Maria Magdalena Tomasiak

Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

BackgroundExercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients.MethodsThe study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed.ResultsIn asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline FENO and the increase in FENO or BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed.ConclusionThe release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients.

RANTES in exhaled breath condensate of stable and unstable asthma patients

RANTES has been implicated in the allergic inflammation of asthma by promoting the migration and activation of the inflammatory cells, including eosinophils. The study was undertaken to evaluate RANTES levels in the exhaled breath condensate (EBC) of asthmatics with different degrees of asthma severity. EBC was collected from 33 patients with allergic asthma (11 with steroid-naïve mild asthma, 10 with ICS-treated, stable mild-to-moderate asthma, 12 with ICS-treated unstable, severe asthma) and seven healthy volunteers. In the three groups of asthmatics, RANTES concentrations in EBC were significantly higher compared with healthy volunteers. RANTES levels were significantly higher in patients with unstable asthma than in the two groups with stable disease. We observed statistically significant correlations between the concentrations of RANTES in EBC and F(ENO) in the three studied groups of asthmatics; notably, the correlation between the parameters described above was strong positive in the group of unstable and steroid-naïve stable asthmatics. We also discovered a significantly positive correlation between RANTES in EBC and the serum ECP or blood eosinophil count in the groups of asthmatics with severe, unstable asthma and between RANTES and serum ECP in the group of steroid-naïve stable asthmatics. Measurements of RANTES in EBC may provide another useful diagnostic tool for detecting and monitoring inflammation in patients with asthma.

The role of endothelium-derived mediators in exercise-induced bronchoconstriction.

Background: Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition whose pathogenesis and effect on airways remain unclear. The aim of the study was to evaluate the changes in endothelial-derived mediators following intensive exercise in asthmatic patients. Methods: The study was conducted in a group of 25 asthmatic patients (15 with EIB, 10 without EIB) and 8 healthy volunteers. Changes induced by intensive exercise in the plasma concentrations of endothelin-1 (ET-1), thrombomodulin and soluble E-selectin were determined. Moreover, the possible correlations of these measurements with the results of baseline lung function, bronchial hyperreactivity (BHR), exhaled nitric oxide (FENO), baseline eosinophil cationic protein, peripheral blood eosinophilia and total IgE were investigated. Results: In the group of asthmatics with EIB, statistically significantly higher baseline concentrations of ET-1 and soluble E-selectin compared with asthmatics with negative exercise test results were revealed. In this group of patients, ET-1, thrombomodulin and soluble E-selectin concentrations significantly increased after exercise. Baseline concentrations of ET-1 as well as an increase in soluble E-selectin concentrations 60 min after exercise showed a statistically significant correlation with baseline eosinophil cationic protein, FENO and BHR. The increase in plasma concentrations of ET-1 15 min after exercise and soluble E-selectin 60 min after exercise showed a statistically significant correlation with the increase in FENO and BHR to histamine 24 h after exercise. Conclusions: We suggest that during EIB changes in the function of pulmonary endothelium occur and these changes may influence inflammation of the airway and remodeling in asthmatic patients.

N-acetyl-beta-hexosaminidase activity in asthma.

Background: N-acetyl-β-hexosaminidase (β-hex) is a lysosomal hydrolase, which is selectively secreted into the extracellular space by inflammatory cells. The aim of our study was to assess the activity of β-hex in the plasma of asthmatic patients, and to establish whether it correlates with asthma severity and airway inflammation. Methods: The study was conducted in a group of 46 asthmatic patients and 13 healthy volunteers. All study participants underwent analysis of exhaled nitric oxide and flow-volume spirometry. β-hex activity, peripheral blood eosinophils, total serum IgE and eosinophil cationic protein were analyzed in blood samples from all asthmatic patients and healthy volunteers. Results: β-hex activity was significantly higher in patients with severe or moderate asthma compared with healthy volunteers and was positively correlated with exhaled nitric oxide levels and serum eosinophil cationic protein in these groups of patients. There was no correlation between β-hex activity and forced expiratory volume in 1 s, blood eosinophil count or total serum IgE in these groups of asthmatics. Conclusions: Our results suggest that β-hex could take part in airway inflammation and remodeling in asthma. Our study is the first report in which the elevated activity of β-hex in subjects with asthma has been observed. However, more studies are needed to establish the precise role of this enzyme in asthma in humans.

Changes in RANTES and β-Thromboglobulin after Intensive Exercise in Patients with Allergic Asthma

Background: There is increasing evidence that exercise-induced bronchoconstriction (EIB) is associated with eosinophilic airway inflammation. In the pathogenesis of EIB the role of chemokines – responsible for promoting the migration and activation of inflammatory cells – as well as blood platelets, a potential source of those chemokines, remains unclear. Methods: The study was conducted in a group of 19 asthmatics (11 with EIB, 8 without EIB) and 8 healthy volunteers. Changes in the plasma concentrations of RANTES and β-thromboglobulin (β-TG) induced by intensive exercise were determined. Moreover, the possible correlation of these measurements with the results of other tests used in the diagnosis of asthma as well as laboratory tests commonly associated with asthma were investigated. Results: A comparison of the concentrations of β-TG in all groups studied at rest did not reveal any significant differences. In all groups studied, 30 min after exercise elevated β-TG concentrations were observed; the most significant increase was revealed in asthmatics with EIB. The baseline concentrations of RANTES before exercise in both groups of asthmatics were significantly higher in comparison to the group of healthy volunteers. After exercise, in the group of patients with EIB, a significant increase in RANTES concentrations was observed. These changes correlated with an increase in other markers of airway inflammation 24 h after exercise. Conclusions: We suggest that platelet activation, resulting in elevated RANTES release, could be one of the factors responsible for the increase of airway inflammation observed in consequence of EIB in asthmatics.