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Background: The introduction of CFTR modulators has changed the landscape in the treatment of cystic fibrosis (CF) and early case series have shown improvements in sinonasal outcomes in this patient population., Methodology: A real-word data study was performed to evaluate the impact of dual therapy with tezacaftor/ivacaftor (TEZ/IVA) and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CF-related chronic rhinosinusitis (CRS), by comparing subjective and objective outcome measures at baseline, 12 months after treatment with TEZ/IVA and six months after treatment with ELX/TEZ/IVA., Results: In total, 43 CF patients, with a mean age of 32 years, were included. After triple therapy, significant improvements in overall visual analogue scale, SNOT-22, Lund Kennedy, nasal polyps, and Lund-Mackay scores were observed, whereas no beneficial effect could be seen in patients treated with dual therapy. Bacterial upper airway colonization did not differ pre- and postmodulator therapy in the present study. The number of responders to dual and triple therapy is 23.8% and 63.2% of the patients, respectively., Conclusions: Triple therapy with ELX/TEZ/IVA is superior to dual therapy with TEZ/IVA in the treatment of CF-CRS, as significantly reduced sinonasal complaints, nasal endoscopy and CT scores were observed after triple therapy, whereas this was not the case for dual therapy.

Background: Nasal hyperreactivity (NHR) is prevalent in all chronic upper airway inflammatory phenotypes, including allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Although NHR in patients with non-allergic rhinitis is mediated by neuronal pathways, AR and CRSwNP are mainly characterized by type 2 inflammation., Methods: Eighteen healthy controls and 45 patients with symptomatic AR/CRSwNP underwent a cold, dry air (CDA) provocation test for objective diagnosis of NHR. Before and after, questionnaires were filled out and nasal secretions and biopsies were collected. Markers for neurogenic inflammation (substance P, calcitonin gene-related peptide, neurokinin A), epithelial activation (IL-33), and histamine were measured in secretions by ELISA; and expression of neuronal markers PGP9.5, TRPV1, and TRPM8 was studied in biopsies by RT-q-PCR. Effects of histamine on TRPV1/A1 were studied with Ca2+-imaging using murine trigeminal neurons., Results: CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/patients CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/patients. Subjective (subjectively reported effect of CDA) and objective (decrease in PNIF) effects of CDA were significantly correlated. Levels of neuropeptides and histamine in nasal secretions and mRNA expression of PGP9.5, TRPV1, and TRPM8 correlated with CDA-induced PNIF-reduction. CDA-provocation induced an increase in IL-33-levels. Both TRPV1 and TRPA1 expressed on afferent neurons were sensitized by exposure to histamine., Conclusion: NHR is not an on/off phenomenon but spans a continuous spectrum of reactivity. A neurogenic inflammatory background and increased histamine-levels are risk factors for NHR in AR/CRSwNP.

Objectives: 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., Methods: 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., Results: 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., Conclusion: 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 of Evidence: Level 3 Laryngoscope, 133:2898-2909, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics., Objective: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology., Methodology: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion., Results: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included., Conclusions: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

"Nasal hyperreactivity" is a key feature in various phenotypes of upper airway diseases, whereby reactions of the nasal epithelium to diverse chemical and physical stimuli are exacerbated. In this review, we illustrate how nasal hyperreactivity can result from at least three types of mechanisms: (1) impaired barrier function, (2) hypersensitivity to external and endogenous stimuli, and (3) potentiation of efferent systems. We describe the known molecular basis of hyperreactivity related to the functional impairment of epithelial cells and somatosensory innervation, and indicate that the thermal, chemical, and mechanical sensors determining hyperreactivity in humans remain to be identified. We delineate research directions that may provide new insights into nasal hyperreactivity associated with rhinitis/rhinosinusitis pathophysiology and therapeutics. The elucidation of the molecular mechanisms underlying nasal hyperreactivity is essential for the treatment of rhinitis according to the precepts of precision medicine., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Purpose of Review: Despite their high prevalence, the pathophysiology of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) remains unclear. Recently, transient receptor potential (TRP) cation channels emerged as important players in type 2 upper airway inflammatory disorders. In this review, we aim to discuss known and yet to be explored roles of TRP channels in the pathophysiology of AR and CRS with nasal polyps., Recent Findings: TRP channels participate in a plethora of cellular functions and are expressed on T cells, mast cells, respiratory epithelial cells, and sensory neurons of the upper airways. In chronic upper airway inflammation, TRP vanilloid 1 is mostly studied in relation to nasal hyperreactivity. Several other TRP channels such as TRP vanilloid 4, TRP ankyrin 1, TRP melastatin channels, and TRP canonical channels also have important functions, rendering them potential targets for therapy. The role of TRP channels in type 2 inflammatory upper airway diseases is steadily being uncovered and increasingly recognized. Modulation of TRP channels may offer therapeutic perspectives.

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS., Methods: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria., Results: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell., Conclusion: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Intraorbital and intracranial complications of acute rhinosinusitis (ARS) are uncommon, but potentially life threatening. Signs of progression of ARS should be recognized early to allow timely surgical treatment in order to avoid irreversible lesions such as vision loss and neurological deficits. In this case series, we provide an overview of 6 representative cases who presented at our tertiary center (2017-2018). The aim of this case series is (1) to draw new attention to the clinical manifestations and management of these complications, since even in highly-developed medical settings we still observe permanent sequellae due to delayed or inadequate treatment, (2) to give an updated analysis of the guidelines, stressing the low threshold for endoscopic sinus surgery, even in children, (3) to underline the benefits of a multidisciplinary approach in these young patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

Objectives/hypothesis: Eosinophils and mast cells are among the key cells in inflammatory diseases like chronic rhinosinusitis (CRS) and asthma. Leukotriene antagonists have proven to be effective in the treatment of asthma, but data about their efficacy in CRS are scarce, whereas data on montelukast as an add-on treatment to intranasal corticosteroids (INCS) in a postoperative setting are completely lacking., Study Design: Prospective, randomized, open-label trial., Methods: In this trial with long-term follow-up, we evaluated the efficacy of montelukast as an add-on treatment to INCS in postoperative CRS with nasal polyp (CRSwNP) patients. CRSwNP patients (N = 72) undergoing endoscopic sinus surgery were randomized in two arms for the postoperative treatment. One group (N = 36) received INCS in monotherapy, whereas the other group (N = 36) received INCS in association with montelukast for 1 year. The efficacy of montelukast with INCS was evaluated by assessing both subjective (total five-symptom score [T5SS]) and objective (nasal polyp score [NPS], Lund-Mackay [LMK] score, and subjective olfactometry [Barcelona Smell Test 24]) outcome parameters and compared with the gold standard of INCS in monotherapy., Results: After 1 year of surgery, T5SS, NPS, and LMK score were significantly reduced in patients treated with either INCS or INCS plus montelukast, without significant differences between the two treatment arms. Improvement of smell loss by olfactometry was also observed with no differences between arms. Similar findings were observed at 3 and 6 months., Conclusions: These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients., Level of Evidence: 1b Laryngoscope, 1743-1751, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.