Search Results (87)

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

Tuberculosis and parasitic infections, including Toxocara, frequently coexist in many regions worldwide, yet their interaction remains poorly understood. Tuberculosis triggers a type 1 immune response characterized by IL-12, IFN-γ, and TNF-α production, while toxocariasis elicits a type 2 response, mediated by cytokines such as IL-4, IL-5, IL-13, and IL-33. The coexistence of these divergent immune pathways can disrupt immune regulation and impair the host’s ability to control both infections, potentially leading to persistent hypereosinophilia. We illustrate this complex interplay through a real-world case involving a heavy smoker in whom Toxocara infection likely reactivated latent tuberculosis, resulting in severe, unexplained hypereosinophilia and late-onset asthma with recurrent exacerbations. After excluding other causes and completing full antituberculosis therapy along with three courses of antiparasitic treatment and systemic corticosteroids, hypereosinophilia persisted. The introduction of benralizumab, a biologic therapy targeting IL-5Rα, led to a rapid reduction in eosinophils to normal ranges and significant clinical improvement. This case underscores the diagnostic and therapeutic challenges posed by the intersection of common infections and highlights that even a neglected parasitic infection such as toxocariasis can underlie severe respiratory complications with eosinophilia, where paradoxically biologic therapy may ultimately provide a very effective intervention. Full article

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 (T2) asthma endotype. Emerging biomarkers, or older biomarkers with emerging utility, include sputum inflammatory cells (eosinophils, neutrophils, interleukins), thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, eosinophil peroxidase (EPX), Clara/club cell secretory protein (CC16), and quantitative computerized tomography (QCT) imaging biomarkers (evaluating mucus plugging, air trapping, airway wall thickness, small airway remolding) and are increasingly used in clinical trials as secondary endpoints in evaluating efficacy, as well as in the clinical setting at specialized centers. The rapid advances in asthma research, due in part to biomarkers and biologic therapies, may soon standardize an end goal: symptom-free asthma remission without exacerbations. Full article

Background: Small airway dysfunction (SAD) plays a critical role in the management of severe asthma, particularly in patients at risk of requiring biological therapies (BTs). Short-term studies have shown that switching to single-inhaler triple therapy (SITT) with extrafine beclomethasone–formoterol–glycopyrronium improves outcomes and helps achieve quiet asthma, a state marked by symptom control, no exacerbations or oral steroids, reduced inflammation, and better small airway function. This study investigated whether, over one year, patients could maintain this state as Steady Quiet Asthma (SQA) and whether baseline measures could predict this sustained response. Methods: Twenty-six patients with severe asthma and SAD were transitioned from open triple-inhaler therapy to a closed, single-inhaler triple therapy containing extrafine beclomethasone–formoterol–glycopyrronium. Assessments at baseline (T0) and at one-year follow-up (T12) included clinical evaluations, spirometry, and impulse oscillometry, with a focus on Fres as a predictor for the need for BT. When prescribed, biologic therapies included mepolizumab, benralizumab, and dupilumab. Results: Of the 26 patients, 9 (34.6%) achieved SQA and did not require biologic therapy at the one-year follow-up, while 17 patients (65.4%) initiated biologic treatment. At T0, patients who required biologics had significantly higher median Fres (21 (19.47; 24.58) vs. 17.61 (15.82; 20.63); p = 0.049) compared to those who remained biologic-free. They also exhibited higher residual volume to total lung capacity ratio (%RV/TLC) values and lower forced expiratory volume in one second/forced vital capacity ratios (FEV₁/FVC). At T12, patients spared from BT showed significant reductions in Fres (p = 0.014) and improvements in small airway function (difference in airway resistance between 5 Hz and 20 Hz (R5–20), forced expiratory flow between 25% and 75% of FVC (%FEF25–75), and better asthma control (ACT). In contrast, patients on BT demonstrated less favorable changes in these parameters. Conclusions: Baseline Fres, FEV1/FVC ratio, and %FEV25–75 are valuable predictors of achieving Steady Quiet Asthma (SQA) and sparing biologic therapy. These findings support the use of SITT in severe asthma and highlight the importance of early functional assessments to guide personalized management. Full article

