Search Results (521)

Asthma represents a chronic inflammatory condition of the respiratory tract, where long-term bronchial inflammation serves as a primary driver of progressive airway remodeling. This complex pathology emerges from the intricate synergy between host genetic susceptibility and diverse environmental triggers, ultimately impairing pulmonary function. At the cellular level, asthmatic responses are orchestrated by a dynamic crosstalk among various immune and structural populations, including airway epithelial cells, T-lymphocytes, eosinophils, and mast cells, which collectively perpetuate the inflammatory milieu. Although inhaled corticosteroids are the conventional cornerstone of therapy, their clinical application is frequently hindered by potential systemic toxicity and the emergence of steroid-resistant phenotypes. Consequently, botanical extracts derived from both aerial and underground plant organs have gained attention as versatile multi-target candidates capable of modulating the multifaceted pathophysiological networks of asthma. This scoping review critically synthesizes the pharmacological efficacy of these plant-based interventions in regulating pivotal signaling cascades, such as MAPK, NF-κB, STAT3/6, and GATA3. Based on a systematic literature search covering the period from 2005 to 2025, this study provides a focused quantitative analysis of preclinical literature from the last decade (2016–2025) to evaluate the in vitro and in vivo models employed to validate these therapeutic effects. The assessment reveals that the vast majority of current research continues to rely on crude botanical preparations, with only a limited subset of studies utilizing enriched fractions or fully characterized isolated compounds. This predominance of unrefined extracts underscores a significant gap in chemical standardization and highlights the necessity for more rigorous mechanistic validation. Ultimately, this paper outlines strategic pathways for translating preclinical findings into clinical practice, offering a robust framework for the development of standardized plant-derived interventions in asthma management. Full article

Background: Asthma is a heterogeneous chronic airway disease characterized by inflammation, airflow obstruction, hyperresponsiveness, and remodeling. Severe eosinophilic asthma is driven by eosinophilic inflammation, which contributes to tissue damage, recurrent exacerbations, and progressive impairment of airway structure and function. Eosinophils play a central role through the release of cytokines, cytotoxic granule proteins, and extracellular traps, and their persistence in the airways is sustained by type 2 inflammatory pathways, particularly interleukin-5-mediated signaling. A better understanding of eosinophil biology has promoted the development of targeted therapies, including anti-interleukin-5/interleukin-5 receptor agents and biologics that indirectly modulate eosinophilic inflammation, such as anti-interleukin-4 receptor alpha and anti-thymic stromal lymphopoietin antibodies. Aim: This narrative review summarizes the immunopathology of eosinophilic asthma and links eosinophil biology to current and emerging pharmacological strategies. We discuss biologics that directly target the IL-5/IL-5 receptor axis, as well as agents that indirectly modulate eosinophilic inflammation, including IL-4 receptor alpha and TSLP blockade. We also review the clinical positioning of available biologics, focusing on blood eosinophils, FeNO, exacerbation history, oral corticosteroid exposure, lung function, type 2 comorbidities, treatment response, remission and switching. Conclusions: Overall, eosinophilic inflammation remains a central therapeutic target and a key component of precision medicine in severe asthma, but biologic selection should be individualized and reassessed through multidomain clinical outcomes. Full article

Multiple interacting risk factors can influence the origin of asthma. Asthma is characterized by different clinical phenotypes, each of which includes different endotypes. There are four main clinical asthma phenotypes: (1) early-onset mild allergic asthma; (2) early-onset allergic moderate-to-severe remodeled asthma; (3) late-onset non-allergic eosinophilic asthma; and (4) late-onset non-eosinophilic non-allergic asthma. The main endotypes of asthma are T-helper (Th)-2 low and Th-2 high. The identification of asthma endotypes might help precision-based care move toward the personalized management of airway inflammation. In this scenario, it is important to know how the risk factors affect the pathophysiology of asthma. Accordingly, we focus our attention on the impact of obesity and air pollutants and how these risk factors together with epigenetic alterations influence the asthma phenotype/endotype and the pathogenesis of airway diseases. Our aim is to disseminate the progress of studies in this area by reporting recent observations on the topic. Finally, we believe that data/observations enclosed in this review suggest the need of further epidemiological studies to be useful to examine simultaneously the effect of more than one risk factor on clinical and biologic parameters of asthma. Full article

