Ischemic stroke as a rare complication of wasp venom allergy: two clinical scenarios.

Neurological complications after a single Hymenoptera insect sting are very rare. The authors of this paper describe two instances of cerebral ischemic stroke that occurred immediately after a wasp sting. Two distinct pathomechanisms involved in the cases are put forward. When diagnosing such cases, it is vital to rule out the possibility of an immunoglobulin E (IgE)-dependent reaction of hypersensitivity. However, if sIgE antibodies against wasp venom extract and/or its allergenic components are detected, after hospitalization the patient should be qualified for venom immunotherapy, which is the only efficient method of protection from severe allergic reactions caused by an insect sting. Although the incidence of ischemic stroke in patients stung by insects is very low, it is important to be aware of this complication. This will allow rapid implementation of appropriate diagnostics and treatment. The optimal stroke treatment (thrombolysis or mechanical thrombectomy) in these rare cases has not yet been established.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

Current practices in diagnosis of Hymenoptera venom allergy in Poland.

Introduction: Hymenoptera venom allergy (HVA) is associated with a high risk of anaphylaxis. Effective treatment of HVA patients requires allergologists' familiarity with the latest HVA recommendations. Aim: Evaluation of current practices in HVA diagnosis in Poland. Material and methods: A survey questionnaire was conducted in 32 HVA centres in Poland. Results: The response rate was 97%. There were 1829 patients evaluated due to HVA in 2015. Sixty six percent (n = 21) of the centres used skin prick tests, out which 90% (n = 19) used 100 µg/ml of the venom extract as the highest concentration. All the centres performed intradermal tests (IDT) and serum specific IgE (sIgE), an initial diagnostic tool in 91% (n = 29). The highest venom concentration in IDT was 1 µg/ml in 75% (n = 24), 0.1 µg/ml in 16% (n = 5), 0.01 µg/ml in 3% (n = 1) and 10 µg/ml in 6% (n = 2). Baseline serum tryptase was assessed in 84% of the centres (n = 27), out of which 53% (n = 17) tested all their patients, whereas 31% (n = 10) checked only those with life-threatening reactions. In case of negative IDT/sIgE, 59% of the centres (n = 19) performed components evaluation, while 19% (n = 6) did the basophil activation test. In case of no identification of the culprit insect and sensitization to both venoms, VIT employed venom with higher sIgE. Conclusions: Most allergology centres in Poland follow HVA guidelines. We identified two inaccuracies in their HVA management including non-adequate venom concentration in IDT and a false belief in correspondence between sIgE concentration and severity of allergic reactions.

Large local reactions to Hymenoptera stings: Outcome of re-stings in real life.

BACKGROUND: Large local reaction to Hymenoptera stings is usually defined as a swelling >10 cm which lasts longer than 24 hours, sometimes associated with erythema, pruritus and blisters. Currently, the risk of subsequent systemic reactions after re-stings is considered low (2%-15%). Therefore, a diagnostic workup in case of large local reaction is often judged unnecessary, as well as adrenaline auto-injector and venom immunotherapy prescription. The aim of this study was to prospectively evaluate the outcome of re-stings in a real-world setting, in patients with a history of one previous large local reaction. METHODS: We consecutively enrolled patients who experienced their first large local reaction (as per EAACI definition), treated with antihistamine and steroids. They were followed for field re-stings and assessed for risk of subsequent systemic reactions. RESULTS: We enrolled 662 patients. Out of the 225 re-stung subjects, 24% did not experience reactions, 52% reported a second large local reaction and 24% had systemic reactions. The risk of subsequent systemic reactions was higher in case of skin test reactivity to Apis mellifera or Vespula species (OR 2.1 and 3.8, respectively), in particular if positive at 0.001 µg/mL concentration (OR 13.4 and 16.5, respectively). CONCLUSIONS: Systemic reactions, after a previous large local reaction, occur more frequently than that reported by literature. After analysing the predictive role of large local reactions for systemic reactions, we demonstrated that an accurate diagnostic workup may be considered, particularly skin tests. Further studies in different countries are needed to confirm these results and large local reaction management.