Background: Severe asthma, which is characterized by persistent symptoms despite standard therapies, presents a significant clinical challenge. Biologic therapies targeting specific inflammatory pathways offer a potential avenue for achieving disease remission. This retrospective study evaluates the effectiveness of biologic therapies in achieving remission in severe asthma within a central Romanian cohort. Methods: Forty-eight patients with severe asthma treated with omalizumab, benralizumab, or dupilumab (2020–2025) were assessed. Clinical remission was defined using ACT scores, exacerbation frequency, corticosteroid use, and FEV1. Biological remission was determined using FeNO and eosinophil levels. Statistical analysis was performed to compare treatment outcomes. Results: At 12 months, 75% of patients achieved biological remission, and 75% reached clinical remission criteria. Significant improvements were observed in FEV1 (p < 0.001), eosinophil counts (p < 0.001), and ACT scores (p < 0.001). Complete remission, encompassing clinical, biological, and functional normalization, was observed in 54.2% of patients. Conclusion: Biologic therapies demonstrate promise in inducing comprehensive remission in severe asthma, supporting their role in improving disease control and lung function. Further research with larger cohorts is warranted. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifaceted inflammatory disorder characterized by distinct immunopathogenic entities, including type 2 inflammation mediated by cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. These cytokines contribute to eosinophilic inflammation, epithelial barrier dysfunction, and mucus overproduction, resulting in polyp formation. Advances in molecular understanding have resulted in the identification of CRSwNP endotypes, suggesting personalized treatment approaches. Conventional therapies, such as intranasal and systemic corticosteroids, provide symptom relief but are restricted by side effects and polyp recurrence, necessitating the development of novel targeted approaches. Biologic therapies represent a breakthrough in CRSwNP management. Monoclonal antibodies such as dupilumab, omalizumab, mepolizumab, and Benralizumab (IL-5 receptor alpha) target key mediators of type 2 inflammation, leading to substantial improvements in polyp size, symptom control, and quality of life. Additionally, emerging therapies like tezepelumab and brodalumab aim to address broader immune mechanisms, including type 1 and type 3 inflammation. These advancements enable tailored treatment approaches that optimize outcomes and reduce reliance on surgical interventions. Biomarker-driven research continues to refine CRSwNP classification and treatment efficacy, emphasizing precision medicine. Future efforts should focus on expanding the therapeutic landscape, investigating long-term impacts of biologics, and exploring their combinatory potential to improve disease control. This review discusses the role of innate and adaptive immunity in the pathogenesis of CRSwNP and suggests novel cytokine-targeted strategies for further considering personalized medicine in future therapeutic plans. Full article

Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma. Full article

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article

Background: Severe asthma is a respiratory condition, involving treatments (i.e., inhaled steroids, systemic steroids, hospitalization) capable of increasing significant carbon footprint, raising concerns about environmental sustainability in healthcare. Sustainable healthcare policies and use of environmentally friendly treatment options are crucial in balancing effective asthma management with climate responsibility. Objectives: With this manuscript, we want to assess the impact, in terms of CO₂ production, of patients suffering from severe asthma and treated with biological drugs, to show the reduction in carbon footprint after the use of these drugs compared to the time when they were not prescribed. We analyzed data from three studies, all conducted in real life in Italy, of patients treated with mepolizumab, benralizumab and dupilumab, for the control of severe asthma. Methods: Data on number of exacerbations and hospitalizations, systemic corticosteroids (CS) cycles and their dose, were collected by three already published real-life trials, on the above-mentioned biologics, and used to calculate carbon footprint impact before and after biological therapy. For the mepolizumab study, the data collected referred to patients who started the drug between June 2017 and January 2019; for dupilumab, there were no age limits with patients enrolled between December 2019 and July 2020, whereas in the benralizumab study, all patients had to be over 18 years old. The statistical analysis was performed with Shapiro–Wilk test, t test and Cohen’s test. Results: The use of biologic drugs showed a significant reduction in CO₂ production after the introduction of these therapies, mainly secondary to a reduction in exacerbations, hospitalizations and CS use. In numerical terms, an average reduction of 75% in CO₂ production, per patient, is shown. Conclusions: Disease control, clinical remission of disease, in patients with severe asthma is certainly a determining factor in assessing the effectiveness of a treatment. Provided these goals are achieved, biological drug therapy has also proved to be particularly virtuous from the fundamental environmental point of view, allowing a significant reduction in CO₂ production for the management of these patients. Full article

