Safety, immunogenicity, and dose ranging of a bivalent respiratory syncytial virus and human metapneumovirus glycoprotein F-molecular clamp vaccine candidate in older adults: 1-month interim analysis of an ongoing randomised, observer-blind, placebo- and active-controlled, phase 1 trial.

Current coronavirus disease 2019 (COVID-19) vaccines effectively prevent severe disease but induce primarily systemic immunity without mucosal protection in the respiratory tract, which is mandatory for protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevention of viral transmission. Vaccination strategies capable of inducing local immunity at the site of infection are therefore needed. Here, we evaluated a poly (lactic-co-glycolic acid) (PLGA) microparticle-based vaccine co-encapsulating the receptor binding domain (RBD) of SARS-CoV-2 Spike protein with the TLR3/RIG-1 agonist Riboxxim, employing a subcutaneous prime and intranasal boost immunization schedule. BALB/c mice received subcutaneous prime immunization followed by intranasal boost with PLGA microparticles containing RBD/Riboxxim. Antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), neutralization by competitive ELISA and T-cell responses by enzyme-linked immune spot assay, intracellular cytokine staining and flow cytometry. Memory responses were evaluated 30 days post boost immunization. Vaccination induced robust RBD-specific IgG and IgA antibody titres in both serum and bronchoalveolar lavage fluid, with neutralizing capacity against the Wuhan-Hu-1 strain. Strong CD4+ and CD8+ T-cell responses were detected systemically and in the respiratory tract. Importantly, the vaccine generated durable immunological memory, including tissue-resident memory T-cells in the respiratory tract and long-lived IgG and IgA memory B-cells in secondary lymphoid organs. PLGA microparticle-based vaccination induces potent systemic and mucosal immune responses against SARS-CoV-2 RBD. This adaptable platform represents a promising approach for mucosal vaccination strategies, with potential for rapid adaptation to emerging variants.

Exhaled breath condensate (EBC) has emerged as a noninvasive liquid biopsy medium that captures aerosolized material from the respiratory tract and may provide insight into local lung biology. Within this matrix, extracellular vesicles (EVs) can carry DNA, RNA, proteins, and lipids that reflect cellular origin and may report tumor-associated inflammation, airway remodeling, and microenvironmental changes. This review summarizes current evidence on the molecular composition, origin, and biogenesis of EVs detected in EBC, with emphasis on their potential for early lung cancer detection and longitudinal disease monitoring. Proteomic, transcriptomic, and genomic analyses have identified tumor-associated signatures, including cytokines, driver mutations, and epigenetic alterations, whereas lipidomic profiling may capture oxidative, inflammatory, and metabolic stress. Recent methodological advances in EV enrichment, microfluidics, single-vesicle analytics, and digital assays are improving the sensitivity of low-biomass EBC analyses. However, EBC-derived EV research remains technically challenging, and standardization of collection, EV isolation, molecular analysis, and reporting is essential. Artificial intelligence (AI) and machine learning (ML) may support integration of multiomic and clinical data, particularly when validated in prospective cohorts. Together, these developments position EBC-derived EVs as an emerging, patient-friendly, lung-proximal platform for biomarker discovery and future precision oncology applications, while underscoring the need for source-resolved validation and clinical translation studies.

Basic life support (BLS) refers to the immediate care provided to individuals experiencing respiratory arrest, cardiac arrest, or airway obstruction. This study aimed to assess the knowledge and attitudes regarding BLS among postgraduate trainee doctors. A descriptive cross-sectional study was conducted among 105 postgraduate trainees from various disciplines at Mymensingh Medical College Hospital, Bangladesh over a six-month period from January to June 2018. Of the respondents, 55.2% were male and 44.8% were female, with a mean age of 30.7±2.5 years. Participants represented Medicine (48.6%), Surgery (23.8%) and Obstetrics and Gynaecology (27.6%) faculties. Most respondents had three years of clinical training (31.3%), followed by two years (21.0%), four years (21.0%), more than one year (18.1%) and more than six months (8.6%). Only 24.8% of the trainees had received prior BLS training and their knowledge scores (8.61±2.55) were significantly higher than those without training (p<0.05). However, overall knowledge gaps were evident, with the majority uncertain about the initial response for an unresponsive patient (70.5%), correct chest compression location in adults (71.4%) and infants (68.6%), compression depth, compression rate, rescue-breath frequency and management of foreign body aspiration in both adults and children. Many were also unsure of the meanings of key abbreviations such as AED (Automated external defibrillator) and EMS (Emergency Medical Services). Regarding attitudes, most participants agreed that all doctors should receive BLS training (49.5%) and that BLS should be included in the undergraduate curriculum (63.8%). Half (50.5%) emphasized the need for supervised hands-on training. Common reasons for hesitation to perform BLS included fear of harming patients (36.2%), lack of practice (28.6%), risk of contamination during mouth-to-mouth ventilation (21.0%) and fear of mishap in public settings (19.0%); 12.4% reported no hesitation. The study concludes that standardized and reinforced practical BLS training is essential for postgraduate medical trainees and practicing physicians to ensure preparedness and competence.

The envelope-anchored trimeric spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates the attachment and entry of the virus within human cells by utilizing the angiotensin converting enzyme 2 (ACE2) as a receptor, present in the epithelial cells of the upper respiratory tract and lungs. The ACE2 interaction interface with the SARS-CoV-2 spike protein was utilized to design an ACE2-derived peptide sequence (FD11) that targeted the viral spike protein. It was found to be non-cell penetrating, while invivo studies revealed the non-cytotoxic nature of the peptide molecule. The minimum effective concentration of the peptide was found to be 10 μM with 95% cell viability in Vero E6 cell line. The IC50 of the peptide was found to be around 6.4 μM. Treatment of the peptide in SARS-CoV-2 infected Vero E6 cells was found to decrease the infectivity as compared to control. This presents a simple approach where host-pathogen protein interaction-interface derived peptides can be used for binding with substrate macromolecules to target and modulate pathogen infectivity.

de Morais Ferreira, AB, Halson, S, Galvão-Coelho, NL, de Almeida, RN, Nakamura, FY, and Mortatti, AL. Impact of sleep restriction and intensified training on mucosal immunity and psychological responses in young soccer players. J Strength Cond Res 40(7): e703-e713, 2026-This study analyzed the effects of training intensification during a period of sleep restriction (SR) on mucosal immunity (salivary IgA), upper respiratory tract health, mood states, and stress tolerance in young soccer players. Sixteen male youth soccer players completed 7 weeks of training with varied workloads. Weeks 3 and 5 involved a 75% increase in internal training load (ITL); however, although sleep was unrestricted in week 3, allowing for an increase in total sleep time (TST) (+53 minutes vs. baseline), week 5 included a ∼10% reduction in TST (-44 minutes vs. baseline). Internal training load was assessed using session-rating of perceived exertion, and sleep was monitored via actigraphy. Salivary IgA, upper respiratory tract infection (URTI) severity (Wisconsin Upper Respiratory Symptom Survey), perceived recovery status (PRS), stress tolerance (Daily Analysis of Life Demands of Athletes), and mood states (Brunel Mood Scale) were evaluated weekly. Salivary IgA concentrations significantly decreased in both intensified training weeks (week 3: β = -87.41, p = 0.007; week 5: β = -114.04, p < 0.001). However, only in week 5, this reduction was accompanied by a significant increase in URTI severity ( p = 0.001), heightened fatigue (χ 2 (6) = 42.499, p < 0.001), reduced vigor (χ 2 (6) = 49.422, p < 0.001), impaired PRS ( p < 0.001), and lower stress tolerance ( p = 0.001). In contrast, during week 3, despite the intensified training, PRS, mood states, and stress tolerance remained stable. These findings emphasize the protective role of adequate sleep during intensified training, as greater sleep availability in week 3 may have mitigated the negative effects observed in week 5. Ensuring sufficient sleep during periods of high training loads is essential to maintain physical and psychological health.

Efficacy and safety of enpatoran, a Toll-like receptor 7/8 inhibitor, in patients with skin manifestations of cutaneous lupus erythematosus or systemic lupus erythematosus: findings from Cohort A of a multicentre, international, double-blind, placebo-controlled, dose-finding phase 2 trial.

Physical restraint of horses for veterinary procedures is necessary to allow completion of tasks effectively and without injury to patient or personnel. To compare physiological effects and behavioural responses to four commonly used restraint techniques for upper respiratory tract (URT) endoscopy in unsedated horses. Blocked and randomised interventional study. Twelve university owned teaching horses were blocked into groups of four and randomly allocated to one of four restraint methods (nose twitch, ear hold, Stableizer® and nil restraint) for URT endoscopy. Horse response to restraint and endoscopy was evaluated subjectively and by objective measures of procedural efficacy (duration and head movement), time domain indices of heart rate variability (HRV), saliva cortisol and plasma β-endorphin concentrations. Horses demonstrated strong individual differences for procedure tolerance and preferred method of restraint, but there were no differences observed in outcome measures related to procedural efficacy or neuroendocrine response associated with restraint type. Repetition of experimental procedures was associated with a progressive decrease in mean (95% CI) minimum heart rate from 34.2 (31.7-36.7) to 30.1 (28.0-32.2) bpm (p < 0.001), and increased HRV measures related to parasympathetic dominance. Cortisol was greatest on Day 2 (1.5, 1.1-2.5 nmol/L; median, 95% CI), compared with Day 1 (0.8, 0.5-1.6 nmol/L; p = 0.02). Convenience sample of horses familiar with most study interventions; intervention was minimally invasive and of short duration. Study findings did not support current recommendations to prioritise one type of restraint over other available techniques.

The small interfering RNA imdusiran as single and multiple doses in healthy, randomised individuals and non-randomised individuals with chronic hepatitis B (AB-729-001): a phase 1a/b trial.

Equine asthma (EA) is a chronic inflammatory disease of the lower respiratory tract in horses, which is mainly triggered by dusty hay. EA is becoming increasingly acknowledged as a valuable animal model for studying human asthma. Research on the pathogenesis of EA has primarily focused on the associated cells and cytokines involved. However, the role of inflammation-related lipid mediators (LM) in the development and progression of equine asthma remains elusive. LMs are categorized into pro-inflammatory arachidonic acid (AA)-derived leukotrienes (LTs) and prostaglandins (PGs), as well as inflammation-resolving LMs derived from omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this study, targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was employed to analyze LM profiles from serum and stimulated whole blood samples collected from 30 healthy horses and from 30 horses with EA. We found that the levels of free fatty acids, as well as their metabolomes, vary substantially among individual horses in serum. In this regard, we observed no significant differences between healthy horses and those with EA, highlighting the complexity of the pathogenesis of respiratory disease in horses. In detail, we detected 12-hydroxyeicosatetraenoic acid (HETE) as the most abundant LM in serum and stimulated whole blood. Furthermore, we found that the levels of LMs decrease with increasing age of the horses. Conclusively, this study presents the comprehensive assessment of LM profiles in serum and stimulated whole blood from horses, which can serve as scientific basis for transferring findings from equine to human asthma.

A practical protocol for the identification of Schizophyllum commune in fungal cultures of respiratory specimens: A pilot study at a single center in Japan.

Lower Respiratory Tract Infections: Precision Diagnostics.

Haemoptysis, defined as the expectoration of blood from the lower respiratory tract, can present to the emergency department (ED) with symptoms ranging from mild, self-limiting to massive haemorrhage. Severe presentations account for approximately 5% of cases, with mortality primarily because airway flooding with blood leading to hypoxia. This underscores the importance of early airway protection and structured resuscitation in emergency settings. This narrative review summarizes the current evidence to guide emergency physicians in the management of haemoptysis. Aetiologies vary geographically: pulmonary tuberculosis accounts for up to 40% of cases in low- and middle-income countries, whereas malignancy, cardiovascular disease, and bronchiectasis predominate in high-income regions. Management begins with differentiating haemoptysis from pseudohaemoptysis and gastrointestinal bleeding, followed by risk stratification and initial stabilization of the patient. CT angiography helps in localization of bleeding and underlying pathology, while flexible bronchoscopy is the gold standard for both diagnosis and therapeutic interventions. Nebulized tranexamic acid is emerging as a rapid, localized, and safe adjunct in emergency settings, reducing the need for invasive procedures. Haemostasis can be achieved by bronchial artery embolization in over 90% of cases, while surgery is reserved for refractory or localized disease. Despite these advances, challenges remain in optimizing the timing and integration of imaging, pharmacological adjuncts, and invasive procedures. A multidisciplinary approach involving emergency physicians, pulmonologists, interventional radiologists, and thoracic surgeons is crucial to improving outcomes in this complex, potentially life-threatening condition. Further studies are needed to standardize protocols and priorities for emergency management of massive haemoptysis.

Muscle-predominant vasculitic myopathy heralding renal MPO-ANCA-associated vasculitis: A case-based mini-review of diagnostic traps and steroid-sparing induction.

Real-world emergence of nirsevimab resistance in breakthrough infections with respiratory syncytial virus-B: a multicentre observational study in France.

We aimed to examine the relationship between acute events and frailty trajectories of community-dwelling adults aged 60 and older. We included 3146 participants, aged 60+, from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). We considered all myocardial infarctions (MIs), lower respiratory tract infections (LRTIs) and falls that resulted in a hospitalization 5 years before to 12 years after SNAC-K baseline (2001-2004). Frailty was operationalized using a data-driven frailty index (FI), scored from 0 to 1. Linear quantile mixed models were used to examine the relationship between number and type of acute events and FI trajectories over a median follow-up of 11 years. Falls (n=690) were most common, followed by LRTIs (n=353) and MIs (n=205). Those with more acute events showed significantly higher frailty levels over time from age 75 to 95. The greatest differences in frailty trajectories by event count were observed at age 80, with increases between zero to one, one to two and two to three or more events of 0.04 (95% confidence interval [CI]=0.03-0.05), 0.08 (95% CI=0.05-0.11) and 0.09 (95% CI=0.05-0.13) FI units, respectively. Falls emerged as most deleterious, but there were also clear differences by MI and LRTI count after imputing frailty at death. Older adults who experience falls, LRTIs and MIs are more likely to sustain unfavourable frailty trajectories, with increasingly higher frailty levels with each additional acute event. Prevention, before age 75, should be optimized to avoid a vicious cycle of acute events and frailty progression as well as reduced lifespan.

Transcriptome alterations induced by acute and persistent human bocavirus 1 infection in human airway epithelial cells.

Effectiveness of nirsevimab immunisation after birth versus RSVpreF maternal vaccination in preventing RSV-related hospitalisations in infants: a population-based retrospective cohort study.

Aerodigestive Disease and Respiratory Health.

To estimate the effectiveness of nirsevimab against respiratory syncytial virus (RSV)-associated acute otitis media (AOM) in ambulatory care. We conducted a test-negative design study, post hoc analysis using data from the prospective Oursyn study involving 37 primary care pediatricians across France from 2020 to 2025. Nasopharyngeal sampling for RSV was performed in infants younger than 1 year diagnosed with AOM during the first 2 RSV seasons with introduction of nirsevimab passive immunization (October 2023 to February 2024 and October 2024 to January 2025). The main outcome of the study was the detection of RSV status in infants with AOM. We performed a multivariable logistic regression with nirsevimab adjusted for age, sex, underlying chronic condition, prematurity, type of childcare, month, year, and geographic region of inclusion. Sensitivity analyses were performed as well. A total of 236 AOM events were included over the study period: 141 during the first season of nirsevimab implementation and 95 during the second season. Among infants with AOM, 41 (29.1%) and 15 (15.8%), respectively, tested positive for RSV. Nirsevimab-adjusted effectiveness was estimated to be 78.2% (95% CI 44.4-92.4) for the prevention of RSV-AOM in this sample. Sensitivity analyses found similar results. These findings highlight the broader protective effect of nirsevimab on complications of respiratory tract infections in infants. NCT04743609.