Transforming Growth Factor-β1 in predicting early lung fibroproliferation in patients with acute respiratory distress syndrome.

Abstract

Fibroproliferative repair phase of the acute respiratory distress syndrome (ARDS) is followed by a restitutio ad integrum of lung parenchyma or by an irreversible lung fibrosis and patients' death. Transforming Growth Factor-β1 (TGF-β1) is involved in collagen production and lung repair. We investigated whether alveolar TGF-β1 was associated with the presence of fibroproliferation and the outcome of ARDS patients. Sixty-two patients were included the first day of moderate-to-severe ARDS. Bronchoalveolar lavage fluid (BALF) was collected at day 3 (and day 7 when the patients were still receiving invasive mechanical ventilation) from the onset of ARDS. Survival was evaluated at day 60. TGF-β1 was measured by immunoassay. The patients were classified as having lung fibroproliferation when the alveolar N-terminal peptide for type III procollagen (NT-PCP-III) measured on day 3 was > 9 μg/L as recently reported. The main objective of this study was to compare the alveolar levels of total TGF-β1 according to the presence or not a lung fibroproliferation at day 3. Forty-three patients (30.6%) presented a fibroproliferation at day 3. BALF levels of total TGF-β1 were not statistically different at day 3 (and at day 7) according to the presence or not lung fibroproliferation. Mortality at day 60 was higher in the group of patients with fibroproliferation as compared with patients with no fibroproliferation (68.4% vs. 18.6% respectively; p < 0.001). Total TGF-β1 measured on BALF at day 3 was not associated with the outcome. Multiple logistic regression showed that the presence of lung fibroproliferation was associated with death. In contrast, TGF-β1 was not independently associated with death. Pulmonary levels of TGF-β1 during the first week of ARDS were not associated nor with the presence of fibroproliferation neither with death. TGF-β1 should not be used as a biomarker to direct anti-fibrotic therapies.