title: Antimicrobial peptide levels are linked to airway inflammation, bacterial colonisation and exacerbations in chronic obstructive pulmonary disease.
abstract: Antimicrobial peptides (AMPs) are effectors of host defence against infection, inflammation and wound repair. We aimed to study AMP levels in stable chronic obstructive pulmonary disease (COPD) and during acute exacerbations of COPD (AECOPD), and to examine their relation to clinical parameters and inflammatory markers.The 3-year Bergen COPD Cohort Study included 433 COPD patients and 325 controls. Induced sputum was obtained and analysed for levels of the AMPs human cathelicidin (hCAP18/LL-37) and secretory leukocyte protease inhibitor (SLPI), and for the inflammatory markers interleukin (IL)-8, IL-6 and tumour necrosis factor-α (TNF-α) using immunoassays. Systemic hCAP18/LL-37 and vitamin D levels were also studied. Treating AMPs as response variables, non-parametric tests were applied for univariate comparison, and linear regression to obtain adjusted estimates. The risk of AECOPD was assessed by Cox proportional-hazard regression.Sputum AMP levels were higher in patients with stable COPD (n=215) compared to controls (n=45), and further changed during AECOPD (n=56), with increased hCAP18/LL-37 and decreased SLPI levels. Plasma hCAP18/LL-37 levels showed a similar pattern. In stable COPD, high sputum hCAP18/LL-37 levels were associated with increased risk of AECOPD, non-typeableHaemophilus influenzaecolonisation, higher age, ex-smoking and higher levels of inflammatory markers.Altered levels of selected AMPs are linked to airway inflammation, infection and AECOPD, suggesting a role for these peptides in airway defence mechanisms in COPD.
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway louise.persson@med.uib.no.
authors.forename: Louise J P
authors.initials: LJ
authors.lastname: Persson
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Aanerud
authors.affiliation: Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Hardie
authors.affiliation: Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
authors.forename: Roy
authors.initials: R
authors.lastname: Miodini Nilsen
authors.affiliation: Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Per S
authors.initials: PS
authors.lastname: Bakke
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.|Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Tomas M
authors.initials: TM
authors.lastname: Eagan
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D000368:Aged; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D054804:Cathelicidins / Q000032:analysis*; D015331:Cohort Studies; D016207:Cytokines / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006192:Haemophilus Infections / Q000453:epidemiology; D006801:Humans; D007249:Inflammation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009664:Norway; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000503:physiopathology*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000032:analysis*; D013183:Sputum / Q000737:chemistry; D014807:Vitamin D / Q000097:blood
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D054804:Cathelicidins; D016207:Cytokines; D053481:Secretory Leukocyte Peptidase Inhibitor; D014807:Vitamin D