Chest
Volume 143, Issue 5, May 2013, Pages 1422-1429
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Original Research
Diffuse Lung Disease
Blood Biomarkers MMP-7 and SP-A: Predictors of Outcome in Idiopathic Pulmonary Fibrosis

https://doi.org/10.1378/chest.11-2735Get rights and content

Background

Because of the variable course of idiopathic pulmonary fibrosis (IPF), it is important to generate an accurate prognosis at the time of diagnosis. The aim of this study was to investigate the prognostic value of blood biomarkers in IPF.

Methods

The plasma level of the biomarkers, matrix metalloproteinase-7 (MMP-7), Krebs von den Lungen-6 antigen, and surfactant protein (SP)-A and SP-D were retrospectively compared with the clinical course of 118 patients with IPF, 68 of whom had biopsy-proven IPF.

Results

The median follow-up period was 24 months. Multivariate Cox analysis showed MMP-7 (HR, 1.056; P = .0063) and SP-A (HR, 1.011; P = .0001) were significant predictors of survival along with age, FVC, and extent of honeycombing. The patients with high levels of both MMP-7 (≥ 12.1 ng/mL) and SP-A (≥ 80.3 ng/mL) had shorter survival (1-year survival rate: 59%) and higher frequency (42%) of lung function decline (> 10% reduction in FVC in 6 months) compared with those with high levels of one biomarker (1-year survival rate: 81%; FVC decline: 27%) or low levels of both (1-year survival rate: 83.3%; FVC decline: 9%). Multivariate models demonstrated marginal improvement in the prediction of mortality (concordance index [C-index]: 0.731; P = .061) when MMP-7 and SP-A were included and compared with standard clinical predictors only (C-index: 0.686); however, it became significant with addition of MMP-7, SP-A, and Krebs von den Lungen-6 antigen (C-index: 0.730; P = .037).

Conclusions

Our retrospective study suggested that at least three biomarkers are necessary to improve predictability of mortality in IPF compared with clinical parameters. Further study in a greater number of patients is warranted.

Section snippets

Study Population

The study subjects were 118 patients with IPF (68 of whom had biopsy-proven IPF) in the pulmonary department at Asan Medical Center in Seoul, South Korea, between September 2004 and December 2008 whose blood was collected at the time of diagnosis. Ten long-term survivors (survival > 8 years) in whom blood sampling was performed several years after diagnosis, while they were still clinically stable, were included. All subjects met the diagnostic criteria of the American Thoracic Society

Baseline Clinical Features

The mean age of the subjects was 62 years and 81% were male (Table 1). The median follow-up period was 24 months. Nonsurvivors were older with lower albumin levels and lung function, poorer exercise capacity, and higher scores of HC and total extent on HRCT compared with survivors (Table 1).

Baseline Levels of Plasma Biomarkers

Mean levels of MMP-7, KL-6, SP-A, and SP-D are shown in Table 2. MMP-7 and KL-6 levels were significantly elevated in nonsurvivors compared with survivors (Table 2).

Correlation of Baseline Levels of Plasma Biomarkers and Mortality

On univariate Cox analysis, all biomarkers

Discussion

Our study showed that plasma levels of the biomarkers MMP-7 and SP-A were useful predictors of poor disease outcomes, including mortality and disease progression (loss of lung function), in patients with IPF. The combination of two indices yielded a more accurate prediction than either index alone. However, the combination of MMP-7 and SP-A with the clinical parameters was only marginally superior to the clinical characteristics alone; the addition of KL-6 made it statistically significant,

Conclusions

Our data showed that blood levels of MMP-7 and SP-A are useful predictors of mortality and disease progression in IPF. The combination of both biomarkers yielded only marginally better prediction than clinical parameters alone, however, with addition of three biomarkers (MMP-7, SP-A and KL-6), the improvement in predictability became statistically significant. Further study with greater numbers of the patients is warranted.

Acknowledgments

Author contributions: Dr Kim had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Song: contributed to the study design, data analysis, writing of the manuscript, and served as first author.

Dr Do: contributed to data acquisition and analysis, and review and revision of the manuscript.

Dr Jang: contributed to data acquisition and analysis, and review and revision of the manuscript.

Dr Colby: contributed to

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  • Cited by (0)

    Funding/Support: This study was supported by grant number 2010-495 from the Asan Institute for Life Sciences, Seoul, South Korea.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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