Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Results of an allergy educational needs questionnaire for primary care.

It is well recognized that knowledge of allergic conditions is suboptimal in primary care. The Primary Care Interest Group of the European Academy of Allergy and Clinical Immunology undertook an educational needs survey to better understand what they were and how best to meet them, in the primary care environment. An electronic questionnaire was devised and distributed as widely as possible. A total of 2226 people from 63 countries opened the e-questionnaire of which 692 provided evaluable responses. In total, 81% were medical doctors with 299 possessing additional qualifications. Self-declared gaps in knowledge were expressed for most manifestations of allergy with a correspondingly high self-expressed educational need. The preferred learning modalities were online guidelines (69.6%) and courses (68.8%) followed closely by workshops (68%), structured online modules (63.9%) and small local working groups (59.75%). Podcasts and webinars scored poorly with only 25% expressing these as preferred learning modes although there was an age gradient. The preferred electronic platform was the personal computer (82.6%). A better understanding of the needs of primary care should help guide the design of educational initiatives to meet those needs.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. RESULTS: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. CONCLUSIONS: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.

Clinical contraindications to allergen immunotherapy: an EAACI position paper.

Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with ß-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.

Contraindications to immunotherapy: a global approach.

BACKGROUND: Recommendations on contraindications to allergen immunotherapy (AIT) have been independently developed by National and International Societies/Academies. AIT contraindications are mainly based on case reports, case-series, or experts' opinion, while evidence-based information is limited. The aim of the present review was to describe existing guidelines on contraindications to AIT and to highlight differences between them. MAIN BODY: An extended review of the literature regarding contraindications to AIT for respiratory allergy and venom hypersensitivity was performed. Furthermore, Societies and Academies registered in the World Allergy Organization and EAACI databases, were asked for additional information. Only AIT guidelines published under official auspicies were included. A large heterogeneity among the various recommendations on contraindications was registered. Common contraindications to most of the guidelines were: lack of adherence, pregnancy before the start of AIT, the use of beta-blockers, certain age groups, uncontrolled asthma, autoimmune diseases and malignancies. CONCLUSION: As new data arise, revisions might soon be needed allowing AIT in the cases of patients treated with ACE inhibitors and beta-blockers, in elderly patients and in patients with concomitant autoimmune diseases and neoplasias in remission. The decision to prescribe AIT is always tailor-made, balancing risk vs benefit. Creating globally accepted guidelines would help Allergologists in their decision making.

Trauma resource designation: an innovative approach to improving trauma system overtriage.

BACKGROUND: Effective triage of injured patients is often a balancing act for trauma systems. As healthcare reimbursements continue to decline,1 innovative programs to effectively use hospital resources are essential in maintaining a viable trauma system. The objective of this pilot intervention was to evaluate a new triage model using 'trauma resource' (TR) as a new category in our existing Tiered Trauma Team Activation (TA) approach with hopes of decreasing charges without adversely affecting patient outcome. METHODS: Patients at one Level II Trauma Center (TC) over seven months were studied. Patients not meeting American College of Surgeons criteria for TA were assigned as TR and transported to a designated TC for expedited emergency department (ED) evaluation. Such patients were immediately assessed by a trauma nurse, ED nurse, and board-certified ED physician. Diagnostic studies were ordered, and the trauma surgeon (TS) was consulted as needed. Demographics, injury mechanism, time to physician evaluation, time to CT scan, time to disposition, hospital length of stay (LOS), and in-hospital mortality were analyzed. RESULTS: Fifty-two of the 318 TR patients were admitted by the TS and were similar to TA patients (N=684) with regard to gender, mean Injury Severity Score, mean LOS and in-hospital mortality, but were older (60.4 vs 47.2 years, p<0.0001) and often involved in a fall injury (52% vs 35%, p=0.0170). TR patients had increased door to physician evaluation times (11.5 vs 0.4 minutes, p<0.0001) and increased door to CT times (76.2 vs 25.9 minutes, p<0.0001). Of the 313 TR patients, 52 incurred charges totaling US$253 708 compared with US$1 041 612 if patients had been classified as TA. CONCLUSIONS: Designating patients as TR prehospital with expedited evaluation by an ED physician and early TS consultation resulted in reduced use of resources and lower hospital charges without increase in LOS, time to disposition or in-hospital mortality. LEVEL OF EVIDENCE: Level II.

Evaluation of circulating vascular endothelial growth factor and its soluble receptors in patients suffering from persistent allergic rhinitis.

BACKGROUND: Overexpression and enhanced release of vascular endothelial growth factor (VEGF) have been detected in various types of allergic inflammation, including asthma. AIM: To further evaluate the pattern of systemic release of VEGF in atopic allergy, free circulating VEGF was measured in patients with persistent allergic rhinitis (PAR). METHODS: The concentrations of VEGF and its soluble receptors (sVEGF-R1 and VEGF-R2) in plasma were measured in patients with PAR sensitized to house dust mites and the healthy subjects. RESULTS: No significant differences were found between PAR patients and healthy subjects with respect to plasma levels of VEGF and its receptors. CONCLUSIONS: It seems that free circulating VEGF may not be elevated in PAR patients. Moreover, on the basis of the present study as well as the earlier ones, it appears likely that systemic release of VEGF varies among patients with distinct clinical manifestation of atopy; may depend on severity/activity and the extent of inflammatory response.

