Nasal Polyps Research Articles

Preoperative laboratory measurements as a predictor for nasal steroid irrigations after sinus surgery for chronic rhinosinusitis with nasal polyps

PurposeTo assess whether preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin E (IgE), and blood eosinophil percentage (EOS) can predict need for steroid irrigations after FESS. Materials and methodsAdult patients at BIDMC from inception until September 8, 2023 with chronic rhinosinusitis with nasal polyps who underwent FESS and had preoperative CRP (n = 129), ESR (n = 79), IgE (n = 107), or EOS (n = 125) were included. Labs were divided into normal (CRP: 0–5.0 mg/L; ESR: 0-15 mm/h; IgE: 150-300Ul/mL; EOS: 1–7 %) and high groups (CRP: >5.0 mg/L; ESR: >15 mm/h; IgE: >300Ul/mL; EOS: >7 %). The primary outcome was need for intranasal steroid irrigations after FESS (≤4 weeks, 4–12 weeks, 12–26 weeks, 26–52 weeks, 1–3 years, 3–5 years, and > 5 years). Receiver operating characteristic curves were created to determine thresholds for predicting postoperative steroid irrigations. ResultsElevated IgE required intranasal steroid irrigation at 1–3 years (normal 34 %, high 62 %, p = 0.02), 3–5 years (normal 24 %, high 48 %, p = 0.04), and > 5 years (normal 19 %, high 43 %, p = 0.02). Elevated EOS required intranasal steroid irrigation at 26–52 weeks (normal 7 %, high 25 %, p = 0.009) and > 5 years (normal 19 %, high 46 %, p = 0.005). The area under the curve for IgE at 1–3 years was 0.696 (95 % CI: 0.597–0.795) with cutoff at 144–148 Ul/mL. CRP and ESR were not predictive of postoperative intranasal steroid treatment. ConclusionsElevated IgE and EOS (but not CRP or ESR) may predict need for intranasal steroid treatment after FESS.

Assessment of the efficacy of comprehensive medical rehabilitation of patients with polypoid rhinosinusitis based on the international classification of functioning, disability and health

Abstract. Purpose of the study. The article discusses an algorithm for using the categories of the International Classification of Functioning, Disability and Health (ICF) for comparative assessment of the effectiveness of various medical rehabilitation programs for patients with polypoid rhinosinusitis. It is shown that the use of the ICF makes it possible to implement a systematic approach to assessing the efficacy of rehabilitation measures, taking into account the biopsychosocial model for assessing health (illness) and the category of functioning, which serves as the basis for the integration process of rehabilitation. The results of comparative monitoring of the formed categorical profile of a patient with polypoid rhinosinusitis convincingly proved the advantages of complex medical rehabilitation of patients with nasal polyposis, based on biological therapy with dupilumab in combination with a course application of an alternating magnetic field and low-intensity laser radiation.

A Comprehensive Review Exploring Allergic Rhinitis With Nasal Polyps: Mechanisms, Management, and Emerging Therapies.

Allergic rhinitis (AR) and nasal polyps (NP) are common inflammatory disorders of the upper airways that often coexist and significantly impact patients' quality of life. This comprehensive review explores the intricate relationship between AR and NP, elucidating the underlying mechanisms, clinical manifestations, and management strategies. Immunological mechanisms, genetic predispositions, and environmental factors contribute to the development and progression of both conditions. Pharmacological therapies, including intranasal corticosteroids and biologic agents, are cornerstone treatments for managing AR with NP. At the same time, surgical interventions such as functional endoscopic sinus surgery (FESS) may be necessary in refractory cases. Emerging therapies, including immunomodulatory agents and precision medicine approaches, hold promise in improving treatment outcomes. A multidisciplinary approach, personalized treatment plans, and patient education are essential for optimizing clinical practice. Future research should focus on identifying novel therapeutic targets, conducting large-scale clinical trials, exploring precision medicine approaches, and investigating the role of the microbiome. Addressing these research priorities and implementing evidence-based treatment strategies can improve outcomes for patients with AR and NP.

