Search Results (3,000)

Background: Fermented polysaccharides derived from Morinda citrifolia (noni) have been suggested to modulate innate immune responses, but clinical evidence remains limited. Objectives: This randomized, double-blind, placebo-controlled trial evaluated the effects of fermented noni polysaccharides on natural killer (NK) cell activity and immune-related biomarkers in adults with recurrent upper respiratory tract infections (URTIs). Methods: A total of 100 adults aged 40 to <75 years with a documented history of ≥2 episodes of upper respiratory tract infection in the prior 12 months were randomly assigned to receive fermented noni polysaccharides (487.5 mg/tablet, two tablets once daily; 975 mg/day of FNP extract) or a matched placebo for 8 weeks. The primary endpoint was the change in NK cell activity at effector-to-target (E:T) ratios of 50:1, 25:1, and 12.5:1, assessed using K562 NK-sensitive target cells. Secondary endpoints included circulating cytokines (IFN-γ, TNF-α, IL-2, IL-6, IL-10, IL-12, IL-1β) and immunoglobulin G (IgG). Eighty-four participants (43 treatment, 41 placebo) were included in the modified intention-to-treat/full analysis set (mITT/FAS); 81 participants (41/40) constituted the per-protocol set (PPS). Primary efficacy was analyzed in the mITT/FAS. This trial was retrospectively registered at CRiS (KCT0011316) after trial completion; the IRB-approved protocol was finalised before enrolment and remained unchanged thereafter. Results: NK cell activity in the treatment group increased from baseline at all three E:T ratios, whereas it slightly decreased in the placebo group. Adjusted between-group LS mean differences (95% CI) were +8.94 (−0.61, 18.50; p = 0.066) at E:T 50:1, +7.68 (−1.14, 16.50; p = 0.087) at 25:1, and +3.29 (−2.95, 9.54; p = 0.145) at 12.5:1, all favouring treatment but not reaching the conventional threshold for significance in the mITT/FAS. Prespecified PPS sensitivity analyses reached significance at E:T 50:1 (+11.03; p = 0.025) and 25:1 (+9.94; p = 0.028). Selected cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-1β) increased to a greater extent in the treatment group than in the placebo group, whereas TNF-α, IL-12, and IgG were unchanged. URTI incidence at week 4, week 8, and cumulatively did not differ significantly between groups. The intervention was well tolerated, with no serious adverse events and no treatment-related discontinuations. Conclusions: Compared with placebo, fermented noni polysaccharide supplementation showed numerically greater increases in NK cell activity at all three E:T ratios (50:1, 25:1, and 12.5:1) in the primary mITT/FAS analysis, although these between-group differences did not reach statistical significance. Prespecified per-protocol set (PPS) sensitivity analyses showed significant between-group differences at E:T ratios of 50:1 and 25:1. The treatment group also showed greater increases in selected cytokines (IFN-γ, IL-2, IL-6, IL-10) relative to placebo. No significant between-group differences were observed in URTI incidence, IgG, GARS, WBC, or leukocyte subset proportions. These exploratory biomarker findings, in the absence of safety signals, suggest a possible immunomodulatory profile but do not establish clinical efficacy. Confirmation in larger, prospectively registered trials with clinically adjudicated infection-related endpoints is warranted. Full article

Background/Objectives: Respiratory tract infections (RTIs) are a leading cause of morbidity in children under five, with over 75% experiencing recurrent episodes and an increased risk of asthma by school age, particularly following respiratory syncytial virus (RSV) and rhinovirus (RV) infections. While current therapies primarily address acute symptoms, effective preventive strategies remain limited. Bacterial-derived immunomodulators have emerged as promising interventions, but their mechanisms and pediatric clinical evidence remain incompletely characterized. This narrative review examines preclinical mechanisms and clinical findings for four such agents, contextualizing current evidence and identifying key gaps. Methods: A targeted narrative review of PubMed-indexed literature (inception to September 2025) was conducted. Mechanistic studies, pediatric (0–18 years) clinical trials, and meta-analyses evaluating OM-85, polyvalent mechanical bacterial lysates (PMBL/Ismigen), MV130, and Lactobacillus rhamnosus CRL1505 were included. Outcomes of interest comprised immunological mechanisms, RTI incidence, wheezing, and asthma-related outcomes. Results: All four agents share convergent immunomodulatory mechanisms involving epithelial barrier reinforcement, innate immune activation, and adaptive immune modulation. OM-85 has the most extensive preclinical evidence. PMBL enhances epithelial repair via the IL-23/IL-22 axis, MV130 induces trained immunity, and CRL1505 acts through the gut–lung axis. Clinical evidence varies markedly, with OM-85 showing the most comprehensive data (18 RCTs and 7 meta-analyses), followed by PMBL and MV130, while evidence for CRL1505 remains predominantly preclinical. Conclusions: Despite variable evidence maturity, these agents share a coherent mechanistic rationale and favorable safety profiles, with ongoing studies expected to clarify their clinical role in early-life respiratory prevention. Full article

