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Evaluation of the Extent of Pulmonary Cysts and Their Association with Functional Variables and Serum Markers in Lymphangioleiomyomatosis (LAM)

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Abstract

Purpose

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.

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Conflict of interest

Bruno Guedes Baldi, Mariana Sponholz Araujo, Carolina Salim Gonçalves Freitas, Gustavo Borges da Silva Teles, Ronaldo Adib Kairalla, Olívia Meira Dias, Daniel Antunes Silva Pereira, Suzana Pinheiro Pimenta, and Carlos Roberto Ribeiro Carvalho have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. 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 Guedes Baldi, Mariana Sponholz Araujo, Carolina Salim Gonçalves Freitas, Ronaldo Adib Kairalla, Olívia Meira Dias, Daniel Antunes Silva Pereira, Suzana Pinheiro Pimenta & Carlos Roberto Ribeiro Carvalho

  2. Department of Radiology, University of Sao Paulo Medical School, São Paulo, Brazil

    Gustavo Borges da Silva Teles

Authors
  1. Bruno Guedes Baldi
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  2. Mariana Sponholz Araujo
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  3. Carolina Salim Gonçalves Freitas
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  4. Gustavo Borges da Silva Teles
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  5. Ronaldo Adib Kairalla
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  6. Olívia Meira Dias
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  7. Daniel Antunes Silva Pereira
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  8. Suzana Pinheiro Pimenta
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  9. Carlos Roberto Ribeiro Carvalho
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Corresponding author

Correspondence to Bruno Guedes Baldi.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Fig. 1OR

Scatter plots showing association between the extent of cysts and pulmonary function tests results. FEV 1 forced expiratory volume in the first second, FVC forced vital capacity, RV residual volume, TLC total lung capacity. Supplementary material 1 (JPEG 51 kb)

Fig. 2OR

Scatter plots showing association between the extent of cysts and six-minute walk test results. 6MWT six-minute walk test, DDR, desaturation–distance ratio, SpO 2 peripheral oxygen saturation. Supplementary material 2 (JPEG 54 kb)

Fig. 3OR

Scatter plots showing association between the extent of cysts and DLCO and serum markers. DL CO diffusion capacity of the lungs for carbon monoxide, MMP metalloproteinase, VEGF-D vascular endothelial growth factor. Supplementary material 3 (JPEG 55 kb)

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Baldi, B.G., Araujo, M.S., Freitas, C.S.G. et al. Evaluation of the Extent of Pulmonary Cysts and Their Association with Functional Variables and Serum Markers in Lymphangioleiomyomatosis (LAM). Lung 192, 967–974 (2014). https://doi.org/10.1007/s00408-014-9641-2

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  • DOI: https://doi.org/10.1007/s00408-014-9641-2

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