The Impact of Dupilumab on Work Productivity and Emotional Health in CRSwNP: A Multicentric Study in Northeast Italy.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration. At baseline (T0) and at each follow-up, patients underwent NPS, Sinonasal Outcome Test (SNOT)-22, Visual Analogue Scale (VAS) for smell, and Sniffin' sticks identification test (SSIT). The SNOT-22 domains for function and emotion were also analysed separately. Two hundred and seventeen patients with at least 6 months of follow-up were included. All parameters have improved during treatment (p < 0.0001). Noticeably, both the function and emotion SNOT-22 domains have improved within 6 months of treatment and have continued to progress during every interval within 12 months from the baseline, positively influencing patients' emotivity and augmenting their social and economic performances. Dupilumab improves the QoL of CRSwNP patients with good effects on the reported productivity and emotional health. Clinicians should pay attention to these two aspects when dealing with patients affected by severe CRSwNP.

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including “positive regulation of intracellular signal transduction”, “arachidonic acid metabolic process”, “spermatogenesis” and “negative regulation of cellular protein metabolic process”. Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies.

Aspergillus Sinusitis: Risk Factors and Phenotyping.

Background: Aspergillus can cause fungal rhinosinusitis (FRS). We aimed to identify risk factors for sinonasal Aspergillus disease. Methods: Patients with a positive sinonasal mycological culture for Aspergillus species diagnosed in our hospital located in a continental climate were included in the 9-year retrospective study. Results: Of the 86 patients, 3 had invasive FRS (IFRS), 51 had fungal ball (FB) disease, and 32 had chronic rhinosinusitis with fungus (CFRS). In the IFRS group, all patients had a malignancy and were immunocompromised. Allergies, allergic rhinitis, asthma, nasal polyps, and the use of inhaled and nasal steroids were more common in the CFRS group, and IgE levels were greater than those in the FB and IRFS groups (p < 0.05). Conclusion: FB disease is a relatively symptom-free single-sinus disease among elderly individuals, and IFRS is dominant among immunocompromised patients. We discovered a third patient group, predominantly with nasal polyps, atopy, asthma, and elevated blood IgE and eosinophils, that did not fulfill the allergic FRS (AFRS) criteria. It is possible that a less fulminant category of underdiagnosed AFRS exists in cold climates. Treatment with local debridement is usually sufficient for FRS, apart from IFRS, and relapses are not common in cold climates.

Quantitative Comparison of Chatbots on Common Rhinology Pathologies.

Understanding the strengths and weaknesses of chatbots as a source of patient information is critical for providers in the rising artificial intelligence landscape. This study is the first to quantitatively analyze and compare four of the most used chatbots available regarding treatments of common pathologies in rhinology. The treatment of epistaxis, chronic sinusitis, sinus infection, allergic rhinitis, allergies, and nasal polyps was asked to chatbots ChatGPT, ChatGPT Plus, Google Bard, and Microsoft Bing in May 2023. Individual responses were analyzed by reviewers for readability, quality, understandability, and actionability using validated scoring metrics. Accuracy and comprehensiveness were evaluated for each response by two experts in rhinology. ChatGPT, Plus, Bard, and Bing had FRE readability scores of 33.17, 35.93, 46.50, and 46.32, respectively, indicating higher readability for Bard and Bing compared to ChatGPT (p = 0.003, p = 0.008) and Plus (p = 0.025, p = 0.048). ChatGPT, Plus, and Bard had mean DISCERN quality scores of 20.42, 20.89, and 20.61, respectively, which was higher than the score for Bing of 16.97 (p < 0.001). For understandability, ChatGPT and Bing had PEMAT scores of 76.67 and 66.61, respectively, which were lower than both Plus at 92.00 (p < 0.001, p < 0.001) and Bard at 92.67 (p < 0.001, p < 0.001). ChatGPT Plus had an accuracy score of 4.39 which was higher than ChatGPT (3.97, p = 0.118), Bard (3.72, p = 0.002), and Bing (3.19, p < 0.001). On aggregate of the tested domains, our results suggest ChatGPT Plus and Google Bard are currently the most patient-friendly chatbots for the treatment of common pathologies in rhinology. N/A Laryngoscope, 134:4225-4231, 2024.

