Search Results (2,142)

Oxidation-reduction (redox) reactions are fundamental to sustaining life, with reactive oxygen and nitrogen species playing pivotal roles in cellular signaling and homeostasis. However, excessive oxidative stress disrupts redox balance, contributing to a wide range of diseases, including inflammatory and pulmonary disorders, neurodegeneration, and cancer. Although numerous antioxidant therapies have been developed and tested for oxidative stress-related diseases, their clinical efficacy remains limited. Here, we introduce the emerging concept of ‘supersulfides’, a class of redox molecule species with unique antioxidant and nucleophilic properties, which have recently been recognized as crucial regulators of cellular redox homeostasis. Unlike traditional antioxidants, supersulfides offer novel mechanisms of action that directly target the underlying processes of oxidative stress. This review summarizes current knowledge on supersulfides, highlighting their roles in oxidative stress and associated diseases, as well as the mechanisms underlying oxidative stress-related pathology. The therapeutic potential of synthetic supersulfides for treating oxidative stress-related diseases is also discussed. A comprehensive understanding of the molecular and cellular basis of redox biology can help to guide the development of innovative redox-based therapeutic strategies aimed at preventing and treating diseases associated with disturbed redox regulation. Full article

Background: Atrial fibrillation (AF) and ischemic stroke (IS) are intricately linked to chronic obstructive pulmonary disease (COPD). Patients who suffer from both COPD and AF demonstrate a 2.85-fold greater risk of IS. However, the long-term risk remains insufficiently explored. Methods: This study utilized data from the Taiwanese National Health Insurance dataset spanning 2000 to 2015. Patients who were newly diagnosed with COPD, identified using the International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] codes of 491, 492, and 496 and diagnosed with AF (ICD-9-CM code 427.3), were included in the study. The measured events included ISs (ICD-9-CM codes 433–437). Multivariate Cox proportional hazard models were employed to evaluate IS risk factors in this longitudinal analysis. Results: The combined presence of COPD and AF increased the risk of IS, with an adjusted hazard ratio of 5.722 (95% CI: 2.737–8.856, p < 0.001), AF without COPD with an adjusted HR of 3.506 (95% CI: 1.459–5.977, p < 0.001), and COPD with AF with an adjusted HR of 2.215 (95% CI: 1.099–3.538, p < 0.001) compared with patients without COPD and AF. Elderly patients exhibited a greater burden of cardiovascular comorbidities, including obstructive sleep apnea, thus further compounding the risk of IS. Conclusions: The coexistence of COPD and AF was associated with a markedly elevated risk of IS. The result highlights the additive and synergistic contributions of COPD and AF to the risk for IS. Aggressive treatment may mitigate the risk of IS. Full article

Introduction/Objective: the concept of clinical control of COPD is a measure proposed in the Spanish COPD Guidelines (GesEPOC), which aims to help clinicians assess the clinical status in order to adapt the treatment plan at follow-up. However, studies that have evaluated clinical practice reveal that the degree of control of COPD is not always assessed, which underlines the need to promote its assessment through a scoring system. To develop a scoring system that quantitatively assesses the validated criteria defining the degree of COPD control. Methods: this study used data from the EPOCONSUL audit in respiratory clinics across Spain. We included in this analysis all patients with a COPD clinical control grade estimated and reported by the physician at the visit, who had registered the criteria necessary to define the degree of clinical control validated and established in GesEPOC. Patients were randomly assigned to either the development or validation cohorts. The development cohort included 485 patients and the validation cohort included 341 patients. Score modelling was conducted using a multivariate logistic regression model, and calibration of the model and score was assessed using the Hosmer-Lemeshow goodness-of-fit test and GiViTi Calibration belts. The model and generated score’s discrimination capacity were analyzed by calculating the Area Under the Curve (AUC). Results: the scoring system was developed using four criteria as predictors of poor clinical control of COPD reported by the treating physician:adjusted dyspnoea severity, use of rescue inhaler more than three times per week, walking less than 30 min per day, and COPD exacerbations in the last three months. The scoring system attributed scores from 0 to 8. Calibration was satisfactory in both development and validation cohorts, and the score’s discrimination power, as indicated by the AUC, was 0.892. Conclusions: this scoring system provides an easy-to-use quantitative assessment of clinical control of COPD that we believe will help to measure COPD control and its evolution during patient follow-up. Future research will be needed to prospectively evaluate this score as a predictor of outcome. Full article

