Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

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.

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.

Safety of Ultrarush Venom Immunotherapy: Comparison Between Children and Adults.

BACKGROUND: The ultrarush protocol is an attractive approach in the buildup phase of venom immunotherapy (VIT-UR). However, the degree of risk of VIT-UR in children remains unknown. The objective of this study was to compare the safety of VIT-UR in children and adults. METHODS: We performed a study based on prospectively gathered medical records of children and adults with hymenoptera venom allergy treated with VIT-UR in 3 allergy centers in Poland. RESULTS: The study population comprised 134 children (mean [SD] age, 12.6 [3.7] years; males, 70.1%) and 207 adults (mean age, 42.4 [14.0] years; males, 47.8%). The number of children in the subgroups of bee venom (BV) allergy and wasp venom (WV) allergy were comparable, although sensitization to WV was more predominant in the adult group (70.1%). Skin reactivity to both venoms was more common in children than in adults (P < .001); however, children had higher concentrations of total IgE and specific IgE to BV (both P < .001). Systemic allergic reactions (VIT-SARs) occurred in 6.2% of the patients (3.7% in children and 7.7% in adults; nonsignificant). In adults, SARs occurred more frequently in patients treated with BV than WV extracts (21.4% vs 2.6%; P < .001). The same pattern was observed in children (7.2% vs 0%; P = .058). However, VIT-SARs to BV were less frequent in children than in adults (P = .034). Similarly, no significant relationship was noted between children and adults receiving WV VIT (2.6% vs 0%; nonsignificant). The severity of VIT-SAR did not differ between children and adults. CONCLUSIONS: VIT-UR is safer in children. Age below 18 is not a risk factor for VIT-SARs.

Safety of ultrarush venom immunotherapy: comparison between children and adults

Background: The ultrarush protocol is an attractive approach in the buildup phase of venom immunotherapy (VIT-UR). However, the degree of risk of VIT-UR in children remains unknown. The objective of this study was to compare the safety of VIT-UR in children and adults. Methods: We performed a study based on prospectively gathered medical records of children and adults with hymenoptera venom allergy treated with VIT-UR in 3 allergy centers in Poland. Results: The study population comprised 134 children (mean [SD] age, 12.6 [3.7] years; males, 70.1%) and 207 adults (mean age, 42.4 [14.0] years; males, 47.8%). The number of children in the subgroups of bee venom (BV) allergy and wasp venom (WV) allergy were comparable, although sensitization to WV was more predominant in the adult group (70.1%). Skin reactivity to both venoms was more common in children than in adults (P<.001); however, children had higher concentrations of total IgE and specific IgE to BV (both P<.001). Systemic allergic reactions (VIT-SARs) occurred in 6.2% of the patients (3.7% in children and 7.7% in adults; nonsignificant). In adults, SARs occurred more frequently in patients treated with BV than WV extracts (21.4% vs 2.6%; P<.001). The same pattern was observed in children (7.2% vs 0%; P=.058). However, VIT-SARs to BV were less frequent in children than in adults (P=.034). Similarly, no significant relationship was noted between children and adults receiving WV VIT (2.6% vs 0%; nonsignificant). The severity of VIT-SAR did not differ between children and adults. Conclusions: VIT-UR is safer in children. Age below 18 is not a risk factor for VIT-SARs (AU)

Introducción: Los protocolos ultra rápidos son considerados de utilidad para realizar la fase de inicio de la inmunoterapia con venenos de himenópteros (VIT-UR). La seguridad de estos protocolos VIT-UR en los niños sigue siendo una cuestión debatida. El objetivo de este estudio fue comparar la seguridad de VIT-UR en niños y adultos. Métodos: Estudio prospectivo de seguimiento de la seguridad de la inmunoterapia en niños y adultos regularmente tratados con VIT-UR seguidos en tres unidades de alergia en Polonia. Resultados: En el estudio fueron incluidos un total de 134 niños (edad media de 12,6 años, SD 3,7; varones 70,1%) y 207 adultos (edad media 42,4 años, SD 14,0; 47,8% varones). El número de niños sensibilizados a veneno de abeja (BV) era comparable al de los sensibilizados a veneno de avista (WV), mientras que la sensibilidad al veneno de avispa prevaleció en el grupo de adultos (70,1%). Los niños con hipersensibilidad a venenos (HVA) mostraron menor reactividad cutánea a ambos venenos que los adultos con HVA (p <0,001) pero, por el contrario, en comparación con los adultos presentan concentraciones de IgE sérica total e IgE específica frente a BV (ambas p <0,001). Un 6,2% de todos los pacientes (3,7% de los niños y 7.7% de los adultos, NS) presentaron reacciones alérgicas sistémicas frente a la inmunoterapia con venenos (VIT-SAR). En los adultos, el SARS fueron más frecuentes en los pacientes tratados con BV que los tratados con WV (21,4% frente a 2,6% p <0,001). El mismo patrón se produjo en niños (7,2% vs 0%; p = 0,058). Sin embargo, las VIT-SAR frente a inmunoterapia con BV fueron menos frecuentes en los niños que en adultos (p = 0,034). Del mismo modo la frecuencia de reacciones frente a WV VIT fue menor en niños que en adultos pero sin diferencias significativas (0% vs 2,6%, NS). La gravedad de las VIT-SAR fue similar para niños y adultos. Conclusiones: Los protocolos VIT-UR son más seguros en los niños. Edad menor de 18 años no es un factor de riesgo de VIT-SAR (AU)

Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

OBJECTIVES: We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. PATIENTS AND METHODS: Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. RESULTS: Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. CONCLUSIONS: In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

[Montelukast in treatment mild chronic asthma]. / Montelukast w leczeniu astmy przewleklej lagodnej u dzieci.

