Sputum proteomics in lung disorders.

Lung diseases affect pulmonary and respiratory function and are caused by bacterial viral and fungal infection as well as environmental factors. Unfortunately, symptom overlap between various pulmonary diseases often prevents clear differentiation and uncertain diagnosis. Accordingly, identification of specific markers of inflammatory activity in early disease stage could potential unveil the intrinsic molecular mechanisms of the underlying pathology. Proteomic studies aimed at understanding the genetic/environmental contributions to the development and progression of lung diseases represent a promising approach for diagnosis and treatment. The fluid phase of sputum represents a rich protein source and is frequently used in these studies. This chapter addresses causes of lung disorders, sputum composition, collection and processing as well as the clinical significance and challenges associated with the presence of interfering factors. Basics of proteomics and mass spectrometry are also described, together with the analytical approaches to investigate the sputum proteome. Finally, we explore the application of sputum proteomics in severe lung disorders including COVID-19 infection, chronic obstructive pulmonary disease, asthma, cystic fibrosis, lung cancer and tuberculosis.

PM2.5 Exposure Inhibits Transepithelial Anion Short-circuit Current by Downregulating P2Y2 Receptor/CFTR Pathway.

Fine particulate matter (PM2.5) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM2.5 on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (Isc) and airway surface liquid (ASL) significantly decreased after PM2.5 exposure. In addition, PM2.5 exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM2.5 exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM2.5. Together, our study reveals that PM2.5 impairs the ATP-induced transepithelial anion Isc through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM2.5-mediated airway epithelial injury.

Causal relationship between type 2 diabetes and common respiratory system diseases: a two-sample Mendelian randomization analysis.

Background: Type 2 diabetes (T2D) frequently co-occurs with respiratory system diseases such as chronic obstructive pulmonary disease (COPD), bronchial asthma, lung cancer, interstitial lung disease, and pulmonary tuberculosis. Although a potential association is noted between these conditions, the available research is limited. Objective: To investigate the causal relationship between patients with T2D and respiratory system diseases using two-sample Mendelian randomization analysis. Methods: Causal relationships were inferred using a two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies. We employed the variance inverse-weighted method as the primary analytical approach based on three key assumptions underlying MR analysis. To bolster the robustness and reliability of our results, we utilized MR Egger's intercept test to detect potential pleiotropy, Cochran's Q test to assess heterogeneity, funnel plots to visualize potential bias, and "leave-one-out" sensitivity analysis to ensure that our findings were not unduly influenced by any single genetic variant. Result: The inverse variance weighted (IVW) analysis indicated a causal relationship between T2D and COPD [Odds Ratio (OR) = 0.87; 95% Confidence Interval (CI) = 0.82-0.96; p < 0.05]. No significant heterogeneity or pleiotropy were observed through their respective tests (p > 0.05), and the statistical power calculations indicated that the results were reliable. The IVW analysis showed a negative causal relationship between T2D and bronchial asthma [OR = 0.85; 95% CI = 0.81-0.89; p < 0.05]. However, the IVW under the random-effects model indicated heterogeneity (p < 0.05), suggesting instability in the results and requiring cautious interpretation. The study found a positive causal relationship between T2D and pulmonary tuberculosis (OR = 1.24, 95% CI = 1.05-1.45, p < 0.05). However, they exhibited pleiotropy (p < 0.05), indicating their instability. No correlation between T2D and interstitial lung disease or lung cancer was observed. Conclusion: T2D is negatively associated with COPD, suggesting that T2D may reduce the risk of developing COPD. A negative causal relationship between T2D and bronchial asthma has been observed, but the results exhibit heterogeneity. There is a positive causal relationship between T2D and pulmonary tuberculosis, yet the findings suggest the presence of pleiotropy. No significant causal relationship between T2D and lung cancer or interstitial lung disease was observed.

Risk and protective factors of asthma and mental health condition multimorbidity in a national sample of Canadian children.

