Findings from a meta-analysis demonstrated greater baseline blood matrix-metalloproteinase-7 (MMP-7) concentrations in patients with untreated idiopathic pulmonary fibrosis (IPF), according to a study published in the European Respiratory Journal.
There was a 27% greater risk of disease progression and a 23% increased risk of mortality in patients, and these findings were independent of age, gender, smoking status, and lung function.
This evidence suggests healthcare providers may be able to use MMP-7 as a biomarker to predict IPF outcomes, in conjunction with forced vital capacity (FVC) tests. FVC measurements are limited in terms of disease prediction due to confounding factors including patient effort and lung diseases like emphysema.
“Biomarkers of disease activity have the potential to facilitate clinical management and transform early-phase clinical trials by acting as surrogate endpoints,” the authors commented. “From a clinical perspective, MMP-7 should be considered for implementation as a prognostic tool at the point of diagnosis, especially where lung function testing is cumbersome or unavailable.”
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Investigators searched for “idiopathic pulmonary fibrosis” and “biomarkers” throughout Medline, Google Scholar, Embase, Cochrane Register, and ClinicalTrials.gov, filtering specifically for prognostic studies. Biomarkers included MMP-7, Krebs von den Lungen-6, surfactant protein-A, surfactant protein-D, matrix metalloproteinase-1, cancer antigen 125, carbohydrate antigen 19-9, vascular endothelial growth factor, and insulin-like growth factor binding protein 2. Biomarkers for both immune dysregulation and extracellular matrix modeling were also included.
Requested individual participant data were available for 9 of the 12 accepted MMP-7 studies and included baseline and 3-month MMP-7 biomarker levels, as well as lung function and overall mortality in 12 months. Researchers performed a risk of bias assessment using the Quality in Prognostic Studies tool and evaluated the quality of evidence for outcomes in each study.
The primary outcome measure was overall mortality, while the secondary outcome measures included change in percent of predicted FVC from baseline at 12 months and measures of disease progression (10% decline in FVC or death within 12 months of baseline). Investigators performed statistical analysis using Stata 16 to assess these 9 MMP-7 studies. The researchers also evaluated 15 other blood biomarkers from other included studies.
Limitations included study language translation barriers preventing the inclusion of some possibly relevant studies, limited inclusion criteria to untreated patients with IPF, and exclusion of studies unrelated to IPF, which limited generalizability to non-IPF interstitial lung diseases. Also, this study only analyzed short-term changes in MMP-7 levels after 3 months, which resulted in limited prognostic value due to the absence of an empirical threshold.
Khan FA, Stewart I, Saini G, et al. A systematic review of blood biomarkers with individual participant data meta-analysis of matrix-metalloproteinase-7 in IPF. Eur Respir J. 2021;2101612. doi.org/10.1183/13993003.01612-2021.