Eosinophil to lymphocyte ratio may predict OCS reduction and change in quality of life (AQLQ) resulting from asthma biological treatment.

OBJECTIVES: Simple clinical parameters that could be helpful in choice of monoclonal antibodies and prediction of their effectiveness are being sought. The aim was to assess if neutrophil-to-lymphocyte, eosinophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict outcomes of biologic therapy for severe asthma. METHODS: Retrospective, single-center study including severe asthma patients treated with three different biologics. The blood ratios were assessed at initiation of treatment (point 0) and after six months (point 1). The chi-square test was used to analyze differences in nominal variables. Quantitative variables were compared by Student's t-test, Mann-Whitney U or Wilcoxon signed-rank tests. RESULTS: 53 patients with severe asthma were included, among them 21 patients (40%) treated with omalizumab and 32 patients (60%) with mepolizumab or benralizumab. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios did not change during six-month-course of biological treatment. Eosinophil-to-lymphocyte ratio was higher at the point 0 (p = 0.016) in the group treated with anti-eosinophils than in the omalizumab group and lower at the point 1 (p = 0.006). In the anti-eosinophil group this ratio decreased between points 0 and 1 (p < 0.001). In the omalizumab group there was an inverse correlation between the initial ratio and oral corticosteroid dose reduction (rs = -0,67). In the a/eos group there were significant correlations between initial ratio and age (rs = 0.36), and ACQ (rs = -0.4) and ACQ (rs = 0.41) measured at the point 1. CONCLUSIONS: Pretreatment eosinophil-to-lymphocyte ratio may predict oral corticosteroid dose reduction resulting from omalizumab treatment and change in quality of life and asthma control resulting from anti-IL-5 and IL-5R treatment.

Allergic Fungal Rhinosinusitis in Europe: Literature Review and Own Experience.

Allergic fungal rhinosinusitis (AFRS) is primary, Th2-mediated, chronic rhinosinusitis, which is diagnosed when the criteria defined by Bent and Khun are met. The disease is most common in countries located in the subtropical and tropical regions characterized by high temperatures and high levels of humidity, which favour the wider occurrence of fungi in the environment. The presence of specific IgE antibodies directed against fungal allergens, which is one of the diagnostic criteria, proves the systemic nature of the disease and allows one to distinguish AFRS from eosinophilic fungal rhinosinusitis. There is no unified treatment method for AFRS described in the literature, and relapses are common. Sinus surgery remains the treatment of choice. Oral and topical steroid therapy plays an important role in the treatment process. The effectiveness of antifungal treatment and immunotherapy is unclear. Biological treatment, the results of which are promising, has raised great hopes. The aim of this study was to reveal how often AFRS occurs in European countries, what environmental factors influence its development, and how important it is to specify its diagnostic criteria and treatment methods. We present an overview of the available literature. In addition, we share our own experience and describe two cases of AFRS diagnosed and treated at our centre.

Phenotypes of Chronic Rhinosinusitis and Peripheral Blood Leukocytes Parameters in Elderly Patients.

Background and Objectives: Chronic rhinosinusitis (CRS) is a common disease that can be differentiated into two phenotypes, with or without polyps (CRSwNP) or CRSsNP), which may be unilateral (UNIL) or bilateral (BIL). CRS may have an impact on absolute neutrophils and lymphocytes count in peripheral blood. The aim of the study was to investigate whether the incidence of a specific CRS phenotype changes with age and to compare the values of neutrophils, lymphocytes and neutrophil-to-lymphocyte ratio in the peripheral blood between groups of patients below and above 65 years of age with different CRS phenotypes. Material and Methods: A total of 235 patients aged 65 and over were examined, including 140 (59.6%) males. The group of patients <65 years of age comprised 160 subjects, including 103 (64.4%) males. In both groups, the sequence of frequency of particular phenotypes was similar: the most common phenotype was bilateral CRSwNP followed by CRSsNP BIL, CRSsNP UNIL, and finally, CRSwNP UNIL. Direct comparisons between determined phenotype in both groups of different ages revealed that, in the group ≥65 years, CRSwNP BIL occurred significantly more often than in the group <65 years of age. In fact, in the <65 group, bilateral CRSsNP was more common. The absolute neutrophils and lymphocytes counts were significantly higher in the whole group of patients with CRS ≥65 years of age and absolute number of neutrophils was higher in ≥65 years of age group with bilateral CRSsNP. Conclusions: The higher number of neutrophils in the whole ≥65 years of age group and in older patients with bilateral CRSsNP may indicate that CRS, despite of phenotype, may be an important source of infection that requires surgical treatment in elderly patients as well.

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.

Nasal cytology can predict clinical efficacy of subcutaneous immunotherapy in intermittent allergic rhinitis.

Introduction: Allergen immunotherapy (AIT) is the only disease-modifying treatment option available for patients with IgE-mediated allergic rhinitis. The identification of specific biomarkers, which may predict response to AIT, is currently an active field of research in the aspect of recommended personalization of medicine. Aim: To assess the changes in rhinological parameters in intermittent allergic rhinitis (IAR) patients resulting from subcutaneous immunotherapy (SCIT). Material and methods: Forty-two patients (female: 19; 45%) with IAR qualified for subcutaneous immunotherapy were enrolled in this study. Fourteen (33.3%) patients were desensitized with grass pollen allergen extracts, 12 (28.6%) with tree pollen allergen extracts, and 16 (38.1%) with grass and tree pollen allergen extracts. The patients were evaluated before AIT during the pollen season and in the next pollen season after introduction of subcutaneous immunotherapy. On both occasions, determination of total nasal symptom score (TNSS), rhinomanometry and nasal cytology were performed. Results: All examined parameters significantly improved after one course of allergen immunotherapy: the percentage of eosinophils in nasal mucosa, TNSS and nasal resistance decreased, whereas the nasal flow rate increased. The decrease in percentage of nasal eosinophils significantly correlated with improvement in TNSS (rs = 0.39, p < 0.05) and was the highest in the subgroup sensitive to grass pollen (44.5 (40-52)). Conclusions: The rhinological assessment confirmed high effectiveness of SCIT in intermittent allergic rhinitis. A high percentage of eosinophils in nasal cytology before subcutaneous immunotherapy can predict its clinical efficacy for intermittent allergic rhinitis, especially in grass pollen allergy.