Influence endothelin ETA receptor antagonist--BQ-123--on changes of endothelin-1 level in plasma of rats with acute vasospasm following subarachnoid hemorrhage.

Endothelin participates in regulating the vascular tone, and it is also involved in the pathogenesis of vasospasm following subarachnoid hemorrhage (SAH). Endothelin-1 (ET-1) induced cerebral vasospasm is inhibited by ETA receptors specific antagonist-BQ-123; this protects the neurons from ischemic damage. The present study evaluates the dynamics of ET-1 concentration changes in the plasma of rats in the acute phase of vasospasm after SAH, which was induced by administering 100 microliters non-heparinized fresh autologous arterial blood into the brain cisterna magna (CM). The study also assesses the effect of blocking ETA receptors on the changes in ET-1 level. BQ-123, the specific ETA receptors antagonist, was administered to cerebrospinal fluid (CSF) through a cannula inserted into CM; the antagonist--40 nmol in 50 microliters CSF--was given 20 minutes prior to SAH. In the control group, sham SAH was induced by administering 100 microliters artificial CSF (aCSF) to CM. ET-1 concentration in the plasma of rats in the acute phase of vasospasm was assessed by radioimmunoassay 30 and 60 minutes after SAH or sham SAH. It has been showed that both SAH and sham SAH cause significant increase in the ET-1 concentration (p < 0.05) in the rat plasma after 30 minutes; the concentration returns to an initial value after following 30 minutes, which may suggest that ET-1 released binds to its receptors in the acute phase of the vasospasm. On the other hand, in the two groups of rats with blocked ETA receptors there was a significant rise in ET-1 concentration 30 minutes after SAH or sham SAH, and a still further rise was observed 60 minutes after the procedure. The rise was significantly higher in animals with SAH (p < 0.05). The dynamics of the ET-1 concentration changes observed in rats with blocked ETA receptor suggests that SAH is an ET-1 production stimulator significantly more potent than other factors assessed in the study, such as a rise in the intracranial pressure resulting from administering aCSF to CM. Blocking ETA receptors makes it impossible for the ET-1 released to bind to the receptors, which may be a factor preventing the occurrence of cerebral vasospasm following SAH.

Immune complexes IgE/IgG in airborne allergy: increase during pollen season.

In the present study we addressed the question of IgE/IgG immune complex serum level in 92 patients with respiratory allergy in relation to their clinical status. Twenty patients with allergy to insect stings and 22 healthy volunteers were also investigated. IgE/IgG immune complexes and IgG anti-IgE antibodies were estimated using double antibody solid-phase immunoassays in IgG serum fractions isolated by protein A affinity chromatography or in fractions obtained by Sephacryl S-300 gel filtration. Three people (14%) from the control group, two patients (10%) with insect allergy and 41 patients (45%) from the group with airborne allergy exhibited an increased serum level of IgE/IgG immune complexes (chi2, p <0.05). IgG anti-IgE serum level was also significantly higher in the examined group of patients with airborne allergy than in the control group. None of the factors analyzed, including the kind of allergic disease, the type of inhalant allergen (pollen or house dust antigens), the severity of allergy judged from the frequency and intensity of symptoms for 1 year preceding blood sampling and the symptoms exhibited during blood sampling, showed a statistically significant relation to the level of IgE/IgG immune complexes or IgG anti-IgE, when the whole group of patients with respiratory allergy was analyzed. A distinct difference between patients investigated during and outside of the pollen season was found in patients with isolated pollen allergy. The latter exhibited an increase of IgE/IgG immune complexes (57% vs. 29%) significantly more often, which indicates the possible involvement of IgE/IgG immune complexes in the pathogenesis of pollen allergy.

A rare case of intravascular coagulation after honey bee sting.

A patient presented with coagulation problems a few days after honeybee sting. The purpuric skin changes developed on the legs and buttocks. She manifested signs of hypotension with disturbance of consciousness. Allergen-specific IgE serum levels against honey bee venom antigens reached >17.5 kU/l. The platelet count was 33,000/ml . The prothrombin index decreased to 28%, prothrombine time was prolonged to 34". Fibrin degradation products were present in serum. After 10 day treatment the girl improved, but necrotic skin changes required further plastic surgery. Honeybee sting problems should be taken into account as a cause of coagulation problems.

Platelet aggregation in IgE-mediated allergy with elevated soluble Fc epsilon RII/CD23 level.

