Search Results (285)

Background/Objectives: Dupilumab was recently approved to treat eosinophilic phenotypes of chronic obstructive pulmonary disease (COPD). This systematic review aimed to collect and appraise the efficacy and safety of dupilumab to treat patients with COPD. Methods: Databases searched included Ovid Medline, Embase, Web of Science, Directory of Open Access Journals, and International Pharmaceutical Abstracts. Experimental and observational studies, including case reports/series, were eligible for inclusion. Reports were independently screened, appraised, and extracted by three investigators; disagreements were resolved through discussion and agreement. Quality appraisal was conducted using the Cochrane Risk of Bias Tool 2.0, Newcastle–Ottawa Scale, and JBI Checklist for experimental, observational, and case studies, respectively. Results: A total of 307 unique reports were identified, of which 17 were included in this systematic review. The majority (n = 11, 64.7%) of reports presented evidence from the BOREAS and NOTUS trials, the landmark trials serving as the basis for dupilumab’s approval to treat refractory eosinophilic COPD. The results from this systematic review found that dupilumab reduced exacerbations of COPD in patients treated with inhaled triple therapy and it was well tolerated. Conclusions: When added to inhaled triple therapy, dupilumab may decrease patients’ risk for acute exacerbations of COPD. Additional research is necessary to substantiate these findings for broader generalizability, including populations with non-eosinophilic COPD phenotypes. Full article

Asthma has long been associated with increased susceptibility to viral respiratory infections, leading to significant exacerbations and poorer clinical outcomes. Contrarily and interestingly, emerging data and research surrounding the COVID-19 pandemic have shown that patients with asthma infected with SARS-CoV-2 experienced decreased severity of disease, lower hospitalization rates, as well as decreased morbidity and mortality. Research has shown that eosinophils could enhance immune defense against viral infections, while inhaled corticosteroids can assist in controlling systematic inflammation. Moreover, reduced ACE-2 expression in individuals with asthma may restrict viral entry, and the Th2 immune response may offset the Th1 response typically observed in severe COVID-19 patients. These factors may help explain the favorable outcomes seen in asthmatic patients during the COVID-19 pandemic. This review highlights potential protective mechanisms seen in asthmatic patients, including eosinophilia, the use of inhaled corticosteroids, reduced ACE-2 expression, and a dominate Th2 immune response. Such a study will be helpful to better manage patients with asthma who have contracted COVID-19. Full article

Objectives: To investigate the role of blood eosinophils in predicting PH in end-stage lung disease. Methods: We conducted a retrospective study of adults with CF, COPD, and ILD who underwent RHC during lung transplant evaluations (2010–2022). Patients were classified by the 2022 ECS/ERS PH guidelines with pulmonary function and laboratory tests, including hemograms. The eosinophil threshold was set at 0.30 G/L. Results: We analyzed 663 patients (n = 89 CF, n = 294 COPD, and n = 280 ILD). Severe PH was more common in ILD (16%) than in CF (4%) and COPD (7%) (p = 0.0002), with higher eosinophil levels in ILD (p = 0.0002). No significant correlation was found between eosinophil levels and hemodynamic parameters (PAPm, PVR, and CI) across CF, COPD, and ILD (PAPm: p = 0.3974, p = 0.4400 and p = 0.2757, respectively; PVR: p = 0.6966, p = 0.1489 and p = 0.1630, respectively; CI: p = 0.9474, p = 0.5705 and p = 0.5945, respectively), nor was a correlation observed in patients not receiving OCS. Linear regression analysis confirmed the lack of association (PAPm: p = 0.3355, p = 0.8552 and p = 0.4146, respectively; PVR: p = 0.6924, p = 0.8935 and p = 0.5459, respectively; CI: p = 0.4260, p = 0.9289 and p = 0.5364, respectively), controlling for 6-MWD, Nt-proBNP, and ICS/OCS dosages. ROC analysis indicated eosinophils were ineffective in distinguishing PH severity levels across these diseases (AUC 0.54, 0.51, and 0.53, respectively). The analysis of eosinophil levels measured 18 ± 6 months prior to baseline found no predictive correlation with the presence of PH either. Eosinophil levels did not differ significantly among PH groups, but eosinophilic COPD was linked to more unclassified PH, higher CO, and greater lung volumes than non-eosinophilic COPD. Conclusions: In our cohort of end-stage CF, COPD, and ILD patients, blood eosinophilia did not predict the presence of PH but was associated with hemodynamic parameters and lung volumes in COPD. Full article

