Search Results (578)

H9N2 low-pathogenic avian influenza viruses (LPAIV) represent an ongoing zoonotic threat due to their enzootic circulation in poultry, reassortment capacity, and increasing human transmission events. This study characterized three H9N2 isolates recovered from apparently healthy poultry in a Changchun live poultry market (September–November 2022) that exhibited unprecedented genetic and phenotypic characteristics indicating enhanced zoonotic risk. Phylogenetic analysis showed a complex mosaic genome combining segments from four distinct lineages: HA from the BJ/94-like lineage (human-associated), PB1/NP/NS from the F98-like lineage, NA from the FJ/30-C-like branch, and PB2/M genes from the G1-like lineage. Bayesian molecular clock analysis estimated the most recent common ancestor at February 2022, with HL55 and HL56 diverging by May 2022, indicating rapid local viral evolution. All isolates retained hallmark LPAIV characteristics (monobasic HA cleavage site, zero intravenous pathogenicity index in chickens). However, receptor-binding assays demonstrated a critical divergence among the isolates: while HL45 exhibited exclusive avian α2-3 receptor preference, both HL55 and HL56 retained strong avian receptor binding while additionally showing measurable affinity for human α2-6 receptors-a dual-binding phenotype associated with enhanced zoonotic potential. Most significantly, the HL55 isolate successfully infected BALB/c mice without prior adaptation, causing transient upper respiratory tract replication, moderate weight loss (~9.2%), and mild disease without mortality or systemic dissemination. These findings demonstrate that the direct mammalian infectivity of this specific mosaic H9N2 lineage adds to the growing body of evidence regarding the zoonotic potential of contemporary H9N2 variants. The presence of known mammalian-adaptation markers (PB2 A588V, NA stalk deletion, HA position 226 leucine), combined with demonstrated dual receptor-binding capacity and inherent mammalian infectivity, underscores the accelerated evolutionary trajectory of H9N2 viruses toward increased zoonotic competence. These findings warrant intensified surveillance in live poultry markets, comprehensive antigenic characterization of emerging variants, and enhanced biosecurity measures to mitigate the risk of spillover events and potential pandemic emergence. Full article

Background: Inappropriate antibiotic use for upper respiratory tract infections (URTIs) is common. However, existing research typically examines single indicators or broad categories of misuse practices, without considering the probabilistic and co-occurring nature of varying behaviours. This study aims to identify and characterise distinct antibiotic behavioural profiles within a general population to inform personalised interventions. Methods: This is a broadly representative population-based study of adult Singapore residents between November 2020 and January 2021. Latent class analysis was first performed to identify distinct profiles, followed by multinomial logistic regression to determine individual characteristics associated with each profile, with interaction effects examined. Results: Amongst 2004 respondents, the majority were “antibiotic appropriates” (53.0%), followed by “antibiotic avoiders” (24.9%), and “antibiotic seekers” (22.2%). “Antibiotic seekers” expected antibiotics for cold/flu, hopped between doctors to source antibiotics, used leftover antibiotics, stopped antibiotic courses prematurely and perceived antibiotics as harmless and useful for treating cold/flu. Individuals with poor knowledge of antibiotic use (AOR 3.71, 95% CI 2.89–4.76, p < 0.001) and antimicrobial resistance (AOR 3.51, 95% CI 1.05–11.76, p = 0.042), low eHealth literacy (AOR 1.34, 95% CI 1.02–1.77, p = 0.038), and high trust in doctors (AOR 2.14, 95% CI 1.44–3.17, p < 0.001) were more likely to be “antibiotic seekers”. Older adults with lower education levels were particularly likely to be “antibiotic seekers”. Conclusions: Approximately one-in-five Singapore residents are antibiotic seekers. Targeted education during multiple clinic visits, given the high trust in doctors, can address antibiotic knowledge gaps and misperceptions, reducing antibiotic misuse. Full article

