title: Matrix metalloproteinases and airway remodeling and function in primary ciliary dyskinesia.
abstract: The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is important in the regulation of airway damage.
  
  
  
  To evaluate whether they are important in the pathophysiology of primary and secondary ciliary dyskinesia (PCD, SCD).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Paediatrics, University Hospital of Pisa, Italy. Electronic address: m.pifferi@med.unipi.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pifferi
authors.affiliation: Imperial College and Royal Brompton Hospital, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital of Pisa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Caramella
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Metelli
authors.affiliation: Department of Paediatrics, University Hospital of Pisa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Cicco
authors.affiliation: Department of Paediatrics, University Hospital of Pisa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Piras
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital of Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gherarducci
authors.affiliation: Visiting Professor at Department of Paediatrics, University of Verona, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Capristo
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Maggi
authors.affiliation: Department of Paediatrics, University Hospital of Pisa, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Peroni
authors.affiliation: Department of Paediatrics, University of Verona, Italy.
authors.forename: Attilio L
authors.initials: AL
authors.lastname: Boner
mesh_terms: D000293:Adolescent; D000328:Adult; D056151:Airway Remodeling; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007619:Kartagener Syndrome / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012129:Respiratory Function Tests / Q000379:methods; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013183:Sputum / Q000382:microbiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014057:Tomography, X-Ray Computed / Q000379:methods; D055815:Young Adult
chemical_list: C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9
keywords: Airway remodeling; Chest HRCT; Lung function; Matrix metalloproteinases; Primary ciliary dyskinesia; Secondary ciliary dyskinesia