ELEVATED TRANSFORMING GROWTH-FACTOR-ALPHA LEVELS IN BRONCHOALVEOLAR LAVAGE FLUID OF PATIENTS WITH ACUTE RESPIRATORY-DISTRESS SYNDROME

The acute respiratory distress syndrome (ARDS) frequently results in a fibroproliferative response that precludes effective alveolar repair. Transforming growth factor-alpha (TCF-alpha), a potent epithelial and mesenchymal cell mitogen, may modulate the response to lung injury. I n this study, we determined whether bronchoalveolar lavage fluid (BALF ) concentrations of TCF-alpha are increased during the first 2 wk afte r the onset of ARDS and, if so, whether increased TCF-alpha levels in lavage fluid are associated with increased levels of procollagen pepti de III (PCP III), a biological marker of fibroproliferation, and with increased fatality rates. We enrolled 74 consecutive patients with ARD S prospectively identified on admission to the intensive care unit of a tertiary care hospital, and 11 patients with chronic interstitial lu ng disease. Thirteen healthy volunteers served as control subjects. TC F-alpha concentrations were measured in BALF recovered on Days 3, 7, a nd 14 after the onset of ARDS (total of 130 lavage samples). TGF-alpha was detected in the lavage fluid of 90% of patients with ARDS (67 of 74), and in 100% of patients with idiopathic pulmonary fibrosis (IPF) (10 of 10), but in none of 13 normal volunteers. At each day tested, t he median lavage TCF-alpha level of patients with ARDS was significant ly higher than that of normals. The overall fatality rate was 45% (33 of 74 patients). In a univariate analysis, the median TGF-alpha levels in nonsurvivors were 1.5-fold higher at Day 7 (p = 0.06) and 1.8-fold higher at Day 14 (p = 0.048). The fatality rate was 4 times higher (C I 1.6, 17.5) for patients with both increased lavage TCF-alpha and PCP III concentrations at Day 7 than for patients with low TCF-alpha and PCP III values, indicating a synergistic relationship between TCF-alph a and PCP III. We conclude that increased levels of TCF-alpha in BALF are common in patients with ARDS and that lavage TCF-alpha is associat ed with a marker of the fibroproliferative response in sustained ARDS.