In 25 house dust mite-sensitive patients with perennial allergic rhinitis, an analysis of platelet aggregation tests (dual-channel aggregometer, Chronolog Corp, 345 model) induced by adenosine diphosphate (ADP) was carried out. The levels of total serum IgE specific antibodies against Dermatophagoides pteronyssinus and the soluble form of the low affinity IgE receptor (sFc epsilon RII/sCD23) were estimated as well. The study was carried out in a dynamic state, before and after 2 years of treatment with specific immunotherapy. We observed a significantly diminished platelet aggregation response, which partially improved after treatment. The results of this study suggest that platelet hyporesponsiveness might be involved in the pathogenesis of house dust mite hypersensitivity.

[Evaluation of bone loss in postmenopausal women during the first 5 years after menopause]. / Ocena utraty tkanki kostnej u kobiet w ciagu pierwszych 5 lat po menopauzie.

Aim of the trial was estimation of the degree of bone loss in first 5 years of menopause. 184 postmenopausal women were evaluated. Bone status was assessed by using quantitative ultrasound. Both parameters decreased in term of 1-5 years of menopause, what was especially expressed in first 2-3 years of menopause. Densitometric values were lower in comparison to British, French and Japan women population. Also dynamic of bone loss was greater in Polish women population. Results confirm necessity of early prevention of osteoporosis in postmenopausal women.

[Viral infections, allergy and bronchial asthma]. / Zakazenia wirusowe, alergia i astma oskrzelowa.

In the paper the current views on interrelationship between viral infections and bronchial asthma and allergy are reviewed. Data of incidence of viruses in bronchial tissue and development of cellular and molecular mechanisms in mucosa are presented.

[Behavior of some parameters of the autonomic nervous system in patients with bronchial asthma]. / Zachowanie sie niektórych parametrów ukladu autonomicznego u chorych na astme oskrzelowa.

It is well known that beta receptors play a crucial role in maintaining tonus of smooth muscles of the airways. In this study the authors have indirectly assessed the beta receptor performance by measuring serum cAMP levels before and after intravenous administration of Salbutamol. Parallelly the activity of the parasympathetic system was analysed. The observed increases of serum cAMP dependent on different duration of the disease. The age of the patients did not affect the observations. These results may imply that disturbances of beta-2 receptors function are acquired in patients with bronchial asthma.

[The role of prevention in osteoporosis]. / Znaczenie prewencji w osteoporozie.

Prevention of osteoporosis plays the major role in care of osteoporotic patients because of limited efficacy of therapy in late stages of the disease. Prevention ought to begin the whole life and its main aims are: achieve maximal peak bone mass, stabilize bone mass in adults and slow bone loss in elderly. The most important are: long-term high diet calcium consumption, physical activity avoiding secondary reasons of osteoporosis and wide use of hormone replacement therapy.

[Immunomodulation with bacterial vaccines in chronic respiratory diseases]. / Immunomodulacja szczepionkami bakteryjnymi w przewleklych chorobach ukladu oddechowego.

The therapeutic approach of immunoprophylaxis by means of bacterial lysate, rybosomal extracts etc. in chronic respiratory diseases and immunomodulatory mode of action of bacterial vaccines are presented.

[Evaluation of bradykinin levels and activation of Tame-esterase in Bronchial alveolar lavage fluid of patients with bronchial asthma]. / Ocena stezenia bradykininy i aktywnosci TAME-esterazy w popluczynach oskrzelowo-pecherzykowych u chorych na astme oskrzelowa.

Airway inflammation is a prominent feature of chronic airway disease as asthma and chronic bronchitis. Multiply cells released mediators and neurotransmitters which are likely to be involved in their origination. The purpose of this study was to establish the levels of kinin, albumin, TAME-esterase activity in BAL fluid of symptomatic and asymptomatic asthmatic patients and to determinate the relationship among mediators. There were significant increases in the mean concentrations of kinin, HSA, TAME-esterase activity in BAL fluid from patients with asthma, chronic bronchitis, compared with the controls (p < 0.005). Kinin mean concentration was in asthmatics 5313, 2 ng/ml, in chronic bronchitis patients 6796.2 ng/ml, versus 468.1 ng/ml in control group. TAME-esterase activity in investigated group was as follow asthmatics 12666 cmp, CB 15131, 3 cmp, versus 3695, 5 cmp in controls. We observed good correlation of kinin and TAME-esterase with HSA in BAL fluid suggest vascular origin of the mediators. The presence of kinins, TAME-esterase in BALs from symptomatic asthmatics and patients with chronic bronchitis provide strong evidence that kinins are involved in this group of lower airway diseases.

[The influence of patient age on the effectiveness of bronchodilators]. / Wplyw wieku chorych na efektywnosc leków rozkurczajacych oskrzela.

The beta adrenergic receptors are exposed to variety of factors modulating their activity. We analyzed the sensitivity to Salbutamol in asthmatic patients divided into three group (I-30 yr; II-30-50 yr; III-50 yr). The effectiveness of beta adrenergic receptors was assessed by means of estimation of plasma cAMP level before and after Salbutamol infusion. We didn't found any significant differences in plasma cAMP changes between investigated group of patients.