Kimura’s disease (KD) is a rare, chronic inflammatory disorder that predominantly affects young men of East Asian descent. It is characterized by painless solid masses primarily localized to the deep subcutaneous tissues of the head and neck, eosinophilia, and elevated serum immunoglobulin E (IgE). While the exact cause remains unclear, the pathogenesis is thought to involve dysregulated immune responses, particularly those mediated by T-helper cells 2 (Th2), eosinophils, and IgE production. Advances in molecular biology have suggested that genetic factors play a significant role in the development and progression of this chronic inflammatory condition. Recent studies have implicated several genes and immune pathways in its development, and understanding these genetic components may provide insights into better diagnostic tools and therapeutic strategies for KD. In this regard, biological therapies, by targeting the immune mechanisms underlying KD, have been used to treat this challenging condition with promising results, contributing to a better understanding of the pathogenesis of this rare disorder. The aim of this study was to review the literature concerning the genetic factors and immune mechanisms that contribute to the pathogenesis of KD, with a special focus on the role of biological therapies. Full article

Background: Drug reaction with eosinophilia and systemic symptoms is a severe cutaneous reaction with a high mortality rate. It is challenging to diagnose due to its similar presentation to infectious disease syndromes, variation with the culprit drug, and lack of awareness. Methods: We searched PubMed, and Embase, for RegiSCAR-scored observational studies, the FDA Adverse Events Reporting System (FAERS) for adverse event reports, and the Allele Frequency Net Database (AFND) for HLA allele frequency. In our meta-analysis, we employed a random effects model to subgroup patients by ethnicity to determine the proportion of DRESS cases compared with various associated medications. Additionally, we identified a correlation between the proportion of cases and the presence of the HLA*A-32:01allele, which is suspected to predispose individuals to DRESS. Results: Twenty-one studies on 1949 DRESS cases in vancomycin and 2558 antimicrobial DRESS reports in the FAERS database were analyzed. Meta-analysis showed a 27% incidence of vancomycin-DRESS, with Caucasians having the highest proportion at 36%. The median latency for symptom onset was 21 days, with no female predisposition. The proportional incidence of vancomycin-DRESS did not correlate with the HLA-A*32:01 allele. The adjusted ROR for vancomycin was 2.40 compared to other antimicrobials, and the risk increased by 77% with concurrent antimicrobials. Piperacillin/tazobactam had a similar DRESS reporting risk at 0.95 (95%CI: 0.88–1.02). Conclusions: Vancomycin significantly contributes to the incidence of DRESS and is more closely related to ethnicity than to allele frequency, indicating that the HLA-A*32:01 allele may not be directly involved. Furthermore, the use of other antimicrobials can influence the reaction, underscoring the need to minimize antimicrobial use for better coverage. Full article

Refugees have different disease patterns than the population in receiving countries. Furthermore, refugees face barriers to accessing health care services and treatment. The purpose of this study was to describe the prevalence of eosinophilia and elevated IgE levels in refugees and assess the clinical follow-up. Using a cross-sectional study design, we offered health assessments, including eosinophil count and IgE level measurements, to all newly arrived refugees in a Danish municipality from January 2016 to November 2018. In a subgroup, we assessed the clinical follow-up. The study population consisted of 793 refugees, all of whom had eosinophil counts measured, with 411 also having IgE levels measured. Notably, 48.6% were female and most participants originated from Syria, Eritrea, Iran or Afghanistan, with smaller representation from several other countries. Notably, 6.8% had eosinophilia and 32.1% had elevated IgE levels. Syrian origin was associated with a lower prevalence of both biomarkers, and Eritrean origin with a higher prevalence. In a subgroup of 116 participants with abnormal results, general practitioners brought attention to the elevated levels in 50.9% of the cases, and 31.0% of these received a diagnosis related to the findings. In total, 98.3% (114) of patients in the subgroup had contact with their GP following the health assessment. In refugees, eosinophilia and elevated IgE levels are common conditions, and underlying causes are often not diagnosed, potentially leading to inadequate treatment and worse health outcomes. Full article

