title: Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes.
abstract: BACKGROUND
  Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment.
  
  
  RESULTS
  By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This "neutrophil signature" was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection.
  
  
  CONCLUSIONS
  Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.
authors.affiliation: Investigación Biomédica del Clínico (ibC), Hospital Clínico Universitario de Valladolid, Avda Ramón y Cajal 3, 47005 Valladolid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Almansa
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Socias
authors.forename: Monica
authors.initials: M
authors.lastname: Sanchez-Garcia
authors.forename: Ignacio
authors.initials: I
authors.lastname: Martín-Loeches
authors.forename: Milagros
authors.initials: M
authors.lastname: del Olmo
authors.forename: David
authors.initials: D
authors.lastname: Andaluz-Ojeda
authors.forename: Felipe
authors.initials: F
authors.lastname: Bobillo
authors.forename: Lucia
authors.initials: L
authors.lastname: Rico
authors.forename: Agueda
authors.initials: A
authors.lastname: Herrero
authors.forename: Vicente
authors.initials: V
authors.lastname: Roig
authors.forename: C Alicia
authors.initials: CA
authors.lastname: San-Jose
authors.forename: Sara
authors.initials: S
authors.lastname: Rosich
authors.forename: Julia
authors.initials: J
authors.lastname: Barbado
authors.forename: Carlos
authors.initials: C
authors.lastname: Disdier
authors.forename: Raúl Ortiz
authors.initials: RO
authors.lastname: de Lejarazu
authors.forename: Maria C
authors.initials: MC
authors.lastname: Gallegos
authors.forename: Victoria
authors.initials: V
authors.lastname: Fernandez
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Bermejo-Martin
mesh_terms: D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D016638:Critical Illness; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism; D009195:Peroxidase / Q000235:genetics* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index; D059467:Transcriptome / Q000235:genetics*
chemical_list: D023181:Antimicrobial Cationic Peptides; D005819:Genetic Markers; D012333:RNA, Messenger; D009195:Peroxidase; D010447:Peptide Hydrolases