With the introduction of biologic therapies for severe asthma, clinical remission has gained increasing relevance as a therapeutic goal; however, real-world data and validated predictors remain limited. We conducted a retrospective real-life study including 75 adults with severe asthma treated with mepolizumab, benralizumab, or dupilumab between October 2023 and September 2025. Clinical remission at 12 months was defined according to the multidimensional framework proposed by Menzies-Gow, requiring absence of oral corticosteroid use and exacerbations, ACT score > 20, and FEV₁ > 80% predicted. Baseline clinical, functional, and biomarker variables were analyzed using bivariate tests and multivariable logistic regression with internal bootstrap validation. At 12 months, 37 of 75 patients (49.3%) achieved clinical remission. Peripheral eosinophilia ≥ 500 cells/µL, higher baseline FEV₁, and the presence of gastroesophageal reflux disease were independently associated with remission, whereas age, body mass index, and grass pollen sensitization were not significant. The final model showed good discrimination and adequate calibration. In this monocentric real-life cohort, biologic therapy was associated with clinical remission in approximately half of patients, and selected baseline characteristics identified individuals with a higher probability of remission, warranting validation in larger multicenter studies. Full article

Asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are major non-communicable respiratory diseases (NCD-RDs) with high morbidity and mortality. Despite distinct clinical features, they share overlapping mechanisms including oxidative stress, epithelial injury, and immune dysregulation. Asthma is mainly driven by type 2 inflammation, with IL-4, IL-5, and IL-13 inducing eosinophilia, IgE production, mucus hypersecretion, and airway remodeling. Biologics targeting IgE, IL-5, and IL-4Rα have transformed treatment, and agents directed against TSLP and IL-33 further extend the range of targeted interventions. In contrast, COPD involves chronic inflammation with macrophages, neutrophils, and CD8+ T cells, persisting after smoking cessation. Advances include biologics such as dupilumab and benralizumab in eosinophilic COPD, and novel inhaled therapies such as ensifentrine, the first dual PDE3/4 inhibitor delivered via inhalation. IPF, on the other hand, arises from defective epithelial repair and fibroblast activation, causing progressive fibrosis. Approved antifibrotics (nintedanib, pirfenidone) slow lung function decline, while new strategies target TGF-β, CTGF, and fibroblast-directed pathways. Across these diseases, biomarkers and the treatable traits framework are reshaping precision care. Personalized approaches integrating biomarkers, omics, and targeted therapies represent the most promising path for improved outcomes. Full article

Background: Diets composed of various components have been shown to influence inflammatory diseases such as asthma. While most studies have focused on fiber-rich diets to investigate their effects on the immune system and, consequently, on asthma, little is known about the impact of sugar-rich diets, particularly when such diets are consumed over short periods of time. Methods: To investigate the short-term effects of a sugar-rich diet on allergic airway inflammation, A/J mice were fed either a standard diet or a sugar-enriched diet and subsequently sensitized and challenged with ovalbumin or PBS. Airway inflammation was assessed by bronchoalveolar lavage (BAL) cell analysis, including eosinophil counts and cytokine levels (IL-4, TNF-α, IL-33), and by lung histology (H&E for inflammatory infiltrate and PAS for mucus). Serum IgE levels were also measured. In addition, glucose tolerance, visceral and subcutaneous adipose tissue mass, and inflammatory markers in visceral adipose tissue were evaluated. Results: Short-term consumption of a sugar-rich diet induced glucose intolerance and expansion of adipose tissue, particularly visceral fat, independent of ovalbumin sensitization. Gonadal adipose tissue analysis revealed a shift toward M1 macrophage polarization, characterized by elevated TNF-α, IL-6, and IL-1β, increased leptin levels, and reduced adiponectin. In OVA-sensitized mice, the sugar-rich diet significantly exacerbated eosinophil infiltration in BAL, increased IL-4, TNF-α, and IL-33, and enhanced PAS-positive mucus accumulation and inflammatory infiltrates in the lung. Moreover, total serum IgE was significantly higher in allergic mice fed the sugar-rich diet compared with allergic mice on the standard diet. Importantly, in non-sensitized mice fed the sugar-rich diet, no pulmonary inflammation was detected by BAL, demonstrating that HSD alone does not induce asthma but amplifies allergic responses when sensitization is present. Conclusions: Our findings demonstrate that short-term consumption of a sugar-rich diet is sufficient to exacerbate, but not initiate, allergic pulmonary inflammation. From a translational perspective, reducing dietary sugar intake may represent a valuable adjuvant strategy in the management of allergic asthma. Full article