BACKGROUND: The coexistence of childhood asthma and mental health (MH) conditions can impact management and health outcomes but we need to better understand the etiology of multimorbidity. We investigated the association between childhood asthma and MH conditions as well as the determinants of their coexistence. METHODS: We used data from the Canadian Health Survey of Children and Youth 2019 (3-17 years; n = 47,871), a cross-sectional, nationally representative Statistics Canada dataset. Our primary outcome was condition status (no asthma or MH condition; asthma only; MH condition only; both asthma, and a MH condition (AMHM)). Predictors of condition status were assessed using multiple multinomial logistic regression. Sensitivity analyses considered individual MH conditions. RESULTS: MH condition prevalence was almost two-fold higher among those with asthma than those without asthma (21.1% vs. 11.6%, respectively). There were increased risks of each condition category associated with having allergies, other chronic conditions, and family members smoking in the home while there were protective associations with each condition status category for being female and born outside of Canada. Four additional variables were associated with AMHM and MH condition presence with one additional variable associated with both AMHM and asthma. In sensitivity analyses, the associations tended to be similar for most characteristics, although there was some variability. CONCLUSION: There are common risk factors of asthma and MH conditions along with their multimorbidity with a tendency for MH risk factors to be associated with multimorbidity. MH condition presence is common and important to assess among children with asthma.

Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

A new Anticalin protein for IL-23 inhibits non-type 2 allergen-driven mouse lung inflammation and airway hyperresponsiveness.

Severe asthma is a syndromic label assigned to patients based on clinical parameters, yet there are diverse underlying molecular endotypes in severe asthma pathobiology. Immunophenotyping of asthma biospecimens commonly includes a mixture of granulocytes and lymphocytes. Recently, a subset of severe asthma patients was defined as non-type 2 with neutrophil-enriched inflammation associated with increased Th17 CD4+ T cells and IL-17 levels. Here, we used an allergen-driven mouse model of increased IL-17 and mixed granulocyte lung inflammation to determine the impact of upstream regulation by an Anticalin protein that specifically binds IL-23. Airway administration of the IL-23 binding Anticalin protein (AcIL-23) decreased lung neutrophils, eosinophils, macrophages, and lymphocytes, IL-17+ CD4 T cells, mucous cell metaplasia and methacholine-induced airway hyperresponsiveness. Selective targeting of IL-23 with a monoclonal antibody (IL-23p19) (αIL-23) also decreased macrophages, IL-17+ CD4 T cells and airway hyperresponsiveness. In contrast, a monoclonal antibody against IL-17A (αIL-17A) had no significant effect on airway hyperresponsiveness, but did decrease lung neutrophils, macrophages, and IL-17+ CD4 T cells. Targeting the IL-23 pathway did not significantly change IL-5+ or IL-13+ CD4 T cells. Together, these data indicate that airway AcIL-23 mirrored the activity of systemic anti-IL-23 antibody to decrease airway hyperresponsiveness in addition to mixed granulocytic inflammation, and that these protective actions were broader than blocking only IL-17A or IL-5, which selectively decreased airway neutrophils and eosinophils, respectively.

Potential association between obstructive lung diseases and cognitive decline.

Introduction: Chronic obstructive lung diseases, such as asthma and COPD, appear to have a more extensive impact on overall functioning than previously believed. The latest data from clinical trials suggests a potential link between cognitive deterioration and chronic obstructive inflammatory lung disease. This raises the question of whether these diseases affect cognitive functions and whether any relevant biomarker may be identified. Methods: This prospective observational study included 78 patients divided equally into asthma, COPD, and control groups (n=26, 27 and 25 respectively). The participants underwent identical examinations at the beginning of the study and after at least 12 months. The test battery comprised 16 questionnaires (11 self-rated, 5 observer-rated, assessing cognition and mental state), spirometry, and blood samples taken for PKA and CREB mRNA evaluation. Results: A 2.3-fold increase in CREB mRNA was observed between examinations (p=0.014) for all participants; no distinctions were observed between the asthma, COPD, and control groups. Pooled, adjusted data revealed a borderline interaction between diagnosis and CREB expression in predicting MMSE (p=0.055) in COPD, CREB expression is also associated with MMSE (ß=0.273, p=0.034) like with the other conducted tests (ß=0.327, p=0.024) from COPD patients. No correlations were generally found for PKA, although one significant negative correlation was found between the first and second time points in the COPD group (ß=-0.4157, p=0.049),. Discussion: Chronic obstructive lung diseases, such as asthma and COPD, may have some linkage to impairment of cognitive functions. However, the noted rise in CREB mRNA expression might suggest a potential avenue for assessing possible changes in cognition, especially in COPD; such findings may reveal additional transcription factors linked to cognitive decline.

Climate change and children's respiratory health.