In severe asthma, symptoms are unstable despite intensive treatment based on high doses of inhaled corticosteroids and on-demand use of oral corticosteroids. Although, recently, various biological agents related to Th2 cytokines have been added to intensive controller medications for severe asthma, a significant progress has not been observed in the management for symptoms (dyspnea, wheezing and cough). Medical treatment focused on Type 2 inflammation is probably insufficient to maintain good long-term management for severe asthma. Airway eosinophilia and decreased reversibility in forced expiratory volume in 1 second (FEV₁) are listed as major predictors for exacerbation-prone asthma. However, it is generally considered that asthma is complex and heterogeneous. It is necessary to establish precision medicine using treatable traits based on a multidimensional approach related to asthma. Since phospholipids generate lysophospholipids and arachidonic acid by phospholipases, lysophospholipids can be associated with the pathogenesis of this disease via action on smooth muscle, endothelium, and epithelium in the airways. Lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosine 1-phosphate (S1P) are increased in bronchoalveolar fluid after allergen challenge. LPA, LPC, and S1P recruit eosinophils to the lungs and cause β₂-adrenergic desensitization. LAP and S1P cause contraction and hyperresponsiveness in airway smooth muscle. Moreover, lysophosphatidylserine and S1P are associated with the allergic reaction related to IgE/FcεRI in mast cells. Lysophospholipid action is probably comprised of corticosteroid resistance and is independent of Type 2 inflammation, and may be corelated with oxidative stress. Lysophospholipids may be a novel molecular target in advancing the management and treatment of asthma. This review discusses the clinical relevance of lysophospholipids in asthma. Full article

Background: Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4/IL-13 pathway, is able to dampen T helper (Th)2-mediated inflammation in several conditions characterized by this particular type of phlogosis. The aim of this study was to review the efficacy and safety of dupilumab treatment in conditions underpinned by Th2-type inflammation in a cohort of real-world patients referred to our outpatient clinic. Methods: Data from all patients with atopic dermatitis, chronic rhinosinusitis with nasal polyps, asthma, and other Th2-type-mediated inflammatory conditions treated with dupilumab were retrospectively reviewed. Results: Twenty-two patients were included in the study: 14 with atopic dermatitis, 5 with chronic rhinosinusitis with nasal polyps, 2 with asthma, and 1 with prurigo nodularis; some of the patients had more than one atopic condition. A complete response was observed in 13 out of 22 patients (59.1%); when partial responses were included in the analysis, the overall response rate was 86.4%. No adverse events were recorded, either locally or systemically. Total IgE levels dropped in all patients, in some cases reaching values close to those typically observed in nonatopic subjects. When eosinophilia was present at baseline, this also normalized during dupilumab treatment. Conclusions: Dupilumab was safe and effective across multiple conditions driven by Th2-type chronic inflammation; effective interference with the Th2-type pathway was inferred by the progressive reduction in serum total IgE levels, which reached the normal range in a fraction of patients, and by the reduction in peripheral blood eosinophil counts. Further studies in different Th2-mediated diseases are warranted. Full article

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign lesion that may arise from the oral mucosa consisting in an ulcerative lesion usually localized in the tongue or cheek. Palate localization is very rare. Background/Objectives: The aim of this study is to describe a case of TUGSE occurring in the hard palate of an 83 y.o. female patient, manifesting as a non-painful growing palatal lesion approximately of 3.5 × 2 cm with firm consistency and a central area of erosion and erythema, the difficulties in clinical diagnosis, and the criteria for the differential diagnosis. Also, considering the rare occurrence of TUGSE in the palate, we performed a review of the literature too. Methods: A comprehensive review of the literature was conducted following the 2020 PRISMA guidelines and a total of seven records were identified as matching the inclusion criteria of this study. Results Conclusions: Although TUGSE is a benign lesion, the clinical presentation as a proliferative and ulcerative lesion may be challenging for clinicians mainly when arising in rare sites of occurrence (e.g., the hard palate). Full article

