Search Results (12,695)

Background/Objectives: Respiratory syncytial virus (RSV) is a major cause of respiratory illness across the lifespan, yet its health-economic burden in adults remains under-recognized. Building on a previously published nationwide analysis of RSV-associated hospitalizations in Switzerland (2017–2023), this study aimed to estimate age-specific direct inpatient hospitalization costs and assess their implications for healthcare systems. Methods: We conducted a nationwide health-economic analysis using Swiss Federal Statistical Office (FSO) hospitalization data (2017–2023) combined with SwissDRG-based cost statistics (2024). Age-specific costs per hospitalization were applied to RSV-associated hospitalization counts. To account for disease severity, additional estimates were derived by applying RSV-specific length-of-stay (LOS) ratios between RSV-associated and all-cause hospitalizations, reflecting the longer duration of RSV-associated admissions. Results: Total RSV-associated hospitalization costs were estimated at CHF 55.1–76.0 million annually. Children aged 0–9 years accounted for the highest number of hospitalizations and the largest share of total costs (CHF 27.8–34.3 million). Despite fewer hospitalizations, adults aged ≥ 60 years generated comparable total costs (CHF 23.6–36.7 million), driven by substantially higher costs per case. Costs increased markedly with age, reflecting longer hospital stays and higher clinical severity. Additional analyses demonstrated a substantial increase in costs in the post-pandemic period, particularly in older adults, suggesting improved detection of RSV-associated hospitalizations. Conclusions: RSV-associated hospitalizations impose a substantial economic burden on the Swiss healthcare system. The disproportionate contribution of older adults highlights the importance of targeted prevention strategies and provides a foundation for future health-economic evaluations and policy decision-making. Full article

The primary route of SARS-CoV-2 entry is via respiratory epithelium. However, many COVID-19 patients developed dermatological lesions, and SARS-CoV-2 RNA has been detected in the patients’ skin. Inflammatory skin diseases, psoriasis and atopic dermatitis (AD), significantly increased the risk of COVID-19. To evaluate the potential role of skin in SARS-CoV-2 host interactions, we utilized 3D human skin organoids (HSO) generated from human epidermal keratinocytes, as well as neonatal skin explants. HSO were treated with cytokines involved in acute and chronic skin inflammation and cytokine storm in severe COVID-19 disease: TNF-α, IL-6, IL-1β, and IFN-γ, individually and in combination. HSO were also treated with Th1 (TNF-α + IL-17) and Th2 (IL-4 + IL-13) cocktails inducing pro-psoriasis and pro-AD HSO changes, respectively. All individual cytokines, and especially their combinations, elevated the expression of ACE2 and TMPRSS2 at mRNA/protein levels. The Th2 cocktail induced only TMPRSS2, the Th1 cocktail predominantly induced ACE2. Topically applied Spike-pseudotyped lentiviral Tomato reporter, which binds ACE2 similarly to SARS-CoV-2, successfully transduced control and cytokine-treated HSO as well as neonatal skin explants. Cytokine treatment, especially TNF-α + IL-6 + IL-1β + IFN-γ and the Th1 cocktail, significantly increased viral entry. Transcriptomic analysis further revealed partial overlap between gene expression signatures induced by Spike-mediated entry in inflamed HSO and those observed in lung tissue from COVID-19 patients, supporting the biological relevance of skin models. Together, these findings demonstrate that inflammation may transiently alter the permissiveness of human skin to SARS-CoV-2 entry, suggesting that the skin may represent a previously underappreciated, although likely limited, interface in viral- host interactions. Full article

