Am. J. Respir. Crit. Care Med., Volume 158, Number 2, August 1998, 424-430

Elevated Transforming Growth Factor- Levels in Bronchoalveolar Lavage Fluid of Patients with Acute Respiratory Distress Syndrome

DAVID K. MADTES, GORDON RUBENFELD, LAWRENCE D. KLIMA, JOHN A. MILBERG, KENNETH P. STEINBERG, THOMAS R. MARTIN, GANESH RAGHU, LEONARD D. HUDSON, and JOAN G. CLARK

Sections of Pulmonary and Critical Care Medicine, Fred Hutchinson Cancer Research Center, Harborview Medical Center, and Seattle VA Medical Center; and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington

The acute respiratory distress syndrome (ARDS) frequently results in a fibroproliferative response that precludes effective alveolar repair. Transforming growth factor- (TGF-), a potent epithelial and mesenchymal cell mitogen, may modulate the response to lung injury. In this study, we determined whether bronchoalveolar lavage fluid (BALF) concentrations of TGF- are increased during the first 2 wk after the onset of ARDS and, if so, whether increased TGF- levels in lavage fluid are associated with increased levels of procollagen peptide III (PCP III), a biological marker of fibroproliferation, and with increased fatality rates. We enrolled 74 consecutive patients with ARDS prospectively identified on admission to the intensive care unit of a tertiary care hospital, and 11 patients with chronic interstitial lung disease. Thirteen healthy volunteers served as control subjects. TGF- concentrations were measured in BALF recovered on Days 3, 7, and 14 after the onset of ARDS (total of 130 lavage samples). TGF- 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, the median lavage TGF- level of patients with ARDS was significantly higher than that of normals. The overall fatality rate was 45% (33 of 74 patients). In a univariate analysis, the median TGF- 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 (CI 1.6, 17.5) for patients with both increased lavage TGF- and PCP III concentrations at Day 7 than for patients with low TGF- and PCP III values, indicating a synergistic relationship between TGF- and PCP III. We conclude that increased levels of TGF- in BALF are common in patients with ARDS and that lavage TGF- is associated with a marker of the fibroproliferative response in sustained ARDS.

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