Search Results (1,514)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines. Full article

Introduction: Asthma is a chronic respiratory disease affecting approximately 5 million children in the US, but little is known about whether asthma alters children’s attention and memory functions. Most studies on this topic focus on psychiatric and QoL outcomes rather than cognitive functions, leaving a gap in the literature. We aimed to conduct a systematic review and meta-analysis to evaluate the attention deficit and memory function outcomes in children with bronchial asthma. Methods: A systematic search was conducted in PubMed, Web of Science, and Cochrane Library from inception to 28 February 2025 for studies evaluating attention deficit and memory function in children with bronchial asthma. Outcomes of interest included attention deficit and memory function. Statistical analysis was performed with R 4.3.1. Heterogeneity was accessed using the I² statistics and Cochrane Q test. The standardized mean difference (SMD) with restricted maximum-likelihood estimator random-effects method was computed for all outcomes. Results: A total of seven studies were included in the final meta-analysis, comprising 104,975 patients, of whom 10,200 (9.7%) had bronchial asthma (mean age ± 8.98 years, mean 45% females). In the pooled analysis, children with asthma had a worsened attention deficit compared to the healthy group (SMD 0.29; 95% CI [0.07; 0.51]; p = 0.01; I² = 92%). However, no statistically significant difference was found in memory function between groups (SMD −0.24; 95% CI [−1.81; 1.33]; p = 0.77; I² = 96%). Conclusions: Children with asthma showed significantly higher attention deficit scores compared to healthy children. No statistically significant differences were observed in memory function between the groups. These findings may have implications for early cognitive screening in pediatric asthma management. Full article

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, whose 2020 outbreak was characterized as a pandemic by the World Health Organization. Restriction measures changed healthcare delivery, with telehealth providing a viable alternative throughout the pandemic. This study analyzed a telemedicine platform database with the goal of developing a diagnostic prediction model for COVID-19 patients. This is a longitudinal study of patients seen on the Conexa Saúde telemedicine platform in 2022. A multiple binary logistic regression model of controls (negative confirmation for COVID-19 or confirmation of other influenza-like illness) versus COVID-19 was developed to obtain an odds ratio (OR) and a 95% confidence interval (CI). In the final binary logistic regression model, six factors were considered significant: presence of rhinorrhea, ocular symptoms, abdominal pain, rhinosinusopathy, and wheezing/asthma and bronchospasm were more frequent in controls, thus indicating a greater chance of flu-like illnesses than COVID-19. The presence of tiredness and fatigue was three times more prevalent in COVID-19 cases (OR = 3.631; CI = 1.138–11.581; p-value = 0.029). Our findings suggest potential predictors associated with influenza-like illness and COVID-19 that may distinguish between these infections. Full article

Respiratory microbiota and lipids are closely associated with airway inflammation. This study aimed to analyze the correlations among the respiratory microbiome, the airway glycerophospholipid–sphingolipid profiles, and airway inflammation in patients with asthma. We conducted a cross-sectional study involving 61 patients with asthma and 17 healthy controls. Targeted phospholipidomics was performed on exhaled breath condensate (EBC) samples, and microbial composition was analyzed via the 16S rDNA sequencing of induced sputum. Asthma patients exhibited significant alterations in the EBC lipid profiles, with reduced levels of multiple ceramides (Cer) and glycerophospholipids, including phosphatidylethanolamine (PE) and phosphatidylcholine (PC), compared with healthy controls. These lipids were inversely correlated with the sputum interleukin-4 (IL-4) levels. Microbiome analysis revealed an increased abundance of Leptotrichia and Parasutterella in asthma patients, both positively associated with IL-4. Correlation analysis highlighted a potential interaction network involving PA, PE, ceramides, Streptococcus, Corynebacterium, Parasutterella, and Leptotrichia. Specific alterations in airway microbiota and phospholipid metabolism are associated with asthma-related inflammation, supporting the concept of a microbiota–phospholipid–immune axis and providing potential targets for future mechanistic and therapeutic studies. Full article

