Search Results (137)

Background/Objectives: Severe asthma in routine practice often involves long-standing disease, multimorbidity, and prior biologic failure—settings underrepresented in pivotal tezepelumab trials. This study evaluated 52-week real-world effectiveness and safety of tezepelumab in a highly comorbid, predominantly T2-high, biologic-experienced severe asthma cohort from the Canary Islands. Methods: TEZNERIFE is a multicenter, retrospective study including consecutive adolescents and adults with GINA Step 5 severe uncontrolled asthma treated with tezepelumab 210 mg every 4 weeks for 12 months. Clinical outcomes, lung function, type 2 biomarkers, upper airway symptoms, and Biologics Asthma Response Score (BARS) were assessed at baseline, 26 weeks, and 52 weeks. Results: Fifty-six patients (mean age 53.5 years, 71% female, mean asthma duration 30 years, 84% T2-high; 71% with ≥1 prior biologic) were analyzed. ACT improved from 11.5 ± 3.7 to 15.9 ± 4.7 at 26 weeks and 17.5 ± 4.7 at 52 weeks (both p < 0.0001), while annualized exacerbations declined from 2.79 ± 2.0 to 0.50 ± 0.72 and 0.51 ± 0.89 (both p < 0.0001). Maintenance oral corticosteroid dose fell from 10.2 ± 8.3 to 6.9 ± 2.4 mg/day at 52 weeks (p = 0.014). FEV1% predicted increased from 69.3 ± 19.2% to 75.3 ± 17.7% and 76.2 ± 20.6% (p = 0.004 and p = 0.001), and blood eosinophils decreased from 234 ± 231 to 146 ± 120 and 147 ± 110 cells/µL (p = 0.001 and p = 0.013). At one year, 18.9% and 67.9% were classified as good and intermediate responders by BARS; 13.2% were insufficient responders. Two patients discontinued due to non-serious adverse events, while no treatment-related serious events occurred. Conclusions: In this difficult-to-treat, multimorbid, biologic-experienced population, tezepelumab achieved sustained improvements in asthma control, exacerbations, lung function, eosinophilic inflammation, and corticosteroid exposure over 52 weeks, supporting upstream alarmin inhibition as a versatile strategy in complex severe asthma. Full article

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article

Background: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. Methods: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in Târgu-Mureș, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV₁% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT ≥ 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO < 20 ppb and blood eosinophils < 150/µL), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. Results: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11–14) at baseline to 23 (21–25) at 12 months and remained stable at 22 (20–25) at 24 months (p < 0.001). Predicted FEV₁% increased from 50 (39–59) to 78 (68–88) at 12 months and 79 (66–96) at 24 months (p < 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2–3) per year at baseline to 0 and 0.5 (0–1) at 12 and 24 months, respectively (p < 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. Conclusions: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice. Full article

Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5–R20) and spirometry FEF25–75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV₁, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5–R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5–R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (p = 0.04), while predicted FEF25–75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (p < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (p < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (p = 0.01). Improvements in R5–R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months. Full article

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a common and debilitating inflammatory disorder primarily driven by type 2 immune mechanisms. Its frequent overlap with asthma, allergic rhinoconjunctivitis and atopic dermatitis highlights the need for therapeutic strategies able to address multimorbidity within the same pathogenic spectrum. The development of monoclonal antibodies targeting signaling pathways provides an effective and well-tolerated option that addresses common comorbidities. Targeting the IL-4 receptor alpha subunit, dupilumab is a completely human IgG4 monoclonal antibody that reduces type 2 inflammation in many organ systems by blocking IL-4 and IL-13 signaling. This study aimed to assess the long-term effectiveness and safety of dupilumab in a real-world cohort of patients with severe CRSwNP, stratified according to the presence of common type 2 comorbidities, over a 52-week treatment period. Methods: We conducted a prospective, multicenter, observational study across ten Italian secondary care centers for Allergy and Clinical Immunology and Otolaryngology. All participating centers were affiliated with the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Enrolled adult subjects with severe CRSwNP received dupilumab treatment in the context of standard care for 52 weeks. Several efficacy parameters were used. Results: A significant improvement was detected for all the applied efficacy parameters, i.e., 22-item Sinonasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the first second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI), Atopic Dermatitis Control Toll (ADCT) and Dermatology Life Quality Index (DLQI) scores for AD. Dupilumab was well-tolerated, with no new safety signals. Conclusions: This multicenter real-world study demonstrates that dupilumab provides sustained, clinically meaningful, and safe benefits for patients with severe CRSwNP and coexisting type 2 comorbidities, supporting its role as an integrated therapeutic option in precision management of type 2 inflammatory diseases. Full article

