Search Results (95)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease predominantly of the small airways and parenchyma. COPD lungs exhibit an influx of circulating innate immune cells, which, when isolated, display impaired functions, including imbalanced protease secretion. In addition to immune cells, the extracellular matrix (ECM) plays a crucial role in COPD pathology. Remodeling of the ECM can generate ECM fragments, which can be released into circulation and subsequently induce pro-inflammatory responses. COPD is a heterogeneous disease, and serological biomarkers can be used to sub-categorize COPD patients for targeted treatments and optimal recruitment in clinical trials. This study evaluated fragments of calprotectin, collagen type VI, and versican, generated by neutrophil elastase and matrix metalloproteinases (MMP-) 2 and 12, respectively, as potential biomarkers of COPD disease, severity, and endotypes. Lower plasma levels of a neoepitope marker of calprotectin, indicative of activated neutrophils (nordicCPa9-HNETM), were detected in COPD donors compared to controls. CPa9-HNE was associated with milder disease, higher degree of air-trapping, and higher serum levels of MMP-2. Deposition of CPa9-HNE levels in lung tissue revealed no differences between groups. Taken together, CPa9-HNE was found to be a potential marker of mild COPD, but further studies are warranted to validate our findings. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Background/Objectives: In this study, we aimed to evaluate probiotics’ clinical efficacy and safety in adults with chronic rhinosinusitis (CRS), and summarize mechanistic evidence related to mucosal immunity and microbiota modulation. Methods: We performed a systematic review and random-effects meta-analysis. MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched until May 2025. Eligibility: Randomized controlled trials (RCTs) and mechanistic studies investigating probiotics (any strain, dose, or administration route) in adults with CRS were eligible. Primary outcomes included changes in Sino-Nasal Outcome Test (SNOT-20/22) scores and CRS relapse rates. Secondary outcomes were adverse events and mechanistic endpoints. Results: Six studies (four RCTs, n = 337; two mechanistic studies) met the inclusion criteria. Probiotics did not significantly improve SNOT scores compared with the placebo, but trended in that direction (pooled mean difference—2.70; 95% CI −7.12 to 1.72; I² = 0%). Furthermore, probiotic use was associated with a non-significant trend towards fewer CRS relapses (risk ratio 0.41; 95% CI 0.16–1.04; p = 0.06; I² = 48%). Adverse events were mild and comparable to the placebo (risk ratio 0.87; 95% CI 0.33–2.34). Mechanistic data indicated that intranasal Lactococcus lactis W136 might downregulate type 1 inflammatory pathways and modestly increase microbiome diversity. Subgroup analyses (by route, duration, and CRS subtype) revealed no statistically significant effect modifiers, though mechanistic insights suggest possible differences in efficacy based on the CRS endotype and delivery method. Conclusions: Probiotics appear safe and may provide a small, non-significant improvement in CRS symptoms; emerging evidence of reduced relapse rates warrants further investigation through larger, endotype-stratified trials utilizing targeted probiotic strains and optimized delivery methods. 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 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

Asthma is a chronic and heterogeneous inflammatory airway disease with diverse clinical endotypes and limited curative treatment options. Recent systems biology analyses identified four potential molecular triggers—AKT1, MAPK13, STAT1, and TLR4—as candidate regulators of asthma-associated signaling pathways. This study aimed to validate the expression of these four proteins and their downstream signaling elements in peripheral blood mononuclear cells (PBMCs) from patients with allergic asthma (AA), nonallergic asthma (NA), and healthy controls (HC), to explore their potential as biomarkers or therapeutic targets. For that, PBMC samples were collected from 45 AA patients, 17 NA patients, and 15 HC subjects. Gene and protein expression of AKT1, MAPK13, STAT1, and TLR4 were quantified using RT-qPCR and Western blotting. Expression patterns were compared across groups and stratified by asthma severity. Correlations with clinical parameters (FEV1, FVC, FeNO, IgE, eosinophil counts) and treatment regimens were also assessed. All four target genes showed significantly reduced expression in asthma patients compared to controls (p < 0.001), with the most marked downregulation in NA patients. At the protein level, MAPK13 and TLR4 showed significant differential expression. Stratification by severity revealed a stepwise reduction in gene expression in AA patients, correlating with disease severity, whereas NA patients showed uniformly low expression regardless of severity. Multiple pathway-related genes, including RELA, SMAD3, NFATC1, and ALOX5, were also downregulated, particularly in NA patients. Notably, differential correlations were observed between gene expression and lung function parameters in AA vs. NA groups. In conclusion, this study supports the potential involvement of AKT1, MAPK13, STAT1, and TLR4 in asthma pathogenesis and highlights differences between allergic and nonallergic asthma at the molecular level. These proteins and their associated pathways may serve as future targets for biomarker development or endotype-specific therapies. Further studies in larger and more diverse cohorts, including functional validation, are warranted. Full article

