Maria M. Tomasiak-Lozowska

Anti-IgE Therapy with Omalizumab Decreases Endothelin-1 in Exhaled Breath Condensate of Patients with Severe Persistent Allergic Asthma

Background: Omalizumab is a humanized monoclonal anti-IgE antibody, especially useful for the treatment of severe persistent allergic asthma, inadequately controlled despite regular therapy. Objectives: The aim of the study was to determine the effect of omalizumab treatment on changes in endothelin-1 (ET-1), which plays an important role in the development of airway inflammation and remodeling in exhaled breath condensate (EBC) in patients with severe asthma. Methods: The study was conducted in a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to the Global Initiative for Asthma, 2006) and with or without omalizumab (9 vs. 10 patients). Changes in ET-1 in EBC compared with other inflammatory parameters [exhaled nitric oxide – (FENO), blood eosinophil count, and serum eosinophil cationic protein (ECP)] were measured after 16 and 52 weeks of therapy. Results: Omalizumab-treated patients demonstrated a statistically significant decrease in the concentrations of ET-1 in EBC, FENO, serum ECP, and blood eosinophil count and an increase in spirometry parameters compared to patients with conventional therapy. In the group of omalizumab-treated patients, statistically significant correlations between the decrease in ET-1 in EBC and a decrease in FENO, ECP, and blood eosinophil count as well as the increase in forced expiratory volume in 1 s after omalizumab therapy were revealed. Conclusions: Our results confirmed that anti-IgE therapy with omalizumab in patients with severe persistent allergic asthma results in decreased expression of ET-1 in the airways. This could be very important in limiting airway inflammation and bronchial structural changes caused by such treatment in asthmatic patients.

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

BackgroundAirway eosinophilia is considered a central event in the pathogenesis of asthma. Eotaxin plays a key role in selective eosinophil accumulation in the airways and, subsequently, their activation and degranulation. The study was undertaken to evaluate eotaxin-1 levels in the exhaled breath condensate (EBC) of asthmatics with different degrees of asthma severity and to establish the possible correlation of these measurements with other recognized parameters of airway inflammation.MethodsEBC was collected from 46 patients with allergic asthma (14 with steroid-naïve asthma, 16 with ICS-treated, stable asthma, 16 with ICS-treated unstable asthma) and 12 healthy volunteers. Concentrations of eotaxin-1 were measured by ELISA.ResultsIn the three groups of asthmatics, eotaxin-1 concentrations in EBC were significantly higher compared with healthy volunteers (steroid-naïve asthma: 9.70 pg/ml ± 1.70, stable ICS-treated asthma: 10.45 ± 2.00, unstable ICS-treated asthma: 17.97 ± 3.60, healthy volunteers: 6.24 ± 0.70). Eotaxin-1 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 eotaxin-1 in EBC and exhaled nitric oxide (FENO) or serum eosinophil cationic protein (ECP) in the three studied groups of asthmatics. We also discovered a significantly positive correlation between eotaxin-1 in EBC and blood eosinophil count in the groups of patients with unstable asthma and steroid-naïve asthma.ConclusionsMeasurements of eotaxin-1 in the EBC of asthma patients may provide another useful diagnostic tool for detecting and monitoring airway inflammation and disease severity.

High-sensitivity C-reactive protein in the exhaled breath condensate and serum in stable and unstable asthma.

BACKGROUND Asthma is a chronic airway inflammatory disease. Measurement of serum high- sensitivity C-reactive protein (hs-CRP) levels has suggested the involvement of low-grade systemic inflammation in several disorders, such as cardiovascular disease and diabetes mellitus. In recent years, there have been some reports concerning hs-CRP assessment as a useful tool for detecting systemic inflammation in asthma. The study was undertaken to evaluate hs-CRP levels in the exhaled breath condensate (EBC) of asthmatics with different degrees of asthma severity and their relationship to hs-CRP levels in serum, clinical characteristics, and the intensification of airway inflammation. METHODS The study group was 62 patients with allergic asthma (20 with steroid-naïve mild asthma, 19 with ICS-treated, stable mild-to-moderate asthma, 23 with ICS-treated unstable, severe asthma) and 15 healthy volunteers. RESULTS In the three groups of asthmatics hs-CRP concentrations in EBC and serum were significantly higher than in healthy volunteers. hs-CRP levels both in EBC and serum were significantly higher in patients with unstable asthma than in the two groups with stable disease. hs-CRP concentrations in EBC strongly correlated with those measured in serum. There was a significant correlation between hs-CRP levels both in EBC and serum and exhaled nitric oxide (F(ENO)) in the three groups of asthmatics or serum ECP in the group of patients with steroid-naïve mild asthma and unstable, severe asthma. CONCLUSION The levels of hs-CRP in EBC are correlated with those measured in serum and may provide another useful diagnostic tool for detecting and monitoring low-grade inflammation in patients with asthma.

