Am. J. Respir. Crit. Care Med.,
Volume 160, Number 6, December 1999, 1910-1915
Changes in Collagen Turnover in Early Acute Respiratory
Distress Syndrome
LYNNE
ARMSTRONG,
DAVID R.
THICKETT,
JASON P.
MANSELL,
MIRELA
IONESCU,
EMMA
HOYLE,
R.
CLARK BILLINGHURST,
A.
ROBIN POOLE,
and
ANN B.
MILLAR
Lung Research Group, University of Bristol Department of Hospital Medicine, Division of Medicine, and Developmental Biology,
University of Bristol Department of Child Dental Health, Bristol, United Kingdom; Joint Diseases Laboratory, Shriner's Hospitals
for Children, Division of Surgical Research, Department of Surgery, McGill University, Montreal, Quebec, Canada; and
Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado
Pulmonary fibrosis is a well-recognized feature of acute respiratory distress syndrome (ARDS). Using
immunoassays of bronchoalveolar lavage (BAL), fluid we investigated the synthesis of type I procollagen (PICP) and type I/II collagen degradation products (COL2-3/4Cshort neoepitope) in patients
with ARDS, acute lung injury (ALI), subjects with risk factors for ARDS (At Risk), and healthy/ventilated control subjects. PICP was measured by ELISA as a marker of type I procollagen synthesis.
COL2-3/4Cshort neoepitope was measured by an inhibition ELISA as a marker of collagenase degradation of type I/II collagen. BAL was performed initially within 48 h of ventilation (Day 1) and then subsequently on Day 4. Dilution of epithelial lining fluid (ELF) was corrected for by plasma urea comparison. Increased PICP levels were observed in the ELF from ARDS and ALI subjects on Day 1 compared
with subjects At Risk (median values, 124.9 and 95.0 ng/ml versus 38.0 ng/ml, respectively, p < 0.0005). By contrast, the levels of COL2-3/4Cshort neoepitope were significantly reduced in the subjects with ARDS versus the At Risk subjects (13.22 ng/ml versus 32.33 ng/ml, p < 0.0005). This translated into a greatly increased PICP:COL2-3/4Cshort ratio in the subjects with ARDS (p < 0.0001). There
was a significant decline in the PICP level in the subjects with ARDS between Days 1 and 4 (n = 15, p < 0.05). Linear regression analysis showed a significant association between PICP and lung injury
score in the subjects with ARDS (p = 0.01). Our data suggests an early shift in balance between type I
collagen synthesis and degradation by collagenase. The resultant increase in type I collagen would
favor matrix deposition and the development of pulmonary fibrosis in the lungs of subjects with
ARDS. Armstrong L, Thickett DR, Mansell JP, Ionescu M, Hoyle E, Billinghurst RC, Poole AR,
Millar AB. Changes in collagen turnover in early acute respiratory distress syndrome.
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Copyright © 1999 American Thoracic Society
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