Changes in collagen turnover in early acute respiratory distress syndrome.
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 (COL2-3/4C(short) 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. COL2-3/4C(short) 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 COL2-3/4C(short) 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:COL2-3/4C(short) 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
L
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. Lynne.Armstrong@bristol.ac.uk
Thickett
D R
DR
Mansell
J P
JP
Ionescu
M
M
Hoyle
E
E
Billinghurst
R C
RC
Poole
A R
AR
Millar
A B
AB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003094:Collagen / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000032:analysis; D011347:Procollagen / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000401:mortality; D012307:Risk Factors; D014508:Urea / Q000097:blood
D009842:Oligopeptides; D011347:Procollagen; D014508:Urea; D003094:Collagen