Background/Objective: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with a significant impact on quality of life and is frequently associated, from a pathogenetic perspective, with type 2 inflammation. The introduction of biologic therapies has marked a turning point in the management of severe forms of the disease, offering a valuable treatment option. However, selecting the most suitable biologic agent for a specific patient remains a clinical challenge. Artificial intelligence, and, in particular, ChatGPT, has recently been proposed as a potential tool to support medical decision-making and guide therapeutic choices. To evaluate the concordance between the therapeutic recommendations provided by ChatGPT and those of a multidisciplinary expert board in selecting the most appropriate biologic therapy for CRSwNP patients, based on the analysis of their phenotype and endotype. Methods: A multicenter observational cohort study was conducted. Clinical data from 286 patients with CRSwNP were analyzed. For each case, the therapeutic choice among Dupilumab, Mepolizumab, and Omalizumab was compared between the board and ChatGPT. Concordance rates and Cohen’s Kappa coefficient were calculated. Results: Overall concordance was 59.2%, with a Cohen’s Kappa coefficient of 0.116. Concordance by drug was 62.8% for Dupilumab, 26.5% for Mepolizumab, and 9.1% for Omalizumab. Patients presented with severe clinical profiles, with an average Nasal Polyp Score of 6.22 and an average SNOT-22 score of 64.5. Conclusions: This study demonstrates that, despite its substantial theoretical potential, ChatGPT is currently not a reliable tool for the autonomous selection of biological therapies in patients with CRSwNP. Further studies are necessary to enhance its reliability and integration into clinical practice. Full article

Background/Objectives: Chronic rhinosinusitis (CRS) is a prevalent inflammatory condition of the nasal cavity and paranasal sinuses that significantly impact patients’ quality of life and imposes a substantial burden on healthcare systems and society, including considerable costs associated with surgical management when required. This review aimed to provide a comprehensive overview of the burden of CRS, encompassing its impact on patients, society, and the economy, while also highlighting the latest advancements in diagnosis and treatment. Methods: A systematic review using PubMed, Embase and Google Scholar databases identified recent literature published in English, adhering to PRISMA guidelines. Search terms included “chronic rhinosinusitis”, “burden”, “quality of life”, “economic impact”, “diagnosis”, “treatment”, and “endotypes”. Original research, reviews, and meta-analyses were included, while case reports, surgical-only studies, and non-English articles were excluded. Results: Characterized by persistent symptoms such as nasal congestion, facial pressure, and discharge, CRS often leads to decreased productivity, missed workdays, and impaired sleep. Recent advances in understanding the pathophysiology of CRS have led to the identification of distinct endotypes, including type 2 inflammation characterized by eosinophilic infiltration, and type 1 inflammation with a neutrophilic predominance. Conclusions: This understanding has paved the way for targeted therapies, including biologic agents that have shown promising results in managing CRS, particularly in patients with type 2 inflammation. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder marked by intricate interplay among skin barrier dysfunction, immune dysregulation, and microbial dysbiosis. While therapeutic advancements targeting T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway have yielded promising outcomes, a significant proportion of patients still experience inadequate relief, particularly from persistent pruritus. Achieving minimal disease activity remains an unmet clinical priority and a cornerstone of effective AD management. This review provides an in-depth analysis of current therapeutic approaches and integrates findings from recent biologic studies, with a particular focus on innovative strategies under active investigation. These approaches include targeting components of the innate immune system, such as thymic stromal lymphopoietin (TSLP) and IL-1 family cytokines; the adaptive immune system, including OX40-OX40L interactions and Th17- and Th22-related cytokines; and mechanisms associated with pruritus, such as IL-31, histamine receptors, and neurokinin 1 receptor. Emerging insights underscore the transformative potential of personalized therapeutic regimens tailored to the distinct endotypes and severity of AD. Advances in deciphering the pathogenesis of AD are unlocking unprecedented opportunities for precision medicine, offering renewed hope for improved outcomes in this multifaceted and heterogeneous condition. Full article

Eosinophils are increasingly recognized as adaptable immune cells that exhibit diverse phenotypes and effector functions across different tissues and disease states. While they can induce pathology through degranulation and cytotoxic mediator release, eosinophils also fulfill regulatory and tissue repair roles. Advances in single-cell and spatial technologies have begun to reveal how microenvironmental cues (including cytokines, chemokines, and cell–cell interactions) shape eosinophil behavior in health and disease. These insights are critical for understanding why certain patients respond variably to therapies targeting eosinophils and related type 2 pathways. By dissecting eosinophil heterogeneity in real human tissues, researchers may identify new biomarkers, refine endotyping approaches, and develop more precise therapeutic strategies. This review summarizes emerging concepts of eosinophil biology in inflammatory conditions, highlights the impact of spatial context on eosinophil functions, and discusses the future of advanced phenotyping in guiding personalized treatments. Full article