UNLABELLED: The efficacy of montelukast, a leukotriene receptor antagonist, in treatment of mild asthma was evaluated. METHODS: Thirty children aged 6 to 14 years with mild persistent asthma (asthma history more than 12 months and > or = 15% FEV1 improvement after inhaled beta 2-agonist in the past, good control of asthma with inhaled cromolyn or budesonide in the last three months) were enrolled. The study included three periods (2 week's each): washout, placebo, and montelukast. Asthma symptoms score (range 0-5) and PEF were estimated twice daily by children. Spirometric parameters FEV1 and MEF50 were measured during three consecutive visits: on the day of study inclusion, on the last day of the placebo and montelukast period. RESULTS: The mean value of asthma symptoms score was significantly lower during the montelukast period in comparison with placebo (p = 0.038). The mean PEF values were significantly higher during the montelukast vs. placebo period (p = 0.0091). Moreover, in the montelukast period, the mean PEF values in the second week were significantly higher than those in the first week (p = 0.003). The mean FEV1 predictive value in the last day of the montelukast period was higher, though not significantly, than on the day of study inclusion and on the last day of the placebo period. A similar change in mean MEF50 values was observed. CONCLUSION: In children aged 6-14 years with mild persistent asthma, montelukast treatment significantly diminishes asthma symptoms and increases mean PEF values comparing to placebo.

Induction of allergy to new aeroallergens during specific immunotherapy (SIT) in grass pollen sensitive patients.

In the group of 50 patients suffering from grass pollen allergy and successfully treated with SIT for three consecutive years, we observed in 5 persons after the end of this treatment the induction of allergy to new allergens (to weeds, mites or tree) manifested by the change of the symptoms season. The induction of the new kind of allergy was confirmed by revealing of the positive skin prick tests to new allergens and by an increase of the specific IgE serum level to them. Despite disappearance of the symptoms of the illness during grass pollen season in all 5 patients we noted the higher total IgE as well as specific to grasses IgE serum level, in comparison to the value at the start of SIT. In the paper the possible mechanisms of this phenomenon are discussed, which seems to be not connected with the natural development of allergy and which confirms once more that during SIT individual changes in humoral and cellular immunity of the patient take place, sometimes very difficult to be predicted. They may among others switch clinical profile of allergy, what indicates that patient during SIT should be under the careful immunological supervision.

[Bronchial asthma: do boys or girls have the highest incidence?]. / Astma oskrzelowa: kto czesciej choruje dziewczeta czy chlopcy?.

The aim of the study was to assess the gender related prevalence of asthma and asthma symptoms in schoolchildren. The survey was performed using standardized ISAAC questionnaire in two age groups: 6-7 yr. (n = 2281; girls 49.7%) and 13-14 yr. (n = 4849; girls 49.8%). It was revealed that in older group the prevalence of ever diagnosed asthma was lower in girls than in boys (2.0% versus 3.3%; odds ratio [OR] = 0.58; p = 0.004). But the prevalence of symptoms: wheeze ever (OR = 1.16; p = 0.056), current wheeze (last 12 mo) (OR = 1.26; p = 0.029), current exercise wheeze (OR = 1.40; p = 0.0008), current night cough (OR = 1.67; p = 0.0001) were higher in girls than in boys. However, in younger group of schoolchildren the prevalence of ever diagnosed asthma and asthma symptoms were higher in boys (5.1% male versus 3.5% female). The girls in comparison to boys revealed lower risk of ever asthma diagnosis (OR = 0.66; p = 0.056) and symptoms: wheeze ever (OR = 0.63; p = 0.0001), current wheeze (OR = 0.69; p = 0.003), current exercise wheeze (OR = 0.59; p = 0.008) and current night cough (OR = 0.70; p = 0.0003).

[Diagnostic value of selected eosinophil activity parameters in children with hay fever]. / Wartosc diagnostyczna wybranych parametrów aktywnosci granulocytów kwasochlonnych u dzieci z alergia pylkowa.