Background and Objectives: Asthma, COPD, and asthma–COPD overlap are obstructive lung diseases with inflammation at their core. Oxidative stress and impaired antioxidant balance play a significant role in etiopathogenesis. This study aimed to determine whether there are differences in total antioxidant capacity (TAC) between asthma, COPD, and asthma–COPD overlap. Materials and Methods: A total of 76 patients participated in this prospective cross-sectional study. TAC levels in fasting venous blood samples were measured using a biochemistry analyzer and the total antioxidant activity method (Architect C1600, Abbott Laboratories, IL, USA). Results: TAC levels were lower in COPD patients compared to asthma and ACO patients (p = 0.049 and 0.026, respectively). TAC levels were lower in current and former smokers compared to never smokers (p = 0.033). There was no significant correlation between TAC level and eosinophil count (p = 0.597) and FEV1 and FEV1/FVC (p = 0.372 and p = 0.189). Conclusions: Our results suggest that TAC levels may serve as a marker to differentiate COPD from asthma or ACO. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Prostate Cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death among men. In Louisiana (LA), Black men are disproportionately diagnosed at later stages compared to White men. This study explores environmental risk factors as potential intermediate variables linking race to cancer diagnosis stage. The Louisiana Tumor Registry data included 24,647 male patients diagnosed with PCa in LA between 2010 and 2018. Among them, 15,875 (64.40%) were Caucasian American (CA) and 8772 (35.59%) African American (AA). Mediation analysis using multiple additive regression trees (MART) identified possible intermediate variables that potentially explain the observed disparity. The study found that individual characteristics and environmental factors jointly explained 84% (95% CI: 44.1%, 94.6%) and 18.6% (95% CI: 7.3%, 53.7%) of the observed racial disparity in PCa stage at diagnosis, respectively. Individual factors included BMI (35.9%), marital status (28.5%), CDI (8.2%), female-headed households (2.3%), comorbidity (3.9%), and insurance status (6.3%). Environmental contributors included cancer risk due to air toxicity exposure (7.2%), asthma prevalence (6.6%), acetaldehyde levels (2.1%), railroad proximity (2.1%), walkability (0.3%), and ozone level (−0.1%). Environmental factors jointly played a significant role in the observed racial disparity. The factors such as air toxicity, acetaldehyde levels, and asthma prevalence highlight the need to address industrial pollutants to reduce the differences. Full article

Respiratory diseases represent a persistent global health challenge, underscoring the need for intelligent, accurate, and personalized diagnostic and therapeutic systems. Existing methods frequently suffer from limitations in diagnostic precision, lack of individualized treatment, and constrained adaptability to complex clinical scenarios. To address these challenges, our study introduces a modular AI-powered framework that integrates an audio-based disease classification model with simulated molecular biomarker profiles to evaluate the feasibility of future multimodal diagnostic extensions, alongside a synthetic-data-driven prescription recommendation engine. The disease classification model analyzes respiratory sound recordings and accurately distinguishes among eight clinical classes: bronchiectasis, pneumonia, upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis, and healthy respiratory state. The proposed model achieved a classification accuracy of 99.99% on a holdout test set, including 94.2% accuracy on pediatric samples. In parallel, the prescription module provides individualized treatment recommendations comprising drug, dosage, and frequency trained on a carefully constructed synthetic dataset designed to emulate real-world prescribing logic.The model achieved over 99% accuracy in medication prediction tasks, outperforming baseline models such as those discussed in research. Minimal misclassification in the confusion matrix and strong clinician agreement on 200 prescriptions (Cohen’s $\kappa$ = 0.91 [0.87–0.94] for drug selection, 0.78 [0.74–0.81] for dosage, 0.96 [0.93–0.98] for frequency) further affirm the system’s reliability. Adjusted clinician disagreement rates were 2.7% (drug), 6.4% (dosage), and 1.5% (frequency). SHAP analysis identified age and smoking as key predictors, enhancing model explainability. Dosage accuracy was 91.3%, and most disagreements occurred in renal-impaired and pediatric cases. However, our study is presented strictly as a proof-of-concept. The use of synthetic data and the absence of access to real patient records constitute key limitations. A trialed clinical deployment was conducted under a controlled environment with a positive rate of satisfaction from experts and users, but the proposed system must undergo extensive validation with de-identified electronic medical records (EMRs) and regulatory scrutiny before it can be considered for practical application. Nonetheless, the findings offer a promising foundation for the future development of clinically viable AI-assisted respiratory care tools. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