Background/Objectives: Probiotic and synbiotic supplementation has been proposed as a preventive strategy against respiratory tract infections (RTIs) in early childhood, although evidence in infants and young children remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of probiotic or synbiotic supplementation administered during the first 24 months of life on respiratory infection outcomes. Methods: PubMed/MEDLINE, Embase, and Scopus were systematically searched for randomized controlled trials published between January 2015 and 30 September 2025. Eligible studies included infants and children aged ≤24 months receiving oral probiotics or synbiotics compared with placebo, no intervention, or standard care. The primary outcome was the incidence of at least one upper respiratory tract infection (URTI), while the secondary outcome was the incidence of any RTI. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated according to the GRADE approach. Results: Nine randomized controlled trials were included. Probiotic or synbiotic supplementation did not significantly reduce the risk of URTI (OR 0.95, 95% CI 0.47–1.95; I² = 78%). A non-significant trend toward a reduced risk of any RTI was observed (OR 0.66, 95% CI 0.35–1.25; I² = 69%). Exploratory subgroup analyses suggested possible strain-specific effects, with signals observed for Bifidobacterium longum subsp. infantis in relation to URTI prevention and Lactiplantibacillus plantarum ATCC 202195 for reduction in any RTI. However, these findings were based on a limited number of studies and should be interpreted cautiously. No serious adverse events attributable to supplementation were reported. Conclusions: Current evidence does not support the routine use of probiotic or synbiotic supplementation for the prevention of respiratory infections in children aged ≤24 months. However, potential strain-specific benefits warrant further investigation in adequately powered randomized trials. Full article

Upper respiratory tract infections and inflammatory nasal disorders are highly prevalent in childhood and represent a major cause of morbidity and healthcare utilization. Humans are continuously exposed to airborne microorganisms, allergens, and pollutants. Although the nasal mucosa provides effective mechanical and immunological defenses, these mechanisms may be impaired by inflammation, environmental pollutants, and mucociliary dysfunction, increasing susceptibility to infection and airway inflammation. Nasal irrigation (NI) contributes to the restoration of nasal homeostasis by mechanically removing mucus, pathogens, allergens, and inflammatory mediators, while also improving mucociliary clearance (MC), mucus rheology, and epithelial barrier function. Hypertonic solutions (HS) may provide additional osmotic and decongestant effects. Current evidence suggests that NI is a safe and well-tolerated adjunctive intervention that may improve symptoms and support mucosal function in acute and chronic upper airway diseases. This narrative review provides an updated overview of NI, with particular focus on pediatric populations. This paper integrates the pathophysiological mechanisms of mucociliary dysfunction, environmental exposures, and pediatric-specific anatomical and functional characteristics into a unified framework to understand the role of NI in childhood respiratory diseases. Clinical indications, administration techniques, solution selection, safety aspects, and age-specific practical considerations are discussed, highlighting the importance of appropriate technique, caregiver education, and adherence to basic hygiene principles. Full article

Background: Following the coronavirus disease 2019 (COVID-19) pandemic, increased reports of severe acute hepatitis of unknown etiology in children have raised concerns about virus-associated liver injury. Acute respiratory tract infections (ARTIs) are a common cause of pediatric hospitalization and may be accompanied by reactive hepatitis; however, virus-specific patterns of hepatic involvement remain incompletely defined. This study aimed to evaluate liver involvement associated with ARTIs in hospitalized children. Methods: This retrospective study included pediatric patients (<18 years) hospitalized with ARTIs between October 2021 and May 2023. Respiratory viruses were identified via multiplex real-time polymerase chain reaction assays. Liver function tests were systematically evaluated during hospitalization. Transaminase elevations were categorized according to the upper limit of normal (ULN = 40 U/L). Acute hepatic failure was defined according to the Pediatric Acute Liver Failure criteria. Results: A total of 179 patients were analyzed (median age: 38 months; 59.2% male). Elevated AST and ALT levels were observed in 24.0% and 8.4% of patients, respectively. Adenovirus was the most frequently detected virus (11.2%), followed by influenza A (7.3%) and parainfluenza virus (6.7%). Severe transaminase elevations (>5 × ULN and >500 U/L) were observed in patients with influenza infection. All cases of acute hepatic failure (n = 3) were associated with influenza infection. Other respiratory viruses were associated with mild or transient liver enzyme abnormalities. Conclusions: Severe hepatic involvement—including severe transaminase elevation and acute hepatic failure—occurred exclusively in children with influenza infection, particularly influenza B, while mild and transient liver enzyme abnormalities were common across other respiratory viral infections. These findings highlight the importance of targeted liver function monitoring in pediatric influenza patients and provide clinically relevant data on virus-specific hepatic involvement in the post-COVID-19 era. Full article

