title: Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis.
abstract: BACKGROUND
  Despite growing evidence for the roles of airway remodeling and bacterial infection in the progression of non-cystic fibrosis bronchiectasis, relationships between collagen-degrading proteases and chronic airway infection are poorly understood.
  
  
  OBJECTIVE
  The aim of this study was to determine which matrix metalloproteinases (MMPs) are elevated in bronchiectasis, whether these MMP levels vary based on patients' dominant infective microbe, and how these levels correlate with clinical measures of disease severity.
  
  
  METHODS
  We determined concentrations of nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in induced sputum from 86 patients with bronchiectasis and 8 healthy control subjects by Luminex protein assay. Concentrations were then assessed in relation to lung function, inflammatory markers, and airway microbiota composition, determined by 16S rRNA gene amplicon sequencing. Airway microbiota composition was classified as Pseudomonas aeruginosa-dominated, Haemophilus influenzae-dominated, or dominated by another species. MMP-8 and MMP-9 activity levels were also measured in a subset of patients.
  
  
  RESULTS
  MMP-1, -3, -7, -8, and -9 and TIMP-2 and -4 levels, as well as MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios, were significantly higher in patients with bronchiectasis than in healthy control subjects (all: P < 0.001, except MMP-7: P < 0.05). Patients with bronchiectasis with H. influenzae-dominated airway infections demonstrated higher MMP-2 levels (P < 0.01) and MMP-8 activity (P < 0.05) than those with P. aeruginosa-dominated airway infections. Among patients with bronchiectasis, there were significant inverse correlations between FEV1 as a percentage of predicted value, MMP-8 and MMP-1 levels, and MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios (P < 0.01).
  
  
  CONCLUSIONS
  Increased MMP levels (particularly MMP-8 and MMP-1) and MMP/TIMP ratios in patients with bronchiectasis compared with healthy control subjects correlated with lower lung function and higher levels of inflammatory markers. Further, MMP profiles differed in patients with bronchiectasis according to the dominant pathogen determined by gene sequencing, raising the possibility of differential airway remodeling according to airway microbiology.
authors: 1 Immunity, Infection, and Inflammation Program, Mater Research Institute, University of Queensland and Translational Research Institute, Woolloongabba, Australia.
authors: Steven L
authors: SL
authors: Taylor
authors: Geraint B
authors: GB
authors: Rogers
authors: Alice C-H
authors: AC
authors: Chen
authors: Lucy D
authors: LD
authors: Burr
authors: Michael A
authors: MA
authors: McGuckin
authors: David J
authors: DJ
authors: Serisier
mesh_terms: D000328:Adult; D001987:Bronchiectasis / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D064307:Microbiota; D008875:Middle Aged; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D013183:Sputum / Q000382:microbiology*
chemical_list: D020782:Matrix Metalloproteinases
keywords: Haemophilus influenzae; Pseudomonas aeruginosa; airway remodeling; tissue inhibitor of metalloproteinase