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Wednesday 23 August 2006

In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury.

By: Perkins GD, Nathani N

Background: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS).

Experimental data demonstrate it also reduces pulmonary neutrophil accumulation/activation and inflammation. The aim of this study was to investigate the effects of salbutamol on neutrophil function.

Methods: The in-vitro effects of salbutamol on neutrophil function determined. In the clinical study, blood and bronchoalveolar lavage (BAL) fluid was collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days treatment with placebo or salbutamol(ALI/ARDS group). Alveolar-capillary permeability was measured in-vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured.

Results: In-vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. In ALI/ARDS, there was increased neutrophil activation, adhesion molecule expression compared to at risk patients and ventilated controls. There were associations between alveolar- capillary permeability and BAL myeloperoxidase (r=0.4, P=0.038) and BAL IL-8 (r=0.38, P=0.033). In patients with ALI/ARDS, salbutamol increased circulating neutrophil numbers, but had no effect on alveolar neutrophil numbers.

Conclusion: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in-vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophil numbers or on neutrophil activation. These data suggest the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil dependent inflammatory pathways.

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