Venom allergy treatment practices in Poland in comparison to guidelines: next edition of the national audit.

INTRODUCTION: Venom immunotherapy treatment (VIT) is the only causal treatment of hymenoptera venom anaphylaxis, which aims to provide long-lasting immunoprotection against severe reactions to subsequent stings. AIM: To reassess the compliance of VIT procedures in the Polish allergy centres with the European guidelines. MATERIAL AND METHODS: A structured questionnaire survey conducted in all 33 VIT-centres. The response rate was 94%. RESULTS: The ultrarush initial protocol was the most common protocol (71%, n = 22), usually lasting for 3.5 h (50%, n = 7). The most frequent (36%, n = 11) time interval from the initial to the first maintenance dose (MD) was 14 days, ranging from 7 to 35 days. All centres used an MD of 100 µg. The most frequent time interval between subsequent MDs was 4 weeks (58%, n = 18). Five years' of VIT was declared by 71% (n = 22). Before the termination of treatment, more than half of the centres (58%, n = 18) performed sIgE and almost half (42%, n = 13) performed skin tests. To confirm VIT efficacy, few centres (26%, n = 8) conducted the sting challenge. About half of centres provided the patients with an adrenalin auto-injector both at the time of initial diagnostics and at the end of treatment. More than half (55%, n = 17) used antihistamines in all patients. Almost half (45%, n = 14) declared to stop treatment with ß-blockers and almost one fourth (23%, n = 7) discontinued angiotensin-converting-enzyme inhibitors. CONCLUSIONS: In the most important procedures, there is a very high compliance with the guidelines. In the areas where the guidelines are not precise, we observed a large spread of results.

Studying allergic inflammation and spirometry over menstrual cycles in well-controlled asthmatic women: Changes in progesterone and estradiol affect neither FENO levels nor lung function.

It has been reported that female sex hormones influence on allergic inflammation and ventilation parameters in asthma but conclusions drawn by different researchers are divergent. The aim of our study was to assess the impact of progesterone (Pg) and estradiol (E) on the dynamics of allergic inflammation and spirometry test results in regularly menstruating women with stable allergic asthma. 13 women (28 days menstrual cycle), aged 18-45, taking no hormonal contraceptives, with mild and moderate asthma, without reported exacerbations at the near-ovulation and/or menstruation time, were monitored during two consecutive menstrual cycles. They had 4 visits per cycle (the first day of menstruation was assumed to be day 1 of the cycle; visits were carried out on days: 3-4, 10-11, 13-14 and 23-24). At each visit asthma symptoms, asthma control test (ACT) results, asthma treatment, fractioned nitric oxide (FENO) levels, spirometry test results, Pg and E, levels were analyzed. As a result of the study, no essential variability in FENO values and ventilation parameters' values in the course of menstruation cycle were observed. Negative correlation between FENO values and Pg concentrations was demonstrated (r = 0.27), but no correlation between FENO values and E levels was shown. No relationship between the ACT values and ventilation parameters and the levels of the sex hormones under investigation was detected. We conclude that changing levels of estradiol and progesterone (regardless of the negative correlation of progesterone and FENO values) affect neither the dynamics of allergic inflammation nor pulmonary function in women with stable allergic mild/moderate asthma.

Simplification of intradermal skin testing in Hymenoptera venom allergic children.

BACKGROUND: The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. OBJECTIVE: To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. METHODS: We reviewed the medical records of 91 children and 121 adults. RESULTS: Bee venom allergy was exposure dependent, regardless of age (P < .001). Atopy was more common in children (P = .01), whereas cardiovascular comorbidities were present almost exclusively in adults (P = .001). In the bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kUA/L; interquartile range, 11.30-66.30 kUA/L) compared with adults (5.10 kUA/L; interquartile range, 2.03-8.30 kUA/L) (P < .001). Specific IgE levels for culprit insect venom were higher in bee venom allergic children compared with the wasp venom allergic children (P < .001). In adults, intradermal tests revealed higher sensitivity, accompanied by larger area of skin reactions, regardless of type of venom. At concentrations lower than 0.1 µg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). CONCLUSION: The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations.

