title: Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD.
abstract: Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics. Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed. Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p < 0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p < 0.01; eNose breathprint r = 0.84, p = 0.002) (MPO: four compounds, p < 0.01; eNose r = 0.72, p = 0.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD. Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.
authors.affiliation: Depts of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, PO Box 22700, NL 1100 DE Amsterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Fens
authors.forename: S B
authors.initials: SB
authors.lastname: de Nijs
authors.forename: S
authors.initials: S
authors.lastname: Peters
authors.forename: T
authors.initials: T
authors.lastname: Dekker
authors.forename: H H
authors.initials: HH
authors.lastname: Knobel
authors.forename: T J
authors.initials: TJ
authors.lastname: Vink
authors.forename: N P
authors.initials: NP
authors.lastname: Willard
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: F H
authors.initials: FH
authors.lastname: Krouwels
authors.forename: H-G
authors.initials: HG
authors.lastname: Janssen
authors.forename: R
authors.initials: R
authors.lastname: Lutter
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000368:Aged; D001249:Asthma / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods; D002452:Cell Count; D047150:Eosinophil Cationic Protein / Q000032:analysis; D045853:Exhalation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D009195:Peroxidase / Q000032:analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000378:metabolism; D012372:ROC Curve; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry
chemical_list: D015415:Biomarkers; D009195:Peroxidase; D047150:Eosinophil Cationic Protein