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic condition associated with substantial global morbidity and mortality. Primarily caused by prolonged exposure to harmful agents such as dust and gases, COPD is characterized by persistent airflow limitation, clinically manifesting as chronic cough, sputum production, and dyspnea. The disease course alternates between stable phases and exacerbations, with the latter often associated with pathogenic colonization of the respiratory tract. This review examines the immunological underpinnings of COPD, emphasizing the interplay between innate and adaptive immunity in disease pathogenesis. Dysregulated immune responses to environmental factors perpetuate chronic inflammation, resulting in progressive pulmonary epithelial damage and connective tissue hyperplasia, which compromise gas exchange. Exacerbations further exacerbate respiratory failure, aggravating patient symptoms and accelerating disease progression. Despite advances in COPD management, effective therapeutic options remain limited. Current treatments primarily aim to alleviate symptoms, reduce immune activation, and manage infections, yet many patients experience suboptimal outcomes. This review highlights the potential of novel therapeutic approaches targeting immune system cells and pathways. In particular, it explores the promise of oral bacterial vaccines as immunomodulatory agents to enhance immune responses and improve clinical outcomes in COPD, addressing critical gaps in current treatment paradigms. Full article

Chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating complications of acute pulmonary embolism (PE) that are characterized by fibrosis and organization of the thrombotic material within pulmonary artery branches. This pathology leads to increased right ventricular afterload and dead space ventilation, posing a risk of progressive pulmonary hypertension, right-sided heart failure, and potentially death if left untreated. Pulmonary endarterectomy (PTE) is a technically complex open-heart surgery considered to be a first-line treatment as it is a potentially curative therapy. Although PTE is highly successful in proximal disease, it may not reach the very distal branches. On the other hand, pulmonary vasodilator therapy is very effective in improving microvasculopathy but does not address the obstructive fibrotic component of the larger vessels. Balloon pulmonary angioplasty (BPA) is a novel percutaneous revascularization therapy in which traditional angioplasty techniques are used to relieve obstruction in the pulmonary arteries. This review discusses the currently accepted indications, patient selection, technical considerations, outcomes, and complications of contemporary BPA. This review will address knowledge gaps and future perspectives in BPA research. Full article

Background: Respiratory syncytial virus (RSV) infection is a common cause of hospital admission. The association between chronic obstructive pulmonary disease (COPD) exacerbation and RSV infection is not well studied. Objective: To analyze the hospitalizations of patients with COPD and RSV infection in Spain between 2018 and 2022. Methods: The data used were obtained from the Spanish Hospital Discharge Database. We selected subjects aged ≥40 years diagnosed with COPD, admitted to the hospital from 1 January 2018 to 31 December 2022. The COPD population that met the selection criteria was subdivided based on the presence of an ICD-10 code for RSV infection. To obtain comparable populations, for each subject with COPD and RSV infection, a subject without an RSV code was selected, with the COPD code in the same diagnostic position (1 to 20), as well as the same year of admission, sex, and age. Results: Among subjects aged ≥40 years, 1,429,288 were identified as having COPD, of whom 5673 also had RSV infection. The number of hospitalizations with COPD and RSV infection increased during the study period. The proportion of RSV infection among patients admitted for COPD increased significantly over time, from 0.32% in 2018 to 0.65% in 2022, p < 0.001. In-hospital mortality (IHM) increased over time, but the differences were not significant (6.23% in 2018 vs. 6.79% in 2022). Patients with COPD and RSV infection had, compared with those without RSV infection, a higher use of mechanical ventilation, both invasive (3.44% vs. 1.34%, p < 0.001) and noninvasive (8.09% vs. 4.51%, p < 0.001) and a higher proportion of intensive care unit (ICU) admission (7.21% vs. 3.9%, p < 0.001). After multivariate adjustment, a significant increase in IHM was found from 2018 to 2022 in subjects with and without RSV infection. The presence of RSV infection was associated with a higher mortality (OR 1.22; 95% CI 1.01–1.46). Conclusions: The proportion of RSV infection among patients admitted for COPD increased significantly over time. Patients with COPD and RSV infection had, compared with those without RSV infection, a higher severity, a higher use of mechanical ventilation, and a higher proportion of ICU admission. The presence of RSV infection was associated with IHM. These results can help to identify patients at higher risk and make decisions to avoid the increased risk of hospitalization and mortality in this population. Full article

The lung is a vital organ for the body as the main source of oxygen input. Importantly, it is also an internal organ that has direct contact with the outside world. Innate immunity is a vital protective system in various organs, whereas, in the case of the lung, it helps maintain a healthy, functioning cellular and molecular environment and prevents any overt damage caused by pathogens or other inflammatory processes. Disturbances in lung innate immunity properties and processes, whether over-responsiveness of the process triggered by innate immunity or lack of responses due to dysfunctions in the immune cells that make up the innate immunity system of the lung, could be correlated to various pathological conditions. In this review, we discuss globally how the components of lung innate immunity are important not only for maintaining lung homeostasis but also during the pathophysiology of notable lung diseases beyond acute pulmonary infections, including chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a frequent but underdiagnosed disease, primarily due to the lack of access to forced spirometry (FS) in primary care. Portable, easy-to-use expiratory flow meters like Piko-6^® and COPD-6^® that measure FEV₁, FEV₆, and FEV₁/FEV₆ ratio provide an alternative. Given that Piko-6^® and COPD-6^® devices measure FEV₆ but not FVC, the aim of the study is to determine the optimal cutoff value for the FEV₁/FEV₆ ratio of each device to avoid false negatives when these devices are used for COPD screening in primary care (PC). Methods: A total of 664 patients of 35 years of age or older with a cumulative tobacco consumption of 10 or more packs/year were recruited at two university hospitals. FS (gold standard) was performed and FEV₁, FVC, and FEV₁/FVC measurements were compared with FEV₁, FEV₆, and FEV₁/FEV₆ measurements acquired using Piko-6^® and COPD-6^® devices. The devices were compared using statistical methods including Pearson correlation coefficients, the Youden index (YI), kappa coefficient, Bland–Altman plots, and ROC curves analysis. Results: Correlations between FEV₁/FEV₆ using Piko-6^® and COPD-6^® and FEV₁/FVC with FS were 0.79 and 0.73, respectively. Piko-6^® achieved the best YI in FEV₁/FEV₆ (0.73), whereas for COPD-6^®, it was 0.80. Concordance between Piko-6^® and FS was 83.9% (kappa 0.67 ± 0.028) and for COPD-6^®, it was 68.7% (kappa 0.42 ± 0.02). Conclusions: This is the first study that compares two hand-held expiratory flow meters with FS. Piko-6^® and COPD-6^® devices are effective tools for COPD detection, as their measurements provide a good correlation with FS. In order to avoid false negative results, the FEV₁/FEV₆ cutoff point needs to be increased to 0.73 and 0.80 with Piko-6^® and COPD-6^®, respectively. Full article

Background and Objectives: The aging population has led to a rise in cognitive impairments, including dementia, often associated with multimorbidity. Early diagnosis of cognitive decline is crucial, especially in primary care, where time constraints and the limitations of diagnostic tools may hinder accurate detection. This study aims to assess the cognitive functions of multimorbid patients using the Mini-Mental State Examination (MMSE) and the Lithuanian version of the General Practitioner Assessment of Cognition (LT-GPCOG). We hypothesized that the LT-GPCOG would perform similarly to the MMSE in suspecting cognitive impairments. Materials and Methods: This cross-sectional study, conducted from 2021 to 2022, included 796 patients aged 40–85, with arterial hypertension and at least one other chronic disease, recruited from seven Lithuanian primary health care centers. Cognitive function was assessed using the MMSE and LT-GPCOG, and statistical analyses were performed using SPSS to determine the association between cognitive impairment and various demographic and clinical variables. Results: Out of 796 participants, 793 completed the study. Cognitive impairment was suspected in 5.1% of participants based on MMSE and 4.2% based on the LT-GPCOG. Statistically significant associations were found between cognitive impairment and chronic obstructive pulmonary disease (COPD) (p = 0.008 and p = 0.003) in both tests and chronic kidney disease (CKD) (p = 0.005) while testing with the MMSE. Lower education and unemployment were also correlated with cognitive impairment (p = 0.008 and p < 0.001). Conclusions: The findings suggest that regular cognitive assessments should be integrated into the management of multimorbid patients, particularly those with COPD and CKD. The LT-GPCOG proved to be an efficient alternative to the MMSE in primary care settings, demonstrating comparable diagnostic accuracy. Further studies are also needed to assess the sensitivity and specificity of the LT-GPCOG test. Full article

