Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study.

INTRODUCTION: Extrafine formulation of beclomethasone/formoterol fixed combination (BDP/F pMDI HFA) is approved for both fixed maintenance and maintenance and reliever therapy (MART) of asthma, and recent data has proven that BDP/F pMDI HFA maintenance and reliever therapy is an effective alternative to other regimens. OBJECTIVE: This study aimed to assess the level of asthma control in a real-life setting in adult patients using extrafine BDP/F pMDI HFA fixed combination in a pressurized metered-dose inhaler (pMDI) as fixed maintenance dosing as well as maintenance and maintenance and reliever therapy. Additionally, we examined patients' satisfaction with the inhaler device and compliance with therapy as essential factors determining asthma control. METHODS: This multicenter prospective non-interventional observational study lasted 4 months with 3 patient visits. We used the Asthma Control Questionnaire 7 (ACQ-7) to evaluate the degree of asthma control and Morisky Medication Adherence Scale (MMAS-4) to assess compliance. A self-developed questionnaire was used to assess satisfaction with the inhaler device. RESULTS: 2179 patients using BDP/F pMDI HFA fixed combination as maintenance and reliever therapy or BDP/F pMDI HFA as maintenance therapy and SABA (short-acting beta2-agonist) as a reliever for at least 2 months were included. During the prospective follow-up, we observed an upward trend in the FEV1% (forced expiratory volume in 1 s) predicted values, improvement in the control of symptoms as indicated by a decline in the mean ACQ-7 score was noted (1.62 at Visit 1 vs. 1.21 at Visit 2 vs. 0.94 at Visit 3, p < 0.001) and increase in patients' compliance (the number of patients that reported forgetting at times to take their medication was reduced from 49.7 % to 27.1 %, p < 0.001). At the same time, we noted a reduction in the number of as-needed doses used for symptom relief (p < 0.001). Most patients were satisfied with the pMDI, considered it easy and convenient to use, and preferred it to a dry powder inhaler (p < 0.001). CONCLUSIONS: The use of extrafine BDP/F pMDI HFA as maintenance as well as reliever therapy seems to be associated with increased asthma control and better compliance to therapy.

Progressive clinical effects of the combination omalizumab and HDM - allergen immunotherapy in asthma.

OBJECTIVE: The combination of allergen immunotherapy (AIT) and omalizumab is used to treat patients at risk of anaphylaxis. There is currently a very little evidence that this combination increases the effectiveness of AIT in patients with inhalant allergies. The study aimed to evaluate the effectiveness of HDM-SCIT therapy (injection immunotherapy for house dust mites) in combination with omalizumab in treating HDM-induced asthma. METHODS: This study was a placebo-controlled, randomized, multicenter trial including 82 patients with HDM-driven mild to moderate asthma. Omalizumab alone (A), HDM SCIT + omalizumab (B), SCIT alone (C), or placebo (D) for 24 months were applied. All patients received asthma treatment in accordance with GINA recommendations. The treatment efficacy was defined by a reduction in the daily dose of inhaled steroids (ICS) and a reduction in the number of asthma exacerbations (AX). RESULTS: After 24 months of therapy, a statistically significant reduction in the daily doses of ICS in groups A and B was observed (p = 0.021 and p = 0.008). Daily ICS reduction was considerably more significant in group B (p = 0.01). During 24 months of observation, the AX was significantly reduced in all study groups, with the greatest significant difference observed between groups A and B and groups C and D (placebo) as follows: 0.42 patient/per year vs. 0.39 vs. 0.84 vs. 0.91 (p = 0.023). CONCLUSION: The combination of HDM SCIT and omalizumab is significantly and progressively reducing ICS use and AX in a 24-month study. The combination is significantly more effective than the single treatments or placebo.

Epithelial-Cell-Derived Cytokines in Patients with Obesity before and after Bariatric Surgery.

