title: Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis.
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 B(4) 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) mug/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.
authors.affiliation: Medical School/Pharmacology, 33014 University of Tampere, Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Lehtonen
authors.forename: Panu
authors.initials: P
authors.lastname: Oksa
authors.forename: Lauri
authors.initials: L
authors.lastname: Lehtimäki
authors.forename: Anna
authors.initials: A
authors.lastname: Sepponen
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.forename: Hannu
authors.initials: H
authors.lastname: Kankaanranta
authors.forename: Seppo
authors.initials: S
authors.lastname: Saarelainen
authors.forename: Ritva
authors.initials: R
authors.lastname: Järvenpää
authors.forename: Jukka
authors.initials: J
authors.lastname: Uitti
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000368:Aged; D001195:Asbestosis / Q000378:metabolism* / Q000503:physiopathology; D001944:Breath Tests; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012129:Respiratory Function Tests
chemical_list: D015850:Interleukin-6; D007975:Leukotriene B4; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D002097:C-Reactive Protein; D015237:Dinoprost; D009195:Peroxidase