title: Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD.
abstract: BACKGROUND
  Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age.
  
  
  METHODS
  All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis.
  
  
  RESULTS
  Young susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients.
  
  
  CONCLUSIONS
  We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT00807469.
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. s.j.m.hoonhorst@umcg.nl.|GRIAC research institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. s.j.m.hoonhorst@umcg.nl.
authors.forename: Susan J M
authors.initials: SJ
authors.lastname: Hoonhorst
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. w.timens@umcg.nl.|Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. w.timens@umcg.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. l.koenderman@umcutrecht.nl.
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. a.t.lotamloi@umcutrecht.nl.
authors.forename: Adèle T
authors.initials: AT
authors.lastname: Lo Tam Loi
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. j.w.j.lammers@umcutrecht.nl.
authors.forename: Jan-Willem J
authors.initials: JW
authors.lastname: Lammers
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.m.boezen@umcg.nl.|Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.m.boezen@umcg.nl.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. a.j.m.van.oosterhout@umcg.nl.|Lab of Allergy and Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. a.j.m.van.oosterhout@umcg.nl.
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: van Oosterhout
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. d.s.postma@umcg.nl.|GRIAC research institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. d.s.postma@umcg.nl.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. n.h.t.ten.hacken@umcg.nl.|GRIAC research institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. n.h.t.ten.hacken@umcg.nl.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: Ten Hacken
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000276:immunology*; D017452:Receptors, IgG / Q000097:blood; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000276:immunology; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D017452:Receptors, IgG