Interleukin-5 (IL-5) has long been positioned as a lineage-restricted cytokine primarily responsible for eosinophil differentiation and survival. However, emerging mechanistic and clinical evidence supports a broader conceptual shift: IL-5 should no longer be viewed solely as an eosinophil growth factor, but as a context-dependent regulator embedded within dynamic airway immune networks. Drawing on advances in eosinophil subset biology, receptor signaling, and tissue-level immune crosstalk, this review reframes IL-5 biology through the lens of systems-level inflammatory regulation across airway and systemic eosinophilic diseases. Recent data reveal functional heterogeneity between resident and inflammatory eosinophil subsets, challenging the assumption that blood eosinophilia uniformly reflects pathogenic activity. In parallel, functional IL-5 receptor expression has been identified on multiple structural and immune cell populations—including epithelial cells, mast cells, plasma cells, basophils, neutrophils, and fibroblasts—supporting a broader tissue-signaling paradigm. Experimental and translational studies further link IL-5 to epithelial integrity, airway remodeling, and mucus pathology, suggesting structural and network-level effects beyond simple eosinophil depletion. Comparative analyses across asthma, chronic rhinosinusitis with nasal polyps, and COPD demonstrate that eosinophilic inflammation is biologically heterogeneous and context-dependent. While IL-5-targeted therapies yield consistent benefit in severe asthma, therapeutic responses in other airway diseases appear to be shaped by local tissue architecture and mixed inflammatory programs. Together, these observations illustrate a paradigm shift from pathway-specific inhibition toward network-informed disease control and highlight key areas for future mechanistic investigation. Full article

Eosinophils are multifunctional granulocytes that reside constitutively within mucosal tissues, where they engage in bidirectional communication with the epithelial cells lining the respiratory and gastrointestinal (GI) tracts. Once regarded solely as terminal effectors of the type 2 immunity, eosinophils are now recognized as key regulators of epithelial homeostasis and barrier integrity. Epithelial cells initiate crosstalk by releasing the alarm cytokines such as interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25, which drive eosinophil recruitment, activation, and tissue retention. Conversely, eosinophils modulate epithelial function through the release of granule proteins, cytokines, and growth factors with both damaging and reparative consequences. In the airway, this crosstalk underpins the pathogenesis of eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), in part via eosinophil-derived mediators that disrupt tight junction integrity and fuel remodeling. In the GI tract, homeostatic eosinophils support villous architecture, epithelial turnover, and goblet cell differentiation through microbiota-driven IL-33 signals and neuropeptide-mediated neuroimmune pathways, whereas dysregulated crosstalk promotes eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD). This review synthesizes recent research to delineate the molecular mechanisms of eosinophil–epithelial crosstalk across mucosal compartments, highlight tissue-specific differences and shared mechanistic themes, and discuss the implications of these findings for targeted therapy. Full article

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg–Strauss syndrome, is a rare necrotizing vasculitis characterized by asthma, eosinophilia, and systemic granulomatosis vasculitis. Perioperative risk is primarily driven by airway hyperreactivity, potential cardiac disease, chronic immunosuppressive therapy, and reported alterations in plasma cholinesterase activity. Evidence specifically addressing anesthetic management remains scarce and largely limited to case-based reports. Methods: A focused narrative review was conducted by searching MEDLINE (via PubMed), Scopus, and Embase from inception to January 2026 for publications reporting perioperative anesthetic management in patients with EGPA/Churg–Strauss syndrome. Case reports and case-based descriptions providing explicit anesthetic details were qualitatively synthesized. Results: Available evidence consists predominantly of isolated case reports across heterogeneous surgical settings, including ENT, abdominal, orthopedic, ambulatory, pediatric, and rare cardiac procedures. Recurring perioperative principles include optimization of bronchial disease and continuation of inhaled therapy; minimization of airway stimulation and avoidance of histamine-releasing drugs; selection of induction agents preserving hemodynamic stability in the presence of myocardial involvement; preference for non-depolarizing neuromuscular blockade with quantitative monitoring (and consideration for sugammadex when appropriate); individualized corticosteroid management and multimodal, opioid-sparing analgesia, often supported by regional techniques. Conclusions: In the absence of dedicated perioperative guidelines, anesthetic care for EGPA should be individualized based on clinical phenotype and organ involvement. A structured approach targeting airway protection, cardiovascular stability, safe neuromuscular management, and opioid-sparing analgesia may represent a pragmatic risk-mitigation framework. These considerations are illustrated by an institutional experience in mitral valve surgery. Full article

