Search Results (250)

Background/Objectives: We conducted the first pharmacogenetic investigation of atopic dermatitis in a cohort of 43 Greek patients, focusing on key variants within the IL6/JAK/STAT signaling axis, a pathway central to inflammation and therapeutic targeting. Methods: Patients receiving dupilumab, JAK inhibitors, or topical corticosteroids were prospectively evaluated, with treatment response assessed by changes in the Eczema Area and Severity Index over four months. Targeted genotyping of IL6R rs2228145 A>C, JAK1 rs2780815 T>G, and TRAF3 rs12147254 G>A were performed using PCR-RFLP. Results: Across the full cohort, no robust pharmacogenetic effects were detected, while baseline disease severity was the strongest predictor of absolute clinical improvement. However, stratified analyses revealed a significant association between the IL6R rs2228145 minor allele and reduced upadacitinib response (p-value = 0.026). Consistently, the same variant demonstrated a nominal association with reduced likelihood of achieving ≥75% improvement (p = 0.065). Conclusions: Although limited by sample size, these findings suggest potential treatment-specific pharmacogenetic effects within the IL6 pathway, supporting further investigation in larger cohorts to inform personalized therapeutic strategies in eczema. Full article

Background: Eosinophilic chronic rhinosinusitis (ECRS) is characterized by refractory nasal polyps and severely impaired mucociliary clearance (MCC). The molecular mechanisms underlying the modulation of mucociliogenesis following IL-4/13 blockade with dupilumab remain poorly understood, notwithstanding its proven clinical efficacy. Methods: Bulk RNA Barcoding and sequencing (BRB-seq) was performed on nasal polyp tissues collected from healthy controls (n = 6), patients with non-ECRS (n = 8), and patients with ECRS both before and four weeks after dupilumab treatment (n = 9) to identify the early molecular drivers underlying ciliary regeneration. Comprehensive gene-set scoring systems were developed to evaluate multiciliogenesis master regulators, master regulators of core/ciliary planar cell polarity (PCP) and PCP components. Interaction scores for epithelial-derived cytokines—thymic stromal lymphopoietin (TSLP), IL-25, and IL-33—were calculated based on ligand and cognate receptor subunit expression. Results: The ciliary master regulatory hierarchy (e.g., FOXJ1, RFX2/3), PCP components (CELSR1 and the ciliogenesis and planar polarity effector (CPLANE) module: FUZ, INTU, WDPCP), and structural ciliogenesis pathways were robustly restored following IL-4/13 blockade. The TSLP interaction score correlated with global mucosal damage, serving as a trigger for compensatory multiciliogenesis. The pre-treatment IL-33 interaction score emerged as a significant predictor of transcriptomic ciliary recovery (p < 0.05). DNASE1L3—the primary endonuclease for degrading eosinophilic extracellular traps (EETs)—remained persistently downregulated post-treatment. Conclusions: IL-4/13 blockade successfully restores the structural and directional “hardware” of the respiratory epithelium but fails to rectify the enzymatic “software” required for mucus degradation. This “residual molecular scar” may explain the persistent mucus hyperviscosity observed in some ECRS patients even after clinical polyp resolution. 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/Objectives: The therapeutic effectiveness of chronic rhinosinusitis with nasal polyposis (CRSwNP) depends on an accurate diagnosis that identifies disease characteristics, evaluates sinus patency, and detects paranasal sinus obliteration. This study aims to assess a novel artificial intelligence (AI) system integrated with radiomic analysis for the radiological evaluation of CRSwNP, developing a reliable and predictive clinical-radiological scoring system. Methods: This study retrospectively evaluates CT scans of patients with CRSwNP. Image analysis was performed using Radiomica LifeX (Local Image Features Extraction) version 7.5. The extracted densitometric volumes were compared to the Lund-Mackay Score (LMS) to develop a novel scoring system (P-ABCD score) and assess its radiomic predictive capability. Results: Twenty patients with CRSwNP undergoing Dupilumab therapy participated in this study. The P-ABCD score, derived from sinus CT imaging data, served as a valuable objective measure of clinical improvement following CRSwNP treatment. Conclusions: Advanced radiomic imaging techniques of the sinus cavity provide precise volumetric data combined with texture analysis. These techniques offer high sensitivity by accurately quantifying the true extent of inflammatory involvement in the paranasal sinuses, enabling effective disease stratification. Full article

