Home self-monitoring in patients with asthma using a mobile spirometry system.

BACKGROUND: Self-management is an appealing strategy for prevention of asthma exacerbations. This study aimed to evaluate the feasibility and safety of a portable spirometer for unsupervised home spirometry measurements among patients with asthma. METHODS: A multi-center, prospective, single-arm, open study recruited 86 patients with controlled or partly controlled asthma (41 women, 38.6 ± 10.4 y/o and 45 men, 36.2 ± 12.1 y/o). After a training session, patients performed daily spirometry at home with the AioCare® mobile spirometry system. Each spirometry examination was recorded and evaluated according to the ATS/ERS acceptability and repeatability criteria. The primary endpoint was defined as three or more acceptable examinations in any given seven-day period (+/- 1 day) during any of the three weeks of the study. The system allowed for online review of measurements by physicians/nurses to provide feedback to patients. RESULTS: Of 78 patients with complete data, 67 (86%) achieved the primary endpoint. Seventy-five (96%) participants used the device correctly once or more, and 10 (13%) patients succeeded every single day over the three-week follow-up. The rate of acceptable spirometry examinations differed between the sites (p = 0.013). Retraining was required in 20 of 62 (32%) eligible patients, and successful in 8 individuals (40%). Satisfaction with the AioCare® system was high, 90% of respondents perceived it as useful and user-friendly. CONCLUSIONS: Self-monitoring of asthma with a connected mobile spirometer is feasible, safe and satisfactory for patients with asthma. It remains to be established whether unsupervised home spirometry measurements may improve early diagnosis and outcomes of self-management in cases of exacerbation or loss of asthma control.

Highlights BoxThis study aimed to evaluate the ability of patients with asthma to perform high-quality daily spirometry examinations at home with using the AioCare^® mobile spirometry system. The study showed that unsupervised home spirometry is safe and feasible in patients with asthma. Most patients used the device on most days of the study, and nearly 90% of all patients achieved the primary endpoint. There were no device-related adverse events.

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.

Polish Society of Allergology statement on the diagnosis and treatment of severe, difficult-to-control bronchial asthma.

Severe asthma requires at least high doses of inhaled corticosteroids (ICS) in combination with a long-acting ß-agonist (LABA) or systemic corticosteroids (SCS) for more than 50% of days/year to avoid loss of control, or remains uncontrolled despite the treatment described above. The diagnosis of severe asthma should be confirmed in a reference centre as it requires careful differential diagnosis and the exclusion of factors hindering the achievement of optimal control. Severe asthma represents a significant burden for the patient, their family and the healthcare system. This is due to the severity of the symptoms, drug costs, significant impairment of everyday functioning and life quality, and limitation in the professional work. In the case of ineffectiveness of the step 4 GINA treatment, the patient should be referred to a specialist centre to consider additional treatment, including anti-IgE receptor (omalizumab), anti-IL-5 receptor (mepolizumab), or an antibody directed against the α-subunit of receptor for IL-5 (benralizumab). In the case of severe asthma, intensification of therapy should first of all include biological therapy and not the use of SCS. Biological drugs are available in Poland as a part of the therapeutic programme for the treatment of severe asthma. In practice, the therapeutic programme may change with subsequent notices of the Ministry of Health and does not have to be consistent with the Summary of Product Characteristics for individual preparations. The current review presents the basic principles of differential diagnosis of severe asthma and the selection of the optimal biological therapy in Polish conditions.

Reduced clot retraction rate and altered platelet energy production in patients with asthma.