Sex-related clinical aspects in insect venom anaphylaxis.

Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects' venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable.

Safety and Efficacy of VIT against Wasp Venom in Ultra-Rush Protocols in Patients Older Than 60 Years.

BACKGROUND: Allergen immunotherapy remains a widely recognized and widely used method for the treatment of selected allergic diseases. Currently, according to the European Academy Of Allergy and Clinical Immunology (EAACI) guidelines, venom immunotherapy (VIT) may be considered for patients over 60. Nevertheless, no separate studies have confirmed the efficacy and safety of this therapy. This study aimed to evaluate the short-term effectiveness of VIT against wasp allergens in an ultra-rush protocol for older patients compared to young patients. METHODS: Among the 113 patients included in this study, 51 were older than 60 years (Group A), and 62 formed the control "young group" (age range: 18-35 years). All patients were desensitized to wasp venom using the ultra-rush protocol according to Muller and aqueous solutions of vaccines containing wasp venom. A basophil activation test (Basotest, Orpegen Pharma, Germany) and intracutaneous tests with dilutions of wasp allergen and specific IgE to extract wasp venom were performed at the start and after six months of VIT. The safety of VIT was assessed on the basis of the international Mueller scale. RESULTS: One hundred and eleven patients with confirmed wasp allergies completed six months of VIT: 51 participants over 60 years of age (Group A) and 60 young people (Group B). No systemic adverse reactions were observed during the VIT induction phase. However, large local reactions were noted in 17% of older patients and 20% of young patients at a similar level (p > 0.05). During maintenance VIT, two mild grade I systemic reactions were confirmed in young patients. These symptoms resolved spontaneously. There were no such reactions in older patients. The effectiveness of VIT was tested using BAT. There was a statistically significant reduction in CD63 reactivity in 86% of patients in Group A, and a comparable and substantial decrease in 84% of young patients in Group B. According to the BAT test, the mean reductions in the area under the curve (AUC) after six months of VIT were significant (p < 0.05) and comparable between Groups A and B: -6.52 vs. 7.21. CONCLUSIONS: VIT against wasp venom is safe and effective in short-term observation, and is comparable to that used for young patients.

Elderly Patients and Insect Venom Allergy: Are the Clinical Pictures and Immunological Parameters of Venom Allergy Age-Dependent?

Insect venom is one of the most common triggers of anaphylaxis in the elderly population. Venom immunotherapy (VIT) remains the only treatment for Hymenoptera venom allergy (HVA). However, little is known about the differences in indication for VIT in the group of patients aged 60 years and older. The objective of this study was to assess the clinical and diagnostic differences of HVA in elderly patients. The study compared data from patients aged ≥ 60 (N = 132) to data from patients aged from 11 to 60 years (N = 750) in terms of HVA severity, comorbidities, and immunological parameters, namely, intradermal testing (IDT), specific IgE (sIgE) levels against extracts and major allergenic molecules, and serum tryptase level (sBT). The severity of systemic HVA (I-IV Müller scale) did not differ between adults and seniors. However, the severity of cardiovascular reactions (IV) increased with age, while the frequency of respiratory reactions (III) decreased. No differences were found in the immunological parameters of sensitization IDT, venom-specific IgE concentrations, or sIgE against Api m 1, 2, 4, 5, and 10 between patients below and above 60 or 65 years of age. Differences were noted for sIgE against Ves v1 and Ves v5; they were higher and lower, respectively, in seniors. In the seniors group, sBT levels were higher. Elevated tryptase levels, along with the aging process, can represent a risk factor within this age category. Nevertheless, advanced age does not influence the immunological parameters of immediate HVA reactions, nor does it impact the diagnosis of HVA.

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.

Fractioned exhaled nitric oxide (FE(NO)) is not a sufficiently reliable test for monitoring asthma in pregnancy.

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial. The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy. We monitored 72 pregnant asthmatics aged 18-38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled. FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2 ppb; 9.5 ppb-188.3 ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6 ppb; 6.2 ppb-103.4 ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameter's considerable intrasubject variability, regardless of the degree of asthma control.

