title: Evaluation of the extent of pulmonary cysts and their association with functional variables and serum markers in lymphangioleiomyomatosis (LAM).
abstract: OBJECTIVE
  Although computed tomography (CT) has been used previously to assess disease severity in lymphangioleiomyomatosis (LAM), the associations between the extent of pulmonary cysts on CT and six-minute walk test (6MWT), matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF-D) are not well established. We performed a cross-sectional study to quantify the extent of pulmonary cysts in CT and to establish their correlations with pulmonary function tests (PFTs), 6MWT results, including a composite index (desaturation-distance ratio, DDR), and levels of VEGF-D and MMPs in LAM.
  
  
  METHODS
  Twenty-three LAM patients underwent CT scanning to automatically quantify the extent of pulmonary cysts and performed PFTs and 6MWT. Serum levels of MMP-2, MMP-9, and VEGF-D were also measured.
  
  
  RESULTS
  The severity of pulmonary cystic involvement was mild (the extent of cysts was 6.8 %) and correlated best with FEV1/FVC (r = -0.84), residual volume (r = 0.66), DLCO (r = -0.82), the DDR index (r = 0.77), and desaturation during the 6MWT (r = -0.81). There was a weak correlation with VEGF-D (r = 0.45), but no association was found with MMP-2 and MMP-9.
  
  
  CONCLUSIONS
  The severity of pulmonary cystic involvement was mild in this sample of LAM patients and correlated best with airway obstruction, air trapping, reduced DLCO, the DDR index, and desaturation during the 6MWT. Serum VEGF-D cannot be completely defined as a valuable marker of disease severity and there may be a mechanism independent of MMPs to explain the formation of pulmonary cysts.
authors.affiliation: Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Dr. Enéas de Carvalho Aguiar Avenue, 44, Fifth floor, São Paulo, 05403-900, Brazil, bruno.guedes2@terra.com.br.
authors.forename: Bruno Guedes
authors.initials: BG
authors.lastname: Baldi
authors.forename: Mariana Sponholz
authors.initials: MS
authors.lastname: Araujo
authors.forename: Carolina Salim Gonçalves
authors.initials: CS
authors.lastname: Freitas
authors.forename: Gustavo Borges
authors.initials: GB
authors.lastname: da Silva Teles
authors.forename: Ronaldo Adib
authors.initials: RA
authors.lastname: Kairalla
authors.forename: Olívia Meira
authors.initials: OM
authors.lastname: Dias
authors.forename: Daniel Antunes Silva
authors.initials: DA
authors.lastname: Pereira
authors.forename: Suzana Pinheiro
authors.initials: SP
authors.lastname: Pimenta
authors.forename: Carlos Roberto Ribeiro
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D003430:Cross-Sectional Studies; D003560:Cysts / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D018450:Disease Progression; D005080:Exercise Test / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology; D008175:Lung Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D018192:Lymphangioleiomyomatosis / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9