Accurate and timely diagnosis of respiratory diseases remains a critical challenge in clinical practice, particularly in resource-limited and remote healthcare settings. This study proposes a web-based automated respiratory disease classification system leveraging a hybrid Convolutional Neural Network–Long Short-Term Memory with Time-Distributed (CNN-LSTM-TD) architecture for lung sound analysis. The proposed model integrates three complementary time-frequency representations—Mel-Frequency Cepstral Coefficients (MFCCs), Mel-spectrograms, and Chroma Short-Time Fourier Transform (Chroma-STFT)—to comprehensively capture both local spectral characteristics and long-range temporal dependencies inherent in respiratory cycles. Specifically, the TimeDistributed CNN block extracts localised acoustic features from sequential frames, while the LSTM layer models their temporal evolution, enabling robust identification of pathological acoustic signatures such as wheezes and crackles. The model was rigorously evaluated on the benchmark ICBHI 2017 dataset across six diagnostic categories: healthy, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, upper respiratory tract infection (URTI), and bronchiectasis. The CNN-LSTM-TD model achieved an F1-score of 0.94, recall of 0.91, precision of 0.97, overall accuracy of 96.40%, and an AUC-ROC of 0.96, significantly outperforming standalone CNN, LSTM, and CNN-LSTM baseline models. The accompanying web interface supports audio file upload, real-time visualisation of waveforms and spectrograms, and confidence score reporting, collectively facilitating clinical decision support and telemedicine integration. These results demonstrate that the synergy of temporally aware deep feature extraction and accessible web deployment positions the proposed system as a clinically viable, scalable tool for automated respiratory disease diagnosis and remote patient monitoring. Full article

Upper respiratory tract infections (URTI) are highly prevalent worldwide. Although probiotics have shown potential in preventing URTI, evidence in healthy adults remains limited. Lacticaseibacillus rhamnosus CRL 1505 is a strain with immunomodulatory effects in preclinical studies and benefits in healthy children. Based on this evidence, a randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted in healthy adults, receiving either L. rhamnosus CRL 1505 (1 bln/day) or placebo for 12 weeks, with a 4-week follow-up. The primary endpoint was the proportion of participants experiencing URTI episodes (at least one, two, or three episode(s)). The secondary endpoints included: number and duration of URTI episodes, URTI-free time, symptom severity, use of symptomatic medication, salivary IgA levels, and safety outcomes. Results show that L. rhamnosus CRL 1505 significantly reduced the number of participants experiencing ≥3 URTI episodes at 16 weeks compared with placebo. The probiotic group experienced fewer URTI episodes per participant, a shorter cumulative duration of URTIs, and a higher URTI-free time rate. Probiotic supplementation significantly reduced the use of symptomatic medications. In conclusion, daily supplementation with L. rhamnosus CRL 1505 reduced the burden of URTI in healthy adults, specifically of those experiencing more episodes, by decreasing infection frequency, duration, and medication use. Full article

