Search Results (1,754)

Pediatric asthma and allergic rhinitis are prevalent chronic inflammatory diseases ruled by complex interactions among genetic, environmental, and nutritional factors. Zinc, an essential trace element, plays a crucial role in immune modulation, oxidative stress regulation, and epithelial barrier maintenance, all of which are significant in the context of allergic airway diseases. This review aimed to explore and synthesize current evidence on the biological mechanisms and clinical implications of zinc in pediatric asthma and allergic rhinitis. A comprehensive literature search was conducted through PubMed and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included observational and interventional research focused on zinc status or supplementation in children with asthma or allergic rhinitis. Numerous observational studies and meta-analyses indicated reduced circulating zinc levels in children with asthma, often correlating with poor symptom control, increased oxidative stress, and lower pulmonary function. In allergic rhinitis, zinc depletion in nasal mucosa was associated with elevated local inflammation, although paradoxical increases in zinc concentrations have been observed in nasal secretions during active disease. Interventional trials in pediatric asthma populations showed that zinc supplementation may improve clinical symptoms, reduce inflammation, and enhance lung function, although the results were inconsistent and limited by methodological variability. In conclusion, zinc plays a multifactorial role in modulating immune responses and maintaining mucosal health in pediatric allergic airway diseases. While zinc supplementation holds promise as a safe and accessible adjunctive therapy, further high-quality randomized controlled trials are needed to define its clinical utility and establish evidence-based guidelines. Full article

Oxidative stress is one of the key elements in lung-related complications such as cystic fibrosis, acute lung injury, pulmonary hypertension, bronchopulmonary dysplasia, chronic airway diseases, lung cancer, COVID-19, and many others. Antioxidant and anti-inflammatory therapy can be considered as supportive alternatives in their management. However, most naturally derived antioxidants face issues with poor aqueous solubility and stability, which hinder their clinical utility. Remarkably, local pulmonary delivery circumvents the severe limitations of oral delivery, including hepatic first-pass metabolism and organ toxicity, and enables a higher drug payload in the lungs. Here, in this review, we present cyclodextrin as a potential drug carrier for pulmonary administration, exploring the possibilities of its surface modification, complexation with other drug transporters, and loading of cannabidiols, siRNA, and antibodies as future trends. However, the lack of a robust physiological model for assessing the efficacy of lung-oriented drug targeting is a significant concern in its path to clinical and commercial success. Full article

Chronic obstructive pulmonary disease (COPD) and asthma are characterised by in-creased oxidative stress in the lungs. The precise contribution of this stress to COPD aetiology remains unclear, partly due to the confounding influence of physiological ageing. Previous reports of increased oxidative stress in bronchoalveolar lavage (BAL) samples from individuals with COPD may at least in part be attributable to the subjects’ age. This study investigated whether increased metal concentrations at the air–lung interface would contribute to oxidative stress in the lungs. We analysed BAL samples from young and old never-smokers, young asthmatic never-smokers, older smokers without COPD and COPD patients (both current and ex-smokers). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify a range of transition metals, including iron, copper, zinc, arsenic and cadmium. BAL concentrations of copper and zinc were significantly lower in young groups compared to the older groups, irrespective of smoking status or disease (p < 0.001 for both). BAL copper was significantly associated with several markers of oxidative stress, all of which were elevated with age: glutathione disulphide (ρ = 0.50, p < 0.001), dehydroascorbate (ρ = 0.67, p < 0.001) and 4-Hydroxynonenal (ρ = 0.43, p < 0.001). These data indicate that age-related increases in respiratory tract copper concentrations contribute to elevated levels of oxidative stress at the air–lung interface independently of respiratory disease. Full article

Recent documents from leading international pediatric respiratory societies have strongly encouraged the use of lung function tests in clinical practice and research. These tests can explore ventilatory function across its volumetric and temporal domains, providing information on the intrapulmonary location and extent of damage caused by respiratory diseases. The choice of which test to use in each case to investigate presenting respiratory symptoms depends on the patient’s symptoms and the diagnostic–therapeutic phase being addresse d. In the most common and representative chronic pediatric condition—bronchial asthma—lung function tests play an especially important role due to the disease’s complexity and the fluctuating nature of airway obstruction. This review aims to examine the potential of various lung function tests in asthma, helping clinicians and researchers to optimize diagnosis and follow-up with the most appropriate methodology. While spirometry and flow resistance measurements using the interrupter technique have historically been the cornerstones of diagnosis and clinical monitoring in childhood asthma, the advent of new technologies—such as multiple breath nitrogen washout (MBNW) and the forced oscillation technique (FOT)—is opening up the door to a more nuanced view of the disease. These tools allow for an evaluation of asthma as a structurally complex and topographically and temporally disorganized condition. FOT, in particular, facilitates measurement acceptability in less cooperative subjects, both in respiratory physiology labs and even at the patient’s home. Full article

