Efficacy of ciclesonide in the treatment of patients with asthma exacerbation.

INTRODUCTION: Progressing deterioration of the lung function, dyspnoea, cough, wheezing and chest tightness are the main features of asthma exacerbations. The first step in the prevention of severe asthma exacerbations is to intensify the anti-inflammatory treatment with high doses of inhaled corticosteroids (ICS). AIM: To assess the efficacy of ciclesonide in patients who have been losing control of asthma despite being treated with medium doses of inhaled corticosteroids and long-acting ß2-agonists (LABA) as the second controller. MATERIAL AND METHODS: The study was conducted in a group of 74 asthmatic patients who have been losing control of their asthma. Subjects entering the study received the following anti-inflammatory interventions: high doses of ciclesonide (1280 µg) or 640 µg of ciclesonide added to a current dose of ICS or a doubled dose of current ICS. RESULTS: Treatment options containing ciclesonide have shown statistically and clinically important advantages (improvement of Asthma Control Test score, reduction in rescue medication consumption, reduction in day and night symptoms score, improvement in spirometry parameters, decrease in exhaled nitric oxide, and no necessity of oral corticosteroids treatment) in comparison to patients for whom medium doses of the previously used inhaled corticosteroid were doubled. CONCLUSIONS: Treating with high doses of ciclesonide is characterised by a quick and potent anti-inflammatory effect as well as prompt clinical improvement along with the proper safety profile in patients experiencing asthma exacerbations.

Asthma and exercise-induced respiratory disorders in athletes. The position paper of the Polish Society of Allergology and Polish Society of Sports Medicine.

Exercise-induced respiratory symptoms describe acute airway narrowing that occurs as a result of exercise. It includes exercise-induced bronchoconstriction (EIB) and exercise-induced asthma (EIA) issues. To provide clinicians with practical guidelines, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB/EIA and to develop evidence-based guidelines for the diagnosis and treatment. Recommendations for the diagnosis and treatment of EIB were developed. High-intensity exercise in polluted environment (cold air, humidity, contamination, allergens) may increase the risk of EIB and asthma symptoms in athletes. Diagnostic procedures should include history taking, physical examination, atopy assessment and functional tests of the respiratory system. A strong recommendation was made for regular use of inhaled glucocorticosteroids and avoidance of short-acting ß2-agonists as the only treatment. The treatment of asthma in athletes should always take into account current anti-doping regulations. This position paper reflects the currently available evidence.

Changes in blood eosinophilia during omalizumab therapy as a predictor of asthma exacerbation.

INTRODUCTION: Omalizumab is a monoclonal anti-immunoglobulin E antibody developed for the treatment of severe allergic asthma. The number of exacerbations used as a parameter of omalizumab therapy efficacy may be insufficient in many cases due to a relatively short time to first evaluation (16 weeks). Therefore, it is advisable to look for parameters of more prognostic value while continuing omalizumab therapy. AIM: To evaluate usefulness of analysis of changes of blood eosinophilia after 16 weeks of omalizumab therapy as a predictor of asthma exacerbations. MATERIAL AND METHODS: The study was conducted on a group of 13 patients with severe persistent allergic asthma treated with omalizumab. Blood eosinophil counts were measured before and after 16 weeks of anti-IgE therapy. On the basis of percentage of eosinophilia decrease (> 50% or < 50% of the initial value), patients were divided into two groups. Analysis of the asthma exacerbation rate during 12 months and time to first exacerbation was performed. RESULTS: In the group with a high decrease in blood eosinophil counts (group 1) we showed a statistically significantly lower asthma exacerbation rate in 12 months compared with the group with a low decrease in blood eosinophil counts (group 2) (p = 0.02). We also observed the tendency to longer time to first asthma exacerbation in group 1 compared to group 2 (p = 0.06). CONCLUSIONS: Our results showed that a decrease in blood eosinophilia during omalizumab therapy can be a predictor of asthma exacerbation. Evaluation of changes in blood eosinophil count should be taken into the consideration while estimating response to anti-IgE therapy in patients with severe allergic asthma.