Background: Mepolizumab is an effective treatment for severe eosinophilic asthma, leading to a depletion of blood eosinophil levels, the clinical relevance of which remains unclear. Objective: The aim of this study was to assess the relationship between mepolizumab-induced blood eosinophil reduction and clinical outcome in patients with severe eosinophilic asthma, in particular, whether the magnitude of blood eosinophil reduction was associated with clinical remission. Methods: We conducted a real-world retrospective analysis of 58 adult patients with severe eosinophilic asthma treated with mepolizumab. Clinical and respiratory functional parameters were evaluated at the start of mepolizumab treatment (T0) and after two years of treatment (T2; mean follow-up: 22.8 ± 7.5 months). Blood eosinophil counts were recorded at T0 and during the first year of treatment (T1; mean follow-up: 7.7 ± 4.1 months). Results: After two years of mepolizumab treatment, 58 severe asthmatic patients showed significant improvements in ACT score, FVC, and FEV₁ and a reduction in acute exacerbations and the use of maintenance therapies. Clinical remission was achieved in 55.1% of patients. Lower blood eosinophil counts during the first year (T1) were associated with greater improvements in lung function and fewer exacerbations. A greater relative decrease in eosinophils from baseline to T1 (ΔEOS%) was significantly associated with remission, reductions in exacerbations, and no maintenance OCS use. ΔEOS% was the only independent predictor of remission in the multivariate analysis. A ≥90% reduction predicted remission with 80% specificity (AUC = 0.726). Conclusions: Monitoring blood eosinophils after mepolizumab initiation could be a useful tool for predicting long-term response to treatment. In particular, a reduction by over 90% of peripheral blood eosinophils during the first year of mepolizumab treatment predicts clinical remission with a specificity of 80%. Considering the accessibility and the low cost of this biomarker, it may help to optimize long-term asthma management. Full article

Background: Inhaled corticosteroids (ICSs) are a cornerstone in asthma management, particularly during exacerbations, when high doses are often prescribed. However, patient concerns about potential side effects such as increased appetite, weight gain, and metabolic disturbances may reduce adherence, compromising treatment outcomes. While oral corticosteroids (OCSs) are well known to induce such effects, the metabolic impact of short-term high-dose ICSs remains poorly studied. Objective: This prospective pilot study aimed to assess whether a 14-day course of high-dose ICSs in adults with stable asthma induces changes in appetite, dietary intake, leptin levels, or body weight. Methods: Thirty-five adults (19 males, 16 females; mean age 48.7 ± 15.1 years) with stable mild asthma received ≥400 µg/day extrafine beclomethasone dipropionate/formoterol via pressurized metered-dose inhaler for 14 days. Participants underwent assessments at baseline and after 14 days, including body weight, BMI, fasting serum leptin levels, dietary intake (evaluated using 24 h dietary recalls), and appetite (measured via a visual analogue scale). Results: No significant changes were observed in body weight (mean change: −0.38 kg; 95% CI: −0.81 to 0.05; p = 0.083) or BMI (p = 0.912) following high-dose ICS use. Similarly, serum leptin levels (mean change: 0.13 ng/mL; 95% CI: −3.47 to 3.72; p = 0.945), subjective appetite scores (mean change: −4.93 mm; 95% CI: −13.64 to 3.79; p = 0.267), and dietary energy intake (mean change: +255 kJ/day; 95% CI: −380 to 891; p = 0.431) did not differ significantly post-intervention. Conclusions: Short-term high-dose ICS therapy in adults with mild asthma may not significantly affect appetite, dietary intake, leptin levels, or body weight. These findings support the metabolic safety of short-term high-dose ICSs and may help alleviate patient concerns, improving adherence during exacerbation management. Full article

