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Search Results (394)

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23 pages, 993 KB  
Review
Neutrophilic Asthma—From Mechanisms to New Perspectives of Therapy
by Ilona Iwaszko, Krzysztof Specjalski, Marta Chełmińska and Marek Niedoszytko
J. Clin. Med. 2025, 14(20), 7137; https://doi.org/10.3390/jcm14207137 - 10 Oct 2025
Viewed by 60
Abstract
Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from >40% to >76%) with low eosinophils (<2%). The prevalence of NA [...] Read more.
Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from >40% to >76%) with low eosinophils (<2%). The prevalence of NA ranges from 16% to 28% of the adult asthma population depending on the definitions and study methods applied. A clinical picture of NA is characterized by late onset of symptoms, higher exacerbation rate, lower level of symptoms control, and poorer response to steroids compared to eosinophilic phenotype. Comorbidities such as obesity and GERD as well as the influence of environmental factors (air pollution, smoking, bacterial infections) contribute to the development and severe course of the disease. NA is T2-low disease with predominantly Th1/Th17-type inflammation. Neutrophils are key cells responsible for initiating and sustaining inflammation. In addition to their primary functions like phagocytosis, degranulation, and NETosis, neutrophils release several pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF) and chemokines (CXCL-1, -2, -8, -9, -10) responsible for the recruitment of other neutrophils or T cells. Increasing knowledge about the biology of neutrophiles and their role in asthma results in new potential therapies that could improve control of NA, particularly new biologicals targeting Th1/Th17-related cytokines. In this review, we discuss the prevalence, mechanisms, and clinical features of neutrophilic asthma. Furthermore, current therapeutic options and some promising perspectives for the near future are presented. Full article
(This article belongs to the Special Issue Advances in Asthma: 2nd Edition)
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16 pages, 1095 KB  
Article
Inflammation-Based Cell Ratios Beyond White Blood Cell Count for Predicting Postimplantation Syndrome After EVAR and TEVAR
by Ebubekir Sönmez, İzatullah Jalalzai and Ümit Arslan
Int. J. Mol. Sci. 2025, 26(19), 9753; https://doi.org/10.3390/ijms26199753 - 7 Oct 2025
Viewed by 341
Abstract
Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the [...] Read more.
Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the systemic inflammatory response index (SIRI) and the eosinophil-to-lymphocyte ratio (ELR) can serve as preoperative predictors of PIS. Clinical data from 300 patients who underwent aortic endograft implantation and laboratory results obtained 24 h before the procedure, and at 24 h, 72 h, and 1 week postoperatively, were prospectively recorded. PIS was defined as culture-negative fever ≥ 37.8 °C accompanied by leukocytosis ≥ 12,000/µL. Inflammation-based indices derived from complete blood count (SIRI and ELR), along with serum C-reactive protein (CRP) and albumin levels, were compared between patients with and without PIS. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors. PIS developed in 55 patients (18.3%). Patients with PIS were younger (70.1 ± 8.6 vs. 72.7 ± 7.3 years; p = 0.042) and had larger aneurysm diameters and greater mural thrombus thickness. Preoperatively, leukocyte count, SIRI, and CRP levels were significantly higher in patients who developed PIS, whereas ELR and albumin levels were lower. Multivariable analysis showed that a larger aneurysm diameter (OR: 1.2; 95% CI: 1.0–1.3; p = 0.003), greater mural thrombus thickness (OR: 1.3; 95% CI: 1.0–1.6; p = 0.012), EVAR procedure (OR: 3.7; 95% CI: 1.2–6.3; p = 0.033), elevated SIRI (OR: 1.9; 95% CI: 1.2–3.1; p = 0.005), and higher CRP (OR: 1.4; 95% CI: 1.1–3.2; p = 0.003) were significantly associated with PIS. In contrast, increasing age, higher ELR, and higher albumin levels were associated with a reduced risk of PIS. Simple biomarkers routinely obtained from standard laboratory tests can contribute meaningfully to the preoperative prediction and postoperative identification of PIS. Their integration into risk stratification models and confirmation against definitive diagnostic criteria will require validation in larger, multicenter studies. Full article
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12 pages, 771 KB  
Review
Early Initiation of Biologic Therapies to Prevent Severe Asthma Progression
by Alessandra Tomasello, Alida Benfante, Stefania Principe and Nicola Scichilone
Medicina 2025, 61(10), 1797; https://doi.org/10.3390/medicina61101797 - 6 Oct 2025
Viewed by 459
Abstract
Asthma is a chronic inflammatory disease with a heterogeneous course, often progressing silently from mild symptoms to severe, treatment-refractory disease. Current guidelines recommend biologic therapies after failure of high-dose inhaled corticosteroids and additional controllers, typically in patients with frequent exacerbations. This reactive approach [...] Read more.
