title: Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections.
  
  
  OBJECTIVE
  To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations.
  
  
  METHODS
  We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, α-defensins and β-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants.
  
  
  RESULTS
  After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5-9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load.
  
  
  CONCLUSIONS
  Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations.
authors.affiliation: National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.forename: Joseph
authors.initials: J
authors.lastname: Footitt
authors.forename: Rosa
authors.initials: R
authors.lastname: Sotero
authors.forename: Annette
authors.initials: A
authors.lastname: Jepson
authors.forename: Marco
authors.initials: M
authors.lastname: Contoli
authors.forename: Maria-Belen
authors.initials: MB
authors.lastname: Trujillo-Torralbo
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kebadze
authors.forename: Julia
authors.initials: J
authors.lastname: Aniscenko
authors.forename: Gregory
authors.initials: G
authors.lastname: Oleszkiewicz
authors.forename: Katrina
authors.initials: K
authors.lastname: Gray
authors.forename: Simon D
authors.initials: SD
authors.lastname: Message
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Luminita A
authors.initials: LA
authors.lastname: Stanciu
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Elkin
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001424:Bacterial Infections / Q000209:etiology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D015331:Cohort Studies; D060085:Coinfection / Q000209:etiology* / Q000503:physiopathology; D018450:Disease Progression; D053492:Elafin / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000150:complications* / Q000503:physiopathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000382:microbiology* / Q000821:virology*; D012229:Rhinovirus; D018570:Risk Assessment; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000032:analysis / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000032:analysis / Q000378:metabolism; D012720:Severity of Illness Index; D012907:Smoking; D013183:Sputum / Q000166:cytology; D018709:Statistics, Nonparametric; D000099153:Pentraxins
chemical_list: D023181:Antimicrobial Cationic Peptides; D002097:C-Reactive Protein; D053492:Elafin; D018836:Inflammation Mediators; D053481:Secretory Leukocyte Peptidase Inhibitor; D000683:Serum Amyloid P-Component; D000099153:Pentraxins