Background/Objectives: Patients with severe asthma (SA) commonly present with coexisting nasal polyposis (NP), often requiring treatment with intranasal corticosteroids (INC). However, adherence to INC in this population remains inadequately characterized despite its clinical significance. This study aimed to evaluate adherence to INC in patients with SA and NP and to identify clinical and pharmacological factors associated with adherence levels. Methods: We conducted a retrospective observational study including adult patients with SA and NP treated with INC and followed at a tertiary asthma unit in Madrid during 2024. Adherence was assessed via medication possession ratio (MPR) over six months, with poor adherence defined as MPR < 50%. Pharmacological, clinical and demographic variables were analyzed for associations with adherence. Results: Of the 188 patients evaluated, 86 (45.7%) were prescribed INC. Poor adherence was observed in 53.5% of these patients. Women exhibited significantly lower adherence compared to men (p < 0.05). Fluticasone was the most commonly prescribed INC (54.6%), with no significant adherence differences across corticosteroid types. Patients on maintenance systemic corticosteroids had higher adherence (85.7%, p < 0.05), whereas those receiving biologic therapies tended toward lower adherence (51% poor adherence), though this was not statistically significant. Higher adherence was associated with increased disease severity, as indicated by multiple endoscopic sinus surgeries (p < 0.05). No significant differences were observed in spirometry or Asthma Control Test scores. Conclusions: Adherence to INC in patients with SA and NP is suboptimal, particularly among women and patients on biologics. Greater disease severity correlates with improved adherence. Targeted interventions are necessary to enhance adherence and optimize disease management in this population. Full article

In respiratory patients, limited adherence to and misuse of devices hinder the effectiveness of inhalation therapy. Switching inhalers for non-clinical reasons poses a risk of deterioration of respiratory disease and/or promotes poor adherence to therapy. The objective of this work was to explore the impact of device changes for non-clinical reasons on clinical outcomes (primary) and costs (secondary), including carbon emissions in Spain. After a comprehensive literature search, the increased use of resources following worsening outcomes was apportioned using Spanish cost data and following the recommended pathways for care. We calculated the cost of re-training these patients and attributed carbon emissions in metric tons of CO₂ equivalent (tCO₂eq) to the excess resource use. In Spain, the impact of uncontrolled switching for non-clinical reasons in COPD has an annual estimated cost of EUR 923/patient, leading to an excess annual expenditure of more than EUR 216 million. For asthma patients, the annual impact is almost EUR 263/patient, representing an additional EUR 118 million excess annual expenditure. The environmental consequence of both conditions can be equated to almost 45 thousand tCO₂eq. Training all these patients on the new device would cost around EUR 35 million and would generate an extra impact reduction of about 2.6 thousand tCO₂eq in carbon emissions levy. Full article

Inhaled corticosteroids (ICSs) are widely used to manage chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and human immunodeficiency virus (HIV). However, prolonged use of ICS is associated with the development of oropharyngeal candidiasis, a fungal infection primarily caused by Candida albicans, due to local immunosuppression in the oral cavity. The incidence of oropharyngeal candidiasis varies depending on geographic region, patient age, and comorbidities, with immunocompromised individuals, those with diabetes, and the elderly being particularly vulnerable. Key risk factors include high ICS doses, poor oral hygiene, and improper use of inhalers. Prevention is the cornerstone of managing oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids. Patient education on proper inhaler technique and oral hygiene is essential to reduce the risk of fungal overgrowth in the oral cavity. Additional preventive strategies include the use of spacers, mouth rinsing after inhalation, and proper denture care. In cases where these measures fail to prevent the infection, prompt detection and early intervention are crucial to prevent progression or recurrence. This narrative review aims to analyze the most effective prophylactic measures to prevent oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids, emphasizing patient education, oral hygiene, and proper use of inhalation devices. Full article