Background/Objectives: To evaluate the safety and feasibility of continuous positive airway pressure (CPAP) in patients with acute myocardial infarction (AMI) and acute decompensated heart failure (ADHF) during percutaneous coronary intervention (PCI). Non-invasive ventilation (NIV) is an established treatment for ADHF. Methods: All consecutive patients admitted to Santa Croce Hospital of Cuneo, receiving CPAP for ADHF in the cath lab during PCI for AMI, were included in a case series. Results: Between December 2018 and March 2021, 25 pts were included (median age 78 yrs, 48% female), with 64% of patients presenting with ST-elevation AMI and 17 (69%) in cardiogenic shock. At admission median left ventricular ejection fraction was 35 (20–60)% and eight (32%) patients had severe mitral regurgitation. Median PaO₂/FiO₂ was 183 (141–261) mmHg/%, lactate level 2.4 (1.3–3.8) mmol/L, and NTproBNP 7882 (3139–35,000) ng/L. CPAP was positioned and managed by nurses in all cases. Median FiO₂ was 50 (35–100)% and median positive end-expiratory pressure was 7.5 (5–12) cmH₂O. CPAP was generally well tolerated in 22 (88%) patients. One patient suffered cardiac arrest that led to CPAP interruption due to resuscitation maneuvers. No patient required orotracheal intubation in the cath lab. The post-procedural PaO₂/FiO₂ ratio substantially improved to 230 (175–356) mmHg/% (p = 0.007) and lactate decreased to 1.5 (1.0–1) mmol/L (p = 0.002). One patient died during hospital stay due to underlying disease, unrelated to the study procedure. Conclusions: CPAP during PCI in patients with AMI and ADHF seems feasible, safe, and well tolerated. Larger studies are warranted to confirm these results. Full article

Background/Objectives: Asthma is a condition caused by chronic lower airway inflammation. Its primary treatment focuses on managing the condition and reducing the frequency of exacerbation episodes. Monitoring the level of asthma control among adults is essential for both clinical care and public health planning. This systematic review aimed to assess the level of asthma control among adults in Saudi Arabia and to determine the prevalence of controlled asthma in this population. Methods: The literature search was conducted using PubMed. We included all English-language, empirical, quantitative studies that investigated the prevalence of asthma control among Saudi adults. National Institutes of Health (NIH) Study Quality Assessment Tools guided determination of the quality of the included studies. This review is registered with PROSPERO (CRD42024484711). Results: Of the 107 initially identified studies, 17 met the inclusion criteria. Quality assessment tool rated 11 studies as good, 5 as fair, and 1 as poor. Most of the included studies used cross-sectional design from different geographical locations and varied in sample size. Overall, the prevalence of uncontrolled asthma among Saudi adults ranged from 23.4% to 68.1%. In some studies, well-controlled asthma was reported in as few as 3% of patients. Factors associated with uncontrolled asthma included lower educational attainment, unemployment, low income, female gender, tobacco use, poor medication adherence, and lack of regular medical follow-up. Environmental triggers and comorbid conditions, such as allergic rhinitis, were also frequently cited as contributing factors. Conclusions: Asthma control among adults in Saudi Arabia remains a significant public health concern. Improving outcomes requires a multifaceted approach that includes patient education, regular follow-up care (including pulmonary function tests, asthma severity assessments, and personalized treatment plans), and broader public health initiatives aimed at reducing exposure to allergens and pollutants. Strengthening primary care services and implementing nationwide asthma management programs may play a critical role in enhancing disease control and improving quality of life. Continued research in this field is strongly recommended. Full article