Detection of Chlamydophila pneumoniae antigens in patients with chronic cough.

The aim of this study was to analyze the rate of Chlamydophila pneumoniae infection in adults with symptoms of chronic cough. The study was conducted in 83 hospitalized patients aged 18-67 suffering of chronic cough. The control group consisted of 20 healthy age-matched subjects without any respiratory symptoms. Bacteriological tests on the presence of Chlamydophila pneumoniae antigen were performed in throat swabs by indirect immunofluorescence technique using monoclonal antibodies labeled with fluorescein isothiocyanate. The rate of Chlamydophila infected patients was examined in relation to age and gender. The Chlamydophila pneumoniae antigen was detected in 15 (18 %) out of the 83 patients; about equally in both genders. Furthermore, we found that the patients aged 28-37 constituted the age group that most frequently tested positive for Chlamydophila pneumoniae. Unraveling the presence of Chlamydia infection in chronic cough patients enables to introduce a timely implementation of effective therapy and thus can prevent distant complications.

[The long-term variability of FeNO in pregnant asthmatic women with controlled asthma]. / Dlugoterminowa zmiennosc stezenia tlenku azotu w wydychanympowietrzu (FeNO) w astmie kontrolowanej u kobiet w ciazy.

INTRODUCTION: Fractional exhaled nitric oxide (FeNO) is considered as a useful, noninvasive marker of airway inflammation in asthma and allergic rhinitis. It has also been suggested that anti-inflammatory treatment guided by monitoring of exhaled NO could improve overall asthma control. However, long-term intra-subject variability of this parameter as well as the rate of its change, which can be clinically significant, have not been established yet. The aim of our study was to assess the long-term variability of FeNO in pregnant asthmatic women with controlled asthma. MATERIAL AND METHODS: Pregnant, non-smoking women with asthma were recruited between 3 and 6 months of gestation. Exhaled nitric oxide (FeNO) spirometric parameters were measured, and the asthma control test (ACT) was completed during monthly visits up to delivery. The data of 26 subjects with well-controlled asthma during pregnancy (ACT values within the range 20-25, normal spirometric parameters, stable treatment) were analysed. The variability of FeNO values was assessed using the variation coefficient CV (standard deviation x 100%/arithmetic mean). RESULTS: The median level of FeNO coefficient of variation (CV) was: 33.8% (range 11.3 to 121.9) in all subjects with well-controlled asthma during pregnancy. There were no statistically significant differences in FeNO variability between groups of patients who had at least one measurement of FeNO higher than 50ppb (39%; 11.8-121.9%) and those with all FeNO values below 50ppb (29.9%; 11.3-71.8%), as well as between atopic (35.7%; 11.8-121.9%) and nonatopic (24.2%; 11.3-71.8%) pregnant asthmatics (p = 0.95 and 0.11, respectively). CONCLUSIONS: High long-term variability of fractional exhaled nitric oxide values revealed in pregnant women with well-controlled asthma indicates that changes in this parameter should be interpreted with caution while being used for asthma treatment monitoring.

Monitoring of NSAIDs adverse effects based on spontaneous reports from Wroclaw regional adverse drug reactions monitoring center.

The mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) in majority of cases is responsible for adverse reactions of these therapeutic agents. Obtaining post-registration information on adverse drug reactions (ADRs) by means of the Yellow Card System is a significant element in the process of enhancing the safety of pharmacotherapy. The aim of the study was to analyze ADRs of NSAIDs (anti-inflammatory and analgesic drugs) reported to the Regional Centre for the Monitoring of Adverse Drug Reactions (RCMADR) in Wroclaw in the years 2007-2009. The study material included 232 spontaneous reports, which were sent by physicians and pharmacists to the RCMADR in Wroclaw, out of which 80 concerned mentioned drugs. Analysis of the obtained data revealed a relationship between the incidence and kind of ADRs and the age, gender of the patients, centre from which the data were supplied, geographical region of administered medication. A significant role of post-registration monitoring of adverse drug reactions during therapy with antiinflammatory and analgesic drugs was confirmed in view of geographically conditioned differences affecting the profile of instituted therapy and the source of information. With an increasing global use of these medications, only thorough monitoring of every adverse reaction, encouraging spontaneous reports, as well as analysis at a global level may increase the knowledge on adverse drug reactions and enable correction of the safety profile of every drug from this group.

