Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis

Respir Res. 2012 Apr 18;13(1):34. doi: 10.1186/1465-9921-13-34.

Abstract

Background: Lymphangioleiomyomatosis is a rare disease occurring almost exclusively in women. Diagnosis often requires surgical biopsy and the clinical course varies between patients with no predictors of progression. We evaluated recent diagnostic guidelines, clinical features and serum biomarkers as diagnostic and prognostic tools.

Methods: Serum vascular endothelial growth factor-D (VEGF-D), angiotensin converting enzyme (ACE), matrix metalloproteinases (MMP) -2 and -9, clinical phenotype, thoracic and abdominal computerised tomography, lung function and quality of life were examined in a cohort of 58 patients. 32 healthy female controls had serum biomarkers measured.

Results: Serum VEGF-D, ACE and total MMP-2 levels were elevated in patients. VEGF-D was the strongest discriminator between patients and controls (median = 1174 vs. 332 pg/ml p < 0.0001 with an area under the receiver operating characteristic curve of 0.967, 95% CI 0.93-1.01). Application of European Respiratory Society criteria allowed a definite diagnosis without biopsy in 69%. Adding VEGF-D measurement to ERS criteria further reduced the need for biopsy by 10%. VEGF-D was associated with lymphatic involvement (p = 0.017) but not the presence of angiomyolipomas.

Conclusions: Combining ERS criteria and serum VEGF-D reduces the need for lung biopsy in LAM. VEGF-D was associated with lymphatic disease but not lung function.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Humans
  • Lymphangioleiomyomatosis / blood*
  • Lymphangioleiomyomatosis / diagnosis*
  • Matrix Metalloproteinase 2 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood*
  • Practice Guidelines as Topic / standards
  • Respiratory Function Tests / standards
  • Vascular Endothelial Growth Factor D / blood*
  • Young Adult

Substances

  • Biomarkers
  • Vascular Endothelial Growth Factor D
  • Peptidyl-Dipeptidase A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9