Asthma is a chronic inflammatory disease with a heterogeneous course, often progressing silently from mild symptoms to severe, treatment-refractory disease. Current guidelines recommend biologic therapies after failure of high-dose inhaled corticosteroids and additional controllers, typically in patients with frequent exacerbations. This reactive approach may delay intervention until irreversible airway remodeling has occurred, limiting the potential benefits of biologic therapy. Therefore, severe asthma may be envisioned as the consequence of missed opportunities for early interventions. Early initiation of biologic therapy—guided by biomarkers such as blood eosinophil count and fractional exhaled nitric oxide (FeNO), as well as symptom burden and risk of lung function decline—may prevent progression to severe asthma and improve remission rates. This position paper advocates for a shift from severity-based to risk-based treatment strategies, recommending earlier biomarker assessment, redefinition of escalation criteria, and clinical trials designed to evaluate biologics in symptomatic non-exacerbating patients. By recognizing persistent inflammation and progression risk earlier in the disease course, clinicians may have a critical opportunity to alter the trajectory of asthma, reduce long-term morbidity, and achieve sustained control before irreversible damage occurs. Full article
(This article belongs to the Special Issue Latest Advances in Asthma and COPD)
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16 pages, 3389 KB  
Article
Elevated Serum Levels of miRNA-155 in Children with Atopic Dermatitis: A Potential Biomarker of Disease
by Natalia Gołuchowska, Aldona Ząber, Sylwia Walczewska, Agata Będzichowska, Klaudia Brodaczewska, Aleksandra Majewska, Bolesław Kalicki and Agata Tomaszewska
Int. J. Mol. Sci. 2025, 26(19), 9689; https://doi.org/10.3390/ijms26199689 - 4 Oct 2025
Viewed by 275
Abstract
Atopic dermatitis (AD) is the most common inflammatory skin disease in the pediatric population. In recent years, the role of microRNAs in inflammatory and immunological mechanisms as specific biomarkers of AD has received growing attention. The aim of the present study was a [...] Read more.
Atopic dermatitis (AD) is the most common inflammatory skin disease in the pediatric population. In recent years, the role of microRNAs in inflammatory and immunological mechanisms as specific biomarkers of AD has received growing attention. The aim of the present study was a quantitative assessment of serum expression levels of miR-100, miR-224 and miR-155 in children with AD compared with healthy peers, and an analysis of their potential associations with clinical disease phenotype, severity of skin lesions (SCORAD), cytokine profile, immunological parameters and the presence of concomitant allergic diseases. The study included 12 children with AD and 9 healthy children. Selected miRNAs were isolated from serum, followed by reverse transcription using universal primers and quantification by qRT-PCR. Children with AD exhibited significantly higher expression levels of miR-155 compared with controls (p = 0.003). No statistically significant differences were observed for miR-100 and miR-224. miR-100 expression was significantly higher in children with a positive history of inhalant allergy compared with those without such a diagnosis (p = 0.014). A positive correlation was observed between miR-100 levels and the percentage of eosinophils (r = 0.599; p = 0.052) as well as absolute eosinophil count (r = 0.600; p = 0.051). MiR-155 is significantly upregulated in children with AD suggesting it as a candidate biomarker worthy of further investigation in larger cohorts. Although miR-100 did not differentiate the groups, its correlation with eosinophilia and inhalant allergy suggests a role in disease phenotyping. Full article
(This article belongs to the Special Issue Molecular Research on Skin Inflammation)
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9 pages, 228 KB  
Article
Low-Grade Inflammatory Hematological Markers in Otolaryngologic Diseases: A Preliminary Report
by María Aurora Maravilla-Domínguez, Beatriz Teresita Martín-Márquez, Flavio Sandoval-García, Verónica Adriana Montes-Varela, Nicté Selene Fajardo-Robledo, Fernanda Isadora Corona-Meraz and Soraya Amalí Zavaleta-Muñiz
Diseases 2025, 13(10), 328; https://doi.org/10.3390/diseases13100328 - 3 Oct 2025
Viewed by 155
Abstract
Background/Objectives: Complete blood count tests are inexpensive and widely available and may help identify low-grade inflammation in otolaryngologic (Ear, Nose and Throat, ENT) diseases, such as facial paralysis and hearing loss. This study aimed to describe the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio [...] Read more.
