infant.

Varicella is the manifestation of primary infection with the varicella-zoster virus, mainly affecting preschool and school-aged children. The children suffer from a generalised, vesicular rash and fever. Despite the infection's typically non-threatening course, a variety of severe complications have been described.The authors present the case of a female infant suffering from varicella and developing preseptal cellulitis with a frontal abscess while being treated with intravenous antibiotics. Otorhinolaryngology consultation was sought since the clinical image was highly suggestive for sinusitis complications, namely orbital cellulitis and frontal bone osteomyelitis (Pott's puffy tumour). However, the child was below the age of frontal sinus development and there was no other apparent sign of sinonasal involvement. Ultrasonography revealed a mid-frontal collection without signs of abscess formation preseptally or postseptally, leading to the diagnosis of cutaneous superinfection of varicella lesions. The frontal abscess was drained, and the child fully recovered under antibiotic treatment.

A systematic review of randomised controlled trials on topical nasal steroids.

Introduction: Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated. Objective: To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability. Materials and methods: Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed. Results: BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety. Conclusions: BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

[Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

Quantification of Budesonide Retained in the Sinonasal Cavity After High-Volume Saline Irrigation in Post-Operative Chronic Rhinosinusitis.

BACKGROUND: Budesonide high-volume saline irrigations (HVSIs) are routinely used to treat chronic rhinosinusitis (CRS) due to improved sinonasal delivery and efficacy compared to intranasal corticosteroid sprays. The off-label use of budesonide is assumed to be safe, with several studies suggesting the systemically absorbed dose of budesonide HVSI is low. However, the actual budesonide dose retained in the sinonasal cavity following HVSI is unknown. The objective of this study was to quantify the retained dose of budesonide after HVSI. METHODS: Adult patients diagnosed with CRS who had undergone endoscopic sinus surgery (ESS) and were prescribed budesonide HVSI were enrolled into a prospective, observational cohort study. Patients performed budesonide HVSI (0.5 mg dose) under supervision in an outpatient clinic, and irrigation effluent was collected. High-performance liquid chromatography was employed to determine the dose of budesonide retained after HVSI. RESULTS: Twenty-four patients met inclusion criteria. The average corrected retained dose of budesonide across the cohort was 0.171 ± 0.087 mg (37.9% of administered budesonide). Increased time from ESS significantly impacted the measured retained dose, with those 3 months post-ESS retaining 27.4% of administered budesonide (P = .0004). CONCLUSION: The retained dose of budesonide in patients with CRS after HVSI was found to be significantly higher than previously estimated and decreased with time post-ESS. Given that budesonide HVSI is a cornerstone of care in CRS, defining the retained dose and the potential systemic implications is critical to understanding the safety of budesonide HVSI.

[Difficult-to-treat chronic rhinosinusitis-when the standard treatment is not effective and biologics are not available]. / Schwierig zu behandelnde chronische Rhinosinusitis ­ wenn die Standardtherapie nicht wirkt und Biologika nicht zur Verfügung stehen.

BACKGROUND: 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 a better 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. OBJECTIVE: Based on the session "Difficult-to-treat CRS, when biologics are not available" at the 29th Congress of the European Rhinologic Society (ERS) 2023 in Sofia, Bulgaria, the treatment options for uncontrolled CRS with the exclusion of biologics will be discussed. MATERIALS AND METHODS: The content of the presentations "Is there a place for antibiotics?" "Indications for revision surgery," "Novel systemic treatment options," "Novel local treatment options," and "Phototherapy for nasal polyps" are outlined and supported by a review of the literature. RESULTS: Various treatment options are available for managing uncontrolled CRS, even if biologic treatments are unavailable. Treatment options for type­2 (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. CONCLUSION: 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.

[Acute and chronic rhinosinusitis age characteristics]. / Vozrastnye osobennosti techeniya ostrogo i khronicheskogo rinosinusita.

Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and treatment. At the same rhinosinusitis is one of the most common in otorhinolaryngology's practice, both in children and adults. The of adults paranasal sinuses (PNS) anatomy differs from children's PNS anatomy. Although ostiomeatal complex occlusion is recognized as a major cause of poor ventilation and drainage of the adult paranasal sinuses, it does not have a strong effect on pediatric rhinosinusitis, but adenoids play a key role. Adenoids are bacteria and biofilms reservoirs that cause chronic refractory rhinosinusitis regardless of pharyngeal tonsil size. The prevalence of chronic rhinosinusitis (CRS) is lower in children than in adults. Diagnosis of children's rhinosinusitis is more difficult because nasal cavity endoscopic examination is performed rarely due to the occasional need of general anesthesia during the procedure. Moreover, it's necessary to take into account prevailing etiological role of viruses in ARS at children's age and chronic adenoiditis often accompanies pediatric CRS, which requires attention prescribing medical therapy as the basis of rhinosinusitis treatment. The DysheLORz based on Pelargonium sidoides roots is highly effective and safe for children's and adults ARS and CRS treatment, both as monotherapy and in combination with topical steroids and antibiotics. This herbal medicine immunomodulatory effect is mediated mainly by stimulating the production of TNF-α, IL-1, IL-12 and IFN-γ. It activates macrophages and improves their phagocytic activity. IL-12, together with TNF-α, enhances NK and cytotoxic CD8+ lymphocytes' activity against infected cells. IL-12 effect on Th1 lymphocytes maturation provides a link between innate and adaptive immunity. This is also increasing MCP-1, IP-10 and MIP-1ß chemokines synthesis and decreasing MIP-1α, ENA-78, GROα and IL-8 production in PNS and nasal mucosa. This leads to decrease of neutrophils chemotaxis to the inflammation site, and decline of serine proteases concentration (neutrophils main enzymes), that increases mucous membrane epithelial barrier permeability, reducing bacterial infections risk. Additionally, Pelargonium sidoides increases epithelial cells beating cilia frequency and inhibits hemagglutinin and neuraminidase present on influenza virus surface. The drug increases antimicrobial peptides production as defensins, human neutrophil peptides (HNP) and bactericidal permeability-increasing protein (BPI), which is also important for rapid inflammation regression in rhinosinusitis. It causes bacterial adhesion to epithelial cells inhibition, phagocytosis stimulation, nitric oxide (NO) release and oxidative burst. The medicine had a direct effect on Streptococcus pneumoniae, Staphylococcus aureus, Neisseria, Moraxella catarrhalis and Haemophilus influenza. Based on these data, it is possible to explain the high effectiveness and safety of the drugs based on Pelargonium sidoides in ENT organs inflammation treatment, for both adults and children over 1 year old.

Characterizing Trends in Diagnosis and Management of Sinusitis in a Large Health Care System: From Primary Care to Otolaryngology.

OBJECTIVES: Variations in management of sinusitis in primary care settings can be associated with inappropriate antibiotic prescriptions and delays in treatment. The objective of this study was to identify patient and provider characteristics associated with possible inaccurate diagnosis and management of sinusitis. METHODS: We performed a cross-sectional retrospective analysis using an established regional healthcare database of patients who received a diagnosis of sinusitis between 2011 and 2022 from a non-otolaryngologist provider. Patient's comorbidities, insurance status, chronicity of sinusitis, and prescriptions were included. We noted if patients were referred to an otolaryngology practice and if they received a diagnosis of sinusitis from an otolaryngologist. RESULTS: We analyzed 99 581 unique patients and 168 137 unique encounters. The mean age was 41.5 (±20.4 years) and 35.7% were male. Most patients had private insurance (88.5%), acute sinusitis (81.2%), and were seen at a primary care office (97.8%). Approximately 30% of patients were referred to an otolaryngology practice for sinusitis. Of referred patients, 50.6% did not receive a diagnosis of sinusitis from an otolaryngology practice. Patients without a sinusitis diagnosis by an otolaryngology practice received significantly more mean courses of antibiotics (5.04 vs 2.39, P < .0001) and oral steroids (3.53 vs 2.08, P < .0001). CONCLUSIONS: Over half of the patients referred to an otolaryngology practice from primary care for sinusitis did not receive a diagnosis of sinusitis from an otolaryngology practice. Further research should investigate implications for increased healthcare costs and inappropriate prescription trends associated with the management of sinusitis.

Evaluation of an automated feedback intervention to improve antibiotic prescribing among primary care physicians (OPEN Stewardship): a multinational controlled interrupted time-series study.

Tools to advance antimicrobial stewardship in the primary health care setting, where most antimicrobials are prescribed, are urgently needed. The aim of this study was to evaluate OPEN Stewarship (Online Platform for Expanding aNtibiotic Stewardship), an automated feedback intervention, among a cohort of primary care physicians. We performed a controlled, interrupted time-series study of 32 intervention and 725 control participants, consisting of primary care physicians from Ontario, Canada and Southern Israel, from October 2020 to December 2021. Intervention participants received three personalized feedback reports targeting several aspects of antibiotic prescribing. Study outcomes (overall prescribing rate, prescribing rate for viral respiratory conditions, prescribing rate for acute sinusitis, and mean duration of therapy) were evaluated using multilevel regression models. We observed a decrease in the mean duration of antibiotic therapy (IRR = 0.94; 95% CI: 0.90, 0.99) in intervention participants during the intervention period. We did not observe a significant decline in overall antibiotic prescribing (OR = 1.01; 95% CI: 0.94, 1.07), prescribing for viral respiratory conditions (OR = 0.87; 95% CI: 0.73, 1.03), or prescribing for acute sinusitis (OR = 0.85; 95% CI: 0.67, 1.07). In this antimicrobial stewardship intervention among primary care physicians, we observed shorter durations of therapy per antibiotic prescription during the intervention period. The COVID-19 pandemic may have hampered recruitment; a dramatic reduction in antibiotic prescribing rates in the months before our intervention may have made physicians less amenable to further reductions in prescribing, limiting the generalizability of the estimates obtained.IMPORTANCEAntibiotic overprescribing contributes to antibiotic resistance, a major threat to our ability to treat infections. We developed the OPEN Stewardship (Online Platform for Expanding aNtibiotic Stewardship) platform to provide automated feedback on antibiotic prescribing in primary care, where most antibiotics for human use are prescribed but where the resources to improve antibiotic prescribing are limited. We evaluated the platform among a cohort of primary care physicians from Ontario, Canada and Southern Israel from October 2020 to December 2021. The results showed that physicians who received personalized feedback reports prescribed shorter courses of antibiotics compared to controls, although they did not write fewer antibiotic prescriptions. While the COVID-19 pandemic presented logistical and analytical challenges, our study suggests that our intervention meaningfully improved an important aspect of antibiotic prescribing. The OPEN Stewardship platform stands as an automated, scalable intervention for improving antibiotic prescribing in primary care, where needs are diverse and technical capacity is limited.

