A 2024 systematic review and meta-analysis evaluated the comparative effectiveness and safety of albuterol administered via metered-dose inhaler with a spacer (MDI+S) versus nebulization (NEB) in children experiencing acute asthma or wheezing exacerbations. This review included 15 randomized controlled trials (RCTs) encompassing a total of 2,057 pediatric patients managed in either emergency departments or inpatient settings. Eligible studies directly compared albuterol delivery via MDI+S and NEB, with hospital admission identified as the primary outcome. Secondary endpoints included arterial oxygen saturation (SaO₂), heart rate (HR), respiratory rate (RR), Pulmonary Index Score (PIS), adverse events (e.g., tremor, nausea, palpitations), and the need for additional bronchodilator therapy. Hospital admission rates demonstrated no statistically significant difference between MDI+S and NEB delivery methods (RR 0.89; 95% CI, 0.55–1.46; p= 0.65). However, MDI+S was associated with a statistically significant reduction in pulmonary index scores (MD −0.63; 95% CI, −0.91 to −0.35; p<0.00001), indicating better clinical improvement. Moreover, patients receiving albuterol via MDI+S experienced a significantly smaller increase in HR compared to NEB (MD −6.47 bpm; 95% CI, −11.69 to −1.25; I²=0%; p= 0.02), suggesting a more favorable cardiovascular profile. No significant differences were observed for SaO₂, RR, or adverse effects such as tremor, nausea, and palpitations. Although variation in dosing strategies across studies and high risk of unblinded designs in several trials posed limitations, the pooled data support MDI+S as a clinically comparable and potentially safer alternative to NEB in pediatric acute asthma therapy. [1]
A 1997 review systematically evaluated 17 prospective clinical trials, including 10 RCTs, comparing the efficacy of metered-dose inhalers with accessory devices (MDI/ADs) versus small-volume nebulizers (SVNs) in treating acute asthma in pediatric patients. The review included data from 301 children treated with MDI/ADs and 274 with SVNs. Among the comparative studies, 2 demonstrated superior efficacy of MDI/ADs, while 8 showed equivalent clinical outcomes between MDI/ADs and SVNs. No study found SVNs to be superior. Clinical outcomes assessed included pulmonary function tests (e.g., forced expiratory volume in 1 second [FEV₁], peak expiratory flow [PEF]), clinical scores, oxygen saturation, heart rate, and treatment duration. For example, Fuglsang et al. reported significantly greater and longer-lasting improvement in FEV₁ with MDI/AD (78% vs 56% improvement, respectively). Lin et al. found greater percentage increases in FEV₁, PEF, and SaO₂ with MDI/ADs. Chou et al. reported shorter mean emergency department treatment times for MDI/ADs (66 minutes) compared to SVNs (103 minutes; p<0.001). Adverse effects were similar or less frequent in MDI/AD groups, with SVN groups sometimes showing more vomiting and higher heart rates. Based on these findings, the authors concluded that MDI/ADs are effective and should be considered the preferred first-line treatment in acute pediatric asthma due to comparable or superior clinical efficacy, reduced cost, faster administration, and lower personnel demands. [2]
A 2004 meta-analysis evaluated the clinical efficacy of β-agonists delivered via MDI with valved holding chamber (VHC) versus nebulizer in children under 5 years of age presenting to emergency departments with acute wheezing or asthma exacerbations. Six RCTs comprising 491 patients were included. The primary outcome—hospital admission—was significantly lower in the MDI+VHC group (odds ratio [OR] 0.42; 95% CI 0.24 to 0.72; p= 0.002), with a number needed to treat (NNT) of 10 (95% CI 6 to 26). This benefit was more pronounced in children with moderate to severe exacerbations (OR 0.27; 95% CI 0.13 to 0.54; p= 0.0003). Secondary outcome analysis revealed a significantly greater improvement in clinical severity scores in the MDI+VHC group compared to nebulizer (standardized mean difference [SMD] −0.44; 95% CI −0.68 to −0.20; p= 0.0003). Subgroup analyses confirmed robustness across study quality and patient subgroups. No significant differences in oxygen saturation were observed, while increased heart rate and respiratory rate were more frequently reported in nebulizer groups in individual studies. Overall, this meta-analysis provides explicit data supporting greater clinical benefit of MDI+VHC over nebulizers in reducing hospital admissions and improving clinical scores in this pediatric population. [3]
A 2020 cost-effectiveness analysis evaluated bronchodilator delivery methods in pediatric asthma exacerbations in the emergency department (ED) setting of a middle-income country (MIC). Using a modified decision-analytic model, the analysis compared metered-dose inhalers with spacers (MDI+S) against jet nebulization (NEB) for the delivery of albuterol in children aged 6 months to 18 years presenting with mild to severe asthma exacerbations in Bogotá, Colombia. Effectiveness data, specifically hospitalization rates, ED stay duration, inpatient length of stay, and persistence of asthma symptoms following discharge, were derived from a Cochrane systematic review focused on beta2-agonist delivery modalities in children. Economic inputs, including drug and device costs, healthcare utilization, and hospital-based resources, were obtained from both national healthcare databases (SISMED) and actual hospital billing data from a tertiary pediatric center. The analytical horizon extended to 14 days post-discharge, with primary outcomes centered on avoidance of hospital admission. All costs were standardized to 2018 U.S. dollars. The base-case analysis demonstrated that MDI+S was economically dominant over nebulization, yielding both superior outcomes and reduced cost. Specifically, MDI+S was associated with a higher rate of hospital admission avoidance (0.9219 vs 0.8900) and lower average treatment cost per patient (US$96.68 vs US$121.41). Probabilistic sensitivity analysis using 10,000 Monte Carlo simulations confirmed the robustness of the model, with MDI+S maintaining superiority in 99.9% of iterations. The 95% uncertainty interval for avoidance of hospitalization with MDI+S ranged from 0.9009 to 0.9418, and the corresponding costs ranged from US$73.71 to US$124.62. A cost-effectiveness acceptability curve indicated that MDI+S remained the preferred strategy across all willingness-to-pay thresholds. These findings reinforce the clinical and economic benefits of transitioning from nebulization to MDI+S in resource-limited healthcare systems. [4]