The treatment of intracellular bacterial infections such as Chlamydia remains a significant clinical challenge due to rising antibiotic resistance and persistent, immunopathology-driven tissue damage. Macrophages are essential for host defense; they can originate from both tissue-resident precursors and circulating monocytes. During infection, macrophages at infected sites are largely derived from monocytes that migrate and differentiate there, where they phagocytose pathogens and orchestrate immune responses. The chemokine receptor CCR2 is a key regulator of this process, yet its role beyond monocyte trafficking is not fully understood. Previous studies have shown that CCR2 deficiency impairs monocyte mobilization and exacerbates disease during Chlamydia infection, shifting immune responses away from protective Th1 immunity toward pathological Th2 and Th17 polarization. Here, we investigate how CCR2 regulates macrophage function to balance protective Th1 versus pathological Th2/Th17 immunity during Chlamydia respiratory infection. Our results show that CCR2 deficiency reduces pulmonary infiltration of Ly6C^hi and Ly6C^low monocytes and shifts macrophage differentiation away from an M1-like toward an M2-like phenotype. Mechanistically, CCR2 deficiency compromises macrophage endocytosis and survival, elevates ROS production, and activates the NLRP3 inflammasome, leading to Caspase-3/GSDME-mediated pyroptosis with increased IL-1β and IL-18, while suppressing the Caspase-1/GSDMD pathway. These findings were recapitulated in vitro using C. muridarum-stimulated Ccr2-deficient bone marrow-derived macrophages (BMDMs), which also showed impaired migration, reduced M1-like polarization, diminished endocytosis, and enhanced ROS/NLRP3/pyroptosis. Furthermore, co-culture of these BMDMs with CD4⁺ T cells revealed that Th1 differentiation was inhibited, whereas Th2 and Th17 responses were promoted. Collectively, CCR2 orchestrates monocyte–macrophage function by driving M1-like polarization and inhibiting NLRP3/Caspase-3/GSDME pyroptosis to rebalance Th1/Th2/Th17 immunity, thereby enhancing bacterial clearance while mitigating immunopathological tissue damage during Chlamydia infection. Full article

Background: Near-infrared spectroscopy (NIRS)-based wearable devices offer non-invasive, continuous monitoring of muscle oxygenation, providing direct microvascular and metabolic information that complements indirect indices of intensity such as heart rate and accelerometry. Their clinical applicability in chronic non-communicable diseases (NCDs) remains under active development. Methods: A structured narrative review was conducted in PubMed, Scopus, Web of Science, and IEEE Xplore (January 2010–January 2026) using pre-specified search strings combining NIRS, muscle oxygenation, SmO₂, StO₂, wearable, exercise intensity, ventilatory/lactate threshold, and individual chronic disease terms. Eligible studies addressed technical validation of wearable NIRS, NIRS-derived exercise intensity estimation, clinical applications in NCDs, or rehabilitation implementation. Evidence was synthesized thematically; quality of validation studies was appraised against AMSTAR-2-informed, COSMIN-informed, or Cochrane RoB-2 criteria. Results: Wearable continuous-wave NIRS shows acceptable concurrent validity with frequency-domain laboratory systems (r = 0.79; range 0.69–0.88; ±8% SmO₂ agreement in 95% of measurements) and good test–retest reliability for moderate-to-severe domains (ICC 0.72–0.91). NIRS-derived breakpoints align more reliably with the second ventilatory/lactate threshold (ICC = 0.80) than with the first (ICC = 0.53), constraining its use for prescribing lower-intensity domains. In chronic obstructive pulmonary disease, peripheral arterial disease, chronic respiratory failure and selected cardiovascular conditions, wearable NIRS detects disease-specific patterns of muscle deoxygenation and post-exercise reoxygenation that track responses to rehabilitation. Conclusions: Current evidence supports wearable NIRS as a complementary, intensity-aware monitoring tool—particularly for delineating the heavy/severe-intensity boundary and detecting peripheral metabolic limitations—rather than as a stand-alone replacement for ventilatory or lactate thresholds. Because much of the evidence derives from small, single-sex or athlete-only cohorts, these findings should be regarded as a promising basis requiring further validation in broader NCD populations. Implementation in NCDs requires standardized placement and calibration protocols, sex- and body composition-stratified reference values, motion-artifact mitigation, and adequately powered longitudinal trials in clinical populations. Full article