Background: Chronic schistosomiasis can lead to significant morbidity. Serology is highly sensitive; however, its role in assessing treatment response is controversial. This study aimed to analyze serological values following treatment of chronic imported schistosomiasis. Methods: A retrospective observational study was performed including patients treated for chronic imported schistosomiasis from 2018 to 2022 who had at least one serological result at baseline and during follow-up. Demographic, clinical, and laboratory data were evaluated. Generalized estimating equation (GEE) models and Kaplan–Meier curves were used to analyze the evolution of serological values. Results: Of the 83 patients included, 72 (86.7%) were male, and the median age was 26 years (IQR 22–83). Most patients, 76 (91.6%), were migrants from sub-Saharan Africa. While 24 cases (28.9%) presented with urinary symptoms, the majority (59; 71.1%) were asymptomatic. Schistosoma haematobium eggs were observed in five cases (6.2%). Eosinophilia was present in 34 participants (40.9%). All patients had an initial positive Schistosoma ELISA serology, median ODI 2.3 (IQR 1.5–4.4); the indirect hemagglutination (IHA) test was positive/indeterminate in 34 cases (43.1%). Following treatment with praziquantel, serology values significantly decreased: −0.04 (IC95% −0.073, −0.0021) and −5.73 (IC95% −9.92, −1.53) units per month for ELISA and IHA, respectively. A quarter of patients (25%) had negative ELISA results 63 weeks after treatment. All symptomatic cases were clinically cured. Conclusions: Serial serological determinations could be helpful for monitoring chronic schistosomiasis in non-endemic regions. The ideal timing for these follow-up tests is yet to be determined. Further research is needed to determine the factors that influence a negative result during follow-up. Full article

Cystic echinococcosis (CE) is a neglected tropical parasitic disease linked with significant social and economic burdens worldwide. The scientific community has minimal information on echinococcosis in Romanian people, and hospital medical records are the only sources that may be used to investigate its status. A 7-year retrospective clinical study on pediatric patients with CE from Southeast Romania was performed, and 39 children and adolescents were included, aged 2–15 years old. They were hospitalized with cystic echinococcosis in the Pediatric Department and Pediatric Surgery Department of Constanta County Clinical Emergency Hospital “St. Apostle Andrew” between 1 January 2017 and 1 October 2024. Twenty-nine (74.36%) pediatric patients came from rural zones, and 10 (25.64%) had urban residences. In total, 28 children (71.79%) had contact with four different animals (dogs, goats, pigs, and sheep); only four were from urban zones, and they had contact only with dogs. Data regarding the length of hospital stay, cyst location, and complications were collected and analyzed. According to the medical files, the diagnosis was established using imaging techniques and serological tests for CE. IgE and IgG reported appreciable variations in correlation with all parameters, and significant differences (p < 0.05) were recorded. IgE levels considerably increased in cases of no animal contact, pulmonary involvement, complications, surgical treatment, and multiple hospitalizations. Moderate IgE values were recorded in cases of urban residences, pig and sheep contact, and hepatic involvement. The IgG concentration considerably increased with sheep contact and moderately increased in cases of rural zones, hepatic involvement, complications, and surgical treatment. The results show that incidental discovery, symptoms, complications, multiple dissemination, pulmonary involvement, and dog and pig contact increase the hospitalization time. Extensive data analysis supports our results. Our findings highlight the complexity of managing E. granulosus infections in children and evidence the importance of a multidisciplinary approach, combining early diagnostic tools, tailored medical therapy, and careful surgical intervention when necessary. Full article

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology. Full article

Eosinophils are central inflammatory cells in asthma; however, a portion of patients with chronic obstructive pulmonary disease (COPD) have blood or sputum eosinophilia, a condition termed eosinophilic COPD (eCOPD), which may contribute to the progression of the disease. We hypothesize that eosinophilic inflammation in eCOPD patients is related to Type 2 (T2)-high inflammation seen in asthma and that serum mediators might help us to identify T2-high inflammation in patients and choose an appropriate personalized treatment strategy. Thus, we aimed to investigate ten serum levels of T2-high inflammation mediators in eCOPD patients and compare them to severe non-allergic eosinophilic asthma (SNEA) patients. We included 8 subjects with eCOPD, 10 with SNEA, and 11 healthy subjects (HS) as a control group. The concentrations of biomarkers in serum samples were analyzed using an enzyme-linked immunosorbent assay (ELISA). In this study, we found that eCOPD patients were distinguished from SNEA patients by elevated serum levels of sIL-5Rα, MET, TRX1, ICTP, and IL-4, as well as decreased serum levels of eotaxin-1 and sFcεRI. Moreover, MET, ICTP, eotaxin-1, and sFcεRI demonstrated high sensitivity and specificity as potential biomarkers for eCOPD patients. Furthermore, serum levels of IL-5 and IL-25 in combination with sIL-5Rα, MET, and IL-4 demonstrated a high value in identifying T2-high inflammation in eCOPD patients. In conclusion, this study highlights that while T2-high inflammation drives eosinophilic inflammation in both eCOPD and SNEA through similar mechanisms, the distinct expression of its mediators reflects an imbalance between T1 and T2 inflammation pathways in eCOPD patients. A combined analysis of serum mediators may aid in identifying T2-high inflammation in eCOPD patients and in selecting an appropriate personalized treatment strategy. Full article