Climate change has significant consequences for children's respiratory health. Rising temperatures and extreme weather events increase children's exposure to allergens, mould, and air pollutants. Children are particularly vulnerable to these airborne particles due to their higher ventilation per unit of body weight, more frequent mouth breathing, and outdoor activities. Children with asthma and cystic fibrosis are at particularly high risk, with increased risks of exacerbation, but the effects of climate change could also be observed in the general population, with a risk of impaired lung development and growth. Mitigation measures, including reducing greenhouse gas emissions by healthcare professionals and healthcare systems, and adaptation measures, such as limiting outdoor activities during pollution peaks, are essential to preserve children's respiratory health. The mobilisation of society as a whole, including paediatricians, is crucial to limit the impact of climate change on children's respiratory health.

Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma.

BACKGROUND: MARCKS (myristoylated alanine-rich C kinase substrates) serves as a substrate for protein kinase C, residing in the plasma membrane while acts as an actin filament crosslinking protein. This investigation aims to elucidate phosphorylated MARCKS (p-MARCKS) levels and activity in allergic asthma patients and explore the therapeutic potential of peptide inhibitors targeting p-MARCKS in an acute mouse model of allergic asthma. METHODS: Immunohistochemistry and histology staining were employed on lung tissue slides to evaluate p-MARCKS expression and allergic asthma symptoms. Airway resistance was measured using invasive whole-body plethysmography. Flow cytometry detected lung dendritic cell migration, and migration/maturation assays were conducted on isolated murine bone marrow-derived dendritic cells (BM-DCs). RESULTS: Elevated p-MARCKS expression was observed in both human asthmatic tissues and animal models immunized with ovalbumin or Alternaria Alternata. Remarkably, asthmatic individuals showed elevated high p-MARCKS expression in lung tissues. Intraperitoneal injection of the peptide MPS, targeting the MARCKS phosphorylation site domain, before allergen challenged, effectively suppressed MARCKS phosphorylation in murine lung tissues. MPS inhibited both in vivo and in vitro migration and maturation of dendritic cells (BM-DCs) and reduced Th2-related lymphocyte activation in bronchoalveolar lavage fluid (BALF). MPS pretreatment additionally suppressed all symptoms associated with allergic airway asthma, including a reduction in inflammatory cell influx, airway mucous cell metaplasia, and airway hyperreactivity. CONCLUSION: These findings suggest that phosphorylated MARCKS occurs in asthmatic lung tissue, and the inhibition of MARCKS phosphorylation by the MPS peptide reduces dendritic cell migration and Th2-related lymphocytes in the lungs in a murine model of acute asthma.

Role and regulators of N6-methyladenosine (m6A) RNA methylation in inflammatory subtypes of asthma: a comprehensive review.

Asthma is a common chronic inflammatory disease of the lungs and airway, yet its inflammatory subtypes and potential pathogenesis have not been completely elucidated and require further study. With advances in epigenetic development, methylation has emerged as a new direction for identifying and decoding the occurrence and subtype manifestations of asthma. N6-methyladenosine (m6A), an RNA methylation modification occurring in the N6-position of adenosine, is a prevalent epigenetic modification observed in eukaryotes. It exerts significant control over mRNA metabolism by regulating alternative splicing, stability, export, and translation. The dynamic process of m6A methylation plays a crucial role in the pathogenesis of asthma and is tightly regulated by three types of regulators: writers, readers, and erasers. This article provides a comprehensive review of the association between m6A regulators and the pathogenesis of inflammatory subtypes of asthma, such as involvement of inflammatory cells and related inflammatory response. Furthermore, the findings presented herein provide new insights and a solid foundation for further research on m6A mRNA methylation as biomarkers for the diagnosis and development of personalized treatment for different subtypes of asthma, particularly neutrophilic asthma and eosinophilic asthma.

Eosinophilic granulomatosis with polyangiitis developed during treatment with benralizmab for severe asthma: A case report and literature review.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune disorder characterized by necrotizing vasculitis, asthma, and eosinophilia. We report a case of EGPA that developed during benralizumab treatment for severe asthma and provide a literature review. A 79-year-old Japanese male with severe asthma presented with generalized purpura 4 months after initiating benralizumab treatment. He had reduced his oral prednisolone dose from 7.5 to 2 mg/day. Laboratory tests revealed eosinophilia, and skin biopsy showed vasculitis with eosinophilic infiltration. He was diagnosed with EGPA and treated with corticosteroids, azathioprine, and mepolizumab, which led to rapid improvement and sustained remission. Five cases of EGPA developing during benralizumab treatment have been reported, with onset ranging from 14 to 36 weeks after initiation. Clinicians should monitor for EGPA development in patients receiving benralizumab, particularly during oral corticosteroid reduction.