In extremely cold environments, inhaling frigid, dry air can pose significant health risks, potentially leading to airway inflammation and respiratory injury. While previous studies have examined thermal exchange within lung airways under hot-air inhalation, the majority have focused on localized regions rather than the entire respiratory tract. This study expands the scope of inquiry by simulating airflow and heat transfer throughout a more complete computed tomography (CT)-based respiratory tract, from the nasal cavity to the larynx and trachea and extending down to the 13th generation of the bronchial tree, under two cold-air inhalation scenarios at −5 °C and −20 °C. Using computational fluid dynamics, this study integrates Large Eddy Simulation with the Smagorinsky–Lilly subgrid-scale model to capture the complex interaction of turbulent flow and thermal transport in the human respiratory system. By analyzing temperature distributions, heat flux, heat-transfer coefficients, Nusselt numbers, and mass flux across the airways, the research shows how varying degrees of cold inhalation influence respiratory thermodynamics and associated biomechanical responses. As such, this study establishes a rigorous scientific foundation for the development of more sophisticated and predictive respiratory-tract models in sub-zero environments in future work. Full article

Objectives: We aimed to describe the healthcare utilization and economic burden of lower respiratory tract infections (LRTIs) among children aged 1–24 months across five tertiary hospitals in Saudi Arabia. Methods: This multicenter retrospective cohort study included 14,320 children diagnosed with LRTIs between August 2021 and July 2025. Data were extracted from the electronic medical records of the Ministry of National Guard Health Affairs. Demographics were analyzed using a patient-level dataset, whereas healthcare utilization and costs were evaluated at the episode level. Data were analyzed using descriptive and inferential statistics and multivariable logistic regression. Results: A total of 14,320 children contributed 22,895 LRTI-related episodes during the study period. Nearly half of the cohort (49.4%) were aged 1–6 months, and bronchiolitis was the predominant diagnosis (84.6%), followed by pneumonia (15.1%). Overall, 34.4% of patients required hospitalization, while 7.1% required ICU admission. LRTIs accounted for 21.0% of all pediatric ward admissions across participating hospitals. Total direct healthcare costs reached USD 23.0 million. Although ICU admissions represented only 7.1% of episodes, they accounted for 45.1% of total healthcare expenditures. In multivariable analysis, pneumonia was independently associated with higher odds of ICU admission compared with bronchiolitis (aOR 2.91, 95% CI 2.43–3.48; p < 0.001). Significant seasonal variation in LRTI episodes was observed, with higher episode volumes during winter months (p = 0.004). Conclusions: Pediatric LRTIs impose substantial clinical and financial burdens, particularly among younger infants, marked by disproportionate ICU-related costs. Full article

Background. Lower respiratory tract infections remain a major cause of morbidity and mortality in infants worldwide. Newborns possess an immature immune system but acquire passive immunity through maternal antibodies transferred via the placenta (IgG) and breast milk (IgA). Maternal vaccination may enhance this protection. This study aimed to quantify antibody levels against respiratory viruses in serum and breast milk from lactating women. Methods. Serum and breast milk samples were collected from 26 lactating mothers. Antibody levels were measured using an indirect enzyme-linked immunosorbent assay (ELISA) targeting seven viral antigens: influenza A (A/Thailand, A/California), influenza B (B/Phuket, B/Austria), SARS-CoV-2 (Spike and receptor-binding domain, RBD) and RSV F pre-fusion protein. Antibody isotypes IgG, IgA and IgM were analysed. Results. Virus-specific IgG and IgA antibodies were detected in all samples. Breast milk showed the highest levels of IgA, whereas serum contained higher IgG levels. A moderate positive correlation was observed between serum and milk IgG. No correlation was found between serum IgG and milk IgA, but both levels were elevated. Conclusions. Breast milk and serum contain relatively high levels of antibodies against the tested respiratory viruses. The elevated levels of serum IgG and milk IgA indicate a coordinated defence between systemic and mucosal immunity in response to infections. The levels and correlation of specific isotypes point to the source of the antibodies: milk IgG probably originates from the blood, whereas milk IgA is produced locally. Full article

Background/Objectives: AA amyloidosis is a serious complication of chronic inflammation, which may arise in the setting of inborn errors of immunity (IEIs) due to recurrent or persistent infections. Common variable immunodeficiency (CVID) is the most frequent symptomatic IEI in adults, yet its association with secondary AA amyloidosis remains rarely reported. Case presentation: We describe a 37-year-old male with a history of recurrent pneumonia, chronic sinusitis, and osteomyelitis with sepsis since childhood. At age 33, he developed bilateral pneumonia after COVID-19, followed by repeated lower respiratory tract infections. At age 36, nephrotic syndrome (proteinuria 10.69 g/day, hypoalbuminemia) led to kidney and gastric mucosa biopsies, which confirmed AA amyloidosis. Immunological workup revealed panhypogammaglobulinemia (IgG 0.1 g/L, IgA 0.01 g/L, IgM 0.28 g/L), markedly reduced switched memory B cells, and an inverted CD4⁺/CD8⁺ ratio. Chest CT showed bronchiectasis, bronchiolitis, and mediastinal lymphadenopathy. Whole-exome sequencing excluded known monogenic IEIs, autoinflammatory, or hereditary amyloidosis genes; a heterozygous likely pathogenic variant in ODAD2 (associated with primary ciliary dyskinesia) was considered incidental. A diagnosis of CVID with secondary AA amyloidosis was established. Conclusions: This case illustrates that CVID may remain undiagnosed for decades and present with secondary AA amyloidosis as the first major complication. In any patient with nephrotic syndrome and a history of recurrent or unusual infections, an IEI should be actively excluded. Early recognition of CVID and appropriate immunoglobulin replacement therapy can prevent infectious exacerbations and potentially halt amyloid progression. Full article

Background/Objectives: Patients in long-term care hospitals (LTCHs) are at increased risk of harboring antimicrobial-resistant organisms due to frequent healthcare exposure and multiple comorbidities. This retrospective observational study aimed to compare the antimicrobial susceptibility of bacterial isolates from LTCH-onset infections (LTCHIs) with those from community-acquired infections (CAIs) in elderly patients. Methods: This study was conducted at a 700-bed urban tertiary university hospital and included patients aged ≥65 years with positive cultures for bacteremia, lower respiratory tract infections (LRTIs), or urinary tract infections (UTIs) within 48 h of admission. Medical records, including antimicrobial susceptibility test results, were reviewed for a total of 1780 patients and their isolates. Antimicrobial susceptibility patterns were compared between LTCHI and CAI patients. Results: Patients with LTCHI exhibited significantly higher antimicrobial non-susceptibility than those with CAIs across multiple pathogens and antimicrobial classes (p < 0.05). In bacteremia, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae from LTCHI cases showed increased non-susceptibility to β-lactams and fluoroquinolones. In LRTIs, Pseudomonas aeruginosa and Acinetobacter baumannii demonstrated high non-susceptibility to carbapenems (52.9% and 90%, respectively) and aminoglycosides. In UTIs, LTCHI isolates exhibited broader resistance among Enterobacterales and P. aeruginosa. Notably, the proportion of multidrug-resistant organisms, including carbapenem-resistant Enterobacterales (15.4–50.0%) and carbapenem-resistant Acinetobacter baumannii (90.5%), was substantially higher in the LTCHI group across all infection sites. Conclusions: Elderly patients with LTCHI are more likely to harbor antimicrobial-resistant pathogens than those with CAIs. Careful consideration of LTCHI origin is therefore essential for empirical antibiotic selection and for strategies aimed at limiting further resistance. Full article

Survivors of primary gastric lymphoma (PGL) face a significantly elevated and persistent risk of developing second primary malignancies (SPMs), with gastric adenocarcinoma representing the most frequent SPM and standardized incidence ratios reaching up to 16-fold above the general population. This excess risk persists for decades after initial treatment and is associated with increased cause-specific mortality compared to matched primary cancers. Among patients with PGL, approximately 5% develop gastric cancer (with two-thirds being metachronous), and nearly 15% harbor precancerous lesions including atrophic gastritis, intestinal metaplasia, and dysplasia. Beyond gastric malignancies, survivors also experience elevated rates of extra-gastric SPMs, particularly digestive system tumors (43%), respiratory cancers (21%), and urinary tract malignancies (13%). Key risk factors include treatment with immunochemotherapy or radiotherapy, advanced age, male sex, advanced stage at diagnosis, ulcerative-type lymphoma morphology, and persistent Helicobacter pylori (HP) infection. Patients receiving combined chemoradiotherapy demonstrate the highest SPM risk, particularly for gastric and pancreatic cancers. These findings underscore the critical importance of lifelong, risk-adapted surveillance strategies integrating both hematology and gastroenterology follow-up. Annual endoscopic surveillance is recommended for high-risk patients, with intervals adjusted according to lymphoma histology, HP status, and the presence of precancerous gastric lesions. Mandatory HP eradication with confirmation of response is essential for reducing gastric cancer risk. Future research priorities include prospective, standardized studies to better quantify SPM risk, validation of molecular and microbiological biomarkers for individualized risk stratification, and development of predictive models to enable personalized surveillance protocols and improve long-term outcomes in this vulnerable population. Full article