Abstract/Purpose: Epithelial signals such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) are stimulators of group 2 innate lymphoid cells (ILCs2) that are integral regulators of adipose tissue type 2 immunity. The purpose of this study was to assess cytokines activating ILCs2 in the serum of patients with obesity and the effect of bariatric surgery on these parameters. MATERIAL AND METHODS: In a single-center prospective study, serum IL-25, IL-33, TSLP, and ST2L levels were assayed at the baseline and at 6 months after bariatric surgery and correlated with anthropometric changes and metabolism parameters. RESULTS: Mean age and median of body mass index (BMI) of study participants were 41.9 years ± 11 and 45.6 kg/m2 (range 36.3-56.3), respectively. Six months after surgery, excess weight loss percentage was 43.1 ± 10.2%. Serum TSLP was significantly lower in patients with obesity both before and after surgery than in healthy controls. TSLP values before operation were significantly correlated to glycated hemoglobin percentage and BMI. Serum IL-25, IL-33, and ST2L levels were comparable to controls both before and after operation. CONCLUSIONS: Decreased serum levels of TSLP may be a characteristic trait for obesity however nonmodifiable by body mass surgical reduction in short time observation. Low serum levels of TSLP are related to disturbances in glucose metabolism and BMI.

sCD48 is elevated in non-allergic but not in allergic persistent rhinitis.

BACKGROUND: CD48 is a costimulatory receptor of the immune response. Interactions between CD48 and CD244 (2B4) on mast cells and eosinophils suggest that these cells can act synergistically in the 'allergic effector unit' to promote inflammation. This report explores the role of CD48 in persistent allergic (PAR) and non-allergic rhinitis (NAR). METHODS: In this study, serum was obtained from 70 subjects (45 female, 64%; mean age, 36; range 18-70 years) to estimate the levels of sCD48 and two eosinophils-related parameters, ECP and eotaxin-1/CCL11. Twenty patients with PAR, 15 patients with NAR, and 35 healthy controls were included. The intensity of rhinitis symptoms was estimated by the Total Nasal Symptom Score. We also assessed the fractional exhaled nitric oxide bronchial and nasal fractions (FeNO) and neutrophil to lymphocyte (NLR) and eosinophil to lymphocyte (ELR) ratios. RESULTS: Significantly higher sCD48 serum levels were observed in the NAR group than in the PAR and control groups, and significant correlations were found between the serum level of sCD48 and the number and percentage of eosinophils. ECP and eotaxin-1/CCL11 serum levels were also found to be significantly higher in the NAR group. CONCLUSIONS: CD48 may be involved in eosinophilic pathophysiological reactions in non-allergic rhinitis.

Usefulness of the drug allergy passport in the drug allergy management.

INTRODUCTION: Nowadays, the number of people with drug hypersensitivity has been increasing and it has become a major problem for the healthcare system. Unfortunately, not everyone is aware of which medications they can safely use. AIM: To assess the suitability of a drug allergy passport in patients with drug hypersensitivity in order to increase knowledge about medicines that can be safely used. MATERIAL AND METHODS: The study was conducted in 54 hospitalized patients with confirmed hypersensitivity to drugs by issuing a drug passport at discharge. The study was carried out with the questionnaire method. The questionnaire was conducted by phone 3, 6 and 12 months after the patients received the drug passport. RESULTS: Fifty-eight people were contacted by phone. The survey was conducted in 54 people (42 women (77%), mean age: 48, range: 19-71), which gives a response rate of 98%. The application of the drug allergy passport by patients increased with time and the number of patients who did not use their passport decreased. With time, patients showed the drug allergy passport to a larger number of doctors, most often to general practitioners and dentists. In the following months, the number of doctors who followed passport recommendations and patients who adhered to the passport recommendations increased. CONCLUSIONS: The analysis of drug allergy passport shows that patients are better informed about medicines they can use and have a greater sense of security. By showing the passport to specialists, they choose the safest and adequate treatment.

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Elevated Serum Level of CD48 in Patients with Intermittent Allergic Rhinitis.