Background: Severe asthma is associated with significant morbidity and risk of complications. Some patients, suffering from eosinophilic asthma, may benefit from biological therapies, especially anti IL-5 (anti-interleukin-5). The purpose of the study was to compare the efficacy evaluation of mepolizumab and benralizumab in the treatment of eosinophilic asthma. Methods: A retrospective, single-centre study including 59 patients with severe eosinophilic asthma treated with biologics (mepolizumab and benralizumab). Clinical outcomes, including peripheral blood morphotic characteristics, spirometry parameters, asthma control questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ) scores, daily oral corticosteroid use, body mass index, exacerbation rate, and exercise tolerance, were examined at the beginning and after 6 months of biological treatment. Results: A total of 38 patients were treated with mepolizumab and 21 with benralizumab. Significant improvements (p < 0.05) in eosinophil count, required daily dose of glucocorticoids, ACQ, mini-AQLQ scores, and exacerbation rate were observed in both groups after six months of treatment. There was no statistical difference (p < 0.05) in the abovementioned parameters between the groups. Conclusions: In patients with severe eosinophilic asthma, mepolizumab and benralizumab were associated with significant improvements in clinical state. Patients with type 2 asthma will benefit from the therapy with both anti-IL5 biologic drugs. Full article

Asthma is a chronic and multifaceted respiratory condition that affects over 300 million individuals across the globe. It is characterized by persistent inflammation of the airways, which leads to episodes of wheezing, breathlessness, chest tightness, and coughing. The most prevalent form of asthma is classified as Type 2 or T2-high asthma. In this variant, the immune response is heavily driven by eosinophils, mast cells, and T-helper 2 (Th2) cells. These components release a cascade of cytokines, including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13). This release promotes several processes: the production of immunoglobulin E (IgE), which is integral to allergic responses; the recruitment of eosinophils—white blood cells that contribute to inflammation and tissue damage. Conversely, non-Type 2 or T2-low asthma is typically associated with a different inflammatory profile characterized by neutrophilic inflammation. This type of asthma is driven by T-helper 1 (Th1) and T-helper 17 (Th17) immune responses, which are often present in older adults, smokers, and those suffering from more severe manifestations of the disease. Among asthmatic patients, approximately 80–85% of cases are classified as T2-high asthma, while only 15–20% are T2-low asthma. Treatment of asthma focuses heavily on controlling inflammation. Inhaled corticosteroids remain the cornerstone therapy for managing T2-high asthma. For more severe or treatment-resistant cases, biologic therapies targeting specific inflammatory pathways, such as anti-IgE (omalizumab), anti-IL-5 (mepolizumab, benralizumab), and anti-IL-4/IL-13 (dupilumab), have shown great promise. For T2-low asthma, macrolide antibiotics like azithromycin and other novel therapies are being explored. This article reviews the safety, efficacy, and indications of the currently approved biologics and discusses potential novel biologics for asthma. Full article

Severe asthma is a subset of difficult-to-treat asthma that requires the verification of inhaler technique, the correction of modifiable risk factors, as well as diagnosis and comorbidity review. When severe asthma is suspected, patients should undergo proper phenotyping (T2-high or T2-low) and be referred to a specialized severe asthma clinic. The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP). The outcomes to evaluate are the reduction in systemic corticosteroid use, the reduction in exacerbations and healthcare use, and improvement in symptoms and lung function. Comorbidities should be carefully considered, and if possible, addressed with the same biologic. Dupilumab, mepolizumab, and omalizumab are also approved for chronic rhinosinusitis with nasal polyps (CRSwNP), the most common asthma comorbidity. There are currently several clinical trials on biologics for severe asthma. Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration. Full article