Background/Objectives: In individuals with a genetic predisposition, acute rheumatic fever (ARF) can manifest as arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. It occurs after a latent period of 1–3 weeks of untreated upper respiratory tract infections caused by group A beta-hemolytic streptococci. The presence and severity of carditis determine the prognosis for ARF. Carditis manifests as pancarditis, and although all patients have pericarditis, not all experience a pericardial effusion. Patients with severe carditis exhibit pericardial effusion more frequently. The physiopathology of ARF remains unclear, specifically which patients will experience carditis, arthritis, or chorea. However, the Turkish population has fully clarified the physiopathology and clinical features of Familial Mediterranean fever (FMF), a common rheumatic disease. In the Turkish population, the heterozygous positivity rate for the FMF gene mutation is 15–35%. For these reasons, we examined the presence of FMF gene mutations in our patients to determine whether there is a correlation between the clinical course of ARF and the FMF gene mutation. Methods: The study included 60 patients with arthritis (n = 11), carditis (n = 26), or both (n = 23), as well as 60 healthy controls. These pediatric patients underwent screening for mutations in exons 2 and 10 of the MEFV gene. Results: There was no statistically significant difference between the patient and control groups in terms of the incidence of MEFV gene mutations in exon 10. However, in patients with ARF, the exon 2 E148Q variant was significantly more common than in the control group. Conclusions: This study suggests a relationship between certain clinical manifestations of ARF and MEFV gene mutations in children. Full article

Background/Objectives: Upper respiratory tract infections (URTIs), including common cold and influenza, remain a major global health burden, and their symptomatic management often includes the use of herbal medicines alongside conventional therapies. The aim of this study was to evaluate the real-world use of herbal medicines as drug candidates in the management of URTIs in Estonia, with a focus on differences between pharmacy customers and pharmacy professionals. Methods: A cross-sectional survey was conducted among 905 participants, including 400 pharmacy customers and 505 pharmacy professionals (pharmacists and pharmacy assistants). Standardized questionnaires were used to assess the frequency of use, perceived effectiveness, and safety considerations of commonly used herbal substances and home remedies in adults and children. Results: Herbal medicines and home remedies were widely used, reported by 68% (95% CI: 63.4–72.6%) of pharmacy customers and 71% (95% CI: 67.0–75.0%) of pharmacy professionals. The most commonly used herbal substances included lemon (79%), ginger (57%), garlic (56%), raspberry (55%), and chamomile (50%). While most respondents perceived these remedies as effective for symptom relief, notable discrepancies were observed between customer and professional assessments of efficacy. The use of several herbal substances in children did not consistently align with European Medicines Agency recommendations, highlighting potential safety concerns. The findings demonstrate that widely used herbal substances represent real-world candidates for supportive URTI management; however, their perceived effectiveness and patterns of use are not always supported by regulatory guidance or clinical evidence. These results underscore the need for further pharmacological and clinical studies, as well as improved evidence-based communication between healthcare professionals and patients. Conclusions: The results allow the identification and prioritization of herbal substances as real-world drug candidates for further pharmacological and clinical development. Full article

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: Nutritional strategies targeting redox and immune pathways may help to stabilize redox hemodynamics and support immune competence. Controlled physiological stress models allow examination of how nutrients influence dynamic antioxidant and inflammatory responses. Methods: In this randomized, double-blind, placebo-controlled trial (RCT), 39 healthy, moderately active men (supplement group: n = 20; placebo group: n = 19) received a yeast cell-derived formulation containing β-glucans and micronutrients or placebo for 8 weeks. Two standardized high-intensity interval training (HIIT) sessions (PRE/POST) transiently induced oxidative and inflammatory stress. Outcomes included reactive oxygen species (ROS; whole-blood EPR), total antioxidant capacity (FRAP), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and upper respiratory tract infection (URTI) incidence and duration. Results: Prior to the intervention period, acute supplement intake resulted in a more pronounced reduction in ROS from 0′ to 60′ compared with placebo (−6.2%; p ≈ 0.14). After eight weeks, fasting FRAP increased only in the supplemented group (p < 0.01). Mixed-model repeated-measures ANOVA demonstrated significant time × group interactions for FRAP in both PRE and POST assessments, indicating differential temporal trajectories. The chronic FRAP increase correlated with the acute ROS reduction (p < 0.05; r² = 0.21). SOD activity was higher in the supplemented group at 60′ in the POST assessment (p < 0.05), and a significant time × group interaction was observed for SOD in POST. TNF-α decreased across the intervention in participants with elevated baseline values, whereas individuals with low initial concentrations showed no change. The supplemented group reported shorter URTI duration (−1.4 days; d = 0.34) and fewer prolonged episodes (>10 days: 5% vs. 15.8%), although these differences were not statistically significant. Conclusions: Eight weeks of supplementation with a yeast cell-derived formulation containing β-glucans and micronutrients was associated with differences in selected redox-related markers, including FRAP and SOD, without altering exercise-induced ROS dynamics. The observed patterns suggest subtle modifications in antioxidant-related response characteristics under standardized physiological stress. These findings warrant further investigation in larger and more heterogeneous cohorts, particularly in populations exposed to higher oxidative or inflammatory burden. Full article