Omalizumab treatment in brittle asthma.

Asthma is a heterogeneous disease with variable characteristics such as lung function, symptoms and control, body weight, pattern of inflammation, and response to treatment. Brittle asthma is one of clinical phenotypes of asthma with unclear pathogenic mechanisms and appropriate treatment. Analysis of 2 described cases suggests that omalizumab could be useful in the treatment of brittle allergic asthma.

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 (F(ENO)), 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, F(ENO) or blood eosinophilia in all three groups of asthmatics. Significant positive correlations between EBC nitrite/nitrate and blood eosinophilia, ECP levels or F(ENO) were observed in all groups of asthmatics. Significant negative correlations between EBC ammonia and nitrite/nitrate, F(ENO), 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.

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 (F(ENO)), 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 F(ENO) and between the decrease in F(ENO) 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.

[Statins and asthma]. / Statyny i astma.

Statins are drugs widely used in the treatment of hyperlipidemia and cardiovascular diseases. They decrease cholesterol synthesis by inhibiting 3-hydroxy-methylglutaryl reductase of coenzyme A (HMG-CoA). It was shown that statins are characterized by a wider spectrum of activity, which was attributed as an extralipid (pleiotropic) one. Although benefits of HMG-CoA reductase inhibitors have been proven in the treatment of cardiovascular diseases, there are attempts to use them in other fields of medicine, such as neurology and rheumatology. At present, anti-inflammatory and immunomodulatory effects of HMG-CoA reductase inhibitors are being particularly examined. Based on the observation mentioned above, the use of statins in allergology has also been attempted. The paper presents selected aspects of statins' effects on immunological reactions and the inflammatory process, pointing to the possibility of statin use in the treatment of asthma.

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

BACKGROUND: Airway 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. METHODS: EBC 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. RESULTS: In 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 (F(ENO)) 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. CONCLUSIONS: Measurements of eotaxin-1 in the EBC of asthma patients may provide another useful diagnostic tool for detecting and monitoring airway inflammation and disease 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 (F(ENO)), 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 F(ENO) and an increase in serum ECP or F(ENO) 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.

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 - (FE(NO)), 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, FE(NO), 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 FE(NO), 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.

[The role of interleukin 13 and interleukin 5 in asthma]. / Rola interleukin 13 i 5 w astmie.

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play roles. Interleukins 5 (IL-5) and 13 (IL-13) are cytokines which play important roles in the pathophysiology of asthma. Selective accumulation and activation of eosinophils in the bronchial mucosa is considered a central event in the pathogenesis of asthma. IL-5 acts as a mediator of activation of eosinophils, influencing adhesion, membrane receptor expression, chemotaxis, and mediator synthesis. Airway eosinophilia has been related to bronchial hyperreactivity, asthma symptoms, and airway narrowing in subjects with asthma. IL-13 has a great influence on bronchial hyperreactivity, inflammation, and airway remodeling. Moreover, this cytokine drives many cellular responses relevant in asthma, including epithelial cell maturation and mucus production, synthesis of extracellular matrix proteins, and enhanced contractility of airway smooth muscle cells. In recent years, efforts have been underway to use substances acting as antagonists of these cytokines in the treatment of asthma. Many studies are being performed to assess the efficacy of anti-IL-5 and anti-IL-13 antibodies as well as substances inactivating receptors of these cytokines in asthma therapy. The results of these studies seem very interesting and induced the authors to discuss this issue.

[Significance of C-reactive protein in asthma]. / Znaczenie bialka C-reaktywnego w astmie.

C-reactive protein (CPR) has been showed to be a specific and sensitive marker in diagnosing and monitoring of many inflammatory diseases. High-sensitive CRP is also a useful diagnostic tool to asses subclinical systemic inflammation in circulatory system diseases and diabetes. There is increasing evidence confirming the presence of systemic inflammation in asthma and the possibility of using hs-CRP in diagnosis and treatment monitoring of this disease.

[Beta-blockers and statins in the context of asthma]. / Beta-blokery i statyny w astmie.