High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers.

The involvement of B cells in allergen tolerance induction remains largely unexplored. This study investigates the role of B cells in this process, by comparing B‐cell responses in allergic patients before and during allergen immunotherapy (AIT) and naturally exposed healthy beekeepers before and during the beekeeping season.

RANTES in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction.

Background: The response of asthmatics to exercise differs from that of healthy subjects, and the mechanisms responsible for exercise-induced bronchoconstriction (EIB) remain to be elucidated. Objectives: The aim of this study was to evaluate changes in RANTES levels in exhaled breath condensate (EBC) following intensive exercise in allergic asthmatics. Methods: The study was conducted in a group of 19 asthmatics (11 with EIB and 8 without EIB) and 7 healthy volunteers. Changes in the concentrations of RANTES in EBC induced during the 24 h after intensive exercise were determined. Moreover, these measurements were tested for possible correlations with the results of other tests commonly associated with asthma as well as with changes in airway inflammation after exercise. Results: In contrast to asthmatic patients without EIB and healthy controls, in asthmatics with EIB RANTES concentrations were statistically significantly increased in EBC collected during the first 24 h after an exercise test. There was a statistically significant correlation between the maximum increase in RANTES concentrations in EBC after exercise and either baseline exhaled nitric oxide (FENO) or bronchial hyperreactivity to histamine and an increase in serum eosinophil cationic protein or FENO 24 h after exercise in the EIB asthmatics. Conclusions: The increase in RANTES in asthmatic airways, promoting the migration and activation of inflammatory cells including eosinophils, may play an important role in the upregulation of airway inflammation after EIB in asthmatic patients.

Inflammatory markers and acid-base equilibrium in exhaled breath condensate of stable and unstable asthma patients.

Background: Nitrosative and acid stress play an important role in the pathogenesis of asthma. The aim of this study was to evaluate whether, in asthmatics, a link exists between the concentrations of nitrite/nitrate, ammonia and pH values in exhaled breath condensate (EBC) and asthma severity, lung function, exhaled nitric oxide (FENO), total IgE, eosinophil cationic protein (ECP) and blood eosinophilia. Methods: The above-mentioned parameters were measured in 19 healthy volunteers and 91 allergic asthmatics divided into three groups, i.e. 22 subjects with steroid-naïve stable asthma, 35 with inhaled corticosteroid (ICS)-treated stable asthma and 34 with ICS-treated unstable asthma. Results: Compared with healthy subjects, EBC from asthmatics had significantly lower pH values and ammonia concentrations and significantly higher levels of nitrite/nitrate. The extent of these changes was higher in patients with unstable than in patients with steroid-naïve and stable ICS-treated asthma. The EBC pH was positively correlated with ammonia and negatively correlated with nitrite/nitrate, FENO or blood eosinophilia in all three groups of asthmatics. Significant positive correlations between EBC nitrite/nitrate and blood eosinophilia, ECP levels or FENO were observed in all groups of asthmatics. Significant negative correlations between EBC ammonia and nitrite/nitrate, FENO, ECP concentrations or blood eosinophilia were demonstrated in the groups of ICS-naïve and ICS-treated stable asthmatics. Conclusions: In asthmatic patients there is a relationship between EBC pH, ammonia and nitrite/nitrate concentrations and other recognized markers of airway inflammation. EBC pH values, ammonia and nitrite/nitrate levels measured together may help to assess airway inflammatory status and asthma severity.

Changes in High-Sensitivity C-Reactive Protein in Serum and Exhaled Breath Condensate after Intensive Exercise in Patients with Allergic Asthma

Background: Exercise-induced bronchoconstriction (EIB) in asthmatics depends on the presence of allergic inflammation. This study was performed to assess the possible association of EIB with low-grade systemic inflammation, whose presence was revealed in asthmatic patients. Methods: The study was conducted in a group of 24 asthmatics (14 with EIB, 10 without EIB) and 8 healthy volunteers. Changes in serum and exhaled breath condensate (EBC) high-sensitivity C-reactive protein (hs-CRP) levels 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: In asthmatic patients with EIB, a statistically significant increase in hs-CRP levels both in serum and EBC after an exercise test was observed. Twenty-four hours after the exercise test in the group of asthmatics with EIB, a statistically significant increase in exhaled nitric oxide (FENO), serum eosinophil cationic protein (ECP) concentrations and bronchial hyperreactivity to histamine was revealed. A statistically significant correlation between the maximum increase in hs-CRP levels both in serum and EBC after exercise and either baseline FENO and an increase in serum ECP or FENO 24 h after exercise in the group of asthmatics with EIB was revealed. Conclusions: We show that, as a result of intensive exercise leading to bronchoconstriction, an increase in serum and EBC hs-CRP occurs. Our observations could suggest that in asthmatic patients, as a consequence of exercise-induced bronchoconstriction, an intensification of low-grade systemic inflammation can be observed.

