Search Results (101)

Background and Objectives: Chronic rhinosinusitis (CRS) frequently recurs following endoscopic sinus surgery (ESS), yet reported recurrence rates, risk factors, and treatment responses differ significantly across regions. This review aims to synthesize current evidence on recurrence patterns, predictive models, and treatment strategies, with a focus on comparing Asian and Western populations. Materials and Methods: A structured narrative review was conducted by searching PubMed, Embase, and Cochrane Library from January 2010 to June 2025. A total of 116 studies were included based on predefined criteria regarding recurrence definitions, risk factors, prediction models, and postoperative management. Results: Recurrence rates ranged from 12% to 76.6%, with wide variability attributed to differences in follow-up duration and recurrence definitions. Key risk factors included tissue eosinophilia, comorbid asthma, and type 2 inflammation. Asian predictive models emphasized inflammatory biomarkers such as tissue and blood eosinophils, whereas Western models incorporated imaging, prior surgical history, and symptom burden. While biologics are widely used in the West, their adoption remains limited in Asia, where endotype-driven corticosteroid strategies are predominant. Conclusions: CRS recurrence after ESS is influenced by inflammatory endotypes, comorbidities, and regional treatment paradigms. Cross-regional differences in immune profiles and healthcare access necessitate the development of standardized definitions and validated, endotype-driven prediction tools. Tailored treatment strategies, especially for non-type 2 CRS, are essential to achieving equitable and effective care globally. Full article

Background: Distinguishing chronic obstructive pulmonary disease (COPD) from asthma–COPD overlap (ACO) remains challenging due to shared clinical and inflammatory features. Interleukin-13 (IL-13) is implicated in airway inflammation and remodeling and may represent a potential treatable trait. This study aimed to evaluate whether serum IL-13 could differentiate between COPD and ACO or define ACO subtypes and to explore its relationship with clinical and phenotype parameters. Materials and Methods: We conducted a cross-sectional bicentric study in 215 COPD and ACO patients recruited from outpatient clinics. The study measured blood IL-13 levels in COPD vs. ACO patients, across five ACO subtypes, and evaluated IL-13’s ability to predict ACO. Additionally, correlations were explored among endotype (IL-13) and different phenotype traits (e.g., fractional exhaled nitric oxide (FeNO), sputum eosinophilia, serum total immunoglobulin E (tIgE) levels, blood eosinophilia, and neutrophilia) and clinical outcomes (annualized exacerbation rate, symptom scores, and pulmonary function parameters). Results: No significant differences in IL-13 levels were found between COPD and ACO patients or among ACO subtypes. IL-13 did not predict ACO occurrence. We observed a weak correlation between IL-13 and tIgE levels in the entire cohort. Additionally, there was a weak correlation between IL-13 and FeNO in patients with eosinophil counts exceeding 300 cells/μL, as well as between IL-13 and age in the COPD cohort. No correlation was found between IL-13 and other phenotypic features or clinical outcomes in the overall cohort, including within both COPD and ACO groups. Conclusions: IL-13 cannot differentiate between COPD and ACO or ACO’s subtypes. Full article

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome with multiple clinical and inflammatory phenotypes. The coexistence of bronchiectasis, known as bronchiectasis–COPD overlap (BCO), identifies a subgroup with increased morbidity and mortality. Non-invasive breath analysis using electronic noses (e-noses) has shown promise in identifying disease-specific volatile organic compound (VOC) patterns (“breathprints”). Our aim was to evaluate the ability of an e-nose to differentiate between COPD and BCO patients, and to assess its utility in detecting inflammatory endotypes (neutrophilic vs. eosinophilic). In a monocentric, prospective, real-life study, 98 patients were enrolled over nine months. Forty-two patients had radiologically confirmed BCO, while fifty-six had COPD without bronchiectasis. Exhaled breath samples were analyzed using the Cyranose 320 e-nose. Principal component analysis (PCA) and discriminant analysis were used to identify group-specific breathprints and inflammatory profiles. PCA revealed significant breathprint differences between BCO and COPD (p = 0.021). Discriminant analysis yielded an overall accuracy of 69.6% (AUC 0.768, p = 0.037). The highest classification performance (76.8%) was achieved when distinguishing eosinophilic COPD from neutrophilic BCO. These findings suggest distinct inflammatory profiles that may be captured non-invasively. E-nose technology holds potential for the non-invasive endotyping of COPD, especially in identifying neutrophilic BCO as a unique inflammatory entity. Breathomics may support early, personalized treatment strategies. Full article

Introduction: Pathophysiological pathways—or endotypes—leading to prematurity can be clustered into two groups: infection/inflammation and dysfunctional placentation. We aimed to perform a systematic review and meta-analysis of studies exploring the association between these endotypes and cystic periventricular leukomalacia (cPVL). Methods: PubMed and Embase were searched for observational studies examining preterm infants and reporting data on the association between endotype of prematurity and cPVL. Chorioamnionitis represented the infectious–inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDPs) and small for gestational age (SGA)/intrauterine growth restriction (IUGR). Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF₁₀ is the ratio of the probability of the data under the alternative hypothesis (H_1; presence of association) over the probability of the data under the null hypothesis (H_0; absence of association). Results: Of 1141 potentially relevant studies; 67 (108,571 infants) were included. The BMA analysis showed strong evidence in favor of a positive association between chorioamnionitis and cPVL (OR 1.58; 95% CrI 1.12 to 2.20; BF₁₀ = 20.5) and extreme evidence in favor of a negative association between HDPs and cPVL (OR 0.63; 95% CrI 0.54 to 0.75; BF₁₀ = 2937). The evidence for the SGA/IUGR group was inconclusive (OR 0.87; 95% CrI 0.75 to 1.01; BF₁₀ = 1.41). Conclusions: This Bayesian meta-analysis provides evidence indicative of an association between antenatal infection–inflammation and an increased risk of developing cPVL in preterm infants. Conversely, infants exposed to HDPs are less likely to develop cPVL. 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

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

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