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

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Exhaled markers
Increased alveolar nitric oxide concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath condensate in patients with asbestosis
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  1. Hannele Lehtonen1,
  2. Panu Oksa2,
  3. Lauri Lehtimäki1,3,
  4. Anna Sepponen1,
  5. Riina Nieminen1,
  6. Hannu Kankaanranta1,3,
  7. Seppo Saarelainen3,
  8. Ritva Järvenpää4,
  9. Jukka Uitti2,
  10. Eeva Moilanen1
  1. 1Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland
  2. 2Finnish Institute of Occupational Health, University of Tampere and Tampere University Hospital, Tampere, Finland
  3. 3Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland
  4. 4Department of Radiology, Tampere University Hospital, Tampere, Finland
  1. Correspondence to:
    Professor Eeva Moilanen
    Medical School/Pharmacology, 33014 University of Tampere, Finland; eeva.moilanen{at}uta.fi

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 the alveolar NO concentration and bronchial NO flux, which reflect inflammation in the lung parenchyma and airways, respectively. The aim of the present study was to investigate whether exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in asbestosis.

Methods: Exhaled NO and inflammatory markers (leukotriene B4 and 8-isoprostane) in exhaled breath condensate were measured in 15 non-smoking patients with asbestosis and in 15 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: The mean (SE) alveolar NO concentration was significantly higher in patients with asbestosis than in controls (3.2 (0.4) vs 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) vs 19.7 (1.8) ppb, p = 0.89). Patients with asbestosis had increased levels of leukotriene B4 (39.5 (6.0) vs 15.4 (2.9) pg/ml, p = 0.002) and 8-isoprostane (33.5 (9.6) vs 11.9 (2.8) pg/ml, p = 0.048) in exhaled breath condensate and raised serum levels of C-reactive protein (2.3 (0.3) vs 1.1 (0.2) μg/ml, p = 0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p = 0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p = 0.034) compared with healthy controls.

Conclusions: Patients with asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in exhaled breath condensate are promising non-invasive means for assessing inflammation in patients with asbestosis.

  • BAL, bronchoalveolar lavage
  • COPD, chronic obstructive pulmonary disease
  • CRP, C-reactive protein
  • FVC, forced vital capacity
  • FEV1, forced expiratory volume in 1 s
  • FEV50%, forced expiratory flow at 50% of expired volume
  • HRCT, high resolution computed tomography
  • IL, interleukin
  • iNOS, inducible nitric oxide synthase
  • LTB4, leukotriene B4
  • MPO, myeloperoxidase
  • NO, nitric oxide
  • Tlco, carbon monoxide transfer factor adjusted for haemoglobin
  • Tlco/Va, specific carbon monoxide transfer factor adjusted for haemoglobin
  • Tlno, nitric oxide transfer factor
  • Vno, a, diffusing rate of nitric oxide from tissue to the alveolar space

https://doi.org/10.1136/thx.2006.067868

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    Footnotes

    • Published Online First 24 January 2007

    • This study was supported by grants from the Academy of Finland, Tampere Tuberculosis Foundation, the Medical Research Fund of Tampere University Hospital and from the Finnish Work Environment Fund.

    • Competing interests: None declared.