Pseudomonas fluorescens is a rare, environmental Gram-negative bacterium that has been rarely reported as a cause of respiratory tract infections. This paper presents a case of a 72-year-old male who developed community-acquired pneumonia due to P. fluorescens. The diagnosis was made by sputum culture and he responded to meropenem treatment. A literature search revealed three previously reported cases of P. fluorescens pneumonia. These cases primarily affected elderly male patients. All reported patients demonstrated positive clinical outcomes following appropriate antimicrobial therapy. This case highlights that although P. fluorescens is often considered a colonizer, it may act as a potential pathogen in selected clinical settings. Full article

Respiratory infections are among the leading causes of healthcare consultations in paediatric populations. The SARS-CoV-2 pandemic significantly altered both the circulation of respiratory pathogens and the utilisation of healthcare services. This retrospective longitudinal observational study analysed temporal trends in consultations for respiratory infections among children under 15 years of age in the Anoia region between 2017 and 2024. Descriptive analyses and time-series modelling using negative binomial regression were performed. A total of 71,918 consultations were recorded, of which 71.7% occurred in primary care and 28.9% in hospital settings. The mean age of patients was lower in the hospital setting (3.4 years) than in primary care (8.7 years). During the pandemic, consultations decreased by 38% compared with the pre-pandemic period, followed by a rebound in 2022, particularly in hospital care. In the post-pandemic period, hospital consultations remained above pre-pandemic levels, whereas primary care activity tended to stabilise. No increase in bronchiolitis consultations was observed compared with the pre-pandemic period. Full article

Mucosal immunity, including antibodies like immunoglobulin A (IgA), function as the body’s first line of defense in the respiratory tract, particularly against viruses. An anti-rS protein IgA enzyme-linked immunosorbent assay (ELISA) was developed using the Omicron XBB.1.5 subvariant of SARS-CoV-2 and was validated to demonstrate the suitability of the method for testing saliva from SARS-CoV-2 vaccine clinical trials. This assay successfully met acceptance criteria for inter-/intra-assay precision, specificity, selectivity, linearity, lower/upper limits of quantitation, and assay robustness. The IgA in saliva was stable for up to 7 freeze/thaw cycles, for up to 48 h at 24 °C, up to 7 days at 4 °C, up to 3 weeks at −20 °C, and up to 1 year at −80 °C. After validation using Omicron XBB.1.5 rS protein, cross-reactivity was demonstrated with the SARS-CoV-2 variant JN.1. This validated IgA assay can be a valuable tool to assess mucosal IgA levels in SARS-CoV-2 clinical trials. Full article

Background: The antimicrobial resistance crisis is driven by antibiotic overuse, often due to the difficulty in distinguishing bacterial from viral infections. In the European Union, acute respiratory tract infections account for about 38% of all antibiotic prescriptions in community and emergency settings, and an estimated 30–50% of these prescriptions are potentially inappropriate. Point-of-care C-reactive protein (CRP) testing can support the distinction between bacterial and viral infections, but its diagnostic accuracy is often compromised by chronic inflammatory comorbidities that elevate baseline CRP levels. Objective: This exploratory, hypothesis-generating study evaluated the diagnostic utility of CRP in an Emergency Department (ED) cohort and proposed a novel “Comorbidity Confounder Score” (CCS) prototyped pilot tool as support to identify patient subgroups in whom CRP retains high diagnostic value. Methods: We conducted an exploratory, hypothesis-driven retrospective cohort study of 92 patients presenting to a tertiary ED with acute flu-like symptoms between 2023 and 2025. Microbiological diagnoses were confirmed using culture and PCR. ROC curve analysis and AUC comparisons were performed using the pROC package in R (v4.2.0; DeLong method). A post hoc power analysis confirmed 81% power at alpha = 0.05. The diagnostic performance of CRP (Area Under the Curve—AUC) was assessed in the total cohort and stratified into “Low-Utility” (high comorbidity, CCS ≥ 2) and “High-Utility” (low comorbidity, CCS < 2) subgroups. Results: In the unselected total cohort, CRP demonstrated suboptimal diagnostic performance (AUC = 0.61, 95% CI: 0.49–0.73). However, exploratory post hoc stratification revealed divergence. In the “Low-Utility” group, CRP had no diagnostic value (AUC = 0.52). In the “High-Utility” group, a preliminary signal of improved CRP discriminatory performance was observed (AUC = 0.84; DeLong test vs. total cohort, p = 0.004), subject to the optimistic bias inherent in derivation-cohort stratification. The AUC improvement was statistically significant (DeLong test, p = 0.004). The empirically derived optimal cutoff in the High-Utility group was 31.5 mg/L (Youden Index J = 0.54). Conclusions: These exploratory, post hoc findings are a first step into evaluation based on a pilot ML tool and require prospective multicenter validation before any conclusions regarding clinical utility can be drawn. The CCS represents a hypothesis-generating construct only and must not be used for clinical decision-making in its current form. Full article