[Occupational diseases related to otorhinolaryngology]. / Berufskrankheiten mit Bezug zur HNO-Heilkunde.

In the German Ordinance on Occupational Diseases (BKV), there are currently 82 occupational diseases listed, of which 18 partially or completely fall within the field of ENT medicine due to the associated health disorders. Noise-induced hearing loss is usually the focus of attention for the ENT specialist, but it has long since ceased to be the only occupational disease. In order to help uncover possible causalities between occupational noxious substances and diseases, it is important that physicians report their own observations and new scientific findings regarding suspected cases to the German Social Accident Insurance, especially in situations where cancer may be linked to occupational influences.

Very long-term data on patients with severe eosinophilic asthma treated with mepolizumab: a case series.

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab. Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit. Results: Three of the patients were men, median age was 52.5 years (range 79-53), median length of asthma before mepolizumab start was 67.5 months (range 24-240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/µL at baseline. The median follow-up was 73.5 months (range 71-74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12-39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3-6) to 0; p=0.0286). Conclusions: Mepolizumab could be a 'disease-modifying' agent, with high tolerability and a good efficacy profile in the long term.

Fractional exhaled nitric oxide (FeNO) among school children in Java and Sumatra, Indonesia: associations with respiratory symptoms, house dust mite sensitization and the home environment.

OBJECTIVE: To study associations between fractional exhaled nitric oxide (FeNO) and asthma, airway symptoms, sensitization to common allergens, outdoor pollution and home environment among 380 students in eight junior high schools in two areas in Indonesia. METHODS: Data on health and home were collected by a face-to face interview before measuring FeNO and performing skin prick test against common allergens. Exploratory linear mixed and logistic regression models were employed. RESULTS: Geometric mean of FeNO was 17.8 ppb (GSD 2.09) and 139 students (36.6%) had elevated FeNO (>20 ppb). In total, 107 students (28.2%) were sensitized to house dust mite (HDM) (Der p1 or Der f1), 4 (1.1%) to cat and 3 (0.8%) to mold (Cladosporium or Alternaria). Moreover, 20 students (5.3%) had diagnosed asthma, 38 (10.0%) had current wheeze, and 107 (28.2%) had current rhinitis. HDM sensitization, diagnosed asthma, current wheeze, and current rhinitis were associated with FeNO. In total, 281 students (73.9%) had mold or dampness, 232 (61.1%) had environmental tobacco smoke (ETS) and 43 (11.3%) had other odor at home. Indoor mold or dampness and other odor at home were associated with FeNO. ETS was negatively associated with FeNO. CONCLUSION: HDM sensitization and elevated FeNO can be common among children in this part of Indonesia. The high prevalence of elevated FeNO indicate that undiagnosed childhood asthma is common. Dampness, mold and odor at home can be associated with increased FeNO while ETS can be associated with decreased FeNO.

Multi-omics analysis identified IL-4-induced IL1RL1high eosinophils characterized by prominent cysteinyl leukotriene metabolism.

BACKGROUND: Clinical studies demonstrated that IL-4, a type 2 cytokine, plays an important role in the pathogenesis of chronic rhinosinusitis (CRS) and eosinophilic asthma (EA). However, the direct effect of IL-4 on eosinophils remains unclear. OBJECTIVE: We aim to elucidate the inflammatory effects of IL-4 on the functions of human eosinophils. METHODS: Multi-omics analysis comprising transcriptomics, proteomics, lipidomics, quantitative RT-PCR, and flow cytometry was performed using blood eosinophils from healthy subjects stimulated with IL-4, IL-5, or their combination. RESULTS: Transcriptomic and proteomic analyses revealed that both IL-4 and IL-5 upregulate the expression of gamma-gultamyl transferase 5 (GGT5), a fatty acid-metabolizing enzyme that converts leukotriene C4 (LTC4) into LTD4. In addition, IL-4 specifically upregulates the expression of IL1RL1, a receptor for IL-33 and transglutaminase 2 (TGM2). Additional transcriptomic analysis of cells stimulated with IL-13 revealed altered gene expression profiles, characterized by the upregulation of GGT5, TGM2, and IL1RL1. IL-13-induced changes were not totally different from IL-4-induced one. Lipidomic analysis revealed that IL-5 and IL-4 additively increased the extracellular release of LTD4. In vitro experiments revealed that STAT6 and IL-4 receptor α control the expression of these molecules in the presence of IL-4 and IL-13. Analysis of eosinophils derived from patients with allergic disorders indicated the involvement of IL-4 and IL-13 at the inflamed sites. CONCLUSIONS: IL-4 induces the pro-allergic phenotype of IL1RL1high eosinophils with prominent cysteinyl leukotriene metabolism via STAT6. These cellular changes represent potential therapeutic targets for CRS and EA.