BACKGROUND: In the pathogenesis of intermittent allergic rhinitis (IAR), the inflammatory reaction is of importance. CD48, belonging to the CD2 family, participates in mast cell-stimulating cross-talk, facilitates the formation of the mast cell/eosinophil effector unit, and is expressed by eosinophils. OBJECTIVES: To assess the serum level of soluble form of CD48 (sCD48) in patients with IAR during and out of the pollen season and correlate with the disease severity and with eosinophil-related parameters. MATERIALS AND METHODS: Sixty-three patients (female: 79%; mean age: 30.58) were included to the study. Forty-five patients were assessed during the pollen season and other 42 patients during out of the pollen season. Twenty-four patients (female: 37.50%; mean age: 27.90) were evaluated twice, during the pollen season and out of the pollen season. sCD48, ECP, eotaxin-1/CCL11 serum levels together with complete blood count, and fractional exhaled nitric oxide bronchial and nasal fraction (FeNO) were performed. The severity of symptoms was assessed using the Total Nasal Symptom Score (TNSS), and neutrophil-to-lymphocyte (NLR) and eosinophil-to-lymphocyte (ELR) ratios were calculated. RESULTS: sCD48 serum level, FeNO nasal and bronchial fractions, and TNSS were significantly higher in the IAR group in the pollen season compared with out of the pollen season. Differences in ECP, eotaxin-1/CCL11 serum levels, and NLR and ELR were not significant between season and out of the season. No correlations were found between sCD48 and eosinophil-related parameters. CONCLUSIONS: sCD48 may be a biomarker to the exacerbation phase in patients with IAR. One can assume that CD48 participates in the pathogenesis of IAR.

Eosinophil/Neutrophil/Platelet-to-Lymphocyte Ratios in Various Types of Immediate Hypersensitivity to NSAIDs: A Preliminary Study.

BACKGROUND: The eosinophil/neutrophil/platelet-to-lymphocyte ratios (ELR, NLR, and PLR) have been used as clinical markers of systemic inflammation. However, they have not yet been tested in various subtypes of immediate hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: To assess the ELR, NLR, and PLR in various types of hypersensitivity to NSAIDs. MATERIALS AND METHODS: A retrospective analysis of complete blood cell count and the ELR, NLR, and PLR was performed. Appropriate types of hypersensitivity to NSAIDs were diagnosed based on the anamnesis and drug provocation tests. The analysis covered 97 patients. Twenty were diagnosed with NERD (NSAID-exacerbated respiratory disease), 20 with NECD (NSAID-exacerbated cutaneous disease), 38 with NIUA (NSAID-inducted urticaria/angioedema), and 19 with SNIUAA (single-NSAID-induced urticaria/angioedema or anaphylaxis). Two controls groups were included: the first covered 15 patients with bronchial asthma and the second 28 patients with chronic spontaneous urticaria without NSAID hypersensitivity. RESULTS: The NLR did not differ significantly between the NSAID hypersensitivity types. The ELR was significantly higher in NERD patients, and the PLR was significantly lower in NECD patients than in patients with other types of NSAID hypersensitivity and in controls. CONCLUSIONS: The ELR and PLR may be useful in differentiating various types of immediate hypersensitivity to NSAIDs. Moreover, the ELR may be helpful in differentiating patients with bronchial asthma with and without NSAID hypersensitivity and PLR in differentiating patients with chronic spontaneous urticaria from NECD.

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.

Is there a relationship between asthma and diabetes?

Background: There is an ongoing discussion regarding the coexistence of bronchial asthma and diabetes. The objective of the study was to assess the relationship between asthma and the diabetes course and the influence of corticosteroid therapy in asthma on diabetes control.Methods: This was a cross-sectional study. There were 2431 adult patients who were selected from 40,015 patients and assigned to subgroups of patients with only asthma, with both asthma and diabetes and with only diabetes. The following parameters were measured: fasting blood glucose level, oral glucose tolerance and glycated hemoglobin (HbA1c).Results: The value of HbA1c in patients with asthma and diabetes was compared to the value of this parameter in patients suffering only from diabetes: 7.23 ± 1.73% versus 7.42 ± 2.09% (P > 0.05). The diabetes control criteria were met in 48.5% patients with asthma and concomitant diabetes and in 50.6% patients who suffered only from diabetes. There was a negative relationship between severe asthma and diabetes control. A daily dose of budesonide up to 825 mcg used by asthmatic and diabetic patients had no significant influence on fasting glucose.Conclusions: The effect of asthma on diabetes does not seem to be significant, except for in patients with severe asthma. Inhaled steroids administered in low or mild doses do not affect fasting glycemia.