Background/Objectives: Complete blood count tests are inexpensive and widely available and may help identify low-grade inflammation in otolaryngologic (Ear, Nose and Throat, ENT) diseases, such as facial paralysis and hearing loss. This study aimed to describe the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), and lymphocyte-to-monocyte ratio (LMR) in ENT diseases and to provide preliminary evidence supporting further research. Methods: Data from 62 patients with ENT diseases were analyzed in a cross-sectional design. Results: The prevalence of ENT diseases was higher in women (63%) and adults (85.5%), highlighting vertigo, hearing loss, and septal deviation. Most marker values were within normal ranges; however, NLR values were elevated in patients with either septal deviation or vertigo, and ELR values were increased in cases of allergic or infectious rhinitis and sinusitis. In contrast, LMR values were at the lower normal limits in patients with septal deviation. Conclusions: These findings highlight the need for further studies to clarify the role of these biomarkers in chronic conditions and morphological alterations associated with ENT diseases, using more complex study designs. Full article
16 pages, 1641 KB  
Article
A Cost-Effective Screening Inflammation Indicator for Atopic Dermatitis Suitable for Primary Care and Self-Assessment
by Chengbin Ye, Xuyang Zhou and Ying Zou
Diagnostics 2025, 15(19), 2483; https://doi.org/10.3390/diagnostics15192483 - 28 Sep 2025
Viewed by 398
Abstract
Background/Objectives: Atopic dermatitis (AD), a chronic inflammatory skin condition, significantly impairs quality of life but remains underdiagnosed in primary care. Blood-cell-count-derived inflammatory indices are emerging as cost-effective biomarkers, but their pathological relevance to AD is limited and requires further discussion. Methods: [...] Read more.
Background/Objectives: Atopic dermatitis (AD), a chronic inflammatory skin condition, significantly impairs quality of life but remains underdiagnosed in primary care. Blood-cell-count-derived inflammatory indices are emerging as cost-effective biomarkers, but their pathological relevance to AD is limited and requires further discussion. Methods: We developed the Atopic Inflammation Index (AII), a novel blood-cell-based biomarker reflecting AD pathogenesis, and initially assessed its levels in AD patients and healthy controls using clinical samples from Shanghai, China. We then analyzed data from the NHANES (National Health and Nutrition Examination Survey) 2005–2006 cohort (n = 6855) to verify the AII-AD association and compared AII’s diagnostic performance with IgE and eosinophils. Results: Clinical analysis showed a nonlinear association between AII and AD severity. AII effectively distinguished AD patients (including mild cases) from healthy controls (p < 0.001) without elevation in psoriasis or urticaria, unlike eosinophils. In NHANES 2005–2006 (n = 720 AD cases, 10.5%), AII levels were higher in AD compared to non-AD patients (2.33 [1.39–4.09] vs. 2.03 [1.19–3.49], p = 0.007) and remained independently associated after adjustment (OR = 1.03, 95%CI = 1.01–1.04, p = 0.003), while IgE/eosinophils showed non-significant trends. Restricted cubic splines confirmed linear prediction (p = 0.006), and subgroup analyses supported consistency (P-interaction > 0.05). AII outperformed eosinophils (AUC:0.568 vs. 0.546, p = 0.025) with improved detection (sensitivity 0.361→0.614). Sensitivity analysis confirmed robustness after excluding medications, chronic diseases and adult populations. Conclusions: AII is stable and reliable in screening and diagnosing AD, offering a low-cost, practical solution for primary care. This verifies the feasibility of integrating existing detection indicators into new biomarkers, providing valuable inspiration for precision medicine research. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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12 pages, 270 KB  
Article
Association of Systemic Inflammation with Inflammatory mRNA Expression in Visceral Adipose Tissue in Gestational Diabetes
by Renata Saucedo, María Isabel Peña-Cano, Mary Flor Díaz-Velázquez, Alejandra Contreras-Ramos, Miranda Moleres-Orduña, Debbie López-Sánchez, Jorge Valencia-Ortega and Javier Pérez-Duran
Metabolites 2025, 15(10), 644; https://doi.org/10.3390/metabo15100644 - 26 Sep 2025
Viewed by 322