OBJECTIVE: Asthma enhances the risk of pulmonary embolism. The mechanism of this phenomenon is unclear. METHODS: We evaluated the kinetics of clot formation, clot retraction rate (CRR), clot volume at 40 min, the rate of lactate production (a marker of aerobic glycolysis in platelets in contracting clots), blood eosinophil count (EOS), nitric oxide in exhaled breath (FENO), and spirometry (FEV1) in 50 healthy controls and in 81 allergic asthmatics (41 subjects with steroid-naïve asthma and 40 with steroid-treated asthma). RESULTS: Thromboelastometry revealed that only steroid-treated asthmatics had slightly activated coagulation. Compared with healthy controls, whole asthmatics demonstrated (p < 0.05) reduced CRR, higher clot volume at 40 minutes, higher FENO, decreased FEV1, elevated EOS, and augmented lactate production in retracting clots. Reduced CRR was observed also in the absence of native plasma. In whole study population (asthmatics and healthy controls), CRR positively correlated with spirometry (rS = 0.668, p = <0.001) and negatively with FENO (rS = -0.543; p < 0.001), EOS (rS = -0.367, p < 0.002), and lactate production (rS = -0.791; p < 0.001). However, in steroid-treated asthmatics, the CRR did not correlate with FENO and EOS. In all study patients lactate production negatively correlated with FEV1 and positively with FENO. CONCLUSION: Collectively, this data is consistent with the hypothesis that, in asthmatics, reactive nitrogen species produced in the lungs may reduce platelet contractility (and CRR) through the diminution of platelet energy production. CRR inhibition would predispose asthmatics to pulmonary embolism.

Vitamin D3 Treatment Decreases Frequencies of CD16-Positive and TNF-α-Secreting Monocytes in Asthmatic Patients.

BACKGROUND: Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties. METHODS: Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry. RESULTS: We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects. CONCLUSIONS: This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC.

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease.

BACKGROUND/AIMS: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. METHODS: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. RESULTS: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. CONCLUSION: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

The statement of the Polish Society of Allergology experts on the treatment of difficult-to-treat asthma.

The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view.

Serum levels of CD163 and TWEAK in patients with pulmonary arterial hypertension.

BACKGROUND: Inflammation may play a pivotal role in the pathogenesis of pulmonary arterial hypertension (PAH). We evaluated the concentrations of serum sTWEAK, its scavenger receptor sCD163 and sTWEAK/sCD163 ratio in patients with PAH. DESIGN: The study enrolled 26 stable patients with PAH confirmed by right heart catheterization and 24 healthy volunteers matched for age, sex and body weight. All patients underwent transthoracic echocardiography, cardiopulmonary exercise test, 6-min walk test, measurement of lung diffusing capacity for the carbon monoxide (DLCO) and venous blood tests. Concentrations of sTWEAK and sCD163 were determined using ELISA kits. RESULTS: The PAH patients were characterized by significantly higher median serum sCD163 levels (1072 vs 890ng/ml, p=0.04) together with lower serum sTWEAK concentrations (200 vs 278.1pg/ml, p=0.003) comparing to control subjects. sTWEAK/sCD163 ratio was therefore significantly lower in PAH group (0.18 vs 0.33, p=0.0005). No correlation was found between sTWEAK and sCD163 concentrations in both groups. We observed statistically significant inverse correlation between peak VO2 consumption and sCD163 concentrations (r=-0.52, p<0.05) and positive with sTWEAK/sCD163 ratio (r=0.45, p<0.05) in PAH group. Moreover, sTWEAK/sCD163 ratio positively correlated with % of predicted values of DLCO (r=0.42, p<0.05). CONCLUSIONS: Patients with PAH present altered serum sTWEAK and sCD163 levels. The sTWEAK/sCD163 ratio appears to be a better indicator of the severity of PAH as compared to sTWEAK or sCD163 alone. The exact role of sCD163 or interaction between CD163 and sTWEAK in the initiation or progression of PAH as well as their potential prognostic significance remains to be established.

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.

Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

Phenotypic correlations between monocytes and CD4+ T cells in allergic patients.