Background: Severe asthma exacerbations (SAEs) significantly contribute to asthma-related morbidity, mortality, and healthcare burden. Despite therapeutic advances, a subset of patients remains exacerbation-prone. This review aims to summarize current evidence on risk factors, phenotypes, and biomarkers associated with SAEs, and explore personalized strategies for their acute management. Methods: We conducted a comprehensive literature review focusing on clinical, inflammatory, and environmental drivers of SAE. Special attention was given to Type 2 (T2) biomarkers—blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO)—as tools for phenotyping and treatment guidance. Emerging evidence on the use of biologics during exacerbations was also analyzed. Results: SAEs are heterogeneous in etiology and inflammatory profile. Respiratory infections, allergen exposure, obesity, and comorbidities increase exacerbation risk. T2-high SAEs respond well to corticosteroids and biologics, whereas T2-low SAEs show limited treatment benefit. BEC and FeNO reliably predict exacerbation risk and corticosteroid responsiveness. Recent case reports suggest potential roles for anti-IL-5 and anti-thymic stromal lymphopoietin (TSLP) biologics in acute care. Conclusions: Biomarker-guided management of SAEs may enhance therapeutic precision and avoid overtreatment. Integrating phenotypic (observable characteristics) and endotypic (biological markers) assessment into acute care could improve patient outcomes and optimize resource use. Prospective trials are needed to confirm these approaches. Full article

Background/Objectives: In recent years, the concept of clinical remission under treatment in asthma has gained increasing attention. It is defined as the absence of exacerbations, asthma symptoms, and oral corticosteroid use for at least 12 months, together with improved or stable lung function. This study aimed to evaluate the clinical remission rates and associated factors in patients with severe asthma receiving biologic therapy with either omalizumab (anti-IgE) or mepolizumab (anti-IL-5). Methods: Adult patients with severe asthma and type 2 inflammation who started omalizumab or mepolizumab between January 2009 and December 2023 in our allergy clinic were retrospectively analyzed. Sociodemographic and clinical characteristics were reviewed. Clinical remission rates were assessed at the first and most recent years of maintenance therapy. Independent markers were identified using multivariable analyses. Results: A total of 160 patients were included (mean age 53.8 ± 14.6 years; 81.9% female). Of these, 85.6% received omalizumab and 14.4% mepolizumab. Remission rates at one year and at the latest follow-up were 60.0% and 43.7%, respectively. Patients achieving remission had higher total IgE levels. Psychiatric comorbidity negatively affected remission. The one-year remission rates were 91.3% in the mepolizumab group and 54.7% in the omalizumab group. Higher baseline blood eosinophil counts and Asthma Control Test (ACT) scores were positive markers, while psychiatric disease was inversely associated. Conclusions: Omalizumab and mepolizumab achieved meaningful clinical remission rates in severe asthma. Elevated ACT scores and eosinophil counts and absence of psychiatric comorbidities were independent markers, underscoring the need for individualized biologic therapy to achieve sustained remission. Full article