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) investigate whether whole blood counts, the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), serum adiponectin levels, and the mRNA expression of inflammatory genes (TLR2, TLR4, pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, anti-inflammatory cytokines: IL-1RA, IL-10, and adiponectin) in VAT are altered in women with GDM in comparison to pregnant women with normal glucose tolerance (NGT), and (2) determine the correlations between systemic and local VAT inflammation in all, GDM, and NGT women. Methods: Study of 50 GDM and 50 women with NGT with a cross-sectional design. Standard biochemical and hematological tests were conducted and relative mRNA expression in VAT was measured by RT-qPCR. Results: Women with GDM showed higher neutrophil, monocyte, NLR, MLR, and VAT TNF-α/IL-10 mRNA expression ratios while lymphocyte and eosinophil counts, serum adiponectin, and mRNA local VAT inflammatory markers such as TLR2, TLR4, IL-1β, IL-6, IL-1RA, and IL-10 were lower in women with GDM relative to women with NGT. Additionally, the circulating monocyte count were associated with TLR2 and TLR-4 VAT mRNA expression levels and eosinophils count were associated with IL-1β, IL-6, IL-10, and IL-1RA VAT expression levels in women with GDM. Conclusions: GDM is characterized by systemic inflammation, and some circulating immune cells, such as monocytes and eosinophils, are associated with the expression of inflammatory markers in VAT. Full article
13 pages, 781 KB  
Article
Retrospective Evaluation of Omalizumab Treatment Efficacy in Patients with Bullous Pemphigoid
by Nazlı Caf, Zafer Türkoğlu, Göknur Özaydın Yavuz, İrem Doğan, Sümeyye Nur Aydın, İkram Kevser Atilla and Hafize Uzun
J. Clin. Med. 2025, 14(18), 6382; https://doi.org/10.3390/jcm14186382 - 10 Sep 2025
Viewed by 401
Abstract
Background/Objectives: Bullous pemphigoid (BP) is a manageable condition, and the primary goal of treatment is to control the disease while minimizing the use of corticosteroids due to their potential side effects with long-term use. The primary aim of this study was to [...] Read more.
Background/Objectives: Bullous pemphigoid (BP) is a manageable condition, and the primary goal of treatment is to control the disease while minimizing the use of corticosteroids due to their potential side effects with long-term use. The primary aim of this study was to assess the effectiveness of omalizumab (OMZ) treatment in bullous pemphigoid patients using both objective and subjective indicators, including bullous pemphigoid disease area index (BPDAI) score, peripheral eosinophil count, serum total IgE level, systemic corticosteroid dosage, and pruritus severity (VAS pruritus). The secondary aim was to explore potential predictors of treatment response, such as baseline BPDAI, age, gender, lesion distribution, serum total IgE, peripheral eosinophil count, maximum and minimum corticosteroid dose, and comorbidities, as well as to evaluate the time to clinical response and corticosteroid tapering. Methods: This retrospective analysis included 25 BP patients treated with OMZ as add-on therapy to systemic corticosteroids between January 2023 and December 2024 at Health Sciences University, Başakşehir Çam and Sakura Training and Research Hospital, Dermatology and Venerology Clinic. No other systemic immunosuppressants were permitted. All patients were already receiving systemic corticosteroids at enrolment. This retrospective analysis included 25 BP patients receiving omalizumab (300 mg/4 weeks) as an add-on to systemic corticosteroids, initiated primarily for steroid-refractory disease and/or persistent, sleep-disrupting pruritus. Baseline was defined immediately before the first OMZ dose; assessments were performed at baseline and week 12. Clinical (BPDAI, VAS pruritus) and laboratory (eosinophil count, total IgE levels) parameters were assessed at baseline and week 12. Results: OMZ treatment significantly reduced disease severity, as evidenced by a mean decrease in the BPDAI score of 105.0 ± 48.9 (95% CI 84.8–125.2) compared to baseline (p < 0.001). Peripheral eosinophil count also decreased by 0.6 ± 0.3 (95% CI 0.4–0.7) after treatment (p < 0.001). Total serum IgE levels declined significantly in 92% of patients (95% CI 244.5–2171.3) compared to pretreatment (p < 0.001), although two patients (8%) showed an increase (202.0 ± 258.8) after OMZ treatment. OMZ treatment led to a mean systemic corticosteroid dose reduction of 37.0 ± 14.1 mg (95% CI 31.1–42.8 mg), with a median corticosteroid tapering time of 4 weeks (3.0–4.0). Additionally, pruritus severity, measured by pruritus VAS, decreased by 6.2 ± 1.4 (95% CI 5.6–6.7) following treatment (p < 0.001). OMZ was well tolerated, with no serious adverse events. Conclusions: Within a 12-week observation window, we observed improvements in disease activity and pruritus alongside reduced corticosteroid exposure. Given the retrospective, uncontrolled add-on design, these findings do not establish causality but support further prospective controlled evaluation of omalizumab as a steroid-sparing option. Importantly, OMZ treatment significantly reduced the mean corticosteroid dose, pruritus VAS score, total IgE levels, and eosinophil count, indicating therapeutic activity and supporting its use as an effective steroid-sparing option in the management of bullous pemphigoid. Full article