The Role of the Microbiome in Pediatric Respiratory Diseases.

Numerous studies have examined the role of the microbiome and microbiome-based therapeutics in many childhood airway and lung diseases. In this narrative review, the authors first give a brief overview of the current methods used in microbiome research. The authors then review the literature linking the microbiome with (1) early-life acute respiratory infections due to respiratory syncytial virus, (2) childhood asthma onset, (3) cystic fibrosis, and (4) bronchopulmonary dysplasia, focusing on recent studies that have used culture-independent methods to characterize the respiratory or gut microbiome in the pediatric population.

Endotypes of severe neutrophilic and eosinophilic asthma from multi-omics integration of U-BIOPRED sputum samples.

BACKGROUND: Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi-omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development. OBJECTIVES: To determine whether multi-omics integration of sputum leads to improved granularity of the molecular classification of severe asthma. METHODS: We analyzed six -omics data blocks-microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing-from induced sputum samples of 57 severe asthma patients, 15 mild-moderate asthma patients, and 13 healthy volunteers in the U-BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi-omics datasets of the 72 asthmatics. RESULTS: Five stable omics-associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL-22 cytokine activation, with the prediction of therapeutic response to anti-IL22 antibody therapy. CONCLUSION: Multi-omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high-dimensional interactions will contribute to a more comprehensive understanding of complex endotypes. KEY POINTS: Unsupervised clustering on sputum multi-omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma. One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia. One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL-22.

Real-Life Clinical Outcomes of Benralizumab Treatment in Patients with Uncontrolled Severe Asthma and Coexisting Chronic Rhinosinusitis with Nasal Polyposis.

Background: The objective of this study was to evaluate, the clinical benefit of benralizumab in patients with uncontrolled severe asthma associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The study included patients with uncontrolled severe asthma associated with CRSwNP who started therapy with benralizumab. Pulmonary function, eosinophilia, IgE, comorbidity, changes in the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Visual Analogue Scale (VAS), Quality of Life (AQLQ), VAS (obstruction, drip, anosmia, facial pressure), SNOT-22, decrease or withdrawal of steroids and other medication, hospital admissions and emergency visits were analysed. The FEOS scale and EXACTO were employed in the assessment of response. Results: We analyzed 58 patients who completed minimal treatment at 12 months. After treatment with benralizumab, exacerbations were reduced by 82% (p < 0.001), steroid cycles by 84% (p < 0.001), emergencies visit by 83% p < 0.001) and admissions by 76% (p < 0.001), improving all the scales for asthma control, (p < 0.001). In terms of lung function, differences were observed in FVC% (p < 0.001), FEV1% (p < 0.001), and FEV1/FVC% (69.5 ± 10 vs. 74 ± 10, p < 0.001). In relation to CRSwNP, differences were observed in SNOT-22 (54.66 ± 17 vs. 20.24 ± 9, p < 0.001), VAS obstruction (7.91 ± 1 vs. 1.36 ± 1, p < 0. 001), VAS drip (7.76 ± 1 vs. 1.38 ± 1, p < 0.001), VAS anosmia (7.66 ± 1 vs. 1.38 ± 1, p < 0.001) and VAS facial pressure (7.91 ± 1 vs. 1.22 ± 1, p < 0.001). The mean FEOS score after treatment was 73 ± 14. A complete response/super response was achieved in 33 patients (57%), good response in 16 (28%) and partial response in 9 (15%). Conclusions: The administration of benralizumab to patients with uncontrolled severe asthma associated with CRSwNP has been demonstrated to improve nasal symptoms, asthma control and lung function. This resulted in a reduction in the need for oral steroids, maintenance and rescue medication, emergency room visits, and hospital admissions, with 57% of patients achieving the clinical remission criteria.