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Type III Procollagen Peptide in the Adult Respiratory Distress Syndrome: Association of Increased Peptide Levels in Bronchoalveolar Lavage Fluid with Increased Risk for Death

Joan G. Clark, MD; John A. Milberg, MPH; Kenneth P. Steinberg, MD; and Leonard D. Hudson, MD
[+] Article and Author Information

From Fred Hutchinson Cancer Research Center; and Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington. Requests for Reprints: Joan G. Clark, MD, Fred Hutchinson Cancer Research Center (M677), 1124 Columbia Street, Seattle, WA 98104. Acknowledgments: The authors thank Thomas R. Martin, MD, for thoughtful suggestions in the development of this study and for providing cell and protein analyses of lavage fluid; Caroline Sawe and Michael Joseph for excellent technical assistance; and Meri Gehrman for assistance in preparation of the manuscript. Grant Support: In part by grant HL-30542 from the National Heart, Lung, and Blood Institute, National Institutes of Health.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1995;122(1):17-23. doi:10.7326/0003-4819-122-1-199501010-00003
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Objective: To determine whether bronchoalveolar lavage fluid levels of the N-terminal peptide of type III procollagen (procollagen III) are increased in patients with the adult respiratory distress syndrome and, if so, whether increased procollagen III levels in lavage fluid are associated with increased fatality rates.

Design: Prospective cohort study.

Setting: Intensive care units of a tertiary care hospital affiliated with a medical school.

Patients: 117 consecutive patients with the adult respiratory distress syndrome prospectively identified on admission; 6 healthy volunteers served as controls.

Measurements: Bronchoalveolar lavage fluid procollagen III levels in 117 patients at 3, 7, and 14 days after onset of the adult respiratory distress syndrome (total of 196 lavage samples).

Results: The median procollagen III level was 1.75 U/mL (range, 0 to 13.4 U/mL) in lavage fluid obtained from patients with the adult respiratory distress syndrome. We detected procollagen III levels in lavage fluid from 80% of patients (94 of 117) but not in 6 normal volunteers. The overall fatality rate was 41% (48 of 117 patients). In a univariate analysis, the relative risk (RR) for death was increased in patients with procollagen III levels of 1.75 U/mL or more obtained on day 3 (RR, 2.4; 95% CI, 1.3 to 4.3), day 7 (RR, 2.7; CI, 1.4 to 5.4), and day 14 (RR, 2.7; CI, 1.1 to 6.3). Inclusion of other variables in a multivariate model only minimally decreased the risk associated with increased procollagen III levels.

Conclusion: Increased levels of type III procollagen in bronchoalveolar lavage fluid are frequently detected in patients with the adult respiratory distress syndrome and are strongly associated with increased risk for fatal outcome independent of other variables related to fatality in patients with the syndrome.

Figures

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Figure 3.
Fatality rates in patients with the adult respiratory distress syndrome according to bronchoalveolar lavage fluid procollagen III concentration and modified lung injury score.

Fatality rates for patients with lavage procollagen III levels less than 1.75 U/mL and levels of 1.75 U/mL or more compared with lung injury scores (LIS) of 2 or more and LIS less than 2. The number of patients in each category is indicated within the bar. At 3 days after onset of the syndrome, increased procollagen III levels were associated with a relative risk (RR) of 3.0 (95% CI, 0.9 to 10.0) when LIS was less than 2 and an RR of 2.2 (CI, 1.1 to 4.5) when LIS was 2 or more. At 7 days, RR was 2.2 (CI, 0.4 to 11.9) when LIS was less than 2 and 2.3 (CI, 1.1 to 4.9) when LIS was 2 or more. At 14 days, RR was 1.4 (CI, 0.2 to 9.5) when LIS was less than 2 and 2.6 (CI, 0.8 to 9.3) when LIS was 2 or more. PCP III = N-terminal peptide of type III procollagen.

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Figure 2.
Fatality rates in patients with the adult respiratory distress syndrome according to bronchoalveolar lavage fluid procollagen III concentration.

Fatality rates for patients with procollagen III levels less than 1.75 U/mL compared with levels of 1.75 U/mL or more. The number of patients in each category is indicated within the bar. The relative risk (RR) was 2.4 (95% CI, 1.3 to 4.3) at 3 days after onset of the syndrome. At 7 days, the RR was 2.7 (CI, 1.4 to 5.4). At 14 days, the RR was 2.7 (CI, 1.1 to 6.3). PCP III = N-terminal peptide of type III procollagen.

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Figure 1.
Bronchoalveolar lavage procollagen III concentrations in patients with the adult respiratory distress syndrome who lived or died.hatched boxopen boxPPP

Median procollagen III levels were higher in patients who died ( ) than in those who survived ( ) at 3 days ( < 0.001), 7 days ( = 0.002), and 14 days ( = 0.09). Horizontal lines indicate the median value. Boxes represent the 25th to 75th percentile. Vertical lines represent the 10th to 90th percentile. Individual values above the 90th percentile are shown as solid circles. PCP III = N-terminal peptide of type III procollagen.

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