[Decision-making in the treatment of chronic rhinosinusitis with nasal polyps in the era of biologics]. / Entscheidungsfindung bei der Behandlung der chronischen Rhinosinusitis mit Nasenpolypen in der Ära der Biologika.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies.

Efficacy of Elexacaftor-Tezacaftor-Ivacaftor on chronic rhinosinusitis in cystic fibrosis.

PURPOSE: Our work aims to add evidence on the effectiveness of Elexacaftor-Tezacaftor-Ivacaftor on chronic rhinosinusitis in cystic fibrosis. MATERIALS AND METHODS: We conducted an observational retrospective cohort study at the Cystic Fibrosis Center of a tertiary care hospital to investigate the effect of Elexacaftor-Tezacaftor-Ivacaftor on chronic rhinosinusitis in cystic fibrosis patients, aged 12 or older. The study's endpoints were the change in the occurrence of acute exacerbations of chronic rhinosinusitis, and the variation of the endoscopic and radiologic findings scored using the Lund-Kennedy endoscopic scale, Lund-Mackay, and modified Lund-Mackay radiologic scales, in patients who underwent both pre-treatment and post-treatment examinations. RESULTS: The study population comprised 136 patients, of which 28 underwent both pre-treatment and post-treatment nasal endoscopy and 15 had pre- and post-treatment CT scans. Elexacaftor-Tezacaftor-Ivacaftor provided a significant improvement in chronic rhinosinusitis. The mean number of acute exacerbations of chronic rhinosinusitis per year in the pre-treatment time was 0.55 versus 0.35 during the treatment (p < 0.0021). The Lund-Kennedy scale had a pre-treatment average score of 4.21 points versus 1.5 points after the start of Elexacaftor-Tezacaftor-Ivacaftor (p < 0.0001). The average Lund-Mackay and modified Lund-Mackay scores in the pre-treatment time were respectively 14.6 and 16.45 points; and after the start of the therapy, they became 5.87 and 6.73 (p < 0.0001). CONCLUSION: Elexacaftor-Tezacaftor-Ivacaftor was associated with fewer acute exacerbations of chronic rhinosinusitis, and a significant improvement of chronic rhinosinusitis evaluated endoscopically and radiologically. To our knowledge, this is the first study investigating the change in the occurrence of acute exacerbation of chronic rhinosinusitis in patients affected by cystic fibrosis in therapy with Elexacaftor-Tezacaftor-Ivacaftor.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

PURPOSE: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. METHODS: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. RESULTS: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. CONCLUSIONS: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

Effects of highly effective modulator therapy on the dynamics of the respiratory mucosal environment and inflammatory response in cystic fibrosis.

BACKGROUND: While the widespread initiation of elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic clinical improvements among persons with cystic fibrosis (pwCF), little is known about how ETI affects the respiratory mucosal inflammatory and physiochemical environment, or how these changes relate to lung function. METHODS: We performed a prospective, longitudinal study of adults with CF and chronic rhinosinusitis (CF-CRS) followed at our CF center (n = 18). Endoscopic upper respiratory tract (paranasal sinus) aspirates from multiple visit dates, both pre- and post-ETI initiation, were collected and tested for cytokines, metals, pH, and lactate levels. Generalized estimating equations were used to identify relationships between ETI and upper respiratory tract (URT) biomarker levels, and between URT biomarkers and lung function or clinical sinus parameters. RESULTS: ETI was associated with decreased upper respiratory mucosal cytokines B-cell activating factor (BAFF), IL-12p40, IL-32, IL-8, IL-22 and soluble tumor necrosis factor-1 (sTNFR1), and an increase in a proliferation-inducing ligand (APRIL) and IL-19. ETI was also associated with decreased URT levels of copper, manganese, and zinc. In turn, lower URT levels of BAFF, IL-8, lactate, and potassium were each associated with ~1.5% to 4.3% improved forced expiratory volume in 1 s (FEV1), while higher levels of IFNγ, iron, and selenium were associated with ~2% to 10% higher FEV1. CONCLUSIONS: Our observations suggest a dampening of inflammatory signals and restriction in microbial nutrients in the upper respiratory tract with ETI. These findings improve our understanding of how ETI impacts the mucosal environment in the respiratory tract, and may give insight into the improved infectious and inflammatory status and the resulting clinical improvements seen in pwCF.