Serum levels of interleukin 33 and its receptor ST2 in patients treated with subcutaneous allergen immunotherapy in intermittent allergic rhinitis.

INTRODUCTION: Interleukin 33 (IL-33) is a pleiotropic cytokine involved in pathological processes in seasonal allergic rhinitis. IL-33 binds to ST2 receptor, which is highly expressed on mast cells and selectively on Th2 cells. Information is lacking on the role of IL-33/ST2 axis in allergen subcutaneous immunotherapy. AIM OF THE STUDY: To determine if allergen immunotherapy changes the IL-33/ST2l axis in seasonal allergic rhinitis patients. MATERIAL AND METHODS: 40 patients with intermittent allergic rhinitis sensitive to grass and/or tree pollen were studied. Among these, 10 patients were longitudinally assessed in the follow-up visit after completing the first course of immunotherapy. Twenty-two healthy subjects were included as controls. Immunotherapy was applied according to a perennial schedule comprising up-building and maintenance phases. Serum levels of ST2/IL-33 R and IL-33 were measured by ELISA (R&D Systems). RESULTS: Serum levels of IL-33 significantly rose after the first course of immunotherapy and reached the controls levels. Serum levels of ST2 were comparable before the pollen season and after the first course of immunotherapy. CONCLUSIONS: Increase in serum levels of IL-33 after the first course of immunotherapy may suggest it is too short period to prevent the expected raise in serum IL-33 levels in the pollen season, and longer treatment is required to observe significant changes of this cytokine. ST2 serum levels are independent of immunotherapy and pollen season.

IgE-dependent sensitization in patients with COPD.

INTRODUCTION AND OBJECTIVE: The aim of the study was to evaluate the differences between asthma and COPD on the basis of the prevalence and profile of IgE-dependent sensitization to inhaled allergens, and the blood serum levels of select Th1/Th2 cytokines. MATERIAL AND METHODS: 103 patients with COPD (114 patients with asthma and 121 controls) were included in the study. A skin prick test with common inhaled allergens was performed, and serum levels of IgE were measured in all subjects. Lymphocyte profiles were measured via the whole-blood method using fresh 10-ml blood samples treated with EDTA. The following surface antigens were measured: CD3, CD29, CD16, CD56, CD4, CD8, and HLA-DR. The Th1/Th2 profile in blood serum was determined using Th1/Th2 cytokine kits. RESULTS: IgE-dependent sensitization to environmental allergens was found in 34 (33.3%) patients with COPD, 46 (40%) patients with asthma and in 14 (11.5%) volunteers. The odds ratio of sensitization in patients with COPD reached 0.89 (95% CI: 0.57-1.08) and it was more frequent than in the control population with an odds ratio of 0.71 (95% CI: 0.64-0.88). The serum concentration of IL-2 was significantly higher in patients with COPD and asthma than in controls. In the subgroup of patients with non-allergic asthma, similar serum concentrations were observed for all analyzed cytokines, except for IFN-gamma, which was lower in patients with COPD. CONCLUSIONS: Both the prevalence and profile of IgE-dependent sensitization to inhaled allergens did not differ between asthma and COPD. Both Th2 and Th1 played a role in the immunopathology of asthma and COPD. ABBREVIATIONS: COPD - Chronic Obstructive Pulmonary Disease; FEV1 - forced expiratory volume in one second; FVC - forced expiratory volume; GINA - Global Initiative for Asthma; GOLD - Global Initiative for Chronic Obstructive Lung Disease; MMRC - Modified Medical Research Council; Th1 - lymphocyte helper 1; Th2 - lymphocyte helper 2.

Asthma control in adult patients treated with a combination of inhaled corticosteroids and long­acting ß2­agonists: a prospective observational study.