(This article belongs to the Section Dermatology)
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12 pages, 795 KB  
Article
Safety and Effectiveness of Dupilumab in Atopic Dermatitis Patients with Hematologic Comorbidities: A Multicenter, Retrospective Study
by Luca Bettolini, Stefano Bighetti, Silvia Mariel Ferrucci, Angelo Valerio Marzano, Francesca Barei, Alessandra Narcisi, Matteo Bianco, Andrea Carugno, Nicola Zerbinati, Simone Ribero, Michela Ortoncelli, Elena Pezzolo, Maddalena Napolitano, Martina Maurelli, Giampiero Girolomoni, Zeno Fratton, Enzo Errichetti, Caterina Foti, Giacomo Dal Bello, Ilaria Trave, Anna Balato, Dario Didona, Niccolò Gori, Federica Veronese, Giovanni Paolino, Franco Rongioletti, Mario Bruno Guanti, Laura Calabrese, Riccardo Balestri, Manfredo Bruni and Mariateresa Rossiadd Show full author list remove Hide full author list
Antibodies 2025, 14(3), 75; https://doi.org/10.3390/antib14030075 - 3 Sep 2025
Viewed by 1058
Abstract
Background: Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor α, is approved for moderate-to-severe atopic dermatitis (AD). However, its safety profile in patients with concomitant hematologic disorders remains unclear, as such populations were excluded from pivotal trials. Objective: To evaluate the safety and [...] Read more.
Background: Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor α, is approved for moderate-to-severe atopic dermatitis (AD). However, its safety profile in patients with concomitant hematologic disorders remains unclear, as such populations were excluded from pivotal trials. Objective: To evaluate the safety and effectiveness of dupilumab in adolescents and adults with AD and underlying hematologic comorbidities. Methods: This retrospective, multicenter study included 139 patients aged ≥15 years with moderate-to-severe AD and at least one hematologic disorder, treated with dupilumab across 21 dermatology centers. Data on disease severity, laboratory markers, and hematologic outcomes were collected over a median follow-up of 52 weeks (range 4–156). Results: The most common hematologic conditions included monoclonal gammopathies, leukemias, lymphomas, myeloproliferative neoplasms, and immune cytopenias. Clinical response to dupilumab was sustained across all endpoints, with median EASI scores decreasing from 26.0 at the baseline to 1.0 at week 52. NRS pruritus and sleep scores similarly declined to 0.0 by week 52. Serum IgE levels and eosinophil counts progressively decreased. The clinical response to dupilumab was sustained across all endpoints, with significant and progressive improvements in EASI, pruritus NRS, and sleep NRS observed up to week 52, followed by long-term stability through week 156. Serum IgE levels decreased steadily at all timepoints, while eosinophil counts declined after week 4 and stabilized beyond week 52. Hematologic conditions remained stable in 82.7% of patients, resolved in 16.5%, and progressed in only one case. Twelve patients (8.6%) received a new hematologic diagnosis during follow-up; no causal relationship could be established due to the retrospective design and absence of systematic screening, and these findings should be interpreted as descriptive associations only. Conclusions: Dupilumab appears to be safe and effective in AD patients with a broad range of hematologic comorbidities, including malignancies. These findings support its use in real-world settings, though prospective studies are warranted to further assess long-term safety in this population. Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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16 pages, 2426 KB  
Article
The Role of Interleukin-13 in Chronic Airway Diseases: A Cross-Sectional Study in COPD and Asthma–COPD Overlap
by Marina Perković, Vesna Vukičević Lazarević, Pavo Perković, Tomislav Perković, Vanja Dolenec, Ana Hađak, Vesna Šupak Smolčić and Ljiljana Bulat Kardum
Diseases 2025, 13(9), 287; https://doi.org/10.3390/diseases13090287 - 1 Sep 2025
Viewed by 531
Abstract
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 [...] Read more.
