title: Haemophilus influenzae from patients with chronic obstructive pulmonary disease exacerbation induce more inflammation than colonizers.
abstract: BACKGROUND
  Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD).
  
  
  OBJECTIVE
  To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD.
  
  
  METHODS
  Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells.
  
  
  RESULTS
  H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-kappaB and p38 mitogen-activated protein kinase signaling pathways.
  
  
  CONCLUSIONS
  The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function.
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive, C33-GH, Iowa City, IA 52242, USA. dwight-look@uiowa.edu
authors.forename: Cecilia L
authors.initials: CL
authors.lastname: Chin
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Manzel
authors.forename: Erin E
authors.initials: EE
authors.lastname: Lehman
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Humlicek
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Starner
authors.forename: Gerene M
authors.initials: GM
authors.lastname: Denning
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Murphy
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.forename: Dwight C
authors.initials: DC
authors.lastname: Look
mesh_terms: D000208:Acute Disease; D000368:Aged; D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases