Non-invasive biomarkers and pulmonary function in smokers

• Published in: International journal of chronic obstructive pulmonary disease Vol. 3; no. 1; pp. 171 - 183
• Main Authors: Borrill, Zoë L, Roy, Kay, Vessey, Rupert S, Woodcock, Ashley A, Singh, Dave
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Ltd 2008; Dove Medical Press
• Subjects: Adult; Biomarkers; Biomarkers - metabolism; Bronchial Provocation Tests; Case-Control Studies; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Female; Humans; Leukotriene B4 - metabolism; Male; Middle Aged; Nitric Oxide - metabolism; Original Research; Pulmonary Gas Exchange - physiology; Reproducibility; Reproducibility of Results; Smoking - metabolism; Smoking - physiopathology; Total Lung Capacity - physiology
• ISSN: 1176-9106; 1178-2005; 1178-2005
• DOI: 10.2147/COPD.S1850

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.