Atopic dermatitis (AD) is a common inflammatory skin disorder which presents with recurrent eczematous lesions and itching. Its pathophysiology is complex and multifactorial. Alterations in cell-mediated immune responses, barrier dysfunction, environmental aspects and IgE-mediated hypersensitivity are all involved. This review aims to provide the clinician with an update on the impact that Th2 inflammation can have on growth and osteoimmunology. The potential adverse or protective effects brought on by the many therapies administered in this condition are also considered. Moreover, through this analysis, we aim to show how, by inhibiting the IL-4 and IL-13 signaling pathways—fundamental in the T helper 2 (Th2) immune axis and in AD pathogenesis—dupilumab may exert a protective role on growth and osteoimmunology in moderate-to-severe AD, particularly in young patients. This focus is essential for the correct, safe management of patients with Th2 inflammation. 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/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease frequently associated with recurrence after endoscopic sinus surgery (ESS). Although biologic therapies such as dupilumab have demonstrated efficacy in severe CRSwNP, the optimal timing of treatment initiation in relation to surgery remains unclear. This study aimed to evaluate the clinical outcomes of early postoperative initiation of dupilumab after revision ESS using a multidimensional assessment of disease control. Methods: This retrospective observational study included adult patients with severe CRSwNP treated with dupilumab at a tertiary referral centre. All patients had undergone at least two previous ESS procedures and initiated dupilumab within 30 days following revision surgery. Clinical outcomes were assessed at baseline and after 12 months, including Nasal Polyp Score (NPS), Sinonasal Outcome Test-22 (SNOT-22), nasal congestion and olfactory visual analogue scale (VAS) scores, and asthma control in patients with comorbid asthma. Treatment response was evaluated using a multidomain assessment. Results: Ten patients were included. After 12 months, significant improvements were observed in NPS (from 4.7 ± 2.3 to 0.4 ± 1.0; p = 0.0019) and SNOT-22 (from 61.9 ± 17.3 to 26.5 ± 14.7; p = 0.0019). Nasal congestion and olfactory VAS scores also improved significantly. Most patients (70%) achieved an excellent multidimensional response, while 30% showed a moderate response. No patients required systemic corticosteroids or revision surgery during follow-up. Conclusions: Early postoperative initiation of dupilumab after revision ESS was associated with improvements in endoscopic findings, symptom severity, and quality of life. These findings suggest that the early postoperative period may represent a therapeutic window in selected patients with severe recurrent CRSwNP. However, results should be interpreted with caution and considered hypothesis-generating. 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: “Remission” is a primary therapeutic goal in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), though definitions vary regarding olfactory function. We evaluated “Dual Remission” kinetics in patients treated with dupilumab over 24 months. Methods: This single-center retrospective study analyzed 28 patients with comorbid severe asthma and CRSwNP. Dual Remission was defined as simultaneous asthma remission (ACT ≥ 20, no exacerbations, no OCS and stable lung function) and CRSwNP remission (SNOT-22 < 40, NPS ≤ 1). We additionally analyzed “Complete Recovery” by applying a stricter composite definition requiring the restoration of normosmia (Sniffin’ Sticks score ≥ 12). Results: At baseline, patients exhibited uncontrolled disease (median ACT 19, NPS 6). Treatment led to rapid asthma remission (85.7% at 12 months, 100% at 24 months). CRSwNP remission was slower but progressive, rising from 57% at 12 months to 88% at 24 months, demonstrating a significant “catch-up” phenomenon. Consequently, Dual Remission rates increased from 54% to 88% by month 24. When applying the stricter “Complete Recovery” criteria requiring normosmia, only 32% met the goal. Conclusion: Dupilumab is highly effective, enabling 88% of patients to achieve Dual Remission after 24 months. However, full olfactory restitution is distinct from structural polyp regression and harder to achieve, likely due to persistent neuroepithelial damage. 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

Background: Chronic rhinosinusitis (CRS) and obstructive sleep apnea (OSA) frequently coexist, sharing inflammatory and anatomical pathways consistent with the “United Airway”. This review examines the synergistic dysfunction linking these conditions. Methods: We conducted a narrative review synthesizing literature on the epidemiology, pathophysiology—including cytokine cascades and microbiome dysbiosis—and therapeutic outcomes of surgical and medical interventions for comorbid CRS and OSA. Results: Large-scale datasets confirm CRS as an independent risk factor for OSA. Pathophysiologically, the disorders are linked by mechanical obstruction, systemic cytokine spillover (IL-6, TNF-a), and nasopharyngeal microbiome dysbiosis (e.g., S. aureus biofilms). Therapeutically, Endoscopic Sinus Surgery (ESS) significantly improves subjective sleep quality (SNOT-22) and reduces CPAP pressure requirements, although it yields only trivial reductions in the Apnea-Hypopnea Index (AHI). Biologics like Dupilumab demonstrate rapid efficacy in improving sleep domains for CRS with nasal polyps. Conclusions: CRS and OSA are inextricably linked via mechanical and inflammatory mechanisms. A holistic “United Airway” management approach—optimizing nasal patency to facilitate CPAP adherence and reduce systemic inflammatory burden—is critical for improving patient outcomes. Full article

