Daily Respiratory Research Analysis

IMPORTANCE: Acute wheezing is a leading cause of pediatric emergency visits. Commercially available valved holding chambers (VHCs), used in inhalation therapy, differ in in vitro drug delivery, but the clinical relevance of these differences in young children is uncertain. OBJECTIVE: To determine whether a higher-delivery VHC improves clinical outcomes of salbutamol treatment compared with a lower-delivery VHC in young children with acute wheezing. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial took place at 4 pediatric emergency departments in Finland with enrollment April 17, 2019, through May 23, 2025 (recruitment pause March 2020 through July 2022), and used intention-to-treat analysis. Patients included children aged 6 to 48 months with moderate or severe wheezing respiratory distress (respiratory distress assessment instrument [RDAI] score of ≥6) who met prespecified inclusion/exclusion criteria. These data were analyzed from May 28, 2025, through September 8, 2025. INTERVENTIONS: Salbutamol (dose 0.6 mg per treatment cycle, up to 3-4 cycles at 20-minute intervals) delivered via 1 of 2 commercially available VHCs: either VHC-1 (high in vitro drug delivery) or VHC-2 (low in vitro drug delivery), each used with its respective mask. MAIN OUTCOMES AND MEASURES: Primary outcomes were posttreatment RDAI score and change from baseline. Secondary outcomes included hospitalization rate, the proportion of children requiring a fourth salbutamol dose, and change in respiratory rate and oxygen saturation. RESULTS: A total of 80 children were randomized and analyzed (mean age, 23.1 months; 36% female and 64% male). Children treated with salbutamol had posttreatment mean (SD) RDAI scores significantly lower in the VHC-1 group (2.7 [2.1]) than in the VHC-2 group (6.8 [3.6]) with a mean difference of -4.1 (95% CI, -5.4 to -2.7; P < .001). The mean reduction in RDAI score was greater with VHC-1 than with VHC-2 (mean difference, -5.4; 95% CI, -6.9 to -3.9; P < .001). The proportion of children requiring hospitalization was lower in children treated with VHC-1 (20%) than with VHC-2 (50%) (difference, 30%; 95% CI, 9%-49% and number needed to treat, 3.3; 95% CI, 2.1-11; P = .005). Relative risk of requiring a fourth salbutamol dose was 0.72 (95% CI, 0.51-0.97; P = .03) for VHC-1 vs VHC-2. After treatment, respiratory rate was lower (42 vs 47 breaths per minute; mean difference, -5; 95% CI of the difference -9.8 to -0.7; P = .04) and oxygen saturation higher (97% vs 94%; mean difference, 3%; 95% CI of the difference, 1.4-3.7; P < .001) with VHC-1. CONCLUSIONS AND RELEVANCE: In this study, young children with acute wheezing experienced greater clinically significant improvement when salbutamol was administered through a VHC with high in vitro drug delivery compared with low in vitro drug delivery. This indicates that device choice matters and that guidelines should provide device-specific recommendations for pediatric inhalation therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03900494.

Antibody-dependent enhancement (ADE) of infection is a well-described phenomenon for several viruses, including dengue, Ebola, respiratory syncytial virus, and HIV. ADE occurs when virus-antibody complexes engage Fc receptors (FcRs) and virus-specific receptors, enhancing infection under conditions of incomplete neutralization. The Coronavirus Immunotherapeutic Consortium (CoVIC) assembled a comprehensive dataset of functional properties for over 400 mAbs, enabling direct comparison of neutralization, Fc-mediated functions, receptor binding, and infection of immune cells. Infection rates in most primary human immune cell types were low, with modest increases observed for some mAbs. In contrast, macrophages were more susceptible to SARS-CoV-2 and exhibited substantial ADE with select mAbs. ADE was completely inhibited by FcR blockade and significantly reduced by antibody- or ceftazidime-mediated blocking of angiotensin-converting enzyme 2 (ACE2). Neutralization potency did not correlate with ADE, as both strongly and weakly neutralizing antibodies induced enhancement. Instead, ADE magnitude depended on an antibody's ability to block spike protein binding to ACE2. Importantly, ADE resulted in productive infection with release of infectious virus. Evaluation of antibodies against the BA.1 (Omicron) variant revealed reduced or lost ADE for most mAbs, with increased ADE observed for several mAbs relative to the USA-WA1/2020 strain.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) in children, characterized by acute lung inflammation and impaired gas exchange, presents unique therapeutic challenges due to developmental differences in respiratory physiology. While prone positioning is established in adult ARDS management, its efficacy in pediatric populations remains debated. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating prone vs. supine ventilation in children and adolescents (0-18 years) with ARDS. Databases including PubMed, MEDLINE, Embase, CINAHL and CENTRAL were searched up to October 29, 2025. Methodological quality was assessed using the Cochrane risk-of-bias tool, and statistical synthesis was performed in R. RESULTS: Thirteen RCTs (1,529 patients) were included. A meta-analysis of ten trials demonstrated a lower risk of death with prone compared with supine ventilation [risk ratio (RR) 0.67, 95% confidence interval (CI) 0.57-0.79; CONCLUSION: Prone positioning may reduce mortality and improve oxygenation in pediatric ARDS, but does not clearly shorten mechanical ventilation duration or ICU stay. These potential benefits support considering prone positioning as an adjunctive strategy in pediatric critical care protocols, while underscoring the need for larger, high-quality RCTs to refine patient selection and optimize implementation strategies.