Background: More than 750 million cases of COVID-19 have been reported worldwide. The respiratory system, particularly the lungs, is one of the main targets of SARS-CoV-2 infection. Although persistent pulmonary function abnormalities have been described in adults, evidence in pediatric populations remains limited and inconsistent. Children usually experience a milder course of COVID-19; however, the long-term impact of SARS-CoV-2 infection on respiratory function in this group is still unclear. Current studies report conflicting findings regarding persistent spirometric abnormalities and their relationship with disease severity and time since infection. Therefore, further research is needed to better characterize post-infectious respiratory sequelae in children and adolescents. The aim of this study was to evaluate spirometric abnormalities in a pediatric cohort following COVID-19 infection. Methods: This retrospective and prospective observational study included 109 children and adolescents aged 6–18 years with a history of asymptomatic, mildly symptomatic, or symptomatic COVID-19 infection. Spirometry was performed following recovery from infection, and pulmonary function parameters were analyzed according to clinical course and time since infection. Results: Spirometry was conducted at a mean of 4.3 ± 2.8 months after infection. Abnormalities in pulmonary function were identified in 23.85% of the study population, with reduced FVC being the predominant spirometric abnormality. No statistically significant association was observed between the severity of COVID-19 and spirometric impairments (p > 0.5). Abnormal spirometry findings were observed across all post-infection time intervals examined; however, no statistically significant differences were identified between the groups. Conclusions: Spirometric abnormalities, predominantly reduced FVC, were observed in a substantial proportion of pediatric patients following SARS-CoV-2 infection. Although no clinical predictors were identified, the absence of pre-infection measurements and a control group limits interpretation. Longitudinal studies are required to clarify the clinical relevance and persistence of these pulmonary function changes. Full article

Background: The increasing incidence and improved survival rates of multiple myeloma (MM) have led to a growing healthcare burden, particularly in terms of hospitalizations. In addition, infection-related complications remain a major cause of morbidity and mortality in these patients. The impact of infection control measures implemented during the COVID-19 pandemic on hospitalization patterns in MM is not well-established. Methods: We conducted a retrospective observational study including all hospital admissions of patients with MM in a tertiary hospital in Spain across three different periods: 2008, 2018, and May 2020 to April 2021 (COVID-19 pandemic period). We analyzed the proportion of admissions, cumulative length of stay, causes of hospitalization, and infection-related complications. Results: The proportion of hospitalizations due to MM increased significantly from 14% in 2008 to 29.8% in 2018 (p < 0.001), along with a parallel increase in cumulative length of stay (14.4% vs. 27.1%, p < 0.001). During the COVID-19 period, a significant reduction in the proportion of admissions was observed compared to 2018 (21.2% vs. 29.8%, p = 0.0029), while cumulative length of stay showed a non-significant decrease. The proportion of infection-related admissions remained stable during the pandemic period, although the absolute number of infections decreased, including respiratory infections. Notably, the incidence of nosocomial pneumonia decreased significantly (26.3% vs. 9.6%, p = 0.028). Conclusions: Compared with 2008, patients with MM accounted for a substantially higher proportion of hospital admissions and cumulative hospital stay in 2018, reflecting the increasing healthcare burden associated with this disease. During the COVID-19 period, a significant reduction in nosocomial pneumonia was observed, suggesting that infection-control strategies may help reduce respiratory complications in patients with MM. Full article

Equine asthma is a chronic inflammatory disease of the lower respiratory tract, primarily associated with inhalation of organic dust, microbial particles and environmental aeroantigens. Although the inflammatory and immunological mechanisms underlying equine asthma have been extensively investigated, the potential contribution of neuroimmune pathways remains poorly understood. In humans and rodent models, asthma is increasingly recognised as a disorder involving complex bidirectional interactions between the nervous and immune systems. Sensory nerve activation, neuropeptide release, autonomic dysregulation and neuronal remodelling contribute to bronchoconstriction, airway hyperresponsiveness, mucus hypersecretion and chronic airway remodelling. This review summarises current knowledge of the neuroimmune mechanisms involved in asthma, with particular emphasis on comparative aspects across humans, rodents and horses. Literature searches were conducted using the PubMed database, focusing on studies investigating neurogenic inflammation, airway innervation, neuropeptides, transient receptor potential channels and neuronal remodelling in asthma and chronic airway disease. Existing equine evidence indicates the presence of substance P- and calcitonin gene-related peptide-immunoreactive nerve fibres in the equine airways, increased neurokinin-mediated bronchoconstriction in severe equine asthma, and enhanced airway innervation in affected horses. However, compared with human and rodent studies, horse-specific data remain extremely limited. Current evidence suggests that neuroimmune pathways are unlikely to be the primary initiating mechanism of equine asthma, but may act as important modulators of chronic airway dysfunction and disease progression. The marked scarcity of equine studies investigating neuroimmune signalling represents a major knowledge gap and highlights an important direction for future research in equine respiratory medicine. Full article

