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P202 Studying The Relationship Between Matrix Metalloproteinases And Lung Tissue Damage During A Clinical Exacerbation Of Cystic Fibrosis
  1. HAP Passman1,
  2. TD Daniels2,
  3. PE Elkington2
  1. 1University of Southampton Faculty of Medicine, Southampton, UK
  2. 2University Hospital Southampton NHS Foundation Trust, Southampton, UK

Abstract

Background Cystic Fibrosis (CF) is the commonest fatal autosomal recessive condition of Caucasians. The lung in CF is characterised by chronic bacterial colonisation, inflammation, and lung tissue destruction. Matrix Metalloproteinases (MMPs) are proteases that are expressed in inflammatory states that degrade lung matrix. Whilst MMPs are known to be raised in many inflammatory lung conditions, their role in CF is poorly understood.

Aims The study aimed to compare lung function and MMP levels throughout an exacerbation.

Methods Sputum samples and clinical information were obtained with written consent from 23 adult subjects with CF. Samples were collected at day 0, day 14 and week 6 of an exacerbation of CF. Samples were frozen, before Luminex bioassay and IL-8 ELISA was performed. The sputum concentration of MMP 1, 2, 3, 7, 8, 9,10,12,13 and IL-8 were measured.

Results A statistically significant increase in IL-8 concentration (pg/ml) occurred between day 14 and week 6 (p = 0.0387). The concentration of MMP-9 decreased from day 0 to day 14 (p = 0.006), and then rose significantly between day 14 and week 6 (p = 0.0412). However, the concentration of MMP-9 at week 6 was significantly less than at day 0 (0.0453). A significant decrease in the concentration of MMP-8 occurred between day 0 and day 14 (p = 0.0124); and between day 0 to week 6 (p = 0.0426).

Conclusions MMPs and other inflammatory markers are raised during exacerbations, and fall with treatment. High proteolytic activity may lead to a worsening lung function and contribute significantly to structural changes within the CF lung. Furthering our understanding of this diverse group of proteases could lead to potential novel therapeutic targets which could help prevent irreversible lung damage.

Abstract P202 Figure 1

The sputum concentration of MMP-9 (pg/ml) at sample time. Values at 3000 represent values above the level of detection. Significant values are represented with a line and an asterix (*). A significant decrease in MMP-9 concentration was found between Day 0 and Day 14 (p = 0.006). An increase in MMP-9 concentration was seen between day 14 and week 6 (p = 0.0412). There was a statistically significant decrease in MMP-9 concentration between day 0 and week 6 (p = 0.0453)

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