INTRODUCTION    Asthma is a highly prevalent disease that often requires maintenance therapy. Combined inhaled corticosteroid (ICS) and long­acting ß2­agonist (LABA) inhalers are one of the available maintenance treatment options. OBJECTIVES    This prospective observational study aimed to assess asthma control in patients treated with ICS/LABA inhalers and to identify factors related to optimal asthma control. PATIENTS AND METHODS    The study included 5789 asthmatic patients from Poland, treated with one of the following ICS/LABA inhalers at clinically appropriate doses: beclomethasone/formoterol, fluticasone/ salmeterol, or budesonide/formoterol. The follow­up lasted 6 months (4 visits in total). The outcomes were physician-reported and patient­reported asthma control and occurrence of adverse drug reactions. A retrospective logistic regression analysis was performed to identify a potential association between age, obesity, and smoking and the level of disease control. RESULTS    A total of 4469 patients completed the study. Throughout the study period, the rate of patient­reported control of asthma increased from 24.8% to 67.7%, while physician­reported control increased from 22.6% to 66.4%. The incidence of exacerbations decreased from 23.4% to 1.9%. Less than 0.1% of the patients reported adverse drug reactions. Age, obesity (body mass index ≥30 kg/m2), and smoking were confirmed as factors negatively affecting disease control, with combined ICS/LABA inhalers potentially reducing their effect. CONCLUSION    Our results confirm the efficacy and safety of combined ICS/LABA inhalers in a real­life clinical setting. They also corroborate the finding that obesity, older age, and smoking are risk factors for poor asthma control.

Asthma, COPD and comorbidities in elderly people.

UNLABELLED: Co-morbidities are a significant problem in the elderly population but are rarely presented and analyzed for interdependencies among the various coexisting chronic diseases. OBJECTIVE: The aim of this study was to present a profile of comorbidities in elderly patients with and without asthma and COPD. METHODS: Respondents were recruited at 20 sites in Poland. Stratified random sampling from patient databases resulted in 15,973 patients older than 60 years of age. A retrospective analysis of medical history and ICD-10 codes was performed. In addition, patients underwent a spirometry test with a bronchial reversibility test and were administered questionnaires on the prevalence of chronic diseases by doctors. RESULTS: The study population consisted of 1023 asthmatic patients, 1084 patients with COPD and 1076 control subjects without any signs of bronchoconstriction and with correct spirometry. Patients with asthma exhibited a similar distribution of cardiovascular and metabolic co-morbidities as the control group. However, asthmatic patients had a higher prevalence of arterial hypertension and depression with an odds ratio (OR) = 1.48 (95% CI: 1.38-1.62) and OR = 1.52 (95% CI: 1.44-1.68), respectively. Coronary disease (OR = 2.12; 95% CI: 1.97-2.33), cor pulmonale (OR = 3.1; 95% CI: 2.87-3.22) and heart failure (OR = 2.71; 95% CI: 2.64-3.11) were predominantly observed in patients with COPD. Patients with severe asthma exhibited a greater predisposition to cardiovascular and neuropsychiatric diseases. CONCLUSION: Asthma coexisted frequently with arterial hypertension and depression in elderly patients. Patients with COPD have a more exaggerated profile of coexisting diseases, specifically cardiovascular problems.

Increased Levels of Interleukin-33 and Thymic Stromal Lymphopoietin in Exhaled Breath Condensate in Chronic Bronchial Asthma.

BACKGROUND: Epithelium-derived cytokines such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 are important contributors to inflammation in asthma. Exhaled breath condensate (EBC) is a noninvasive method used to assess the inflammation of airways. Our aim was to assess the levels of TSLP, IL-25, IL-33, and its receptor ST2l/IL-1 R4 in EBC in patients with asthma and to correlate these with serum levels and asthma control. METHODS: EBC and serum levels of TSLP, IL-25, IL-33, and ST2l/IL-1 R4 were measured in 44 patients with chronic bronchial asthma (14 in the uncontrolled phase) and 19 healthy control participants. RESULTS: EBC levels of IL-33 and TSLP and serum levels of IL-33 were statistically higher in patients with asthma than in controls. IL-25 and ST2l/IL-1 R4 were present in EBC at barely detectable levels and were not analyzed. The EBC and serum levels of all studied mediators did not differ between controlled and uncontrolled asthma patients, except for the serum level of ST2l/IL-1 R4, which was higher in uncontrolled asthma. There were no correlations between serum and EBC levels of TSLP and IL-33 or between either serum and EBC levels and the forced expiratory volume in 1 s or the total IgE level. CONCLUSIONS: Higher levels of IL-33 and TSLP in EBC provide evidence supporting a role for these mediators in asthma. Their levels do not discriminate between controlled and uncontrolled asthma. The local reaction within the epithelium is independent of the systemic reaction.

