Objective: Myofibroblasts express alpha-smooth muscle actin (alphaSMA), are important in tissue repair, and are present in the early phase of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We wished to determine whether bronchoalveolar lavage fluid (BALF) from ALI/ARDS patients can induce myofibroblast differentiation and if this induction is associated with outcome.
Design: A single-center cohort study enrolling patients between 2002 and 2005.
Setting: Medical intensive care unit of a tertiary care medical center.
Patients: Adult patients meeting the American-European Consensus Conference definition of ALI/ARDS.
Interventions: BALF was collected from ALI/ARDS patients within 48 hrs of intubation and incubated with normal human lung fibroblasts in vitro, and alphaSMA expression was assessed by reverse transcription polymerase chain reaction. BALF was also collected and tested from negative control patients. ALI/ARDS patients were followed for 28 days or death.
Measurements and main results: Thirty-one lung injury and 11 negative control patients were enrolled from 2002 to 2005. ALI/ ARDS BALF demonstrated potent alphaSMA induction with a mean value 92% greater than negative controls (34.5% +/- 7.6% vs. 18% +/- 2.4% of maximal transforming growth factor [TGF]-beta1 [5 ng/mL], p < .02). The specific TGF-beta1 receptor inhibitor SB431542 reduced ALI/ARDS BALF-stimulated alphaSMA induction by 52% (p < .005). There was no correlation between ALI/ARDS BALF-induced alphaSMA and procollagen 3 induction (r = -.08, p = .66). The odds ratio for survival was 6.75 (1.15-39.80) times higher for ALI/ARDS patients with alphaSMA induction between 15% and 75% of maximal TGF-beta1 induction (5 ng/mL) than outside this range.
Conclusions: ALI/ARDS BALF-induced myofibroblast differentiation is partially attributable to TGF-beta1. Procollagen 3 and alphaSMA are regulated by distinct mechanisms in ALI/ARDS and there may be an optimal level of myofibroblast induction that is associated with better outcome.