The FOT is a non-invasive method for assessing respiratory mechanics. It enables the measurement of respiratory system impedance by applying pressure oscillations through a loudspeaker at the subject mouth and then studying its deformation, which is commensurate to the resistance opposed by the respiratory system. The main parameters which can be determined with the FOT are the impedance (Z) and the components of respiratory resistance (Rrs) and reactance (Xrs). The FOT has been predominantly applied to the study of respiratory mechanics for research purposes; however, preclinical experiments and subsequently observational clinical studies have demonstrated that FOT can effectively assess airway obstruction, bronchodilator response, bronchial hyperresponsiveness, and the presence of small airways disease. More recently, studies on the FOT in restrictive lung diseases have also been reported. Nonetheless, international guidelines on the precise applications of the FOT in lung diseases are still lacking. The aim of the review was to describe the technical aspects related to the FOT methodology in clinical practice and to provide a concise state of the art on the applications of the FOT in obstructive and restrictive lung diseases. Full article

Asthma is a multifactorial respiratory disease that naturally occurs in horses, humans, and cats, presenting common clinical signs and species-specific mechanisms. This review addresses the impact of asthma on the cardiovascular and neurological systems, with a primary focus on horses. It highlights the need for new biomarkers beyond the respiratory system due to diagnostic difficulties in animals. A comprehensive literature search was conducted using PubMed and Google Scholar, focusing on cardiovascular and neurological manifestations of asthma in humans, horses, cats, and experimental animal models. Studies were qualitatively compared, noting species-specific differences and mechanisms. Humans with asthma show an increased risk of cardiovascular disease and elevated cardiac biomarkers during exacerbations, while horses develop pulmonary hypertension and vascular remodeling. Cats exhibit significant pulmonary vascular changes. Heart rate variability analysis reveals altered autonomic function in humans and horses. Increased peripheral airway innervation and cough reflex sensitivity are noted across species. The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in asthma pathophysiology in murine models. Asthma impacts the cardiovascular and nervous systems differently across species, emphasizing the importance of comparative medicine. Future research should integrate cardiovascular, autonomic, and inflammatory pathways to develop effective therapeutic approaches in human and veterinary medicine, leveraging insights from naturally occurring asthma models. Full article

Obstructive sleep apnea (OSA) is a common condition characterized by repeated airway collapses during sleep, contributing to oxygen desaturation, arousals, and significant cardiovascular complications. This meta-analysis aims to evaluate the association between blood ICAM-1 levels and OSA, exploring its potential as a biomarker for cardiovascular disease (CVD) and for identifying factors contributing to result heterogeneity. Following PRISMA guidelines, this meta-analysis addressed a PECO framework to assess circulating ICAM-1 levels in adults with OSA compared to controls. A systematic search was conducted across PubMed, Web of Science, Scopus, Cochrane Library, and CNKI until 23 April 2025, complemented by citation reviews and Google Scholar. Statistical analyses, including subgroup and meta-regression, were performed using RevMan, CMA 3.0, and TSA software to calculate mean differences, assess heterogeneity, and evaluate publication bias. Results were analyzed under random-effect models, with significance set at p < 0.05 for all metrics except publication bias (p < 0.10). This systematic review and meta-analysis included 34 articles. The pooled mean difference (MD) of ICAM-1 levels was 184.06 ng/mL (95% CI: 143.83 to 224.28; p < 0.00001), significantly higher in OSA patients with high heterogeneity (I² = 100%). Subgroup analysis highlighted larger MDs in Asians and plasma samples, as well as greater ICAM-1 elevations in severe OSA cases. Despite publication bias indicated by Begg’s (p = 0.036) and Egger’s (p = 0.016) tests, the findings remained robust, supported by sensitivity and meta-regression analyses. This meta-analysis underscores a significant association between elevated ICAM-1 levels and OSA, highlighting its potential as a biomarker for CVD risk stratification in OSA patients. Full article

Respiratory syncytial virus (RSV) remains a leading cause of acute lower respiratory tract infections globally, particularly affecting infants, older adults, and immunocompromised individuals. While recent advances in prophylaxis, such as long-acting monoclonal antibodies and maternal immunization, offer promise for prevention, therapeutic options for active infection remain limited. Severe RSV disease is often driven not solely by viral replication but by dysregulated host immune responses, including excessive cytokine production, T helper type 2 (Th2) and T helper type 17 (Th17) cell polarization, and impaired interferon signaling. RSV has evolved sophisticated immune evasion strategies, such as inhibition of dendritic cell maturation, degradation of signal transducer and activator of transcription 2 (STAT2) via nonstructural proteins 1 and 2 (NS1/NS2), and interference with pattern recognition receptor signaling, particularly Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. These mechanisms result in attenuated innate immune responses and defective adaptive immunity, contributing to viral persistence, immunopathology, and recurrent infections. Moreover, age-dependent vulnerabilities, such as immune immaturity in infants and immunosenescence in older adults, exacerbate disease severity. Excessive immune activation leads to bronchiolitis, airway remodeling, and long-term sequelae including wheezing and asthma. Emerging immunomodulatory therapies aim to restore immune balance, targeting cytokines (e.g., interleukin-6 [IL-6], interleukin-1 beta [IL-1β]), the Janus kinase–signal transducer and activator of the transcription (JAK-STAT) pathway, or inflammasome activity. Host-directed therapies and direct-acting antivirals are also under investigation. A better understanding of RSV–host immune interactions is critical for optimizing therapeutic strategies and designing effective vaccines. This review synthesizes current knowledge on RSV immunopathogenesis and highlights immunomodulation as a promising frontier for therapeutic intervention. Full article