Introduction: Chronic obstructive pulmonary disease (COPD) has a diverse negative impact on patients, affecting them both physically and mentally. Psychosocial factors such as anxiety, depression, social isolation, and financial stress have been found to be positively associated with more exacerbations, hospital readmissions, poor adherence to medication, and lower quality of life among patients with COPD. However, healthcare professionals, who have a crucial role in diagnosing and managing COPD, often overlook these psychosocial factors of the disease, despite growing evidence suggesting their crucial role in improving disease outcomes. Consequently, this study will evaluate the effectiveness of a personalized individualized informational intervention on the quality of life, adherence, and psychosocial economic status of patients with COPD in healthcare settings of Greece. Methods: A prospective, mixed-methods design will be used, incorporating both quantitative data through questionnaires, including the Short Form (SF-12), Clinical COPD Questionnaire (CCQ), Test of Adherence to Inhalers (TAI), Patient Health Questionnaire (PHQ-4), Multidimensional Scale of Perceived Social Support (MSPSS), and Financial Ability Scale (FAS), alongside qualitative data with questions exploring themes such as general health perception, treatment adherence, mental status, socioeconomic status, and disease management. Participants will consist of patients receiving care at primary healthcare facilities and respiratory hospital departments in Crete, Greece. The intervention will involve providing structured information on social, financial, and psychological support services, along with psychosocial counseling over a six-month period. The impact of the intervention will be measured using validated tools to assess health status, quality of life, treatment adherence, mental health, and socioeconomic status before and after the intervention. Conversely, qualitative interviews will be conducted to gain deeper insights into the impact of the intervention. Finally, when the analyses of both data types are finalized, they will be triangulated to achieve convergence. This procedure entails the creation of a figure or illustration that demonstrates the convergence or divergence of both data types. Conclusions: The findings of this study are expected to highlight the importance of integrating an individualized informational intervention into the management of COPD. Thus, this study could guide healthcare professionals and policymakers in improving COPD care and patient outcomes. Full article

Chronic obstructive pulmonary disease (COPD) exacerbations are major contributors to morbidity and mortality, highlighting the need to better understand their molecular mechanisms to improve prevention, diagnosis, and treatment. This study investigated differential gene expression profiles and key biological processes in COPD exacerbations categorized based on sputum microbiome profiling. An observational study was performed on a cohort of 16 COPD patients, who provided blood and sputum samples during exacerbations, along with five stable-state samples as controls. Exacerbations were classified using 16S rRNA sequencing to analyze the sputum microbiota and multiplex PCR to detect respiratory viruses. Blood transcriptomic profiling was conducted using Oxford Nanopore technology, followed by differential gene expression and pathway enrichment analyses. A total of 768 regulated genes were identified across the exacerbation groups, with 35 shared genes associated with neutrophil activation. Bacterial exacerbations activated pathways related to phagocytosis and toll-like receptor signaling, while viral exacerbations were linked to pro-inflammatory responses and mitochondrial damage. Exacerbations of unknown origin showed activation of pathways involved in protozoan defense and neutrophilic asthma. Biomarkers such as IFITM3 and ISG15 for bacterial exacerbations, DEFA3 for viral, and CD47 for unknown-origin exacerbations were identified. These findings highlight distinct transcriptomic profiles and biological pathways in COPD exacerbations, emphasizing the central role of neutrophil-driven inflammation and identifying potential biomarkers for improved differential diagnosis and personalized management. Full article

Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses. Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet’s disease. Off-label use has been reported in diverse dermatological conditions, including aphthous stomatitis, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus. Roflumilast is a PDE4 inhibitor that was approved by the FDA and the EMA as an oral treatment of chronic obstructive pulmonary disease. Since patent expiration, several generic formulations of oral roflumilast have become available, and various studies have documented its off-label use in psoriasis and other dermatological conditions such as hidradenitis suppurativa, recurrent oral aphthosis, nummular eczema, lichen planus, and Behçet’s disease. Topical roflumilast has received FDA approval for treatment of plaque psoriasis and seborrheic dermatitis. The favorable safety profile encourages its long-term use as an alternative to corticosteroids, addressing the chronic nature of many dermatological conditions. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology. Full article

