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RATIONALE: The effects of fluid administration during acute asthma exacerbation are likely unique in this patient population: highly negative inspiratory intrapleural pressure resulting from increased airway resistance may interact with excess fluid administration to favor the accumulation of extravascular lung water, leading to worse clinical outcomes.

OBJECTIVES: Investigate how fluid balance influences clinical outcomes in children hospitalized for asthma exacerbation.

METHODS: We analyzed the association between fluid overload and clinical outcomes in a retrospective cohort of children admitted to an urban children's hospital with acute asthma exacerbation. These findings were validated in two cohorts: a matched retrospective and a prospective observational cohort. Finally, ultrasound imaging was used to identify extravascular lung water and investigate the physiological basis for the inferential findings.

MEASUREMENTS AND MAIN RESULTS: In the retrospective cohort, peak fluid overload [(fluid input - output)/weight] is associated with longer hospital length of stay, longer treatment duration, and increased risk of supplemental oxygen use (P values  0.001). Similar results were obtained in the validation cohorts. There was a strong interaction between fluid balance and intrapleural pressure: the combination of positive fluid balance and highly negative inspiratory intrapleural pressures is associated with signs of increased extravascular lung water (P  0.001), longer length of stay (P = 0.01), longer treatment duration (P = 0.03), and increased risk of supplemental oxygen use (P = 0.02).

CONCLUSIONS: Excess volume administration leading to fluid overload in children with acute asthma exacerbation is associated with increased extravascular lung water and worse clinical outcomes.