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Thorax 2005;60:639-644; doi:10.1136/thx.2004.035279
Copyright © 2005 BMJ Publishing Group Ltd & British Thoracic Society

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ASTHMA

Small airways function and molecular markers in exhaled air in mild asthma

S Battaglia1,2, H den Hertog1, M C Timmers1, S P G Lazeroms1, A M Vignola2, K F Rabe1, V Bellia2, P S Hiemstra1, P J Sterk1

1 Department of Pulmonology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
2 Istituto di Medicina Generale e Pneumologia, Cattedra di Malattie dell’Apparato Respiratorio, Università di Palermo, Palermo, Italy

Correspondence to:
Correspondence to:
Professor P J Sterk
Lung Function Laboratory C2-P, Leiden University Medical Centre (LUMC), P O Box 9600, NL-2300 RC Leiden, The Netherlands; p.j.sterk{at}lumc.nl

Background: Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (FeNO) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of FeNO and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test.

Methods: Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second >80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. FeNO was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III ({delta}N2) and the closing volume (CV) were assessed from the single breath washout curve.

Results: The median FeNO level was 30.4 ppb (range 10.1–82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6–2.7), and the mean (SD) {delta}N2 value was 1.1 (0.4)% N2/l. FeNO was positively associated with {delta}N2 (rs = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV1% predicted (rs = –0.58; p = 0.017) and CV as a percentage of vital capacity (rs = 0.58; p = 0.019).

Conclusions: FeNO and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.


Abbreviations: CV, closing volume; EBC, exhaled breath condensate; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; PC20MCh, provocative concentration of methacholine causing a 20% fall in FEV

Keywords: nitric oxide; oxidative stress; exhaled markers; 8-isoprostane; asthma




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Molecular markers in exhaled air in asthma
Chiara Zinelli, et al.
Thorax Online, 7 Sep 2005 [Full text]



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