The concept of united airway disease (UAD) highlights the bidirectional relationship between inflammatory disorders of the upper airways—such as allergic rhinitis and chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP)—and lower airway diseases, most notably asthma. This paradigm is supported by epidemiological, embryological, and immunological evidence demonstrating that airway inflammation represents a single, interconnected process rather than isolated compartmental pathology. Central to many UAD phenotypes is type 2 (T2) inflammation, driven by cytokines including IL-4, IL-5, and IL-13, and mediated by effector cells such as eosinophils and group 2 innate lymphoid cells (ILC2s). Epithelial barrier dysfunction often serves as the initiating trigger for this shared inflammatory cascade by production of TSLP, IL-25 and IL-33. Optimal diagnosis and management of UAD require an integrated, multidisciplinary framework. Clinical evaluation remains essential for patient characterization but must be complemented by pheno-endotypic assessment using imaging (CT), allergy testing, biomarker profiling (FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, impulse oscillometry). Therapeutic strategies are layered, targeting both symptom control and inflammation across airway compartments. Standard approaches include intranasal and inhaled corticosteroids as well as saline irrigations, while severe T2-high disease increasingly benefits from biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP), which reduce dependence on systemic corticosteroids and surgical interventions such as endoscopic sinus surgery (ESS). Emerging precision-medicine models, particularly the “treatable traits” approach, further underscore the need to view the airway as a unified system. Collectively, these insights reinforce the clinical imperative of addressing upper and lower airway disease as a continuum, ensuring that inflammation in one district is neither overlooked nor treated in isolation. Full article

Background/Objectives: In recent years, the recognition that type 2 inflammation plays a leading role in CRSwNP has enabled the more tailored treatment of the disease through improved patient endotyping. We studied 45 patients with severe CRSwNP who were treated with dupilumab or mepolizumab. The aim was to evaluate the efficacy of these treatments on endoscopic, clinical and patient reported parameters, and to assess whether nasal cytology could be useful for identifying responsive patients and monitoring their response to biologic drugs. Methods: Follow-up visits were scheduled at baseline (T0), and at 3 (T3), 6 (T6), 12 (T12), and 24 months (T24). At each visit, patients underwent blood analysis, nasal endoscopy, and nasal scraping for cytology. They also completed the SNOT-22 questionnaire, a visual analog scale (VAS) for nasal obstruction and smell perception, and the Asthma Control Test (ACT) test in cases of concomitant asthma. Results: Biological therapy demonstrated broad efficacy in disease management, based on both clinical and cytological findings. The Nasal Polyp Score, SNOT-22 questionnaire, VAS scores for nasal obstruction and smell, and ACT score showed progressive improvement. Blood eosinophil counts and total IgE levels also decreased over time (T0 vs. T24: p = 0.008 and p < 0.001, respectively). At nasal cytology, a reduction in eosinophil cell count and in the mixed mast cell–eosinophil pattern during treatment with both biologics were observed (T0 vs. T24: p < 0.001). Positive effects were typically recorded within six months of treatment and were sustained after two years. Conclusions: Although the histological evaluation of infiltrated tissues remains the gold standard for assessing mucosal eosinophilia, nasal cytology appears to be a simpler, non-invasive, and repeatable method for evaluating local eosinophilia. Identifying endotypes and assessing the severity of inflammation are crucial for predicting the efficacy of different treatment options. Full article

Asthma and obesity are two common chronic diseases of growing clinical and social importance. One of the recognised phenotypes of asthma is obesity-related asthma, which is characterised by a more severe course, resistance to glucocorticosteroids, increased inflammation and poorer symptom control. This article discusses the complex pathophysiological mechanism of this phenotype, considering the role of chronic inflammation, immune dysregulation and metabolic disorders resulting from obesity. The potential role of glucagon-like peptide-1(GLP-1) receptor analogues as an innovative therapeutic option in the treatment of asthma in obese individuals, both with and without type 2 diabetes mellitus (T2DM), is also analysed. A literature review indicates that glucagon-like peptide-1 receptor analogue (GLP-1RA) drugs, in addition to their hypoglycaemic and weight-reducing effects, also exhibit anti-inflammatory activity in the respiratory system and may reduce the frequency of asthma exacerbations and improve asthma control. The article reviews current data from experimental and clinical studies, emphasising the need for further research on the use of GLP-1RA as an adjunct to conventional asthma therapy in the context of the obese asthma phenotype. Full article

Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from >40% to >76%) with low eosinophils (<2%). The prevalence of NA ranges from 16% to 28% of the adult asthma population depending on the definitions and study methods applied. A clinical picture of NA is characterized by late onset of symptoms, higher exacerbation rate, lower level of symptoms control, and poorer response to steroids compared to eosinophilic phenotype. Comorbidities such as obesity and GERD as well as the influence of environmental factors (air pollution, smoking, bacterial infections) contribute to the development and severe course of the disease. NA is T2-low disease with predominantly Th1/Th17-type inflammation. Neutrophils are key cells responsible for initiating and sustaining inflammation. In addition to their primary functions like phagocytosis, degranulation, and NETosis, neutrophils release several pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF) and chemokines (CXCL-1, -2, -8, -9, -10) responsible for the recruitment of other neutrophils or T cells. Increasing knowledge about the biology of neutrophiles and their role in asthma results in new potential therapies that could improve control of NA, particularly new biologicals targeting Th1/Th17-related cytokines. In this review, we discuss the prevalence, mechanisms, and clinical features of neutrophilic asthma. Furthermore, current therapeutic options and some promising perspectives for the near future are presented. Full article

Background: This study aimed to evaluate the clinical effectiveness of dupilumab and its impact on CRSwNP and type 2 inflammatory biomarkers in patients with severe uncontrolled asthma, with or without comorbidities, within a real-life cohort. Methods: This was a single-center, prospective, and observational real-life study conducted at the Severe Asthma Unit of Germans Trias i Pujol University Hospital. The objective of this study was to assess the real-world response to dupilumab treatment in patients with severe asthma, with or without nasal polyposis, bronchiectasis, obesity, or switching from another biologic drug for their asthma. Results: The ACT score significantly increased (13.7 vs. 20.6; p = 0.001), while the number of exacerbations decreased (3.1 vs. 0.7; p = 0.005). Patients with CRSwNP showed an increase in the ACT score (13.1 vs. 19.8; p = 0.011) and a decrease in the number of exacerbations (3.0 vs. 1.3; p = 0.217). Patients with nasal polyps showed an increase in both SNOT22 (78.3 vs. 38.3; p = 0.013) and global VAS (8 vs. 4.2; p = 0.028). Patients with bronchiectasis receiving dupilumab showed an increase in the ACT score (12.7 vs. 21.3; p = 0.039) and a marked decrease in the number of exacerbations (2.8 vs. 0; p = 0.025). Obese patients treated with dupilumab showed an improvement in the ACT score (14.1 vs. 21.3; p = 0.044) and a decrease in the rate of exacerbations (3.2 vs. 1.3; p = 0.030). Patients with rhinoconjunctivitis receiving dupilumab showed an increase in the ACT score (13.4 vs. 19.1; p = 0.017) and a decrease in the number of exacerbations (3.3 vs. 0.8; p = 0.024). Conclusions: Dupilumab is a highly effective treatment for severe asthma, showing significant improvements in lung function, reductions in exacerbations, and enhanced quality of life for patients with and without nasal polyps. The results of this real-life study support dupilumab as a valuable addition to the therapeutic armamentarium for asthma, particularly for those with type 2 inflammation despite the presence of comorbidities such as bronchiectasis or obesity, or for patients in whom a previous biologic treatment failed. Full article

Background: Dupilumab, a monoclonal antibody targeting the IL-4/IL-13 receptor, has shown significant efficacy in improving asthma control and reducing exacerbations in patients with severe eosinophilic asthma. However, there is a lack of knowledge about real-world data on clinical remission rates and their predictors. Objective: This study aimed to evaluate clinical outcomes, remission rates, and predictive factors of remission in a real-life cohort of patients with severe eosinophilic asthma treated with dupilumab. Methods: We conducted a retrospective, bicentric, observational study including 52 patients with severe eosinophilic asthma treated with dupilumab. Clinical, functional, and biomarkers were assessed at baseline, 6 months, and 12 months. Statistical analyses included logistic regression to identify independent predictors of clinical remission. Results: After 12 months of treatment, 48.2% of patients achieved clinical remission. Dupilumab significantly improved asthma control and lung function (including FVC and FEF_25–75), reduced exacerbation rates, and maintenance therapy. High blood eosinophil levels (>490 cells/µL), high FeNO levels (>25 ppb), a history of CRSwNP, and better baseline FEV1 were associated with asthma remission. Conversely, obesity (BMI > 30) and related comorbidities (such as GERD, OSAS, and hypertension) and bronchiectasis were associated with a lower likelihood of remission. Multivariate analysis confirmed higher baseline FEV1 (OR 2.94; IC 1.13–7.6), positive history of CRSwNP (OR 8.03; IC 1.41–45.5), and higher baseline blood eosinophils (OR 1.003 IC 1.001–1.006) as independent predictors of clinical remission. Conclusions: These results are in line with the known effectiveness of dupilumab in severe eosinophilic asthma and identified a history of CRSwNP, higher baseline FEV1, and elevated blood eosinophils as key predictors of clinical remission. These findings may contribute to a more personalized approach to treatment selection, emphasizing the importance of comorbidity assessment together with type 2 inflammation biomarkers. Further prospective studies are needed to validate these results. Full article