Seventy three children aged 5-15 years were involved in the survey. Thirteen children suffered from seasonal allergic rhinitis (SAR), fourty four children suffered from seasonal allergic rhinitis and bronchial asthma (SAR-A), sixteen patients with no allergic symptoms were treated as a control group (CG). All the patients were examined twice: in July--during the highest pollen season and in December--period free of pollen. During each examination samples were collected to measure the following parameters: blood eosinophilia, serum eosinophil cationic protein (ECP) and eosinophil percentage in the nasal mucosal smears (nasal eosinophilia). In statistical analysis values of all parameters in pollen and free of pollen seasons were compared the groups of patients as well as within the groups. In winter values of: blood eosinophilia, ECP and nasal eosinophilia were statistically higher in SAR-A group in comparison to SAR group and CG, simultaneously there was no statistical difference in blood eosinophilia and ECP between SAR group and CG. In the pollen season the highest values of all parameters were observed in SAR-A group. SAR group values were higher in comparison to control group. The difference between groups was significant. Both groups of allergic patients (SAR, SAR-A) revealed statistically higher values of all measured parameters in pollen season in comparison to winter. In CG only level of ECP was significantly higher in July than in December.

[Pollen allergy. I. Pathophysiology and clinic]. / Alergia pylkowa. Czesc I: Patofizjologia i klinika.

Pollen allergy constitutes about 1/3 of allergic disorders in people. Clinical manifestation of the disease depends on the natural allergen exposure. Main clinical symptoms are dealing with conjunctivitis, allergic rhinitis, bronchial asthma. Permanent increase in number of pollen sensitive patients observed during last years, depends on atopic genetic background, as well as natural allergen exposure and other environmental factors. Better understanding of pathophysiological mechanisms underlying the disease and opportunity to monitor the degree of allergen exposure seems to play the vital role in current treatment and prophylaxis. The allergic reaction takes place in two phases--the first one--early response (EAR) depends on IgE receptors binding which results in mast cell and basophils activation, in the second one--the late response (LAR), adhesive molecules, eosinophils, lymphocytes and their products, as well as neuropeptides are engaged. Also homeostasis of respiratory tract mucous membrane plays an important role at this stage.

[Pollen allergy. II. Diagnosis and treatment]. / Alergia pylkowa. Czesc II: Diagnostyka i leczenie.

Pollen allergy--one of the most frequent allergies in people is diagnosed by combined data, derived from patient's history together with in vitro and in vivo examinations. Basic in vivo examinations consist of skin prick tests with chosen allergens, functional tests of upper and lower respiratory tract, specific as well as non-specific nasal and bronchial challenge tests. The major role among in vitro examinations is played by those tests, which confirm atopic background of the disease (total and specific IgE). Other tests, like those for T-cell function and tests for effector cells activation, have secondary importance. Patients who are asymptomatic but endangered by the possibility of symptoms occurrence, are treated by primary prevention. Complex therapeutical approach consists of causal treatment (identification of allergens, specific immunotherapy), secondary prevention and symptomatic pharmacology.

[Value of selected parameters for monitoring efficacy of specific immunotherapy in allergic disorders]. / Wartosc wybranych parametrów dla monitorowania skutecznosci swoistej immunoterapii w przebiegu schorzen alergicznych.

Prevention, pharmacotherapy and specific immunotherapy are used as methods to treat patients with allergic disorders of respiratory system. SIT as a method of controlled supply of allergen, releases immunological mechanisms related to humoral, cellular and effector organic response. Role of those mechanisms and type of changes, taking place can be monitored with given immunological parameters. Most convincing proof of effectiveness of desensitisation, is diminishing of manifestation of clinical symptoms. In patients treated with obvious therapeutical progress, tolerance of increased dose of allergen was noted.

Congenital stridor.

Fifty-two infants and children with stridor were examined. The median age was 5 months and the boy/girl ratio was 2:1. Fiberoptic bronchoscopy was performed when other diagnostic methods had failed to establish the origin of stridor. The most common cause of stridor was laryngomalacia, which was found in 34 children (65%). The most common form of laryngomalacia was due to large, floppy arytenoid cartilages; this was observed twice as often as other forms of laryngomalacia and boys suffered from this abnormality more than twice as often as girls. Children with laryngomalacia had significant weight (24%) and height (8%) deficits in comparison with the normal healthy population (P < 0.001). In all but four patients with laryngomalacia, blood gases were within normal limits. In 18 children (35%) stridor was not caused by laryngomalacia. This group showed significant etiologic heterogeneity. However, identification of the cause of stridor in these patients is important because specific treatment can be offered and prognosis depends on the type and cause of the anatomical and functional abnormality present.

[Foreign bodies in respiratory tracts of children treated at the Institute of Pediatrics in Krakow during the years 1987-1991]. / Ciala obce w drogach oddechowych u dzieci leczonych w Instytucie Pediatrii w Krakowie w latach 1987-1991.

Foreign bodies aspirated into respiratory tract may produce severe lung damage and threaten life. We have analysed retrospectively symptoms, physical findings, chest roentgenograms and bronchoscopy reports in 20 children with foreign body aspiration. Boys dominated in this group. Foreign body aspiration often accompanied by coughing, wheezing and vomiting. In chest X-ray examination it was revealed unilateral body trapping and obstructive emphysema. Foreign body aspiration should be considered in children with prolonged respiratory tract problems even when no adequate history is present and with negative chest roentgenograms.