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.

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.

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.

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.

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.

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.

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.

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.

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.

Concentration of endothelin in plasma and BALF fluid from asthmatic patients.

The bronchoconstrictive peptide endothelin-1 (ET-1) has been demonstrated in the airway epithelial and endothelial cells. In this study we investigated the pathophysiological significance of endothelin-1 in asthma. We addressed the issue by assessing the concentration of ET-1 in plasma and bronchoalveolar lavage fluid (BALF) in patients with a different intensity of asthma. Twenty one asthmatic patients (11 men,10 women) and 6 healthy control subjects (C) were included in the study. Eleven asthmatic patients were classified as moderate persistent asthma (SA), all of them were atopic, and another 10 were mild persistent asthmatics (AA). Lung function tests were carried out in all patients investigated. The ET-1 concentration was determined by an ELISA method in plasma and BALF. We found that the SA patients had the highest level of ET-1 (SA - 11.4 +/-3.6 fmol/ml; AA - 7.1 +/-2.7 fmol/ml; C - 5.6 +/-1.8 fmol/ml) in BALF. The same concerned the ET-1 level in plasma (SA - 27.8 +/-3.8 fmol/ml; AA - 18.1 +/-4.3 fmol/ml; C - 17.3 +/-3.0 fmol/ml). A positive correlation between the plasma ET-1 level and lung function indices was observed. We conclude that the higher levels of ET-1 in more severe asthma suggest that endothelins may contribute to the pathophysiology of the disease, its severity, and the regulation of bronchial tone.

Dyspnea and quality of life in patients with pulmonary fibrosis after six weeks of respiratory rehabilitation.

The aim of the study was to estimate the level of dyspnea and quality of life in patients with pulmonary fibrosis after 6 weeks' respiratory rehabilitation. The study comprised of 31 patients (F/M-12/19) with interstitial lung diseases (21 with idiopathic interstitial pneumonia, 4 with lung fibrosis due to allergic alveolitis, 4 with lung fibrosis due to collagenosis, 2 with lung fibrosis due to silicosis) who successfully finished the rehabilitation program. Each patient underwent an intensive (every day for 30 min) inpatient pulmonary rehabilitation program of an average length of 4 wk, continued later at home for up to 12 wk. The program consisted of respiratory muscle training and bicycle riding to the limits of the patient's tolerance. Dyspnea (MRC, OCD, BDI and Borg scale) and the quality of live (SF-36, St. George's Respiratory Questionnaire) were assessed at the time of admission and discharge. Rehabilitation caused dyspnea sensation to diminish (Borg scale: 2.97 before vs. 2.19 after). Some domains of the quality of life in SF-36 questionnaire (Role-Physical 40.6 vs. 60.2) and St. George's Respiratory Questionnaire (activity: 52 vs. 45, impact 47 vs. 40 and total 47 vs. 42) also were improved compared with the pre-rehabilitation results. We conclude that 12 weeks of combined inpatient and home-based rehabilitation programme improves the quality of live and sensation of dyspnea in patients with interstitial lung disease, despite changes in pulmonary function tests.

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.

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.

Concentration of s-ICAM-1 in nasal polyps tissue.

INTRODUCTION: Polyps are a nasal condition considered to be inflammatory in nature. Pathophysiology of that disorder is not fully known. The role of ICAM-1 in inflammatory and immune response through its involvement in leukocyte adhesion dependent phenomena is proved to be important. The aim of the study was to establish the role of sICAM-1 in the inflammatory process in nasal polyps. MATERIAL AND METHODS: 27 patients (23 males and 4 females) with nasal polyposis and 12 (7 males and 5 females) controls with septal deviation were included in the study. All patients underwent routine surgical treatment (polypectomy, septoplasty). The collected tissues of polyps and nasal mucosa were homogenized, placed in 0.04M EDTA and centrifuged. sICAM-1 concentration in supernatant of polyps and nasal mucosa tissue were determined with the ELISA method (Genzyme, UK). RESULTS: In the polyps tissue we found a significantly higher concentration of sICAM-1 compared to the nasal mucosa of healthy subjects (6.74 +/- 5.31 ng/ml vs 0.28 +/- 0.13 ng/ml; p < 0.001). The elevated concentration of sICAM-1 was positively correlated with total tissue eosinophil count (r = 0.51; p < 0.01) and the duration of the disease (r = 0.628; p < 0.001). No correlation was found between sICAM concentration and the age of the patients subjected to examination. CONCLUSIONS: The increased level of sICAM-1 in polyps tissue indicates the role of the molecule in the development of chronic inflammation and probably in the patophysiology of nasal polyps.

[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.

[The evaluation of atrial natriuretic peptide and endothelin in serum of the patients with non-atopic bronchial asthma during exacerbation]. / Ocena stezen przedsionkowego peptydu natriuretycznego i endoteliny u chorych na astme oskrzelowa nieatopowa podczas zaostrzenia choroby.

The aim of the study was to evaluate concentrations of atrial natriuretic peptide (ANP) and endothelin in blood serum of the patients with nonatopic bronchial asthma in the exacerbation phase and during non-symptomatic period. The study included 20 patients with nonatopic bronchial asthma (10 women and 10 men, mean age 34.2) treated in the Allergological Outpatient Clinic in Zabrze (Poland). A control group consisted of 5 healthy volunteers without atopy. The study consisted of evaluation of the ANP and endothelin in blood serum by radioimmunoassay and by functional respiratory tests. It was shown that ANP concentrations during bronchial asthma exacerbation were two times lower than in the same group examined in the remission phase (7.8-13.7 pmol/ml, p < 0.05). At the time of bronchospastic symptoms occurrence, the concentrations of endothelin were statistically significant and higher than in the non-symptomatic group (11.6-6.9 pmol/ml, p < 0.05). In the examined group the reverse proportion relation between concentrations of the studied peptides in blood serum was observed r = -0.56, p < 0.05 according to Spearman test.

[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.

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.

[Levels of endothelin-I in bronchoalveolar fluid of patients with selected respiratory tract diseases]. / Zawartosc Endoteliny-I w popluczynach oskrzelowo-pecherzykowych u chorych na wybrane choroby dróg oddechowych.

UNLABELLED: Endothelin-I (ET-I) levels in BALF of symptomatic (n = 7) and asymptomatic (n = 10) asthmatic patients, sarcoidosis (n = 10), allergic alveolitis (n = 6) and healthy volunteers (n = 6) was evaluated. In all patients BALF level of endothelin-I was assessed by radioimmunoassay. We observed that patients with symptomatic asthma had more increased amounts of ET-I in BALF in comparison with asymptomatic asthmatics, patients with sarcoidosis, allergic alveolitis and control group. CONCLUSIONS: 1. Presence of ET-I in BALF indicates that this peptide is involved in the pathogenesis of bronchial asthma, sarcoidosis and allergic alveolitis. 2. Endothelin-I is involved in bronchial smooth muscle contraction.