ACUTE LUNG INJURY

In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury

G D Perkins^1,2, F Gao^1,2, D R Thickett³

¹ Warwick Medical School, University of Warwick, Coventry, UK
² Department of Intensive Care Medicine, Birmingham Heartlands Hospital, Birmingham, UK
³ Lung Injury and Fibrosis Treatment Program (LIFT), Department of Medical Sciences, The Medical School, University of Birmingham Edgbaston Birmingham, UK

D R Thickett, Lung Injury and Fibrosis Treatment Program (LIFT), Nuffield House, Queen Elizabeth Hospital, Department of Medicine, University of Birmingham, Birmingham B15 2TH, UK; d.thickett{at}bham.ac.uk

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. β 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 1β 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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

Airwaves

Wisia Wedzicha, Editor-in-
Thorax 2008 63: 187. [Extract] [Full Text] [PDF]

β₂ Adrenergic agonist therapy may enhance alveolar epithelial repair in patients with acute lung injury

Michael A Matthay and Joyce Lee
Thorax 2008 63: 189-190. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Thickett, D R, Perkins, G D (2008). IL1 may be elevated but is it all bad in ARDS?. Thorax 63: 750-751 [Full Text]  
• Matthay, M. A, Lee, J. (2008). {beta}2 Adrenergic agonist therapy may enhance alveolar epithelial repair in patients with acute lung injury. Thorax 63: 189-190 [Full Text]