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

Abstract

Introduction: Sarcoidosis is a disease of unknown aetiology. Little is known of the predictive factors of fibrosis. It has been suggested that PAI-1, uPA, TGF-β1, VEGF, IL-8, TNF-α influence this process. The aim of the study was to assess airway inflammatory and fibrosis markers in EBC in sarcoidosis and the effects of fibreoptic bronchoscopy (FOB), bronchoalveolar lavage fluid (BALF), transbronchial lung biopsy (TBLB) and bronchial mu- cosa membrane biopsy on their production in the airways. Material and methods: The study group consisted of 11 patients (five women, six men, mean age 40 ± 9 yrs, mean ± SD) with sarcoidosis stage I–III. PAI-1 (ng/mL), uPA (ng/mL), TGF-β1 (pg/mL), VEGF (pg/mL), IL-8 (pg/mL), TNF-α (pg/mL) levels were measured in BALF and EBC collected before, and 48 h after, FOB. Results: No significant changes in EBC levels of VEGF, PAI-1, TGF-β1, TNF-α (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 vs. 0.061 ± 0.1, p = 0.006) and was significantly lower than in BALF (BALF 0.95 ± 0.62, p < 0.05). Also, the 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). A significant relationship between TNF-a in post-FOB EBC and BALF was also shown (β = 0.63, p = 0.04). Conclusions: 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 marker levels in EBC and BALF indicates that these methods are not equivalent. Due to the possibility of repetition, and the less invasive, simpler method of the EBC test, it would seem reasonable to continue this research on a larger number of patients.

Diagnosing complex regional pain syndrome using an electronic nose, a pilot study

“…Studies on sarcoidosis have shown that it is possible to identify inflammatory markers (e.g. TNF-alpha) in exhaled breath condensate using an enzyme immunoassay [16,17]. So the ability of the Aeonose™ to distinguish patients with sarcoidosis from healthy controls could (also) be due to the influence of inflammation [18].…”

“…Another inflammatory marker that is supposed to play a role in the pathogenesis of both CRPS and sarcoidosis is TNF-alpha [6,9,10,15]. In patients with sarcoidosis TNF-alpha was found together with other inflammatory markers, IGF-1, PAI-1, TGF-beta1 and VEGF in exhaled breath condensate using an enzyme immunoassay [16,17]. This was followed by a study of Dragonieri et al who showed that an electronic nose was able to distinguish between sarcoidosis and healthy controls [18].…”

A collection system for dry solid residues from exhaled breath for analysis via atomic force microscopy

“…Collection and analysis of exhaled breath condensate (EBC) is a promising new approach in the diagnosis of lung diseases [1,2]. As a non-invasive and painless way of getting samples of lung liquid for detection of disease biomarkers, EBC attracts both researchers and medical practitioners because of the considerable advantages it offers over the rather painful and complicated bronchoalveolar lavage procedure [3][4][5].…”

Measurement of neopterin, TGF-β1and ACE in the exhaled breath condensate of patients with sarcoidosis

“…Comparisons of the established technique of bronchoalveolar lavage (BAL) with EBC show little correlation between biomarkers in other diseases, with total protein levels being higher in BAL than EBC, but the dilution of BAL with the lavage fluid, and suction causing airway bleeding all contribute to make the results difficult to interpret [7]. Nevertheless, cytokines, chemokines, growth factors and markers of oxidative stress have been detected in the EBC of patients with sarcoidosis [4,[8][9][10][11][12][13][14][15][16].…”