Matrix metalloproteinases and airway remodeling and function in primary ciliary dyskinesia

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.