Changes in RANTES and beta-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 beta-thromboglobulin (beta-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 beta-TG in all groups studied at rest did not reveal any significant differences. In all groups studied, 30 min after exercise elevated beta-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.

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.

Endothelin-1 in exhaled breath condensate of stable and unstable asthma patients.

Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides, which play an important role in the development of airway inflammation and remodeling in asthma. The study was undertaken to evaluate the endothelin-1 (ET-1) levels in exhaled breath condensate (EBC) of asthmatics with different degree in asthma severity. EBC was collected from 31 patients with allergic asthma (11 with steroid-naïve mild asthma, 10 with ICS-treated, stable mild-to-moderate asthma, 10 with ICS-treated unstable, severe asthma) and 7 healthy volunteers. In the three groups of asthmatics, ET-1 concentrations in EBC were significantly higher than in healthy volunteers. ET-1 levels were significantly higher in patients with unstable asthma than in the two groups with stable disease. There was a significant correlation between ET-1 levels and FENO in the three groups of asthmatics and between ET-1 and blood eosinophil counts in the group of patients with unstable asthma. Measurements of ET-1 in EBC may provide another useful diagnostic tool for detecting and monitoring inflammation in patients with asthma.

Soluble CD40 ligand and soluble P-selectin in allergic asthma patients during exercise-induced bronchoconstriction.

BACKGROUND: The interactions between CD40 and its ligand, CD40L, control humoral and cell-mediated immune responses. CD40 ligation may promote asthma-associated inflammatory responses in the airways. Many reports confirm the inflammatory basis of exercise-induced bronchoconstriction (EIB) in asthmatics. METHODS: The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 8 healthy volunteers. We analyzed the changes in plasma concentrations of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) induced by intensive exercise. We also studied possible correlations with the results of measurements commonly associated with asthmatic inflammation. RESULTS: The study revealed statistically significant higher baseline concentrations of sCD40L--but not sP-selectin--in the group of asthmatics with EIB than in those without. In the asthmatic patients with EIB, sCD40L and sP-selectin concentrations increased significantly 30 minutes after exercise and returned to baseline 24 hours after exercise. Baseline concentrations of sCD40L correlated with baseline sP-selectin or fractional exhaled nitric oxide concentration (FE(NO)), an increase in sP-selectin 30 minutes after exercise, and changes in FE(NO) or bronchial hyperresponsiveness 24 hours after exercise. A statistically significant correlation between an increase in sCD40L concentrations 30 minutes after exercise and an increase in FE(NO) 24 hours after exercise or baseline eosinophil cationic protein was observed. CONCLUSION: After exercise in the group of allergic asthmatics with EIB, upregulation of CD40L by increased expression of inflammatory molecules and improved sensitivity of CD40-responsive cell types to the effects of proinflammatory cytokines may play an important role in the increased airway inflammation observed after postexercise bronchoconstriction.

Comparison of exhaled nitric oxide measurement with conventional tests in steroid-naive asthma patients.

BACKGROUND: Nitric oxide (NO) is a molecule with potent biological activity that plays an important role in the physiology of the respiratory system. Increased expression of inducible nitric oxide synthase (iNOS) and elevated fractional concentration of exhaled nitric oxide (F(ENO)) are seen in asthmatic patients. Measurement of F(ENO) has become increasingly recognized for use in the evaluation of bronchial inflammation during monitoring of antiinflammatory treatment. OBJECTIVES: The aim of this study was to evaluate F(ENO) in a group of steroid-naive asthmatics and assess the relationship of this parameter with the results of other tests used in the diagnosis of asthma and monitoring of antiinflammatory treatment in asthmatic patients. METHODS: The study was conducted in a group of 101 steroid-naive asthmatics (56 allergic and 45 nonallergic) and 39 healthy volunteers. All patients underwent measurement of F(ENO), skin prick tests with common inhaled allergens, analysis of serum eosinophil cationic protein (ECP) and blood eosinophilia, and flow-volume spirometry. When the forced expiratory volume in the first second (FEV1) was less than 80% of predicted, reversibility of airway obstruction with a beta2-agonist was assessed. A nonspecific bronchial provocation test with histamine was carried out in asthmatic patients with a baseline FEV1 of more than 70% of predicted. RESULTS: Compared to the healthy volunteers, F(ENO) was elevated in both groups of asthmatics. F(ENO) in the allergic asthma group was higher than in the group of nonallergic asthmatics. In allergic and nonallergic asthmatics, F(ENO) was significantly correlated with bronchial hyperresponsiveness to histamine, reversibility of airway obstruction, serum ECP levels, and blood eosinophilia. F(ENO) did not correlate with baseline FEV, in either group of asthmatics. In 31% of nonallergic and 9% of allergic patients, F(ENO) was less than 20 parts per billion. CONCLUSIONS: We suggest that measurement of F(ENO) could be clinically useful in steroid-naive asthmatics and should be more widely used in clinical practice. Measurement of F(ENO) is a noninvasive, simple, and reproducible procedure, the results of which correlate with other routinely used methods in the diagnosis of asthma. However, it is worth noting that some patients, especially those with nonallergic asthma, do not display elevated F(ENO).