Background: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. Methods: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in Târgu-Mureș, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV₁% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT ≥ 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO < 20 ppb and blood eosinophils < 150/µL), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. Results: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11–14) at baseline to 23 (21–25) at 12 months and remained stable at 22 (20–25) at 24 months (p < 0.001). Predicted FEV₁% increased from 50 (39–59) to 78 (68–88) at 12 months and 79 (66–96) at 24 months (p < 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2–3) per year at baseline to 0 and 0.5 (0–1) at 12 and 24 months, respectively (p < 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. Conclusions: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease effectively treated with dupilumab, a monoclonal antibody that inhibits IL-4 and IL-13 signaling. Dupilumab is an effective treatment for type 2 inflammatory diseases such as CRSwNP. Although efficacy of dupilumab in controlling upper airway inflammation is well established, concerns have emerged regarding its potential cardiovascular effects. Emerging evidence suggests that IL-4/IL-13 signaling plays a protective role in post-myocardial infarction remodeling by promoting anti-inflammatory macrophage polarization, angiogenesis, and controlled fibrosis, especially during the early healing phase. Pharmacological blockade of the IL-4/IL-13 signaling pathway, such as that induced by dupilumab, may theoretically impair myocardial repair mechanisms, particularly in male patients who appear more responsive to these cytokines. Although rare, dupilumab-associated hypereosinophilia and myocarditis have been reported. In patients with pre-existing ischemic heart disease or heart failure, a multidisciplinary risk–benefit evaluation should be considered. Concomitant use of cardioprotective agents such as sacubitril/valsartan or SGLT2 inhibitors may help mitigate potential cardiac risks. Future studies are needed to clarify the safety and therapeutic implications of combining dupilumab with cardiovascular therapies in patients with coexisting CRSwNP and heart disease. This review critically evaluates emerging evidence of potential interference with post-infarction myocardial repair and highlights the importance of a multidisciplinary approach in managing patients with coexisting inflammatory and cardiovascular diseases. The aim of this review is to explore the available data on the cardiovascular impact of dupilumab and to provide possible future perspectives. Full article

Background/Objectives: Drug repurposing represents a promising strategy to expand therapeutic options for inflammatory bowel disease (IBD), a chronic condition with persistent unmet clinical needs. This study aimed to identify existing drugs with potential relevance for IBD by exploring inverse associations in the FDA Adverse Event Reporting System (FAERS) as a hypothesis-generating, real-world data approach. Methods: In this retrospective observational pharmacovigilance study, drug–IBD associations were extracted from the FAERS database using OpenVigil 2.1. Inverse associations were identified based on reporting odds ratios (ROR) < 1 with adjusted p-values < 0.05. Identified drug–event pairs were further evaluated for pharmacokinetic feasibility, clinical applicability, and biological plausibility in the context of IBD, with the exclusion of drugs with implausible indications, contraindications, or mechanisms inconsistent with IBD pathophysiology. Given the immune-mediated nature of IBD and the breadth of the identified candidates, detailed evaluation focused on immunomodulatory agents. Results: Among the 3585 initial drug–IBD combinations, 73 candidates met the predefined criteria for statistical significance and feasibility. From these, nine drugs were prioritized based on inverse signal strength and mechanistic relevance to immune modulation pathways implicated in IBD. The strongest inverse association with IBD was observed for lenalidomide (ROR 0.056, 95% CI 0.043–0.073), followed by dupilumab (ROR 0.213, 95% CI 0.185–0.245), cyclophosphamide (ROR 0.215, 95% CI 0.175–0.265), fingolimod (ROR 0.216, 95% CI 0.205–0.334), dimethyl fumarate (ROR 0.332, 95% CI 0.275–0.400), apremilast (ROR 0.357, 95% CI 0.296–0.431), imatinib (ROR 0.423, 95% CI 0.339–0.527), glatiramer acetate (ROR 0.446, 95% CI 0.352–0.565), and interferon beta-1a (ROR 0.594, 95% CI 0.533–0.662). These agents possess immunomodulatory properties relevant to inflammatory pathways implicated in IBD; however, clinical evidence supporting the therapeutic efficacy of some candidates remains variable or incomplete. Conclusions: By integrating inverse signal detection with clinical and biological assessment, this study demonstrates how pharmacovigilance data can be extended from traditional safety surveillance toward systematic drug repurposing applications. The findings generate testable hypotheses and highlight candidate therapies that warrant further experimental and clinical investigation in IBD. Full article