Influenza and Other Prophylactic Vaccination Coverage in Polish Adult Patients Undergoing Allergen Immunotherapy-A Survey Study among Patients and Physicians.

Vaccines against infectious diseases may raise safety concerns in patients undergoing allergen immunotherapy (AIT). The objective of our study was to investigate influenza vaccine and other selected prophylactic vaccines coverage in patients treated with AIT and the attitude of physicians towards vaccinations in this group of patients. We conducted a questionnaire-based study among patients undergoing AIT and physicians. The patients' survey evaluated influenza and other prophylactic vaccines coverage. The physicians' survey assessed their experience and opinions on prophylactic vaccinations during AIT. In total, 176 patients (aged 18−79 years) and 120 doctors filled the questionnaires. Patients were assigned to two groups­inhaled allergens group (n = 101) and insect venoms group (n = 68). The number of patients who received any dose (36% and 45%, p = 0.26), as well as two or more doses (17% and 22%, p = 0.43) of influenza vaccine was comparable between two groups. However, in both groups there was a significant (p < 0.0001) decrease in influenza vaccine uptake after the beginning of AIT. Patients from the inhaled allergens group declared a higher tetanus vaccine rate (41% vs. 19%, p = 0.004). The groups did not differ in the pneumococcal and tick-borne encephalitis vaccination coverage. A majority of doctors believe that prophylactic vaccinations in patients undergoing AIT are safe and effective (96% and 94%, respectively); however, as many as 87% of them identify with the need to create clear recommendations regarding vaccinating patients undergoing AIT. Prophylactic vaccine coverage is not satisfactory among Polish adult patients undergoing AIT. Polish doctors are convinced of the validity of prophylactic vaccinations during AIT.

Component-Resolved Evaluation of the Risk and Success of Immunotherapy in Bee Venom Allergic Patients.

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of molecular IgE (Immunoglobulin E) responses are associated with an increased risk of systemic side effects and/or the treatment's inefficacy. The study group numbered 64 bee venom allergic patients (BVA) who received venom immunotherapy modo ultra-rush (VIT-UR), (f/m: 32/32, mean age 43.4 ± 17.2). In total, 54.84% of them manifested allergic reactions of grades I-III (acc. to Mueller's scale), while 48.66% manifested reactions of grade IV. In all the patients, IgE against bee venom extract, rApi m 1 and tryptase (sBT) were assessed. In 46 patients, assessments of IgE against rApi m 2, 3, 5, 10 were also performed. BVA patients manifesting cardiovascular symptoms (SYS IV0) showed higher levels of both sIgE-rApi m 5 (p = 0.03) and tryptase (p = 0.07) than patients with SYS I−III. Systemic adverse events during VIT with bee venom were more frequent in the induction phase than in the maintenance phase: 15.22% vs. 8.7%. In BVA patients who experienced systemic adverse events during VIT, higher concentrations of sIgE-rApi m 5 (p < 0.05), rApi m 1 (p = 0.009), and sBT (p = 0.019) were demonstrated. We conclude that higher levels of sIgE against rApi m 1, rApi m 5, and tryptase many constitute a potential marker of the severity of allergic reactions and therapeutic complications that can occur during VIT with bee venom.

Monitoring of molecular profiling of allergen-antibody responses in HDM-immunotherapy patients.