Sublingual immunotherapy (SLIT)--indications, mechanism, and efficacy: Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy.

SLIT (sublingual immunotherapy,) induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy), with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50-100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1-3 years has been provided by the large scale double-blind, placebo-controlled (DBPC) trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis) in both children and adults sensitized to pollen allergens (trees, grass, Parietaria), house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 - 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.

Chemokine receptors expression on CD3+ blood cells in bronchial asthma.

PURPOSE: Chemokines and their receptors participate in pathomechanism of bronchial asthma. The aim of the study was to analyze the pattern of chemokine receptor expression on T cells in severe asthmatics and to compare to mild-to-moderate patients and controls. MATERIAL/METHODS: Flow cytometric analysis of CXCR1, CXCR2, CXCR3, CCR3, CCR4, CCR5, CCR7, CCR8 expression on CD3(+)CD8(-) and CD3(+)CD8(+) cells was performed in patients with different severity of chronic asthma and in controls. RESULTS: Percentages of CD3(+)CD8(+) cells expressing CXCR1 were significantly lower in severe asthmatic than in mild-to-moderate asthmatics and in controls. Percentages of CD3(+)CD8(+) cells expressing CCR7 were significantly lower in the severe asthma group than in control group. Percentages of CD3(+)CD8(-) cells expressing CXCR1, CXCR2 and CCR8 were significantly lower in the severe asthma group than in mild-to-moderate asthmatics and in controls. The number of cells CD3(+)CD8(-) and CD3(+)CD8(+) expressing of CXCR1 was significantly lower in the group of patients using more than 800µg of budesonide daily than in the group of patients using less than 400µg of budesonide. Percentages of CD3(+)CD8(-) cells expressing CXCR3, CCR4 and CCR5 were visibly higher (not significantly) in chronic mild-to-moderate asthma than in healthy controls and severe asthmatics. CONCLUSIONS: These results may indicate impairment of some chemokine expression on T cells in severe asthma patients. Moreover participation of both chemokine receptors related to Th1 and Th2 responses in mild-to-moderate asthma and attenuation of these responses in severe asthma has been suggested.

Prevalence of IgE-mediated allergy and evaluation of Th1/Th2 cytokine profiles in patients with severe bronchial asthma.

INTRODUCTION: The pathogenesis of asthma remains unclear, especially in cases of the severe disease. AIM: To explore IgE-mediated inhalant sensitization in severe asthma compared with a group of patients with chronic mild disease and evaluate the Th1/Th2 cytokine profiles in asthma by different disease severities. MATERIAL AND METHODS: One hundred and fifty-four patients (age range: 28-69) with severe chronic asthma (study group) and 141 patients with chronic mild disease (control group) diagnosed according to GINA criteria were included in the study. Seventy-eight severe asthmatics and 43 subjects with mild disease were randomly selected for serum Th1/Th2 cytokine level estimation. The groups were matched in terms of age and atopy features (skin prick tests, specific and total serum IgE). RESULTS: Positive skin tests to at least one allergen were observed with comparable frequencies. Sensitization to Dermatophagoides pteronyssinus was the most prevalent positive result in both groups. An earlier onset of asthma together with a greater number of exacerbations was noted in severe asthmatics compared to patients with mild disease. Serum levels of interleukin 4 and 2 (IL-4 and IL-2) were detectable only in severe asthmatics irrespective of atopy features. The levels of interferon γ and tumour necrosis factor α were undetectable in both groups. IL-10 and IL-5 were detected in the serum of only 7 and 12 severe asthmatics, respectively. CONCLUSIONS: The serum level of IL-2 and IL-4 could be perceived as a marker of severe asthma. Neither IL-2 nor IL-4 levels in the serum could differentiate allergic and non-allergic asthma.