title: Effects of bacterial infection on airway antimicrobial peptides and proteins in COPD.
abstract: BACKGROUND
  Pathogenic bacteria colonize the airways of 30% to 40% of patients with COPD and cause approximately 50% of exacerbations. New strains of nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are associated with exacerbations. Antimicrobial protein/peptides (AMPs) play important roles in innate lung defense against pathogens. To our knowledge, the changes in AMP baseline levels in respiratory secretions during bacterial colonization and exacerbation have not been described. The objective of this study was to elucidate the effects of the acquisition of a new strain of pathogenic bacteria on the airway levels of AMPs in patients with COPD.
  
  
  METHODS
  One hundred fifty-three samples from 11 patients were selected from COPD sputum samples collected prospectively over 6 years. Samples were grouped as culture-negative (no pathogenic bacteria), colonization, and exacerbation due to new strains of NTHI and M catarrhalis. Levels of lysozyme, lactoferrin, LL-37, and secretory leukocyte protease inhibitor (SLPI) were measured by enzyme-linked immunosorbent assay and compared among groups by paired analysis.
  
  
  RESULTS
  Compared with baseline, sputum lysozyme levels were significantly lower during colonization and exacerbation by NTHI (P = .001 and P = .013, respectively) and M catarrhalis (P = .007 and P = .018, respectively); SLPI levels were lower with exacerbation due to NTHI and M catarrhalis (P = .002 and P = .004, respectively), and during colonization by M catarrhalis (P = 032). Lactoferrin levels did not change significantly; LL-37 levels were higher during exacerbation by NTHI and M catarrhalis (P = .001 and P = .018, respectively).
  
  
  CONCLUSIONS
  Acquisition of NTHI and M catarrhalis is associated with significant changes in airway levels of AMPs, with larger changes in exacerbation. Airway AMP levels are likely to be important in pathogen clearance and clinical outcomes of infection in COPD.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY; VA Western New York Healthcare System, Buffalo, NY. Electronic address: gp36@buffalo.edu.
authors.forename: Ganapathi Iyer
authors.initials: GI
authors.lastname: Parameswaran
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY; VA Western New York Healthcare System, Buffalo, NY.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY; Division of Microbiology, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Murphy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006192:Haemophilus Infections / Q000453:epidemiology*; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007781:Lactoferrin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D001936:Moraxella catarrhalis / Q000276:immunology; D045828:Moraxellaceae Infections / Q000453:epidemiology*; D009113:Muramidase / Q000032:analysis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000382:microbiology* / Q000503:physiopathology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000032:analysis; D013183:Sputum / Q000201:enzymology / Q000382:microbiology; D023083:beta-Defensins / Q000276:immunology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D053481:Secretory Leukocyte Peptidase Inhibitor; D023083:beta-Defensins; D009113:Muramidase; D007781:Lactoferrin; D054804:Cathelicidins