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.

Inflammatory lesions in the paranasal sinuses in patients with ischemic stroke who underwent mechanical thrombectomy.

INTRODUCTION: Chronic rhinosinusitis is one of the most widespread chronic diseases in the world, whereas stroke is the leading cause of death and disability. There are numerous reports on the relationship between chronic inflammatory diseases and cardio­cerebrovascular diseases. OBJECTIVES: The study aimed to assess whether inflammatory lesions in the sinuses can be a risk factor for stroke, similar to other known risk factors such as arterial hypertension, atrial fibrillation, atherosclerosis, diabetes, or cigarette smoking. PATIENTS AND METHODS: We analyzed the results of head computed tomography performed in 163 patients with ischemic stroke (79 men) at a mean (SD) age of 68.5 (12.7) years who were deemed eligible for mechanical thrombectomy. The control group included 75 patients (31 men) with neurological diseases of nonvascular origin. RESULTS: Among patients with stroke, inflammatory lesions in the sinuses were found in 95 individuals (58.3%), with a frequency comparable to that of atrial fibrillation (77 [47.2%]). Chronic rhinosinusitis occurred more often than diabetes (33 [20.2%]; P <0.001) and self­reported nicotinism (18 [11%]; P <0.001), yet less frequently than arterial hypertension and generalized atherosclerosis (124 [76.1%]; P <0.001 and 116 [71.2%]; P = 0.02, respectively). Inflammatory sinus lesions of moderate or high severity were more often observed in patients with stroke than in the control group and they mainly involved the ethmoid sinuses. CONCLUSION: Moderate­to­severe inflammatory lesions indicating chronic rhinosinusitis are common in patients with stroke, which suggests the role of local inflammation in inducing acute cerebral ischemia.

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.

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.

The Effect of Antileukotrienes on the Results of Postoperative Treatment of Paranasal Sinuses in Patients with Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease.

BACKGROUND: Based on endoscopic examination, chronic rhinosinusitis (CRS) is divided into chronic inflammation with (CRSwNP) or without nasal polyps (CRSsNP). On the basis of the pathomechanism of inflammation, CRS is divided into endotypes. Eosinophilic CRSwNP with coexisting bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is a real therapeutic challenge. AIM: Comparative analysis of the results of treatment of patients with CRSwNP, bronchial asthma, or hypersensitivity to NSAIDs (NSAID-exacerbated respiratory disease, NERD), using antileukotrienes (leukotriene receptor antagonists, LTRAs) or intranasal glucocorticoids or both drugs together after endoscopic sinus surgery (ESS). MATERIAL AND METHODS: 33 patients (11 male, 33%) with NERD divided into three groups treated with LTRAs or intranasal glucocorticoids or both drugs together were assessed in terms of general well-being, state of pathological changes, and olfactory disorders using the following tools: Sino-Nasal Outcome Test, Visual Analogue Scale, Brief Identification Smell Test, and Lund-Kennedy score before and at 12 months after surgery. CT assessments were made prior to surgery using the Lund-MacKay scale. RESULTS: Comparable efficacy of treatment with nasal steroids and antileukotrienes was found after 12 months of observation of patients. CONCLUSIONS: The results suggest comparable efficacy of treatment with nasal steroids and antileukotrienes in patients with NERD after ESS. Treatment with montelukast and mometasone has not been shown to be superior to both drugs administered separately.

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.

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.

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.

Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy.

Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn't correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.

Coexistence of angioedema alone with impaired glucose tolerance.

BACKGROUND: Most patients with chronic spontaneous urticaria (CSU) exhibit recurrent angioedema. As of yet, the pathogenesis of angioedema in CSU is largely unclear, especially when angioedema occurs in patients who do not develop wheals. Over the past years, we and others have repeatedly observed that patients with recurrent angioedema alone exhibit impaired glucose tolerance. AIM: To assess blood glucose levels and glucose tolerance in these patients and to compare the results to those of CSU patients who do not develop angioedema. METHODS: A total of 29 patients with angioedema alone (15 women, mean age 43.2 ± 12.8 years) and 33 CSU patients (17 women, mean age 41.9 ± 17 years) were investigated and compared for clinical features and laboratory values, including fasting and random blood glucose levels, and glycated hemoglobin (HbA1c%). All patients were subjected to oral glucose tolerance testing (OGTT). RESULTS: Fasting plasma glucose levels, random blood glucose levels and OGTT glucose levels were significantly higher in patients with angioedema alone as compared to CSU patients. Glucose tolerance was impaired in 17 of 29 patients with angioedema alone (58.6%) and only in 2 of 33 CSU patients (6.1%). Patients were found to have an increased risk of high glucose (OR 1.74) and HbA1c (OR 1.83) blood levels and of developing a high BMI (OR 1.97). CONCLUSION: Recurrent angioedema in patients who do not develop wheals appears to be associated with impaired glucose tolerance and elevated blood glucose levels. We recommend blood glucose measurements in patients with recurrent angioedema alone.