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Small airways function and molecular markers in exhaled air in mild asthma
  1. S Battaglia1,2,
  2. H den Hertog1,
  3. M C Timmers1,
  4. S P G Lazeroms1,
  5. A M Vignola2,
  6. K F Rabe1,
  7. V Bellia2,
  8. P S Hiemstra1,
  9. P J Sterk1
  1. 1Department of Pulmonology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
  2. 2Istituto di Medicina Generale e Pneumologia, Cattedra di Malattie dell’Apparato Respiratorio, Università di Palermo, Palermo, Italy
  1. 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;


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 (δN2) 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) δN2 value was 1.1 (0.4)% N2/l. Feno was positively associated with δN2 (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.

  • 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
  • nitric oxide
  • oxidative stress
  • exhaled markers
  • 8-isoprostane
  • asthma
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  • Deceased December 2004.

  • This study was funded by Università di Palermo and Leiden University Medical Centre (LUMC), Valeas Italy and Italian Nitric Oxide Club (INOC).

  • Competing interests: SB has received unrestricted educational grants from Valeas Italy, GlaxoSmithKline and AstraZeneca. HdH, MCT, SPGL have no competing interests. AMV has been a consultant, participated in advisory board meetings and received lecture fees from GlaxoSmithKline and AstraZeneca. KFR has been a consultant, participated in advisory board meetings and received lecture fees from AstraZeneca, Boehringer, Pfizer, Novartis, AltanaPharma, MSD, and GlaxoSmithKline. VB has participated in advisory board meetings and received lecture fees from GlaxoSmithKline. The Department of Pulmonology (and thereby KFR, PSH and PJS as staff members) have received grants from AltanaPharma, Novartis, Bayer, AstraZeneca, Pfizer, MSD, Exhale Therapeutics and GSK in the years 2001–2004. The Istituto di Medicina Generale e Pneumologia (and thereby AMV and VB as staff members) have received grants from Bayer, Rhone Poulenc, AstraZeneca, MSD, and Aventis Pharma in the years 2001–2004.

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