Search Results (111)

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 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

Asthma has traditionally been viewed as a single disease, but recent research reveals its clinical and molecular complexity. This perspective highlights the need to shift from a traditional, uniform treatment paradigm to one that embraces the heterogeneity of asthma across individuals. Each patient presents a unique clinical story shaped by a complex interplay of genetic predispositions, developmental programming during critical early-life windows, the influence of sex and hormones, and lifelong environmental exposures. Asthma comprises multiple subtypes with distinct clinical and biological features. Furthermore, lifestyle factors such as obesity and smoking, along with highly prevalent comorbidities like allergic rhinitis and gastroesophageal reflux disease, significantly modify the disease’s course and response to treatment. This article explores how classifying the disease into clinical phenotypes (observable characteristics) and molecular endotypes (underlying mechanisms)—particularly the distinction between T2-high and T2-low inflammation—provides a crucial framework for managing this complexity. The application of this framework, guided by biomarkers, has enabled the development of targeted biologic therapies that can transform care for specific patient subgroups. Despite these advances, significant challenges remain. The pathophysiology of certain subgroups, particularly non-T2 asthma, remains poorly defined, and there is an urgent need for reliable predictive biomarkers to guide therapy and monitor outcomes. It is our opinion that future studies must adopt a systems-biology strategy, with a multi-omics approach that constructs a comprehensive molecular profile of each patient. This integrative methodology will require the use of advanced computational methods, including machine learning and artificial intelligence, to decipher the complex pathways linking genetic and environmental inputs to clinical disease. In conclusion, this article argues for a more personalized understanding of asthma, urging clinicians and researchers to consider each patient’s unique clinical presentation. 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

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

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

During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, concerns arose regarding the susceptibility of asthmatic children, one of the most common chronic conditions in childhood and a major cause of hospitalization in pediatric settings. Unexpectedly, evidences showed milder clinical courses and fewer asthma exacerbations in these patients, even if cases of critical and fatal infection, often related to specific clinical features of the patient, are not negligible. In this regard, obesity is considered not only an important comorbidity in patients with difficult-to-treat asthma but also a risk factor for more severe forms of COVID-19. These observations are of even greater concern in the context of an increase in childhood obesity that began even before the SARS-CoV-2 pandemic and has continued also as a consequence of it. Given asthma’s heterogeneity, especially in children, an endotype-based approach is crucial. This is possible through a detailed analysis of the complex metabolic pathways that correlate asthma, COVID-19 infection and obesity thanks to new high-through-put technologies, especially metabolomics, which with minimally invasive sampling, including on exhaled breath condensate (EBC), can provide precise and unbiased evidence in support of existing endotypes, making it possible to identify not only the most vulnerable individuals and thus risk stratification through specific biomarkers, but also new molecular and therapeutic targets. This review explores asthma endotypes by highlighting their shared immunometabolic pathways with COVID-19. Findings suggest that metabolomics could enable more accurate risk stratification and guide personalized interventions during viral pandemics, especially in the presence of relevant comorbidities such as obesity. Full article

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition classically associated with pulmonary emphysema and liver disease. However, the potential link between AATD and other respiratory diseases, particularly bronchial asthma, remains poorly understood and highly debated. This narrative review explores the current evidence regarding the epidemiological, clinical, and pathophysiological relationship between AATD and asthma. Data from prevalence studies show marked variability in the frequency of AATD-associated alleles among asthma patients, ranging from 2.9% to 25.4%, suggesting either a true association or selection biases. Conversely, asthma prevalence among AATD patients also varies widely, from 1.4% to 44.6%, with higher frequencies observed in countries with long-standing national registries. However, methodological inconsistencies and a lack of standardized diagnostic criteria limit the interpretation of these findings. Current evidence is insufficient to support a direct causal role for AATD mutations in asthma development, and no clear impact of AATD on asthma severity or prognosis has been established. Furthermore, there is no conclusive evidence that augmentation therapy is beneficial in asthma patients carrying AATD mutations. Despite these uncertainties, screening for AATD in selected asthma populations—especially those with severe or atypical phenotypes—may be warranted, as recommended by major respiratory societies. Future research should focus on large, well-powered, prospective studies that evaluate the potential pathophysiological interactions between AATD and specific asthma endotypes, particularly T2-low asthma. These efforts may help clarify the relevance of AATD mutations in asthma pathogenesis and identify potential therapeutic targets. Full article