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
(This article belongs to the Section Respiratory Diseases)
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11 pages, 227 KB  
Article
Hematological Inflammatory Markers Across Neurodevelopmental Disorders: Preliminary Findings of an Observational Retrospective Study
by Raffaele Garotti, Maria Pia Riccio, Chiara Staffa, Mariangela Pezone and Carmela Bravaccio
Brain Sci. 2025, 15(9), 937; https://doi.org/10.3390/brainsci15090937 - 28 Aug 2025
Viewed by 541
Abstract
Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this [...] Read more.
Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p < 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder. Full article
19 pages, 2120 KB  
Article
Levels of Exhaled Fraction of Nitric Oxide (FeNO) and Type 2 Biomarkers in Individuals Naturally Exposed to Helminth Parasites in a Tropical Region
by Maria M. De Vivero, Randy Reina, Jonathan Ramírez, Josefina Zakzuk, Jose Miguel Escamilla Gil, Bayron Zelaya, Lucila Teresa Florez de Arco, Daniel P. Potaczek, Luis Caraballo and Nathalie Acevedo
Int. J. Mol. Sci. 2025, 26(17), 8344; https://doi.org/10.3390/ijms26178344 - 28 Aug 2025
Viewed by 664
Abstract
The exhaled fraction of nitric oxide (FeNO) is a biomarker of type 2 inflammation, reflecting the activity of inducible nitric oxide synthase (iNOS) in the bronchial epithelium in response to IL-4 and IL-13. Elevated FeNO levels support asthma diagnosis; however, it is unclear [...] Read more.
The exhaled fraction of nitric oxide (FeNO) is a biomarker of type 2 inflammation, reflecting the activity of inducible nitric oxide synthase (iNOS) in the bronchial epithelium in response to IL-4 and IL-13. Elevated FeNO levels support asthma diagnosis; however, it is unclear whether active helminth infections and rural environments influence this biomarker. The aim of this study was to compare FeNO levels among subjects naturally infected with helminth parasites and to evaluate their correlation with eosinophil counts and other inflammatory mediators. A total of 275 adult asthmatic patients and 161 healthy controls were involved; also, 223 asthmatic children and 114 healthy controls from the urban area of Cartagena were compared to 90 healthy children from a rural area. We found significant differences in FeNO levels between asthmatic patients and healthy controls in both adult and children’s cohorts (p < 0.0001). There was no difference in FeNO levels between Ascaris-positive and Ascaris-negative adults nor between subjects with active helminth infection and the non-infected. However, FeNO levels were significantly lower in rural healthy children (median 7.50 ppb, [IQR 4–14 ppb]) compared to urban healthy children (median 13.5 ppb, [IQR 10–18.5 ppb], p < 0.0001) and asthmatic children (median 20 ppb, [IQR 11–51 ppb], p < 0.0001). Rural healthy children had the highest total IgE levels (median 508 kU/L, [IQR 168–1020 kU/L]), high eosinophil counts (median 550 eos/μL, [IQR 360–800 eos/μL]) and plasma IL-5 levels (median 0.276 pg/mL, [IQR 0.19–0.53 pg/mL]). In conclusion, FeNO levels are not influenced by either natural exposure to helminth parasites or active infection, which supports its usefulness as a robust asthma biomarker in the tropics. Rural children have the lowest FeNO levels together with the highest total IgE levels, IL-5, and eosinophil counts, suggesting that lung-specific mechanisms are in place controlling iNOS expression during type 2 responses in healthy children. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Allergy and Asthma: 3rd Edition)
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20 pages, 347 KB  
Article
Site-Specific Inflammatory Signatures in Metastatic NSCLC: Insights from Routine Blood Count Parameters
by Vlad-Norin Vornicu, Alina-Gabriela Negru, Razvan Constantin Vonica, Andrei Alexandru Cosma, Sorin Saftescu, Mihaela Maria Pasca-Fenesan and Anca Maria Cimpean
Medicina 2025, 61(9), 1521; https://doi.org/10.3390/medicina61091521 - 25 Aug 2025
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Abstract
Background and Objectives: Systemic inflammatory markers from an ordinary complete blood count (CBC) may foreshadow where non-small-cell lung cancer (NSCLC) will first spread, but organ-specific signatures remain poorly defined. Materials and Methods: We retrospectively reviewed 302 adults (mean age 60.7 ± [...] Read more.