RANTES in Exhaled Breath Condensate of Patients with Severe Persistent Allergic Asthma during Omalizumab Therapy

Background: Omalizumab is a humanized monoclonal anti-IgE antibody developed for the treatment of IgE-mediated diseases, including asthma. The aim of the study was to determine the effect of omalizumab treatment on changes in RANTES in exhaled breath condensate and other inflammatory markers in patients with persistent severe asthma. Methods: The study was conducted on a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to GINA 2006) and with or without omalizumab (9 vs. 10 patients). Changes in inflammatory parameters [RANTES in exhaled breath condensate, exhaled nitric oxide, blood eosinophil count and serum eosinophil cationic protein (ECP)] were measured before and after 16 weeks of therapy. Results: Omalizumab-treated patients showed a statistically significant decrease in the concentrations of RANTES in exhaled breath condensate, exhaled nitric oxide (FENO), serum ECP, and blood eosinophil count compared with patients with conventional therapy after 16 weeks of treatment. In this group of patients, statistically significant correlations were revealed between the decrease in RANTES and a decrease in FENO and between the decrease in FENO and a decrease in ECP or blood eosinophil count after omalizumab therapy. Conclusions: Our results confirmed that during anti-immunoglobulin E therapy with omalizumab in patients with severe persistent allergic asthma, RANTES expression is decreased. This process in turn could lead to a limitation of airway inflammation and could be essential for the beneficial effect of anti-IgE therapy with omalizumab.

Airway inflammation and eotaxin in exhaled breath condensate of patients with severe persistent allergic asthma during omalizumab therapy.

PURPOSE The central role of IgE in allergic inflammation in asthma has provided a rationale for the development of omalizumab, the humanized monoclonal anti-IgE antibody. The aim of the study was to determine the effect of omalizumab treatment on changes in airway inflammatory process and eotaxin in exhaled breath condensate in patients with persistent severe allergic asthma. MATERIAL AND METHODS The study was performed on a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to GINA 2006) and with or without omalizumab (9 vs 10 patients). Eotaxin in exhaled breath condensate, exhaled nitric oxide, blood eosinophil count and serum ECP were measured before and after 16 weeks of therapy. RESULTS In the group treated with omalizumab, a statistically significant decrease in the concentrations of eotaxin in EBC, FENO, serum ECP, and blood eosinophil count after 16 weeks of treatment was observed. Statistically significant correlations were revealed between the decrease in eotaxin and the decrease in FENO, serum ECP and blood eosinophil count after omalizumab therapy. CONCLUSIONS Downregulation of eotaxin expression in the airways through limitation of eosinophilic inflammation could be essential in the beneficial effect of anti-IgE therapy with omalizumab in asthma patients.

Asthma is associated with reduced fibrinolytic activity, abnormal clot architecture, and decreased clot retraction rate.

The aim of this study was to assess whether steroid‐naïve asthma modulates hemostasis. We evaluated the clot retraction rate (CRR), fibrinolysis rate (FR), clot density (CD) (by confocal microscopy), plasma levels of plasminogen activator inhibitor (PAI‐1), and factor XIII (FXIII), NO in exhaled breath (FENO), spirometry (FEV1) and eosinophil count (EOS) in 36 patients with allergic, steroid‐naïve asthma and in 34 healthy controls. We observed significantly (P < 0.001) reduced CRR, FR, and FEV1 and increased FENO, EOS, PAI‐1, FXIII, and CD in patients with asthma compared with controls. In patients with asthma, FR negatively correlated with CD, FXIII, PAI‐1, FENO, and EOS and positively with FEV1. FXIII positively correlated with CD. Clot retraction rate negatively correlated with FENO and positively with FEV1 (all P < 0.001). These novel findings suggest that asthma itself is associated with decreased CRR and reduced fibrinolytic potential resulting from alterations in clot architecture and elevated levels of plasma FXIII and PAI‐1.