Chronic obstructive pulmonary disease (COPD) extends beyond the respiratory system and is closely linked to an increased risk of cardiovascular complications. Exacerbations represent critical periods of cardiovascular vulnerability, with a marked rise in major adverse cardiovascular events observed in the early post-exacerbation phase. This narrative review synthesizes current evidence on the epidemiology, pathophysiological mechanisms, and therapeutic implications of cardiovascular risk following COPD exacerbations. A structured literature search was conducted to identify relevant studies in this setting. Cardiovascular risk is elevated following exacerbations, particularly within the first weeks, and remains increased for months thereafter. Multiple pathophysiological mechanisms contribute to this vulnerable window. Systemic inflammation, marked by elevated cytokines such as IL-6, IL-8, and CRP, promotes endothelial dysfunction, vascular oxidative stress, and impaired nitric oxide bioavailability. Despite the well-established link, cardiovascular disease remains overlooked and undertreated in patients with COPD, and the use of guideline-directed cardiovascular therapies is suboptimal. A more systematic, integrated approach to cardiovascular assessment and management in patients with COPD is warranted to improve outcomes. Full article

Background: Antimicrobial resistance, driven by inappropriate use and overuse of antibiotics, is a major public health threat. Diarrhea and respiratory illness are the leading causes of pediatric healthcare visits in low- and middle-income countries like Bangladesh. Despite clear WHO guidelines recommending limited use of antibiotics for these conditions, potentially inappropriate or non-prescription antibiotic use remains a concern. Methods: We interviewed caregivers of 3025 under-5 children via cellphones to assess common illnesses, associated care-seeking practices, and antibiotic use for diarrhea and respiratory illnesses experienced by their children in the prior 14 days. Caregivers were identified through hospital outpatient screening and were contacted over the phone for the interview at least two months after that hospital visit. Results: Among the participants, 116 (3.8%) reported diarrheal disease and 570 (18.8%) experienced respiratory illness during the preceding 2-week recall period. Among the children with diarrhea, 52.6% received antibiotics, and 73.8% obtained them over the counter from pharmacies. Among those with respiratory illness, 26.3% received antibiotics, and 58% procured them from local drugstores without a prescription from a registered physician. For diarrhea, azithromycin and metronidazole were the commonly used antibiotics, while for respiratory illness, cefixime and azithromycin were frequently used. Notably, 68% of the diarrheal children either sought care from local drugstores, were self-medicated, or did not receive any formal treatment. Conventional practice, long wait times at healthcare facilities, distance, and poverty were the main reasons for not seeking care from a registered healthcare provider. Conclusions: Understanding community-level antibiotic use and care-seeking behavior is essential to strengthening antibiotic stewardship and child health programs. Our findings suggest the need for context-sensitive community education, improved access to appropriate care, and enforcement of regulations restricting the over-the-counter sale of antibiotics to curb irrational and excessive antibiotic use. Full article

Background and objective: Hypoxemia and respiratory failure (RF) in chronic obstructive pulmonary disease (COPD) are associated with exacerbations, comorbidities and increased mortality. However, the prevalence of hypoxemia and RF in stable COPD is unknown. We aimed at investigating the prevalence and determining predictive factors for chronic gas exchange abnormalities in COPD patients. Methods: A retrospective cohort study that enrolled clinically stable COPD patients referring to a pulmonary outpatient clinic. Anthropometrics, clinical characteristics, blood gas analysis and lung function were analyzed. Patients were grouped according to hypoxemia (PaO₂ <80 and ≥60 mmHg), type 1 (PaO₂ < 60 mmHg) or type II (PaO₂ < 60 and PaCO₂ > 45 mmHg) RF. A sensitivity analysis adopting an age-adjusted definition of hypoxemia was performed. Predictive factors for hypoxemia or RF were assessed with multifactorial analysis. Results: We analyzed data from 515 patients. Fixed-ratio hypoxemia, RF type 1 and type 2 were observed in 352 (68.3%), 27 (5.2%) and 43 (8.3%) patients, respectively. Risk of hypoxemia was associated with preserved alveolar volume, residual volume/total lung capacity, and lung diffusion capacity. Heart failure, ischemic heart disease, atrial fibrillation, and metabolic syndrome were predictive factors for RF. Patients with age-adjusted hypoxemia (n = 321 patients, 62.3%) showed no difference in terms of anthropometrics, lung function, and clinical characteristics as compared with fixed-threshold hypoxemia. Conclusions: Hypoxemia is frequent in stable COPD. Lung function parameters and comorbidities can support the identification of patients at risk of RF. Blood gas analysis should be always performed in patients with COPD to allow for personalized therapy and management. Full article

Assessing autophagy may offer insights into the pathogenesis of chronic obstructive pulmonary disease (COPD). However, measuring the dynamic aspect of autophagy is challenging, and sample manipulation can cause signal fluctuations that deviate from physiological conditions. We applied an organotypic method to quantify autophagy in COPD, where it frequently demonstrates disease-related dysregulation. Blood from control and COPD participants was treated with or without chloroquine. Microtubule-associated protein 1 light chain 3B II (LC3B-II) abundance was quantified in peripheral blood mononuclear cells (PBMCs), and findings were validated by transmission electron microscopy. Our observations show that while basal LC3B-II abundance was similar between groups (p = 0.60), autophagic flux was significantly lower in the COPD cohort, suggesting disruption in the regulatory factors that direct autophagosome clearance (p = 0.004). This was supported by less frequent observations of autophagy-related vacuoles in the cytosol of COPD-derived PBMCs. Our findings indicate that the suppression of autophagy can be detected in the blood of individuals with COPD, which warrants further investigation into its contribution to extrapulmonary disease processes. Full article

Allergy is the most common hypersensitivity disorder, affecting around 30% of the global population. Due to its rapidly increasing prevalence and significant reduction in quality of life for patients, allergy represents a major public health problem, and the improvement of diagnostic and treatment options for allergic diseases is of utmost importance. Moreover, the development of preventive allergen-specific immunization strategies is an emerging research direction in mitigating allergy incidence, especially for respiratory diseases such as allergic rhinitis and asthma. Since environmental allergen exposures differ substantially depending on climatogeographical, ecological, and behavioral factors, investigating local IgE sensitization profiles could significantly contribute to optimizing allergy management. We performed a systematic database review to summarize available knowledge on IgE sensitization profiles in Russia across different regions of the country. The study was conducted in compliance with PRISMA and SWiM guidelines and registered in the PROSPERO database (CRD420250650847). We identified major differences in sensitization profiles across certain geographical areas, reported in 60 studies. However, heterogeneity of methods and gaps in the existing evidence were noted, and, as the available data appear insufficient for reliable profiling, an outline was proposed for systematic and methodologically harmonized studies necessary to develop further region-tailored approaches. Full article