Background and Objectives: Systemic inflammatory markers from an ordinary complete blood count (CBC) may foreshadow where non-small-cell lung cancer (NSCLC) will first spread, but organ-specific signatures remain poorly defined. Materials and Methods: We retrospectively reviewed 302 adults (mean age 60.7 ± 13.4 years; 80.8% men) with stage IV NSCLC managed at OncoHelp Medical Center, Timișoara, between January 2022 and December 2024. Eligibility demanded a single radiologically confirmed distant site at diagnosis and pre-treatment CBC. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) ratios were compared across pleural (n = 52), bone (n = 86), liver (n = 66), and brain (n = 98) metastases using Kruskal–Wallis tests with Bonferroni adjustment; z-standardized logistic models identified independent predictors. Results: Metastases clustered most often in brain (32.5%), followed by bone (28.5%), liver (21.9%), and pleura (17.2%). Median PLR rose selectively in pleural disease (274 vs. 217–253 in other sites; p = 0.006). LMR fell to 2.0 in bone but climbed to 2.8 in brain lesions (p = 0.032 and 0.008, respectively). NLR was globally elevated (6.7–7.6), yet differed significantly only for bone and liver deposits. Logistic modeling showed that each standard-deviation rise in absolute neutrophil count quadrupled the odds of hepatic involvement (Odd Ratio (OR) 4.26; 99% Confidence inerval (CI) 2.20–6.25), monocytosis nearly doubled bone risk (OR 1.83; 1.01–3.33), while higher erythrocytes, eosinophils, and lymphocytes independently protected against pleural seeding (all p < 0.01). Age-stratified analysis revealed that osseous and cerebral metastases predominated in patients ≤ 50 years, whereas inflammatory indices were age-invariant. Conclusions: Routine CBC ratios encode distinct “inflammatory fingerprints” that mirror the first metastatic destination in NSCLC: platelets herald pleural spread, neutrophils favor liver and bone, and divergent lymphocyte–monocyte balances separate bone from brain. Although no substitute for cross-sectional imaging, these low-cost markers could refine clinical suspicion, guide targeted work-up, and illuminate the biology of organ-selective dissemination, particularly in resource-limited settings. Full article
(This article belongs to the Special Issue Insights and Advances in Cancer Biomarkers)
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10 pages, 272 KB  
Article
Blood Inflammatory Markers as Predictors of Effusion Characteristics and Postoperative Hearing Outcomes in Children with Otitis Media with Effusion: A Retrospective Study
by Amani Abdullah Almutairi, Ibrahim K. Aljabr, Zahra Saleh Alsindi, Amnah Ali Alkhawajah, Jinan Mohammed Aljasem, Mohammed Mousa Alzahrani and Abdullah Almaqhawi
Medicina 2025, 61(9), 1520; https://doi.org/10.3390/medicina61091520 - 25 Aug 2025
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Abstract
Background and Objectives: Otitis media with effusion (OME), frequently associated with obstructive adenoid hypertrophy (OAH), is a leading cause of paediatric hearing loss. Clinically distinguishing effusion types (serous vs. mucoid) and predicting postoperative hearing recovery are unresolved challenges. This study evaluated the [...] Read more.