Chronic rhinosinusitis (CRS) is a persistent inflammatory condition of the sinus mucosa characterized by significant tissue remodeling. This study aimed to evaluate the gene expression of extracellular matrix (ECM) proteins, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) in post-operative tissues of CRS patients. A total of 30 patients diagnosed with CRS, divided into CRSwNP (with nasal polyps) and CRSsNP (without nasal polyps) groups, were compared with a control group of 10 individuals undergoing nasal surgeries for non-CRS conditions. Gene expression analysis was conducted using quantitative real-time PCR, and plasma cytokine levels were measured via ELISA. Results indicated significantly higher expression of collagen I, collagen III, fibronectin, vimentin, periostin, and tenascin C in CRS tissues, especially in CRSsNP patients. Conversely, elastin expression was markedly lower. MMP-2, MMP-9, TIMP-1, and TIMP-2 expression was significantly altered, with CRSsNP showing lower levels compared to CRSwNP and controls. TGF-β1 expression was elevated in both CRS groups, particularly in CRSsNP, highlighting its role in fibrosis and ECM remodeling. Additionally, increased plasma concentrations of TSLP and TGF-β1 suggest epithelial activation and immune dysregulation in CRS. These findings underscore distinct remodeling profiles in CRS endotypes, emphasizing the need for targeted therapeutic strategies based on molecular phenotyping. Understanding ECM dysregulation and inflammatory pathways in CRS may lead to improved, individualized treatment approaches. Full article

Asthma is a complex, multifactorial inflammatory disorder of the airways, characterized by recurrent symptoms and variable airflow obstruction. So far, two main asthma endotypes have been identified, type 2 (T2)-high or T2-low, based on the underlying immunological mechanisms. Recently, extracellular vesicles (EVs), particularly exosomes, have gained increasing attention due to their pivotal role in intercellular communication and distal signaling modulation. In the context of asthma pathobiology, an increasing amount of experimental evidence suggests that EVs secreted by eosinophils, mast cells, dendritic cells, T cells, neutrophils, macrophages, and epithelial cells contribute to disease modulation. This review explores the role of EVs in profiling the molecular signatures of T2-high and T2-low asthma, offering novel perspectives on disease mechanisms and potential therapeutic targets. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant implications for patient quality of life and a well-documented association with the atopic march. Recent advancements in biomarker research have unveiled critical insights into AD pathogenesis, diagnosis, prognosis, and therapeutic monitoring. This comprehensive review evaluates the utility of emerging biomarkers, including cytokines, chemokines, genetic markers, and microbiome-related components, in understanding the disease mechanisms and stratifying patient care. The role of minimally invasive diagnostic techniques, such as tape stripping and RNA monitoring, is highlighted, offering innovative approaches to pediatric populations. Furthermore, this review explores the biomarkers that predict disease progression, therapeutic response, and comorbidities, including food allergies and asthma. Personalized treatment strategies based on endotype-specific biomarkers are discussed as a future direction for improving clinical outcomes. Despite promising findings, the integration of biomarkers into routine practice necessitates further validation through large-scale studies. This work underscores the transformative potential of biomarker-driven approaches in enhancing the management of AD in children and its associated conditions. Full article

Severe asthma (SA) is a chronic inflammatory condition affecting approximately 10% of asthmatic patients, and eosinophils are considered key pathogenetic actors in a significant number of patients. Biological therapies have been demonstrated to improve asthma control by decreasing exacerbation rates and reducing the use of oral corticosteroids. In this context, phenotyping and endotyping patients with SA is essential for selecting the most effective therapeutic approach. For this purpose, biomarkers such as IgE, absolute blood eosinophil count, and fractional exhaled nitric oxide (FeNO) are crucial in defining a patient’s inflammatory profile. Their integration provides a framework for classifying asthma into T2-high, T2-mild, or T2-low categories, guiding personalized treatment strategies. By incorporating multiple biomarkers into a unified model, it is possible to better stratify patients and optimize biologic therapy selection, paving the way for improved outcomes in SA management. This review aims to evaluate the role of phenotyping and endotyping SA patients, with particular attention to the impact of eosinophilic inflammation and combinatory biomarkers on decision-making processes for the selection of biological therapies. Full article

Asthma is a chronic inflammatory lung disease with high prevalence, making it one of the most common chronic conditions worldwide. Its pathophysiology is influenced by a range of genetic and environmental factors, resulting in a complex and heterogeneous disease profile. Asthma is primarily associated with a type 2 (T2) immune response, though non-T2 endotypes also contribute to disease pathology. Generally, asthma is characterized by the infiltration and activation of various cell types, including dendritic cells, eosinophils, innate lymphoid cells, lymphocytes, mast cells, and neutrophils, which participate in T1, T2, and T17 immune responses. Despite advances in understanding, many questions remain unresolved. Therefore, emerging omic techniques, such as single-cell RNA sequencing (scRNA-seq), offer novel insights into the underlying mechanisms of asthma and the roles of these immune cells. Recent scRNA-seq studies in asthma have identified multiple novel immune cell subtypes and clusters, suggesting their potential functions in disease pathology. The rapid advancement of scRNA-seq technology now enables in-depth investigation of individual cells within tissues, allowing for precise cell-type classification and detailed molecular profiling. Nonetheless, certain limitations persist, which require further refinement in future studies. Full article