Background: The use of plant-derived agents is a common approach in integrative care for respiratory conditions. However, the evidence of clinical trials has not yet been comprehensively presented. Aim: To summarize the antibacterial, antiviral, immunomodulatory, antioxidant, and expectorant properties of Echinacea spp., Pelargonium sidoides, Hedera helix, Thymus vulgaris, Althaea officinalis, Sambucus nigra, Zingiber officinale, and Curcuma longa, and to evaluate the evidence level from clinical trials (CTs) involving these agents in patients with respiratory tract infections (RTIs). Methods: We conducted a literature search using the PubMed database focusing on clinical studies of plant-derived agents in upper and lower RTIs. PRISMA-based reporting elements were used only as a guiding tool for comprehensibility of the literature search (Reporting Items for Systematic Reviews and Meta-Analyses guidelines). Results: A summary and structured overview of the properties of these most-cited plant-derived agents in the literature, in the context of RTIs, was provided. A total of 94 reports met the eligibility criteria and were included in our review. Of these, 66 reported randomized and placebo-controlled trials investigating the efficacy and tolerability of these adjuncts in patients with RTIs. The non-randomized and uncontrolled trials were 22. Sufficient evidence to be regarded as an appropriate treatment to reduce the severity and duration of RTIs was found for all discussed plant-derived agents. Robust evidence available was found for Echinacea spp., Pelargonium sidoides, Sambucus nigra, Curcuma longa and Zingiber officinale. Conclusions: Regarding other plant-derived agents reported in the traditional medicine for the treatment of RTIs, further research is needed to clarify the evidence gaps. Full article

Background: Allergic rhinitis (AR) is commonly treated with intranasal and oral pharmacotherapy or allergen immunotherapy (AIT), each associated with distinct safety considerations. This study aimed to systematically evaluate and compare the safety profiles of these therapeutic approaches by analysing adverse events (AEs) reported in completed randomised controlled trials (RCTs). Methods: A meta-epidemiological analysis was conducted using completed RCTs registered in ClinicalTrials.gov up to 20 October 2023. Trials investigating intranasal drugs, oral medications, or AIT for AR were identified using predefined search terms. Adverse events were manually extracted and categorised according to treatment class and dosage. Other adverse events (OAEs) were classified using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) and Medical Dictionary for Regulatory Activities (MedDRA) terminology. Meta-analyses compared OAE incidence across treatment groups, including standard-dose, higher-dose, and placebo arms. Results: A total of 216 RCTs were included. Intranasal therapies accounted for 55.56% of trials, predominantly intranasal corticosteroids (INCS) and intranasal antihistamines (INAH). OAE incidence was 16.37% for INCS, 29.43% for INAH, and 8.71% for combination therapy. INAH was associated with higher rates of dysgeusia and nasal discomfort, while higher INCS doses were linked to an increased risk of urinary tract infections. AIT trials comprised 22.69% of studies and demonstrated higher OAE rates, particularly for sublingual immunotherapy (64.96%), followed by subcutaneous (53.98%) and intralymphatic immunotherapy (62.50%). Oropharyngeal AEs were most frequent with sublingual immunotherapy. Oral medications (18.06%) showed the lowest OAE incidence, with upper respiratory tract infections occurring more frequently with oral antihistamines. Conclusions: Among intranasal therapies, INCS demonstrated the most favourable safety profile. Sublingual immunotherapy was associated with a higher frequency of OAEs compared with other AIT modalities. Combination oral antihistamine and leukotriene receptor antagonist therapy appeared to be the safest oral treatment option. Further well-designed studies are needed to refine comparative safety assessments across AR treatments. Full article