Background and Objectives: Otitis media with effusion (OME), frequently associated with obstructive adenoid hypertrophy (OAH), is a leading cause of paediatric hearing loss. Clinically distinguishing effusion types (serous vs. mucoid) and predicting postoperative hearing recovery are unresolved challenges. This study evaluated the utility of preoperative blood inflammatory markers in predicting effusion characteristics and short-term hearing outcomes following adenoidectomy with tympanostomy tube (TT) insertion. Materials and Methods: In this retrospective cohort study, 232 children under 12 years old in 2024 and undergoing adenoidectomy (with or without TT insertion) were categorised into serous OME (n = 42), mucoid OME (n = 78), and non-effusion (n = 112) groups. Preoperative blood sample analyses assessed neutrophil, lymphocyte, eosinophil, basophil, and platelet counts, along with derived indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-basophil ratio (EBR), mean platelet volume (MPV), and systemic immune–inflammation index (SII). Hearing was evaluated at 2 weeks and 1 month postoperatively. Statistical analyses used SPSS v.28, with significance set at p < 0.05. Result: Mucoid OME patients exhibited significantly elevated neutrophil counts, platelet counts, eosinophils, NLR, and SII compared to those in serous OME and non-effusion groups (p < 0.05). All serous OME children achieved normal hearing by the first follow-up, whereas 15.4% of mucoid OME cases had transient mild hearing loss persisting after 2 weeks (p = 0.008; OR=15.97) but resolving by 1 month. Preoperative neutrophil count independently predicted delayed hearing recovery (p = 0.021). Conclusions: Systemic inflammatory markers, particularly neutrophil count, NLR, and SII, effectively differentiate mucoid OME from other effusion types and correlate with short-term hearing recovery. Neutrophil count may serve as a prognostic tool for surgical planning and patient counselling. Prospective studies are warranted to validate these findings in broader paediatric populations. Full article
(This article belongs to the Section Pediatrics)
16 pages, 2731 KB  
Article
BCL-2 Multi-Strain Probiotics for Immunomodulation In Vitro and In Vivo Alleviation of Atopic Dermatitis
by MinKyung Sung, Seongrok Sim, Ahyoung Lim, Jin Seok Moon, JongIk Jeon, Keon Heo, Woongkwon Kwak, Myeong Soo Park, Jungki Kwak, EunYoung Park and Seokmin Yoon
Microorganisms 2025, 13(8), 1950; https://doi.org/10.3390/microorganisms13081950 - 21 Aug 2025
Cited by 1 | Viewed by 961
Abstract
Atopic dermatitis (AD) is a chronic inflammatory disorder with immune imbalance, including elevated IgE levels and mast cell activation mediated by Th2 cytokines, leading to allergic inflammation and impaired skin barrier function. Current treatment limitations highlight the need for safer and more effective [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory disorder with immune imbalance, including elevated IgE levels and mast cell activation mediated by Th2 cytokines, leading to allergic inflammation and impaired skin barrier function. Current treatment limitations highlight the need for safer and more effective AD alternatives. We aimed to evaluate the therapeutic effects of multi-strain probiotics, BCL-2 (comprising Lactiplantibacillus plantarum LRCC5264 and Bifidobacterium longum RAPO), in alleviating AD clinical signs and elucidate its underlying immunomodulatory mechanisms. In vitro, BCL-2 treatment significantly reduced IL-4 secretion in RBL-2H3 cells, with higher inhibitory effects than single-strain treatment. In vivo, BCL-2 (106–108 CFU/day) was orally administered for 28 days to AD-induced Nc/Nga mice. BCL-2 treatment improved the clinical signs and histopathological features of AD, including epidermal hypertrophy, hyperkeratosis, and mast cell infiltration (p < 0.05). It also reduced neutrophil and eosinophil counts and modulated cytokine and chemokine profiles, notably decreasing IL-17, IL-5, IL-6, TNF-α, IL-1β, TARC, and eotaxin, while increasing IL-10, IFN-γ, and IL-12 (p < 0.05). Among the tested concentrations, 107 CFU exhibited the most effective immune modulation with no adverse effects on body weight. These findings demonstrate the therapeutic potential of BCL-2 in AD; however, further studies are required to validate its clinical relevance. Full article
(This article belongs to the Section Microbial Biotechnology)
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