Asthma and chronic rhinosinusitis (CRS) are prevalent chronic inflammatory conditions of the airways that frequently occur together, contributing to increased disease burden and reduced quality of life. This study aimed to synthesize findings from retrospective research to better understand the clinical and pathophysiological interrelations between these two conditions. A narrative review was conducted, including studies (2002–2025) assessing prevalence, lung function, biomarkers, quality of life, and treatment outcomes in patients with confirmed asthma and/or CRS. The results revealed a high prevalence of comorbidity, particularly in patients with CRS with nasal polyps (CRSwNP), where asthma co-occurrence exceeds 50% in certain phenotypes. Shared type 2 inflammatory mechanisms, including eosinophilic infiltration, cytokine overexpression (IL-4, IL-5, and IL-13), and tissue remodeling via matrix metalloproteinases, were frequently identified. These findings support the unified airway model and highlight the systemic nature of inflammation in these patients. Biologic therapies demonstrated effectiveness in reducing exacerbations and improving clinical outcomes, especially in patients with more severe phenotypes. The inclusion of dentistry and oral health as components of the systemic inflammatory burden offers an innovative perspective and reinforces the importance of holistic, interdisciplinary care. This study underscores the need for a multidisciplinary, phenotypically guided approach to treatment. Recognizing and systematically addressing this comorbidity can improve disease control and enhance patient quality of life. Full article

Background/Objectives: Severe asthma remains difficult to treat, even with the range of biologics we now have that target type 2 inflammation. Some patients do not respond well enough to the first biologic they try, which raises the question of whether switching to another option can help. In this study, we looked at how patients who had unsatisfactory therapeutic outcomes on other biologics responded—both clinically and at the biomarker level—after switching to dupilumab. Methods: We reviewed data from the Allergy and Clinical Immunology Unit of Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy, between January and June 2025. The study included fifteen adults with uncontrolled severe asthma who had previously been treated for at least six months with benralizumab, omalizumab, or mepolizumab before switching to dupilumab. We evaluated demographic, clinical and laboratory data. Lung function (Forced Expiratory Volume in 1 s (FEV₁)), blood eosinophils, total and specific IgE to staphylococcal enterotoxins, eosinophil cationic protein (ECP), free light chains (FLC), and FeNO were assessed at the time of the switch and again after 12 months. Comparisons were made using paired tests, and a p-value < 0.05 was considered statistically significant. Results: After a year on dupilumab, we saw clear improvements: mean FEV₁ went up by about 10.8% predicted (p = 0.002), FeNO dropped by an average of 22 ppb (p = 0.005), blood eosinophils fell by roughly 400 cells/µL (p = 0.003), and ECP levels decreased by 13 µg/L (p = 0.009). Kappa FLCs also showed a significant drop (p = 0.04). Clinically, 40% of patients met criteria for a meaningful response, and 20% achieved complete remission. Dependence on oral corticosteroids was notably reduced. Baseline levels of eosinophils, ECP, IgE, and FLCs correlated with response to treatment. Conclusions: Our study, despite the small sample size, highlights that in patients with severe asthma who do not show a good response to their first biologic, switching to dupilumab can lead to significant improvements. Markers of type 2 inflammation at baseline might help predict who benefits most. Larger, multi-center, prospective studies are needed to confirm these results. Full article