Background: Upper respiratory tract infections (URTIs), allergic rhinitis (AR), and chronic rhinosinusitis (CRS) are prevalent and burdensome inflammatory disorders. Probiotics may modulate immune responses via gut–respiratory axis signaling, but their clinical efficacy across these conditions remains uncertain and highly heterogeneous. Methods: We conducted a PRISMA-guided systematic review and random-effects meta-analysis of randomized controlled trials (RCTs) evaluating oral or topical probiotics for URTIs, AR, or CRS (MEDLINE, EMBASE, CENTRAL, and Web of Science; inception to July 2025). Disease severity category (acute, subacute, chronic), episode incidence, and duration of illness were extracted alongside symptom scores. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was graded using the GRADE framework. Results: Thirty-two RCTs were included. In URTIs, certain strains [e.g., Lactiplantibacillus plantarum DR7, Lactobacillus rhamnosus GG] reduced symptom duration and antibiotic use; however, the pooled incidence reduction was non-significant (RD = −0.07; 95% CI: −0.23 to 0.09; p = 0.38), with very high heterogeneity (I² = 93.12%), limiting interpretability. In AR, probiotics reduced TNSS and improved quality of life (SMDs −0.72 to −2.30) in individual trials supported by immune marker changes [e.g., increased IL-10, decreased IgE]. In CRS, only two small trials—differing in delivery route (topical vs. oral), CRS phenotype, and publication era (2009 and 2017)—with conflicting effect directions were identified; formal meta-analysis was not performed given insufficient and methodologically heterogeneous data, and CRS findings are reported descriptively only. GRADE certainty ranged from very low (URTI incidence) to low (AR symptoms, URTI illness burden). Conclusions: Probiotic effects appear strain- and condition-specific. URTI pooled incidence data are unreliable due to extreme heterogeneity; individual strains show consistent benefits on illness burden and AR symptoms/quality of life. Evidence for CRS is insufficient for meta-analytic conclusions; findings are reported descriptively pending adequately powered dedicated trials. Strain-targeted RCTs with standardized outcomes, formal GRADE appraisal, and adequate power are needed before clinical recommendations can be made. Full article

Asthma is a heterogeneous inflammatory airway disease with variable clinical phenotypes. Dysregulation of the arginine–nitric oxide (NO) pathway contributes to airway hyperresponsiveness and endothelial dysfunction, but its role across stages of pediatric asthma remains unclear. In order to replicate real-world clinical heterogeneity, this investigation assessed serum levels of L-arginine, symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA), L-citrulline, and the SDMA/ADMA ratio in children with managed asthma, asthma exacerbation, upper respiratory tract infections (URTIs), pneumonia, COVID-19, and healthy controls. Discovering stage-specific arginine pathway changes and evaluating their ability to distinguish asthma and asthma exacerbations from other clinically similar respiratory disorders was the primary aim of our research study. Receiver operating characteristic (ROC) analysis demonstrated that the SDMA/ADMA ratio achieved the strongest individual discriminative performance for distinguishing asthma exacerbation from controlled asthma (AUC: 0.917), while the combined multimarker model incorporating all four metabolites yielded an AUC of 0.983 with a sensitivity of 87.5% and specificity of 95.5%. These results indicate that arginine pathway metabolites, especially the SDMA/ADMA ratio, may merit additional research as possible markers of acute disease activity in asthma, even though they are exploratory and need external confirmation. Full article