Markers of Fibrosis and Inflammation in Exhaled Breath Condensate (EBC) and Bronchoalveolar Lavage Fluid (BALF) of Patients with Pulmonary Sarcoidosis: A Pilot Study

Abstract

Sarcoidosis is a disease of unknown etiology. Little is known of predictive factors of fibrosis. It was suggested that PAI-1, uPA, TGF-beta1, VEGF, IL-8, TNF-alpha influence this process. To assess airway inflammatory and fibrosis markers in EBC in sarcoidosis and the effect of fiberoptic bronchoscopy (FOB), bronchoalveolar lavage fluid (BALF), transbronchial lung biopsy (TBLB) and bronchial mucosa membrane biopsy on their production in the airways. The study group consisted of 11 patients (5 women, 6 men; mean age 40 +/- 9 yrs, mean +/- SD) with sarcoidosis stage I-III. PAI-1 (ng/ml), uPA (ng/ml), TGF-beta1 (pg/ml), VEGF (pg/ml), IL-8 (pg/ml), TNF-alpha (pg/ml) levels were measured in BALF and EBC collected before and 48 hours after FOB. No significant changes in EBC levels of VEGF, PAI-1, TGF-beta1, TNF-alpha (respectively: 8.02 +/- 4.97 pg/ml; 1.1 +/- 1.2 ng/ml; 2909.7 +/- 206.6 pg/ml; 10.7 +/- 19.9 pg/ml) after FOB were observed when compared to baseline. In contrast, IL-8 concentration in EBC (pg/ml) decreased after FOB (0.073 +/- 0.13 v. 0.061 +/- 0.1, p = 0.006) and was significantly lower than in BALF (BALF 0.95 +/- 0.62, p < 0.05). Also, mean level of VEGF was higher in BALF than in EBC both pre- and post- FOB (BALF 66.38 +/- 36.95, EBC pre-FOB 6.75 +/- 3.67 and EBC post-FOB 8.02 +/- 4.97). Significant relationship between TNF-alpha in post-FOB EBC and BALF was also shown (b = 0.63, p = 0.04). FOB does not significantly affect levels of airway inflammation and fibrosis markers present in EBC before and after FOB; they were also comparable to the concentrations marked by BALF. The lack of correlation between markers levels in EBC and BALF indicates that these methods are not equivalent. Due to repeatibility, and less invasive, simple method of EBC test it seems reasonable to continue the research on the larger number of patients.