Increased alveolar nitric oxide concentration, and high levels of leukotriene B4 and 8-isoprostane in exhaled breath condensate in patients with asbestosis

Hannele Lehtonen ¹, Panu Oksa ², Lauri Lehtimäki ¹, Anna Sepponen ¹, Riina Nieminen ¹, Hannu Kankaanranta ¹, Seppo Saarelainen ³, Ritva Järvenpää ⁴, Jukka Uitti ² and Eeva Moilanen ^1*

¹ The Immunopharmacology Research Group, University of Tampere and Tampere University Hospital, Finland
² Finnish Institute of Occupational Health, Finland
³ Department of Respiratory Medicine, Tampere University Hospital, Finland
⁴ Department of Radiology, Tampere University Hospital, Finland

^* To whom correspondence should be addressed. E-mail: eeva.moilanen{at}uta.fi.

Accepted 18 December 2006

Abstract

Background: Inhaled asbestos fibres can cause inflammation and fibrosis in the lungs, called asbestosis. However, there are no non-invasive means to assess and follow the severity of the inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess alveolar NO concentration and bronchial NO flux which reflect inflammation in lung parenchyma and airways, respectively. The aim of the present study was to investigate if exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in asbestosis.

Methods: Exhaled NO and inflammatory markers (LTB4 and 8-isoprostane) in exhaled breath condensate were measured in fifteen non-smoking patients with asbestosis and in fifteen healthy controls. Exhaled NO concentrations were measured at four constant exhalation flow rates (50, 100, 200 and 300 ml/s), and alveolar NO concentration and bronchial NO flux were calculated according to the linear model of pulmonary NO dynamics.

Results: Alveolar NO concentration was significantly higher in patients with asbestosis (3.2 ± 0.4 ppb; mean ± SEM) than in controls (2.0 ± 0.2 ppb, p=0.008). There was no difference in bronchial NO flux (0.9 ± 0.1 vs 0.9 ± 0.1 nl/s, p=0.93) or NO concentration measured at ATS standard flow rate of 50 ml/s (20.0 ± 2.0 ppb vs 19.7 ± 1.8 ppb, p=0.89). Patients with asbestosis had elevated levels of leukotriene B4 (39.5 ± 6.0 pg/ml vs.15.4 ± 2.9 pg/ml, p= 0.002) and 8-isoprostane (33.5 ± 9.6 pg/ml vs.11.9 ± 2.8 pg/ml, p= 0.048) in exhaled breath condensate. Patients with asbestosis had elevated serum levels of CR (2.3 ± 0.3 vs. 1.1. ± 0.2 ug/ml, p=0.003), IL-6 (3.5 ± 0.5 vs. 1.7 ± 0.4 pg/ml, p=0.007), and MPO (356 ± 48 vs. 240 ± 20 ng/ml, p=0.034) as compared to healthy controls.

Conclusions: Patients with asbestosis had increased alveolar NO concentration and high levels of LTB4 and 8 isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in breath condensate are promising non-invasive means to assess inflammation in patients with asbestosis.

Keywords: alveolar NO concentration, asbestosis, bronchial NO flux, exhaled NO, exhaled breath condensate

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