Asthma represents a chronic inflammatory condition of the respiratory tract, where long-term bronchial inflammation serves as a primary driver of progressive airway remodeling. This complex pathology emerges from the intricate synergy between host genetic susceptibility and diverse environmental triggers, ultimately impairing pulmonary function. At the cellular level, asthmatic responses are orchestrated by a dynamic crosstalk among various immune and structural populations, including airway epithelial cells, T-lymphocytes, eosinophils, and mast cells, which collectively perpetuate the inflammatory milieu. Although inhaled corticosteroids are the conventional cornerstone of therapy, their clinical application is frequently hindered by potential systemic toxicity and the emergence of steroid-resistant phenotypes. Consequently, botanical extracts derived from both aerial and underground plant organs have gained attention as versatile multi-target candidates capable of modulating the multifaceted pathophysiological networks of asthma. This scoping review critically synthesizes the pharmacological efficacy of these plant-based interventions in regulating pivotal signaling cascades, such as MAPK, NF-κB, STAT3/6, and GATA3. Based on a systematic literature search covering the period from 2005 to 2025, this study provides a focused quantitative analysis of preclinical literature from the last decade (2016–2025) to evaluate the in vitro and in vivo models employed to validate these therapeutic effects. The assessment reveals that the vast majority of current research continues to rely on crude botanical preparations, with only a limited subset of studies utilizing enriched fractions or fully characterized isolated compounds. This predominance of unrefined extracts underscores a significant gap in chemical standardization and highlights the necessity for more rigorous mechanistic validation. Ultimately, this paper outlines strategic pathways for translating preclinical findings into clinical practice, offering a robust framework for the development of standardized plant-derived interventions in asthma management. Full article

Background/Objectives: Bronchiolitis is the leading cause of hospitalization among infants, and early prediction of disease severity and clinical outcomes remains challenging. The Modified Tal (M-Tal) score is a clinical tool used to assess severity; however, its utility in predicting outcomes requires further validation. Methods: This prospective study was conducted over a 2-year period at a tertiary care teaching hospital. Infants aged 1–12 months diagnosed with moderate-to-severe bronchiolitis were enrolled. Demographic, clinical, management, and outcome data were recorded. Results: A total of 120 infants were included (mean age 7.7 months; 61.7% males). Moderate bronchiolitis accounted for 81.7% of cases. The mean duration of illness at admission was 4.1 days. Severe bronchiolitis was associated with significantly longer duration of oxygen therapy (p = 0.034) and hospital stay (p = 0.028). Each one-point increase in M-Tal score was associated with an increase of 0.69 days in hospital stay (p = 0.012), 9.8 h in oxygen requirement (p < 0.01), and 0.32 days in PICU stay (p = 0.04). Conclusions: The M-Tal score at admission is a useful predictor of clinical outcomes in infants with moderate-to-severe bronchiolitis. Higher scores are associated with increased need for respiratory support and prolonged hospitalization, supporting its role in early risk stratification and management planning. Full article

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants, older adults, and immunocompromised individuals. Over the past decade, advances in structural biology, particularly cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), have transformed our understanding of RSV architecture, dynamics, and the mechanisms of entry and replication. High-resolution structures of the prefusion F glycoprotein (pre-F) and its complexes with neutralizing antibodies established the rationale for structure-guided antigen stabilization and directly enabled the development of the first licensed RSV vaccines. Complementary structures of the ribonucleoprotein, polymerase complex, and matrix lattice have broadened therapeutic targets beyond F. Here, we summarize these structural advances; review current structure-guided vaccine, antibody, and antiviral development efforts; and highlight priorities for next-generation vaccines and therapeutics. Full article