Valved Holding Chambers in Young Children With Acute Wheezing: A Randomized Clinical Trial.

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.