Background: Asthma is a heterogeneous disease characterized by variable bronchial obstruction, hyper-responsiveness, and inflammation. Evaluating the immunological changes following pneumococcal immunization in patients with different asthma endotypes is of great importance. This study aimed to evaluate the effects of PCV13 on the clinical parameters and the changes over time in the levels of the main cytokines in asthma patients. Methods: This was a single-center, open-label, non-randomized, prospective, cohort, controlled study of 31 patients aged 18 to 80 with a known diagnosis of asthma. The study subjects were given one injection of PCV13. Their clinical parameters and serum concentrations of certain Th1/Th2/Treg cytokines were assessed over a year following the vaccination. Results: Compared to the pre-vaccination period, there was an 81.5% reduction in the number of patients with asthma exacerbations (p < 0.001), a 76.5% increase in the number of patients free from hospitalization (p < 0.001), and an improvement in the level of asthma control. Positive changes were observed both in patients with T2-high and T2-low asthma; however, only those with T2-low asthma showed a significant improvement in the level of asthma control. Significant changes were reported for IFN-γ: its serum concentrations increased six weeks following the vaccination (p < 0.05), primarily in patients with T2-high asthma. Conclusions: In asthma patients, immunization with PCV13 was clinically effective, irrespective of the asthma endotype. Its clinical effects were accompanied by a reduction in the rates of exacerbations and hospitalizations and an increase in IFN-γ serum levels. This finding suggests that this cytokine plays an important role in restoring immune response in asthma patients. 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

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are mutually correlated with Type-2 inflammation. Dupilumab is effective in uncontrolled and relapsing CRSwNP. However, the precise characterization of Type-2 inflammation and the impact of previous surgery on clinical outcomes need clarification. Methods: We present a prospective observational study on a 38 CRSwNP-patient cohort, whose Type-2 endotype was confirmed after a multidisciplinary approach shared among ENTs, pneumologists and allergologists. Patients were treated with dupilumab and evaluated at 15 days and 1-3-6-12-18-24-30 months, focusing on clinical (VAS, nasal polyp score—NPS), radiological (Lund-Mackay) and quality of life (SNOT-22) parameters, as well olfactory function, asthma control, variation of Type-2 markers and number and extent (ACCESS score) of previous surgeries. Results: We confirmed the efficacy of dupilumab in total and sub-items VAS, NPS, SNOT-22 and sniffing score, as well as Lund–Mackay score improvements, observable and significant after 2 weeks of treatment (p < 0.0001) and long-lasting over 30 months. Good to excellent response criteria to biologic treatment at 6 months was observed in 30/32 patients. Comorbid asthma reached rapid control (p < 0.0001) and exhaled nitric oxide normalization was achieved. One single “not adequate” surgery showed a trend to milder improvement, as well as a higher ACCESS score to better olfactory outcome. Conclusions: The accurate selection of uncontrolled relapsing CRSwNP in terms of Type-2 endotyping by multidisciplinary approach can maximize dupilumab efficacy. The number and extent of previous surgeries may differentiate the response, although this effect is difficult to catch in real life. “Adequate” ESS surgery before dupilumab may drive mostly effective disease control. Full article

Hyperpolarized xenon-129 MRI (¹²⁹XeMRI) has emerged as a powerful tool in the identification, evaluation, and assessment of disease endotyping and in response to interventions for a myriad of pulmonary diseases. Growing investigative efforts ranging from basic science to application in translational research have employed ¹²⁹XeMRI in the evaluation of pulmonary conditions such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and cystic fibrosis (CF). The novel feature of ¹²⁹XeMRI is its ability to generate anatomic and physiologic readouts of the lung with resolution from the whole lung down to the lobar level. Additional advantages include being non-invasive and non-radioactive, and utilizing an inexpensive and ubiquitous noble gas as an inhalation contrast agent: xenon-129. In this review, we outline the clinical advances provided by ¹²⁹XeMRI among common pulmonary diseases with high healthcare burdens in recent decades. Full article