Coughing is a symptom of many respiratory diseases. An increased amount of coughs may signal an (upcoming) health issue, while a decreasing amount of coughs may indicate an improved health status. The presence of a cough can be identified by a cough classifier. The cough density fluctuates considerably over the course of a day with a pattern that is highly subject-dependent. This paper provides a case study of cough patterns from Chronic Obstructive Pulmonary Disease (COPD) patients as determined by a stationary semi-automated cough monitor. It clearly demonstrates the variability of cough density over the observation time, its patient specificity and dependence on health status. Furthermore, an earlier established empirical finding of a linear relation between mean and standard deviation of a session’s cough count is validated. An alert mechanism incorporating these findings is described. Full article

Background/Objectives: Patients on chronic anticoagulation undergoing metabolic surgery represent an increased risk of complications, including both bleeding and thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). The optimal perioperative management of patients who are receiving chronic anticoagulation therapy (CAT) is complex. In the colorectal surgery literature, patients on CAT have a 10% rate of peri-procedural bleeding and a 3% rate of thromboembolism. The aim of this study was to evaluate and compare the safety and postoperative outcomes between patients with and without CAT undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at a tertiary referral center in the United Arab Emirates (UAE). Methods: All patients who underwent primary bariatric surgery between September 2015 and July 2019 were retrospectively reviewed. The first group included patients with CAT, and the second group included patients without CAT. Demographics, perioperative outcomes, and postoperative results were examined. Results: Our study included 542 patients, 22 (4%) with CAT and 520 (96%) without CAT. Mean age was 46.3 ± 10.5 years in the CAT group and 36.0 ± 11.7 years in the non-CAT group (p < 0.001); median BMI was 41.8 (range 33.1–61.3) and 42.7 (range 30.1–78.4) kg/m², respectively (p = 0.52). The CAT group had significantly higher rates of hypertension (77.2% vs. 32.5%, p < 0.001), obstructive sleep apnea (81.8% vs. 31.5%, p < 0.001), and coronary artery disease (31.8% vs. 2.8%, p < 0.001). In the CAT group, 8/22 (36.4%) patients underwent Roux-en-Y gastric bypass and 14/22 (63.6%) sleeve gastrectomy, compared to 228/520 (43.8%) and 292/520 (56.2%), respectively, in the non-CAT group (p = 0.51). There were no statistically significant differences in postoperative emergency department (ED) visits (18.1% vs. 24.2%, p = 0.51), early major complications (4.5% vs. 3.4%, p = 0.54), readmission rates within 30 days (4.5% vs. 3.6%, p = 0.56), or late complications (4.5% vs. 4.2%, p = 0.60). Mean length of stay was significantly longer in the CAT group (4.6 vs. 2.6 days, p < 0.001). The mean follow-up was 10 ± 7.3 months for the CAT cohort and 11 ± 9.7 months for the non-CAT cohort (p = 0.22). Weight loss outcomes at 12 months were comparable, with a percent total body weight loss (TBWL) of 27.0 ± 7.3% in the CAT group and 28.9 ± 8.3% in the non-CAT group (p = 0.29). There were no deaths in either group. Conclusions: In this series, at a tertiary referral center in the UAE, metabolic surgery is safe for CAT patients. Multidisciplinary preoperative preparation might be warranted to avert potential complications. Full article

Objectives: The impact of long-term complications after robotic hybrid coronary revascularization (HCR), including persistent angina, repeat revascularization, and myocardial infarction (MI), remains limited. This study aims to determine the risk factors for coronary events after robotic HCR and their time-varying effects on outcomes. Methods: We identified all consecutive patients who underwent robotic HCR at our institution. Baseline characteristics were explored as possible risk factors for angina, MI, and repeat revascularization with stents at any time during the follow-up. Results: A total of 875 patients (mean age 71.1 ± 11.1 years) were included. After a median follow-up of 3.32 years (IQR 1.18–6.34 years), angina occurred in 134 patients (15.3%), repeat revascularization with stents in 139 patients (15.8%), and MI in 36 patients (4.1%). The hazard rates for all outcomes increased with follow-up time, with a notable early rise around two years of follow-up for angina and, to a lesser extent, repeat revascularization. The risk factors were the lack of radial artery graft use, black race, diabetes, obesity, chronic obstructive pulmonary disease, low ejection fraction <50%, severe left main coronary artery stenosis (>50%), and more than three-vessel disease. Conclusions: Optimization of modifiable periprocedural risk factors may positively impact long-term prognosis in patients undergoing robotic HCR. Full article