title: Non-invasive biomarkers and pulmonary function in smokers.
abstract: Limited information exists regarding measurement, reproducibility and interrelationships of non-invasive biomarkers in smokers. We compared exhaled breath condensate (EBC) leukotriene B4 (LTB4) and 8-isoprostane, exhaled nitric oxide, induced sputum, spirometry, plethysmography, impulse oscillometry and methacholine reactivity in 18 smokers and 10 non-smokers. We assessed the relationships between these measurements and within-subject reproducibility of EBC biomarkers in smokers. Compared to non-smokers, smokers had significantly lower MMEF % predicted (mean 64.1 vs 77.7, p = 0.003), FEV1/FVC (mean 76.2 vs 79.8 p = 0.05), specific conductance (geometric mean 1.2 vs 1.6, p = 0.02), higher resonant frequency (mean 15.5 vs 9.9, p = 0.01) and higher EBC 8-isoprostane (geometric mean 49.9 vs 8.9 pg/ml p = 0.001). Median EBC pH values were similar, but a subgroup of smokers had airway acidification (pH < 7.2) not observed in non-smokers. Smokers had predominant sputum neutrophilia (mean 68.5%). Repeated EBC measurements showed no significant differences between group means, but Bland Altman analysis showed large individual variability. EBC 8-isoprostane correlated with EBC LTB4 (r = 0.78, p = 0.0001). Sputum supernatant IL-8 correlated with total neutrophil count per gram of sputum (r = 0.52, p = 0.04) and with EBC pH (r = -0.59, p = 0.02). In conclusion, smokers had evidence of small airway dysfunction, increased airway resistance, reduced lung compliance, airway neutrophilia and oxidative stress.
authors.affiliation: Medicines Evaluation Unit, University of Manchester, Wythenshawe Hospital, Southmoor Rd, Manchester, UK. zborrill@meu.org.uk
authors.forename: Zoë L
authors.initials: ZL
authors.lastname: Borrill
authors.forename: Kay
authors.initials: K
authors.lastname: Roy
authors.forename: Rupert S
authors.initials: RS
authors.lastname: Vessey
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Woodcock
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000502:physiology; D015203:Reproducibility of Results; D012907:Smoking / Q000378:metabolism* / Q000503:physiopathology*; D014109:Total Lung Capacity / Q000502:physiology
chemical_list: D015415:Biomarkers; D007975:Leukotriene B4; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost