Increased alveolar nitric oxide concentration and high levels of leukotriene B4 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) mg/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.

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

“…In addition, cysteinyl LTs were elevated. Lehtonen 15) found increase of LT B4 in patients with asbestosis, which finding differed from our previous study in 92 asbestos-exposed subjects 17) , where about 76% of patients had pleural hyalinosis and 61% interstitial lung fibrosis. In contrast, in recent study, hyalinosis and/or asbestosis were present in all subjects.…”

“…It was shown that patients with idiopathic pulmonary fibrosis exhibit overproduction of both LT B4 and cysteinyl LTs 13,14) . LT B4 15) and cysteinyl LTs were also elevated in the EBC of patients with pneumoconioses 16,17) .…”

Increased 8-isoprostane, a Marker of Oxidative Stress in Exhaled Breath Condensate in Subjects with Asbestos Exposure

“…EBC contains several bio- markers of inflammation and oxidative stress, and collection can be repeated several times without any adverse effects, even in children 6) or severely ill patients. 8-isoprostane has been observed to increase in the EBC of patients with idiopathic pulmonary fibrosis 7) and in our limited study with asbestos exposed subjects 8) ; it was recently confirmed in 15 patients with asbestosis, in parallel with the inflammation marker, alveolar nitric oxide concentration 9) . Because the effect of recent smoking, another source of reactive oxygen species on the concentrations of 8-isoprostane on breath condensate has been described 5) , cotinine, a metabolite of nicotine in the urine and a tobacco smoke biomarker 10) was also analyzed in our study to eliminate this possible influence.…”

Oxidative Stress Markers in Exhaled Breath Condensate in Lung Fibroses Are Not Significantly Affected by Systemic Diseases

“…In humans, determination of the concentration of 8-iso-prostaglandin F 2α (8-isoprostane) in exhaled breath condensate (EBC) has proven to be valuable in assessing oxidative stress. The analysis of this derivative of arachidonic acid, produced in free radical-catalyzed reactions, appears to be a promising non-invasive means for assessing the activity of both silica and asbestos-induced diseases [2][3][4] . Moreover, no effect of sex or smoking status was observed in these studies.…”