Matrix metalloproteinases and airway remodeling and function in primary ciliary dyskinesia

Respir Med. 2017 Mar:124:49-56. doi: 10.1016/j.rmed.2017.02.001. Epub 2017 Feb 2.

Abstract

Background: The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is important in the regulation of airway damage.

Objective: To evaluate whether they are important in the pathophysiology of primary and secondary ciliary dyskinesia (PCD, SCD).

Methods: We measured sputum bacteriology, lung CT changes, MMPs, TIMPs and lung function in 86 patients (51 PCD, 35 SCD) in a cross-sectional study; the 10 controls studied did not have HRCT or sputum cultures. MMPs, TIMPs and lung function were evaluated longitudinally for up to one year in 38 PCD patients.

Results: At baseline, there were no differences in MMPs, TIMPs and MMPs/TIMPs, between PCD and SCD but lower levels were found in controls. There was an association between poorer lung function with increasing levels of MMPs in PCD, while in SCD only MMP-9/TIMP-1 values correlated with FRC z-scores. Levels of MMPs and TIMPs significantly correlated with severity HRCT changes. Longitudinally, there were significant correlations between slope of changes in spirometric parameters and slope of change in sputum MMPs in PCD patients.

Conclusions: In conclusion, we report for the first time that increased MMPs are associated with worse airway damage in PCD and SCD, and thus are potential therapeutic targets.

Keywords: Airway remodeling; Chest HRCT; Lung function; Matrix metalloproteinases; Primary ciliary dyskinesia; Secondary ciliary dyskinesia.

MeSH terms

  • Adolescent
  • Adult
  • Airway Remodeling*
  • Child
  • Cross-Sectional Studies
  • Female
  • Humans
  • Kartagener Syndrome / metabolism
  • Kartagener Syndrome / microbiology
  • Kartagener Syndrome / physiopathology*
  • Lung / diagnostic imaging*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Prospective Studies
  • Respiratory Function Tests / methods
  • Respiratory System / metabolism*
  • Respiratory System / pathology
  • Respiratory System / physiopathology
  • Sputum / microbiology
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Tomography, X-Ray Computed / methods
  • Young Adult

Substances

  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 9