Egyptian Dynasties to Biologics: A Historical Review of Nasal Polyposis.

The history of nasal polyposis originates even before Hippocrates described a nasal mass that he likened to a sea polyp. References to sinonasal disease and treatment can be found in ancient texts, such as the Ebers Papyrus and the Edwin Smith Papyrus of Ancient Egypt, as well as in the foundational texts of Ayurvedic medicine. Greek philosophers marked a significant shift away from the belief that illness was a result of divine intervention and embraced medical theory. Over the subsequent millennia, the understanding of nasal polyposis expanded, resulting in notable progress in surgical procedures and medical treatments. However, the complex pathophysiology of this condition remained enigmatic until breakthroughs in basic science and immunology. This historical journey takes us from the tomb of the first rhinologist in 2500 BC to the development of immune-modulating biologics.

Relationship between blood eosinophilia and disease severity in chronic rhinosinusitis with nasal polyps.

Relationship between blood eosinophilia and disease severity in chronic rhinosinusitis with nasal polyps.

Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study

Plain Language SummaryImmunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

193 A Case of Chronic Rhinosinusitis with Nasal Polyps in a Patient with a Single Heterozygous RNU4ATAC Pathogenic Variant

193 A Case of Chronic Rhinosinusitis with Nasal Polyps in a Patient with a Single Heterozygous RNU4ATAC Pathogenic Variant

Baseline characterization of a cohort of colombian patients with chronic rhinosinusitis with nasal polyps

To present the baseline clinical and demographic characteristics of CRSwNP patients over the age of 18 enrolled in a Patient Support Program (PSP) prior to biologic treatment. Descriptive, cross-sectional study performed in a Colombian CRSwNP asthma PSP sponsored by Sanofi from Aug-2021 to Jul-2022. Data was collected from CRSwNP patients, prior to the start of Dupilumab treatment, who consented to the use of their data. The following information was reported: Age, reporting city, treating medical specialty, comorbidities, and persistence of treatment. 339 patients were included, 171 (50,4%) were women and 168 (49,6%) were men. The mean age at Dupilumab treatment initiation was 52,4 years. 62,8% began treatment during adulthood (26-59y), while 34.1% started at elderly (+60y) and 3.1% were young adults (18-25y). Most cases (29,7%) were included in Bogotá, followed by Antioquia (19%), Valle del Cauca (7,3%) and the remaining 44% nationwide. Comorbidities were present in 67,1% of the patients, with diagnosis of allergic rhinitis, atopic dermatitis, asthma, and other non-type 2 inflammatory diseases. Nasal surgical history was present in 89,6% of the patients, most of them with one to three previous surgeries. Continuous treatment was observed in 70,3% of patients for 6 to 12 months, in 21,3% for more than 12 months and in 8,4% for less than six months. The most frequently treating medical specialty was otorhinolaryngology (79,6%), followed by allergology (16%) and other medical professionals (4,4%). There is concordance with the literature on a higher presentation of the disease in women than in men. There is a large proportion of patients with nasal surgical history and type 2 inflammatory comorbidities by the moment of biologic treatment initiation. The care and identification of CRSwNP colombian patients is mainly provided by otorhinolaryngologists, followed by allergologists.