Background/Objectives: The prevalence of allergic diseases has markedly increased in developed countries, with environmental and dietary factors considered important contributors. Folic acid is an essential micronutrient involved in one-carbon metabolism and DNA methylation, playing a key role in epigenetic regulation of immune function. Both high and low folate exposure have been associated with allergic outcomes, but the data on postnatal folate status in paediatric populations remain limited. This study aimed at assessing serum folate status in children with atopic diseases compared with children without chronic allergic disease in Croatia. Methods: This cross-sectional study included 292 paediatric patients from the University Hospital in Split and a paediatric primary care practice between January 2024 and January 2025. Serum folic acid concentrations were measured using electrochemiluminescence immunoassay. Additional laboratory parameters included vitamin B12, total IgE levels, and eosinophil counts. Demographic and clinical data were obtained from medical records. Statistical analyses included Chi-square tests, Mann–Whitney U tests, linear regression modelling, and analysis of covariance with statistical significance set at p < 0.05. Results: Folic acid deficiency was present in 66.4% of all participants. Children with atopic diseases were significantly more likely to have folate deficiency and had lower mean serum folate concentrations compared to children without allergic disease. There were no significant differences in folate levels between children with and without asthma. Lower folate levels were associated with higher IgE levels, higher eosinophil counts, and older age. When controlling for the effects of age on folic acid levels, the differences between participants with and without atopic diseases remained significant. Conclusions: Folic acid deficiency is highly prevalent among children in the Mediterranean region of Croatia and is significantly associated with atopic diseases and markers of allergic inflammation. These findings highlight a potential role of folate status in paediatric allergic disease and support the need for longitudinal studies to clarify causality and potential clinical implications. Full article

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns. Full article

Background: Airway mucus plugging is a key but long-overlooked mechanism of persistent airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Type 2 (T2) cytokines, particularly interleukin (IL)-4 and IL-13, drive goblet cell metaplasia, MUC5AC overexpression, and impaired mucociliary clearance, while eosinophil-derived products increase mucus viscosity and promote plug persistence. Methods: A comprehensive narrative review was conducted by searching PubMed and ClinicalTrials.gov databases from inception to February 2026. Search terms included “mucus plugs,” “mucus plugging,” “biologics,” “dupilumab,” “tezepelumab,” “mepolizumab,” “benralizumab,” “IL-4,” “IL-13,” “MUC5AC,” “quantitative CT,” “functional respiratory imaging,” “asthma,” and “COPD.” Studies were included if they reported original data or systematic evidence on mucus plug quantification, biologic-mediated changes in mucus plug scores, or imaging modalities for mucus assessment in asthma or COPD. Editorials, case reports with fewer than three patients, and studies not available in English were excluded. Two authors (P.-V.M. and A.C.) independently screened titles and abstracts; discrepancies were resolved by consensus. Randomized controlled trials, observational studies, and preclinical studies evaluating mucus plug outcomes and T2-targeted therapies were included. Reference lists of retrieved articles were hand-searched for additional relevant publications. Results: A recent systematic review identified multiple randomized controlled trials and observational studies that showed CT-assessed mucus plug scores go down with biologic therapies targeting the T2 pathway in asthma. Observational data extend this evidence to anti-IL-5/IL-5Rα agents. The VESTIGE trial provided the first functional respiratory imaging evidence of mucus plug resolution with dupilumab. In COPD, the BOREAS/NOTUS and MATINEE trials established the efficacy of dupilumab and mepolizumab in eosinophilic phenotypes; however, differences in inclusion criteria—particularly regarding FeNO thresholds and prior exacerbation burden—may explain divergent effects on lung function endpoints. Mucus plug outcomes have not been evaluated in COPD biologic trials. Quantitative imaging modalities, including HRCT mucus plug scoring, functional respiratory imaging, and hyperpolarized gas MRI, now enable objective assessment of mucus burden. Conclusions: Mucus plugging meets the definition of a treatable trait: it can be measured with CT scoring, it matters clinically, and it responds to T2 cytokine blockade. Adding mucus plug assessment to routine clinical evaluation, together with mucolytic strategies where needed, could move treatment decisions from empirical to biology-based across the asthma–COPD spectrum. Further studies are needed to confirm that mucus plug scoring works as a biomarker of treatment response in COPD and to test whether combining biologics with mucolytics improves outcomes. Full article

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

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

This study evaluated serum eosinophil cationic protein (ECP) as a biomarker for pediatric allergic airway diseases. A cross-sectional analysis was performed on children (1–17 years) with allergic asthma (AA, n = 124), allergic rhinitis (AR, n = 74), acute bronchitis (AB, n = 72), and healthy controls (HC, n = 58). Serum ECP, total IgE, eosinophil counts, allergen sensitization, and lung function were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, and correlations among biomarkers were examined. Compared with HC, serum ECP levels were significantly elevated across all disease groups (AA, AR, and AB), with a particularly marked difference observed between AA and AR patients (p < 0.0001). The combination of ECP and IgE significantly improved the diagnostic accuracy for AA (AUC = 0.9494) and AR (AUC = 0.9501). Higher ECP levels were associated with increased sensitization to specific inhalant allergens and impaired pulmonary function, particularly in small airway indices. Serum ECP reflects eosinophil-mediated airway inflammation and enhances diagnostic performance for pediatric AA and AR, supporting its role as an auxiliary biomarker in evaluating pediatric allergic airway diseases. Full article