In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury.
BACKGROUND
Acute lung injury is an important cause of respiratory failure in the critically ill patient. It is caused by damage to the alveolar barrier with subsequent alveolar flooding leading to the development of refractory hypoxaemia. beta Agonists stimulate alveolar fluid clearance in animal models of lung injury. In a clinical trial (BALTI-1), intravenous beta agonists reduced extravascular lung water, an effect that took 72 h in contrast with what animal studies suggest. One possible explanation for the delay in change in extravascular lung water is the time required for salbutamol to stimulate alveolar epithelial repair.


OBJECTIVE
To investigate whether salbutamol can stimulate alveolar epithelial repair in vivo and in vitro.


RESULTS
Intravenous salbutamol reduced measures of alveolar-capillary permeability in patients with acute respiratory distress syndrome (ARDS). In vitro, salbutamol stimulated both wound repair, and spreading and proliferation of A549 cells and distal lung epithelial cells. Lung lavage fluid from patients treated with salbutamol enhanced wound repair responses compared with placebo treated patients in vitro by an interleukin 1beta dependent mechanism.


CONCLUSIONS
Our in vivo and in vitro work suggests that salbutamol may stimulate epithelial repair--potentially a pharmacological first in ARDS. Clearly establishing the mechanisms and pathways responsible for this is important for the future, and may allow identification of novel therapeutic targets to promote alveolar epithelial repair in humans with ARDS.
Perkins
G D
GD
Warwick Medical School, University of Warwick, Coventry, UK.
Gao
F
F
Thickett
D R
DR
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000368:Aged; D000420:Albuterol / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D002199:Capillary Permeability; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D020545:Respiratory Mucosa / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D000318:Adrenergic beta-Agonists; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D000420:Albuterol