Among the potential hazards of HDM immunotherapy (AIT) with HDM allergenic extracts is the possible initiation of de novosensitizations caused by a lack of complementarity between a given HDM vaccine's content and a patient's molecular sensitization profile. To investigate whether immunotherapy with HDM extracts affects changes in the profile of sensitizations to allergens contained in the extract and whether neosensitizations occur. Serum samples from patients with HDM allergies (N=63) who received 1 year of treatment with subcutaneous AIT were tested for allergen-specific IgE (sIgE) reactivity to 7 microarrayed HDM allergen molecules (Der p 1, 2,10,11,23; D far 1 and 2) with ImmunoCAP. The HDM non-AIT patients (N=22) who did not receive immunotherapy constituted the study's control group. The obtained data were analysed at baseline and after 6 and 12 months. In the HDM-AIT group, no neosensitizations after 6 and 12 months of immunotherapy were reported. Conversely, in the HDM non-AIT group, only neosensitizations to Der p 10 were observed. In the study group, sIgE levels against the HDM extract of D. pteronyssinus, D. farinae, rDer p 1, rDer p 2 and Der f 2 decreased after 12 months of AIT (p< .05). SIgE levels against Der f 1, Der p 10, 11 and 23 remained unchanged in the course of 12 months of immunotherapy. In patients with allergic rhinitis with or without concomitant HDM-induced asthma treated with HDM AIT for 12 months, no neosensitizations related to the examined HDM molecules were observed.

Atopy and Multisensitizations in Specific IgE Microarrays and Their Impact on Severe Asthma.

(1) Asthma is a chronic inflammatory airway disease. Around 3-10% of patients experience severe refractory asthma. These patients with high symptom intensity and frequent exacerbations present a challenge for allergologists. Their allergic vs. non-allergic profile might be different from the standard asthmatic group and this difference is vital in qualifying for anti-IgE biologicals. The aim of the study was to analyze multiple sensitizations in patients with severe asthma and assess their impact on the course of the disease. (2) Forty-two patients with severe asthma according to GINA were enrolled. They experienced at least two exacerbations during the past year and had uncontrolled asthma despite high inhaled steroid use. A microarray serum Alex test (allergen-specific IgE to 295 extracts and components) was performed together with Complete Blood Count tests, the Asthma Control Questionnaire (ACQ), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), and spirometry. (3) There were 29 female and 13 male patients. The patient mean age was 50.4 (22-70). In 25 (60%) patients, inhalant sensitizations were detected. In 9 (21%) cases, a new perennial allergen was discovered that might enable anti-IgE treatment in the future. In the entire studied group, 8 patients (19%) would still not qualify for anti-IgE, anti-IL4, or anti-IL5 treatment. A linear regression analysis revealed that a Canis familiaris allergen (Can f 1) correlated with worse asthma control in ACQ. An Aspergillus allergen (Asp f 6) correlated negatively with Forced Expiratory Volume in one second (FEV1). (4) The study presents the usefulness of the ALEX test in 21% of patients with severe asthma in qualification for anti-IgE treatment. It highlights the impact of canine and Aspergillus sensitizations on worse control in patients with severe asthma.

Influence of specific immunotherapy on the activity of human T lymphocyte Kv1.3 voltage-gated potassium channels in insect venom allergic patients.

Kv1.3 channels play an important role in T lymphocytes function. CD4(+) and CD4(+)CD25(+) T cells are two broad categories of T cells that are critically involved in the immunoresponse to allergens and that are also a major target for allergen immunotherapy. The aim of the study was to evaluate the effects of venom immunotherapy (VIT) on the activity of Kv1.3. channels on noncultured subsets: CD4(+) and CD4(+)CD25(+) T cells of insect venom allergic patients. Eleven patients with allergic reactions to bee or wasp venoms participated in the study. The patients were provided VIT according to the ultrarush protocol. CD4(+) and CD4(+)CD25(+) T cells were isolated from peripheral blood mononuclear cells of VIT-treated patients by an immunomagnetic method. We used the whole-cell patch clamp technique to investigate the whole potassium chord conductance (gK) of Kv1.3. channels in CD4(+) and CD4(+)CD25(+) T cells of venom-sensitive patients before and during the course of VIT. The conductance of Kv1.3. channels on CD4(+)CD25(+) T cells decreased during the course of VIT. On day 0 it was 0.054 ± 0.07 [nS], and on day 70 it was 0.008 ± 0.09 [nS] (P = 0.03). The observed decrease of the gK of the Kv1.3 channels in the subpopulation of activated T cells may contribute to T cell tolerance and functional unresponsiveness of these cells to allergen in the early stages of VIT.