Background and Objectives: Chronic rhinosinusitis (CRS) is a complex inflammatory condition of the nasal passages that severely impairs quality of life. Type 2 CRS is characterized by eosinophilic inflammation, driven by cytokines like IL-4, IL-5, and IL-13. These cytokines are key to CRS pathogenesis and contribute to a heavy disease burden, especially with comorbidities. This study assessed dupilumab, a monoclonal antibody targeting IL-4 and IL-13 signaling, to evaluate its efficacy in reducing the disease burden in patients with CRS with nasal polyps (CRSwNP). Materials and Methods: The patients received subcutaneous dupilumab for 42 weeks. The outcomes included Nasal Polyp Score (NPS); Sino-Nasal Outcome Test (SNOT-22), Numeric Rating Scale (NRS), and Visual Analog Scale (VAS) scores; total IgE; and olfactory function. Results: Significant improvements were observed across the NPS and SNOT-22, NRS, and VAS scores after 42 weeks. Their total IgE levels were reduced, though a transient increase in peripheral eosinophilia appeared at 16 weeks. The patients also reported substantial improvements in olfactory function and high satisfaction with the treatment, supporting dupilumab’s potential in reducing both symptom severity and inflammation in CRSwNP. Conclusions: These results indicate that dupilumab may be an effective treatment for CRSwNP, offering significant symptom relief, improved olfactory function, and enhanced quality of life. High satisfaction levels suggest that dupilumab may provide therapeutic advantages over the conventional CRS treatments, though further studies are warranted to confirm its long-term benefits. Full article

Background/Objectives: The objective of this study was to provide real-world data on prognostic factors in children with severe eosinophilic asthma and to assess biomarkers of outcome. Methods: Fifty-nine children (aged 6–17 years) were included in a prospective cohort attended in a Severe Asthma Unit of a tertiary care teaching hospital in Badalona (Barcelona, Spain) and visited at baseline and at 1-year follow-up. Study variables included asthma control using the Asthma Control Test (ACT), forced expiratory volume in one second (FEV₁), exacerbation episodes, fractional exhaled nitric oxide (FeNO), and inflammatory biomarkers (blood tests, sputum cells, immunoallergic tests, and levels of cytokines and effector cells in blood and sputum). Results: There were 36 boys and 23 girls, with a mean (SD) age of 11.9 (2.8) years. Uncontrolled severe asthma was diagnosed in 83.1% of cases, with poor symptom control (ACT score < 20) in 52.5%, obstructive pattern (FEV₁ < 80% predicted) in 35.6%, and more than one exacerbation in the previous year in 30.5%. The mean duration of asthma was 9.2 (3.6) years. Positive prick tests were recorded in 55 patients, with polysensitization in 6. The mean percentage of sputum eosinophils was 2.5% (3.1%), and the mean eosinophil blood count 543.4 (427.7) cells/µL. Ten patients (32%) showed sputum eosinophilia (>3% eosinophils). Sputum eosinophils did not correlate with blood eosinophils, FeNO, and serum periostin. At 12 months, 13 (22%) children had uncontrolled asthma and 46 (78%) had controlled asthma. Variables significantly associated with uncontrolled asthma were duration of asthma (OR = 1.23, 95% CI 1.01–1.49, p = 0.04) and an ACT score < 20 (OR = 0.80, 95% CI 0.69–0.93, p = 0.004). Lower serum levels of IL-9 appeared to be related with uncontrolled asthma, but statistical significance was not reached. Conclusions: Pediatric severe eosinophilic asthma showed a predominant allergic phenotype with symptomatic disease as a main contributor of uncontrolled asthma at 1 year. Predictive biomarkers of outcome were not identified. Further studies are needed to confirm the present findings especially considering additional variables for a better phenotypic characterization of severe eosinophilic asthma in children and to study in-depth the role of inflammatory biomarkers. Full article