Introduction: Benralizumab has demonstrated rapid efficacy in treating severe eosinophilic asthma (SEA). This study aims to characterize early responses to benralizumab, the patient features observed in those with early responses, and the potential patient features that could predict them, and it also evaluates whether these improvements are sustained during a one-year follow-up (FUP) in clinical practice. Methods: This analysis was conducted using the ORBE II study database. ORBE II is an observational, retrospective study that included uncontrolled SEA adult patients treated with benralizumab according to routine clinical practice in Spain. We analysed patients with available data on the asthma control test (ACT) at baseline and within the first 120 days after benralizumab initiation, identifying ACT “Early Super-Responders” (ACT-ESR) as patients with a ≥9 point-improvement in the ACT score or reaching an absolute score of ≥24. Likewise, we assessed patients with available data on the pre-BD FEV₁ during the same study periods, defining those with a pre-BD FEV₁ increment of ≥230 mL as FEV₁-ESR patients. Clinical outcomes were described up to 1 year of FUP. Results: A total of 45 and 65 patients with data for ACT and FEV₁, respectively, during the first 120 days of treatment were analysed. Of those, 55.5% and 58.5% of patients were categorized as ACT-ESR and FEV₁-ESR, respectively. At baseline, both groups showed high T2 inflammation markers and a high prevalence of comorbidities (chronic rhinosinusitis with nasal polyposis: 56% and 50%; gastro-oesophageal reflux disease: 24% and 40%, respectively). Poor asthma control (ACT < 20) was observed at baseline in 96% of ACT-ESR, while impaired lung function (pre-BD FEV₁ < 80%) was present in 71.7% of FEV₁-ESR. Oral corticosteroid (OCS) dependency affected 25% and 30% of ACT-ESR and FEV₁-ESR, respectively. The early gains observed in ACT-ESR and FEV₁-ESR were sustained up to 1 year of FUP, with 90.5% and 66.7% of patients achieving a super-response (zero exacerbations and no OCS use) and 92.0% and 71.1% meeting clinical remission criteria (zero exacerbations, no OCS use, ACT ≥ 20 and pre-BD FEV₁ increment of ≥100 mL), respectively. Conclusions: Benralizumab provides early benefits for SEA patients in clinical practice, with more than half achieving early super-responses in both ACT score and lung function. These improvements were sustained over a 1-year FUP, resulting in high rates of clinical remission. Full article

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care. Full article

Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by the presence of marked eosinophilia resulting in end organ damage. The diagnostic approach is multidisciplinary and treatment goals include reductions in flares and eosinophils with minimal drug-related side effects. Results: Eleven patients (n = 11) with a diagnosis of idiopathic HES were included in the study [M/F: 6/5, median age: 54 (95% CI: 38.2 to 68.5), smokers/never smokers: 5/6]. Asthma was present in the majority of them (n = 8, 72.7%); four patients (n = 4, 36.4%) presented with eosinophilic pleural effusions, two patients (n = 2, 18.2%) with cardiac arrhythmias, and one with bilateral eyelid angioedema. Eight patients (72.7%) were treated with mepolizumab (300 mg/month) and three (27.3%) with benralizumab (30 mg/4 weeks). The median values of eosinophils at baseline and 12 months after initiation of biologic agent were 3000 (95% CI: 2172 to 11,365) K/μL and 50 (95% CI: 3 to 190) K/μL, respectively, p = 0.0002. All patients with concomitant asthma (n = 8) experienced elimination of asthma flares, asthma control (ACQ < 0.75), functional improvement (mean ΔFEV1: 857 ± 594 mL), and an 82% reduction in oral corticosteroids, p = 0.0001. Materials and Methods: Patients with highly characterized idiopathic HES treated with anti-eosinophilic agents between 1 October 2019 and 1 October 2023 were retrospectively included in the study. The aim of this study was to present clinical, laboratory, and functional features and outcomes in patients with thoroughly investigated idiopathic HES treated with biologic agents targeting eosinophils. Conclusions: Biologic agents in patients with idiopathic HES—following thorough diagnostic investigation—are both safe and effective, sparing the toxicity of immunosuppressive agents. Real-life data from larger registries are greatly anticipated. Full article