title: Neonates with reduced neonatal lung function have systemic low-grade inflammation.
abstract: BACKGROUND
  Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced lung function.
  
  
  OBJECTIVE
  We sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation.
  
  
  METHODS
  Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children of the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort who had completed neonatal lung function testing at age 4 weeks. Associations between neonatal lung function indices and inflammatory biomarkers were investigated by conventional statistics and unsupervised principal component analysis.
  
  
  RESULTS
  The neonatal forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP (β-coefficient, -0.12; 95% CI, -0.21 to -0.04; P < .01) and IL-6 (β-coefficient, -0.10; 95% CI, -0.18 to -0.01; P = .03) levels. The multivariate principal component analysis approach, including hs-CRP, IL-6, TNF-α, and CXCL8, confirmed a uniform upregulated inflammatory profile in children with reduced forced expiratory volume at 0.5 seconds (P = .02). Adjusting for body mass index at birth, maternal smoking, older children in the home, neonatal bacterial airway colonization, infections 14 days before, and asthmatic symptoms, as well as virus-induced wheezing, at any time before biomarker assessment at age 6 months did not affect the associations.
  
  
  CONCLUSIONS
  Diminished neonatal lung function is associated with upregulated systemic inflammatory markers, such as hs-CRP.
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health and Medical Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bo L K
authors.initials: BL
authors.lastname: Chawes
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health and Medical Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics, Naestved Hospital, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Stokholm
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health and Medical Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health and Medical Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: bisgaard@copsac.com.
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D003718:Denmark; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D018811:Maternal Exposure; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D011446:Prospective Studies; D012907:Smoking / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Asthma; children; high-sensitivity C-reactive protein; proinflammatory cytokines; spirometry