Effectiveness and safety profile of mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a tertiary care

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation. Mepolizumab was approved for the treatment of CRSwNP in 2021, it may be useful to evaluate its safety profile in a real-world setting. AimThis work aimed to prospectively highlight the effectiveness and safety profile of Mepolizumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. MethodsAn observational cohort study was carried out considering all patients treated with Mepolizumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. ResultsA total of 30 patients were treated with Mepolizumab, one patient discontinued the treatment. A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, −33 and − 43, p < 0.001 for both comparisons; NPS, 0 and − 1, p < 0.001 for both comparisons). The median (Q1–Q3) sniffin' sticks test score increased from 7 (6–8) at the 6th month to 11 (10−13) at the 12th month. Seven patients (24.1 %) reported pain at the injection site, accompanied by redness, warmth, and tenderness within the first 24 h post-injection with a median duration of three days from the onset. ConclusionsGiven the optimal treatment response and the minimal adverse effects observed, clinicians should consider Mepolizumab a safe and effective treatment in CRSwNP patients. Further studies in real-life setting are necessary to better understand the long-term effects.

Dupilumab in the Treatment of Eosinophilic Otitis Media: A Case Report

Eosinophilic otitis media (EOM) differs from classic chronic otitis media as it is a refractory disease with the accumulation of eosinophils in thick mucinous middle ear effusion and mucosa. A 66-year-old male with a history of asthma, chronic sinusitis with polyposis, nasal polyposis, and multiple sets of ventilation tubes was presented to our center for the management of hearing loss and otorrhea. He had a history of consistent otorrhea and hearing loss even with the ventilation tube insertions and medical treatment. Both systemic and intratympanic steroid was administered, but the effect was insignificant and other systemic adverse effects occurred. Finally, the otologic symptoms including hearing loss and otorrhea improved after being given a Dupilumab injection. This case report discusses Dupilumab treatment resulting in remission in a patient suffering from refractory EOM.

Increased SERPINB2 potentiates 15LO1 expression via STAT6 signalling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling. SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA. SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs invitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1. SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.

Biologic Therapies across Nasal Polyp Subtypes.

Chronic rhinosinusitis with nasal polyposis is a common inflammatory condition, with subtypes like aspirin-exacerbated respiratory disease, allergic fungal rhinosinusitis, and central compartment atopic disease sharing a common type 2 inflammatory pathway. Respiratory biologic therapies have been developed that target type 2 inflammation. In this article, we discuss the use of respiratory biologic therapies for nasal polyposis in general, as well as within the various subtypes of nasal polyps. Further, we discuss future roles of novel biologic therapies targeting type 2 inflammation in nasal polyposis.

Dupilumab improves sleep quality in chronic rhinosinusitis with nasal polyps

PurposeChronic rhinosinusitis with nasal polyps (CRSwNP) often alters sleep quality. Dupilumab emerged as an innovative and effective therapy for refractory/recurrent severe CRSwNP. The aim of this observational retrospective study was to evaluate the sleep quality in patients with CRSwNP who underwent treatment with dupilumab. Materials and methodsForty-five patients treated with dupilumab for CRSwNP were enrolled. Clinical parameters (age, sex, comorbidities, Nasal Polyp Score - NPS, Asthma Control Test - ACT), nasal cytology, quality of life (Sino Nasal Outcome Test 22 – SNOT-22), sleep quality (Pittsburgh Sleep Quality Index – PSQI, Epworth Sleepiness Scale - ESS), and risk of sleep apnea (STOP-BANG) were recorded before treatment (T0), and after 3 (T1), 6 (T2), and 12 months (T3). ResultsNPS, ACT and SNOT-22 total score improved during treatment (p < 0.05). Meanwhile, all sleep parameters evaluated with SNOT-22, ESS and PSQI improved over time (p < 0.001), expect for PSQI Use of sleeping medications. Indeed, sleep drugs are rarely used before and during the treatment. The global sleep quality was classified as poor in 88.9 % of cases at T0 and decreased to 5.7 % at T3. A high risk of sleep apnea was revealed by the STOP-BANG in 68.9 % of cases at T0 and 2.8 % of patient at T3 (p < 0.001). ConclusionsDupilumab improves the sleep quality and reduce the risk of sleep apnea in patients with severe CRSwNP. Its favorable effect occurs within 3 months and is maintained during the treatment.