Background/Objectives: Daytime sleepiness in obstructive sleep apnea (OSA) shows substantial variability and is not fully explained by disease severity. This study aimed to evaluate whether a history of cancer is associated with subjective daytime sleepiness independently of respiratory burden. Methods: In this observational cohort study, 402 untreated patients with OSA were included. Cancer history was defined as a documented diagnosis of malignancy prior to baseline polygraphy. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Multivariable linear and logistic regression models were used to evaluate the association between cancer history and ESS (continuous and dichotomized as >10), adjusting for age, sex, body mass index, smoking status, chronic obstructive pulmonary disease, and apnea–hypopnea index (AHI). Sensitivity analyses additionally adjusted for heart disease and nocturnal hypoxic burden. Results: Sixty-two patients (15%) had a history of cancer. OSA severity and hypoxemia indices were comparable between groups. In multivariable analysis, cancer history was independently associated with modestly lower ESS scores (B = −1.66, 95% confidence interval [CI] −2.96 to −0.37; p = 0.012) and a reduced likelihood of excessive daytime sleepiness (ESS > 10) (odds ratio [OR] = 0.25, 95% CI 0.07 to 0.85; p = 0.027). Conclusions: In this real-world cohort of untreated patients with OSA, cancer history is associated with modestly lower subjective daytime sleepiness despite comparable disease severity, supporting a potential dissociation between physiological burden and symptom perception. These findings indicate that reliance on subjective sleepiness alone may contribute to under-recognition of clinically relevant OSA in patients with a cancer history. Full article

Pediatric respiratory infections remain among the leading causes of emergency department visits, hospitalization and pediatric intensive care unit (PICU) admission. Although most acute respiratory infections in children are viral, clinical manifestations overlap substantially among viral, bacterial and atypical pathogens, creating diagnostic uncertainty and promoting empirical antimicrobial use. Rapid antigen tests, nucleic acid amplification tests, multiplex respiratory panels and metagenomic sequencing have expanded the ability to detect pathogens within clinically actionable timeframes. However, evidence from pediatric emergency trials indicates that rapid pathogen detection alone does not necessarily reduce antibiotic prescribing or healthcare costs. These findings suggest that the value of rapid diagnostics depends less on analytical breadth than on whether testing is applied to the right child, in the right clinical scenario and within a predefined decision pathway. This narrative review reorganizes the evidence around a scenario-driven top-pathogen framework. Top pathogens are defined as organisms that, in a specific age group, syndrome, season or care setting, have high prevalence, severe disease potential, transmissibility, treatment implications, antimicrobial resistance relevance or infection-control value. We discuss how top-pathogen testing should differ across emergency triage, inpatient ward management, severe pneumonia, PICU care, hospital-acquired pneumonia, ventilator-associated pneumonia and outbreak settings. We further examine the economic mechanisms through which rapid testing may generate value, including reduced unnecessary antibiotics, timely antiviral therapy, optimized isolation, shorter length of stay, reduced repeated testing and prevention of healthcare-associated transmission. Finally, we propose implementation principles centered on diagnostic stewardship, antimicrobial stewardship, local epidemiology and real-world cost-effectiveness evaluation. A scenario-driven top-pathogen strategy may provide a practical bridge between broad syndromic testing and precision infectious disease management in children. Full article

Oxidative stress is a central pathogenic mechanism in acute and chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary fibrosis. Excessive production of reactive oxygen and nitrogen species (ROS/RNS), combined with impaired antioxidant defenses, contributes to epithelial and endothelial injury, inflammation, mitochondrial dysfunction, airway remodeling, and progressive loss of lung function. Plant-derived polyphenols and polyphenol-rich herbal mixtures have emerged as promising candidates for respiratory protection due to their multimodal activity. They exert effects through direct antioxidant action, enhancement of glutathione-dependent and enzymatic defenses, activation of the Nrf2/HO-1 pathway, and suppression of NF-κB, MAPK, inflammasome, and profibrotic signaling. Experimental studies have demonstrated protective effects of compounds such as quercetin, resveratrol, rosmarinic acid, epigallocatechin gallate, and phenolic-rich extracts. However, clinical translation remains limited by poor bioavailability, variability of botanical preparations, lack of standardization, and insufficient high-quality human studies. This review summarizes key mechanisms of oxidative lung injury and critically evaluates the therapeutic potential and translational challenges of herbal polyphenolic mixtures in respiratory diseases. Full article