Despite widely acknowledged contributions of innate and adaptive immune systems to the pathogenesis of allergic diseases, mutual interactions occurring in vivo between components of those two systems have not been studied in sufficient detail. Here, we wished to investigate whether phenotypic features of monocytes and CD4+ T cells in allergic patients are reciprocally related. Therefore, we recruited 50 untreated house dust mite-sensitive allergic rhinitis patients and 29 non-atopic healthy individuals and performed comprehensive simultaneous flow cytometric analysis of mutual correlations between levels of CD14, CD16, CD163, CD206, CD124 (IL-4R), CD210 (IL-10R) and CD25, CD124, CD127 (IL-7R), CD210, ICOS expression on monocytes and CD4+ T cells, respectively. We found that CD163 monocyte expression in allergic but not healthy subjects is positively correlated with monocyte IL-10R, and, to a lesser extent, CD206, but not IL-4R expression. Levels of CD163 expression were not related to frequencies of CD14++CD16-, CD14++CD16+, and CD14+CD16++ monocyte subsets. In contrast to healthy controls, intensities of monocyte IL-10R in allergic individuals were significantly correlated with monocyte CD206 and IL-4R expression. In addition, levels of monocyte IL-4R and IL-10R monocyte expression were positively correlated to expression of IL-4R and IL-10R on CD4+ T cells in both groups of studied subjects. Interestingly, we demonstrated a significant positive correlation between levels of monocyte CD206 expression and levels of IL-10R and IL-4R expression on CD4+ T cells in allergic but not healthy individuals. In summary, we conclude that allergic rhinitis is associated with a number of phenotypic alterations of circulating monocytes and CD4+ T cells.

Decreased CD127 expression on CD4+ T-cells and elevated frequencies of CD4+CD25+CD127- T-cells in children with long-lasting type 1 diabetes.

Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127- phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127- T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127- T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25- T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127- T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype.

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.

Fluticasone/formoterol combination therapy versus budesonide/formoterol for the treatment of asthma: a randomized, controlled, non-inferiority trial of efficacy and safety.

OBJECTIVES: The inhaled corticosteroid fluticasone propionate (fluticasone) and the long-acting ß2 agonist formoterol fumarate (formoterol) have been combined in a single aerosol inhaler fluticasone/formoterol (flutiform(®)). This study compared the efficacy and safety of fluticasone/formoterol with the combination product budesonide/formoterol (Symbicort(®) Turbohaler(®)). METHODS: A randomized, double-blind, double-dummy, multicenter, Phase 3 study comprising a 7- (± 3) day screening, 2-4-week run-in, and 12-week treatment periods. Patients aged ≥ 12 years with moderate to severe persistent asthma for ≥ 6 months before screening and forced expiratory volume in one second (FEV1) 50-80% predicted and ≥ 15% reversibility following salbutamol inhalation were randomized to fluticasone/formoterol 250/10 µg twice daily (n = 140) or budesonide/formoterol 400/12 µg twice daily (n = 139). RESULTS: Fluticasone/formoterol was comparable to budesonide/formoterol with respect to the primary endpoint, change in pre-dose FEV1 from baseline to Week 12. The LS mean treatment difference was -0.044 L, with a lower 95% confidence interval (CI) greater than the pre-defined non-inferiority limit of -0.2 L (95% CI: -0.130, 0.043 L; p < 0.001). Non-inferiority was also demonstrated for the secondary endpoints mean change in FEV1 from baseline (pre-dose) to 2 hours post-dose at Week 12, and discontinuations due to lack of efficacy. Similar results were obtained for both treatment groups for all other secondary endpoints. Fluticasone/formoterol had a good safety profile that was comparable with budesonide/formoterol. CONCLUSIONS: This study demonstrated comparable efficacy of fluticasone/formoterol to budesonide/formoterol in terms of the primary endpoint, change in pre-dose FEV1 from baseline to Week 12. This was supported by comparable results for both treatments for all secondary endpoints.

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.

Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study.

BACKGROUND: The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting ß2-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, flutiform ®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol. METHODS: Patients aged ≥ 18 years (N = 202) with mild-to-moderate-severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4-10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV1), at week 12. RESULTS: Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV1 at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV1, change from pre-dose FEV1 at baseline to 2-hour post-dose FEV1 at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol. CONCLUSIONS: The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.

Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase.

BACKGROUND: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT. METHODS: In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models. RESULTS: Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy. CONCLUSION: Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.

[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.