IRF4 Knockdown Inhibits the Chronic Rhinosinusitis Without Nasal Polyps Development by Regulating NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis.

Chronic rhinosinusitis without nasal polyps (CRSsNP) is a CRS phenotype. However, the mechanisms of CRSsNP remains unclear. Differentially expressed genes (DEGs) were obtained from the GSE36830 and GSE198950 datasets through the GEO2R tool. The six hub genes were screened by the protein-protein interaction (PPI) network analysis and Cytoscape software. Then we constructed the mouse models of CRS and verified the expression levels of hub genes by reverse transcription quantitative PCR (RT-qPCR). Hematoxylin-eosin (HE) staining was employed to observe pathological alterations in mouse tissues. Casepase-3 expression was detected by immunohistochemistry (IHC). The levels of TNF-α, IL-12, IL-6, IL-1β, LDH, and IL-18 were evaluated using enzyme-linked immunosorbent assay (ELISA). Pyroptosis-related protein expressions were measured by western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were performed to assess the proliferation and apoptosis of lipopolysaccharide (LPS)-induced NP69 cells. Six hub DEGs were identified. The expression levels of IRF4, IKZF1, and CD79A were obviously increased in CRSsNP, while those of ADH6, ADH1A, and LDHC were significantly decreased. IRF4 knockdown attenuated the pathologic features of CRSsNP. IRF4 knockdown reduced levels of the TNF-α, IL-12, IL-6 IL-1β, LDH, and IL-18 as well as the proteins expression of Casepase-1, GSDMD, and NLRP3 both in vivo and in vitro, implying that inflammation and pyroptosis were inhibited. IRF4 knockdown hinders the development of CRSsNP by inhibiting the inflammatory response and NLRP3/Caspase-1/GSDMD-mediated pyroptosis, which offers novel promising treatment strategies for clinical intervention.

Outcome of Post Functional Endoscopic Sinus Surgery Nasal Irrigation with Normal Saline Versus Normal Saline with Budesonide in Patients with Sinonasal Polyposis: A Randomized Control Trial.

Chronic rhinosinusitis(CRS) is a condition characterized by inflammation of the lining of nose and sinuses lasting for 12weeks or more. CRS with nasal polyp nasal polyp(CRSwNP) is seen in 0.5-4% of the population and is present in about 20% of patients with CRS. Functional endoscopic sinus surgery aids in restoring the ventilation and drainage of paranasal sinuses. Postoperatively, various solutions are used to irrigate the sinus cavity for pharmaceutical and mechanical lavage. Hence, it is imperative to compare different solutions to choose the best to give a favorable outcome. A total of 24 postoperative CRSwNP patients were randomly divided into two groups. Group A received routine post-FESS medication as per the institute guidelines. Group B received budesonide nasal irrigation in addition to regular care. Both groups were evaluated endoscopically at 1, 4, and 12weeks after the surgery. Pre and postoperative quality of life were compared. Endoscopic Lund-Kennedy scoring (objective measurement) and Sino-Nasal Outcome Test 22 score were used to compare the two groups. The mean preoperative Sino Nasal Outcomes Test 22 score(SNOT-22) was 46.58 ± 6.18 in group A and 50.5 ± 5.7 in group B. It was reduced to 15.00 ± 2.00 and 9.75 ± 1.95 postoperatively in both groups respectively at the end of 3months. Postoperatively, the mean endoscopic score was 2.36 ± 0.80 in group A and 1.18 ± 0.40 in group B at the end of 3months. In conclusion, saline plus budesonide nasal irrigation is a better option when compared to saline only irrigation in terms of efficacy and therapeutic effect in patients undergoing FESS for CRSwNP, hence, it should be advocated in regular clinical practice.

Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived cells, cell cultures, and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified biallelic pathogenic variants in WAP four-disulfide core domain 2 (WFDC2) in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and, thus, secretion of mature WFDC2. Conclusions: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis.