Effectiveness of short-acting beta-2 agonists delivered by metered-dose inhaler with spacer versus nebulizer in acute asthma exacerbations: a systematic review and meta-analysis

OBJECTIVE: -agonist (SABA) delivery via metered-dose inhaler with spacer versus nebulizer in patients with acute asthma exacerbations. DATA SOURCES: A comprehensive search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to July 14, 2025. STUDY SELECTION: Randomized controlled trials (RCTs) involving patients aged 2 years or older comparing SABA administration via metered-dose inhaler with spacer versus nebulizer were included. The primary outcome was hospital admission; secondary outcomes included length of stay, return visit within 72 hours, peak expiratory flow, forced expiratory volume in one second, oxygen saturation, respiratory rate, heart rate, and tremor. Two reviewers independently selected studies, extracted data, and assessed risk of bias using the RoB 2 tool. Random-effects meta-analyses were conducted, with separate analyses for pediatric and adult populations. The certainty of evidence was assessed using the GRADE approach. The protocol was registered in PROSPERO (CRD42023445698). RESULTS: = 0%), nor in adults, children, or severe exacerbations. Secondary outcomes showed no significant differences overall. In children, however, MDI with spacer was associated with shorter ED stays and a lower risk of tremor. Certainty of evidence ranged from moderate to very low. CONCLUSION: SABA delivery via MDI with spacer showed comparable clinical outcomes to nebulization for acute asthma exacerbations, with potential pediatric advantages in reducing ED length of stay and the risk of tremor.