Asthma is a disease with a complex pathogenesis and differentiated clinical picture with airway inflammation in its background. Many cells and cell-released substances are engaged in the course of the disease. The basic treatment strategy in asthma is based on chronic administration of inhaled glucocorticosteroids (with a strong anti-inflammatory effect) and beta2-adrenoreceptor agonists (bronchodilatory effect). Much attention has been recently paid to the effects of other medicines on mechanisms important in the pathogenesis of asthma, including beta-blockers and statins. Many researchers have suggested a potentially useful role of some beta-blockers in chronic asthma therapy, particularly considering their effect on the pharmacodynamics of beta receptors in the bronchi. Moreover, statins, due to their anti-inflammatory and immunomodulatory effects, can also be useful in the management of asthma.

[Anti-IgE therapy in persistent allergic asthma]. / Przeciwcialo monoklonalne anty-IgE w leczeniu przewleklej ciezkiej astmy.

Asthma is a chronic inflammatory disease of airways. Approximately 40% of asthma cases can be attributed to atopy. An increased immunoglobulin E (IgE) production is the strongest predisposing factor for the development of asthma. IgE is a key component of asthma pathophysiology and contributes to both the early- and late-phase inflammatory cascade in the airways. Omalizumab is a recombinant anti-IgE monoclonal antibody developed for the treatment of allergic diseases associated with high circulating IgE levels. By reducing serum IgE levels, as well as FceRI and FceRII receptor expression on inflammatory cells, omalizumab inhibits development of inflammatory cascade. Omalizumab is currently the only IgE-targeted therapy approved by EMEA (European Agency for the Evaluation of Medicinal Products) and FDA (Food and Drug Administration) for asthma treatment. It is efficacious in the treatment of moderate-to-severe and severe persistent allergic asthma poorly controlled with regular treatment. The drug reduces symptoms, exacerbations, emergency visits, hospitalizations, inhaled and systemic corticosteroid and rescue medication requirements and improves quality of life.

N-acetyl-beta-hexosaminidase activity in asthma.

BACKGROUND: N-acetyl-beta-hexosaminidase (beta-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 beta-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. beta-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: beta-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 beta-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 beta-hex could take part in airway inflammation and remodeling in asthma. Our study is the first report in which the elevated activity of beta-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.

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

BACKGROUND: Exercise-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. METHODS: The 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. RESULTS: In 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. CONCLUSION: The 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.

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 (F(ENO)), 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, F(ENO) 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 F(ENO) 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.

Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthma.

Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma.

[Syndrom Corrao--cough variant asthma]. / Zespól Corrao--kaszlowa postac astmy.

Asthma is one of the most common aetiologies of chronic cough. In a subgroup of asthmatics, cough may be the predominant or sole symptom. This condition is referred to as cough variant asthma (CVA). The diagnosis of CVA often presents a challenge since physical examination and spirometric tests may be normal. Up to 50% of patients with CVA have associated eosinophilic bronchitis, with the degree of eosinophilia being similar to that of other asthmatics. Demonstration of bronchial hyperresponsiveness by methacholine inhalation challenge, elevated level of exhaled nitric oxide and sputum eosinophilia support the presence of CVA, but the diagnosis is confirmed only upon resolution of the cough with specific antiinflammatory treatment.

[Exhaled breath condensate in the assessment of airway inflammation]. / Kondensat powietrza wydychanego w diagnostyce przewleklych chorób zapalnych ukladu oddechowego.

Exhaled breath condensate (EBC) is a novel, non-invasive method for obtaining samples from the lung. Use of exhaled condensate as a source of biomarkers is based on the hypothesis that aerosol particles of exhaled breath reflect the composition of airway lining fluid. The technique is simple to perform, effort-independent, rapid, may be repeated frequently, and can be easily perform even in young children, adults, or patients with severe disease. EBC contains large number of various mediators including isoprostanes, cysteinyl-leukotrienes, adenosine, hydrogen peroxide, peptides, cytokines. Concentrations of these biomarkers are influenced by inflammation, oxidative stress and modulated by therapeutic interventions. EBC can be used to assess airway inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the treatment monitoring.