Severe asthma imposes a significant burden on public health worldwide, mainly due to its morbidity and high cost. The management of severe asthma has dramatically changed in the past few years with the introduction of biologics. Zero exacerbations, zero systemic corticosteroids, better asthma control, and better lung function are the outcomes that the era of biologics has made attainable in a large proportion of severe asthmatics, ending up in a better quality of life. Still, even today, the changes at the tissue level that reflect these outcomes are not that clear. As a chronic inflammatory disease, asthma often involves airway remodeling in its severe forms; endobronchial biopsies may provide critical insights into these tissue-level changes before and after biologic treatment. However, bronchoscopy is an invasive tool for severe asthma, thus limiting its use in daily clinical practice. This review focuses on summarizing the changes that biologics exert in biopsies obtained from severe asthmatics under biological treatment, providing an opportunity to shed light on what really happens there where it is not easy to see, and especially on what does not happen in patients under biologics who fail to respond as expected. Moreover, the armamentarium of biomarkers used for making the proper choice in patients eligible for more than one biologic needs to be enriched. Biopsy-related markers could be an ideal adjunct to the current ones—blood eosinophils, FeNO, and IgE—to assist the clinician to choose the right biologic for the right patient with severe asthma to achieve disease remission. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Obstructive sleep apnea (OSA) syndrome is a severe, debilitating, and pervasive sleep disorder. OSA mainly affects people with obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia and is strongly associated with cardiovascular complications. Based on the bidirectional relationship between T2DM and OSA, the latter represents a risk factor for the former, and, vice versa, people with T2DM have a high risk of OSA. Mechanical and hormonal factors, inflammatory mediators, and a dysregulated autonomic nervous system contribute to the mechanisms underlying the disease. Treatment of OSA is necessary even if the available remedies are not always effective. In addition to traditional treatments, including lifestyle adaptations and bariatric surgery, CPAP equipment, i.e., a breathing device ensuring continuous positive pressure to keep the airways open during sleep, represents the most common treatment tool. More recently, pharmacological research has paved the way to newer seemingly effective therapeutic strategies involving, in particular, two hypoglycemic agent classes, i.e., sodium–glucose co-transporter 2 inhibitors (SGLT2-is) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1-ras). This narrative review provides an update on all of the above. Full article

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

Cystic fibrosis (CF), the most common hereditary lung disease in Caucasians, is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). We evaluated CFTR function using a newly developed Ussing chamber system, the Multi Trans Epithelial Current Clamp (MTECC), in an in vitro model of human airway epithelia. Air–liquid interface (ALI) cultures were established from nasal brushings of healthy controls (HC) and CF patients with biallelic CFTR variants. ALI layer thickness was similar between groups (HC: 62 ± 13 µm; CF: 55 ± 9 µm). Immunofluorescence showed apical CFTR expression in HC, but reduced or absent signal in CF cultures. MTECC enabled continuous measurement of transepithelial resistance (Rt), potential difference (PD), and conductance (G_t). G_t was significantly reduced in CF cultures compared to HC (0.825 ± 0.024 vs. −0.054 ± 0.016 mS/cm²), indicating impaired cAMP-inducible ion transport by CFTR. Treatment of CF cultures with elexacaftor, tezacaftor, and ivacaftor (Trikafta^®) increased G_t, reflecting partial restoration of CFTR function. These findings demonstrate the utility of MTECC in detecting functional differences in CFTR activity and support its use as a platform for evaluating CFTR-modulating therapies. Our model may contribute to the development of personalized treatment strategies for CF patients. Full article