Serological profiling reveals hsa-miR-451a as a possible biomarker of anaphylaxis

BACKGROUND. There is a need to support the diagnosis of anaphylaxis by objective markers. miRNAs are promising noncoding RNA species that may serve as serological biomarkers, but their use in diagnosing anaphylaxis has not been systematically studied to our knowledge. We aimed to comprehensively investigate serum biomarker profiles (proteins, lipids, and miRNAs) to support the diagnosis of anaphylaxis. METHODS. Adult patients admitted to the emergency room with a diagnosis of anaphylaxis (<3 hours) were included. Blood samples were taken upon emergency room arrival and 1 month later. RESULTS. Next-generation sequencing of 18 samples (6 patients with anaphylaxis in both acute and nonacute condition, for 12 total samples, and 6 healthy controls) identified hsa-miR-451a to be elevated during anaphylaxis, which was verified by quantitative real-time PCR in the remaining cohort. The random forest classifier enabled us to classify anaphylaxis with high accuracy using a composite model. We identified tryptase, 9 alpha,11 beta-PGF2, apolipoprotein A1, and hsa-miR-451a as serological biomarkers of anaphylaxis. These predictors qualified as serological biomarkers individually but performed better in combination. CONCLUSION. Unexpectedly, hsa-miR-451a was identified as the most relevant biomarker in our data set. We were also able to distinguish between patients with a history of anaphylaxis and healthy individuals with higher accuracy than any other available model. Future studies will need to verify miRNA biomarker utility in real-life clinical settings

EAACI Task force Clinical epidemiology of anaphylaxis: experts’ perspective on the use of adrenaline autoinjectors in Europe

Background Worldwide, guidelines recommend the use of adrenaline autoinjectors (AAIs) for self-medication in patients who experience severe allergic reaction. The European Medical Agency recommends the prescription of two AAIs, which should be carried by patients at all times. The European Academy of Allergy and Clinical Immunology guidelines propose to prescribe a second AAI under some defined conditions. In the present study, we aimed to examine the adherence to these guidelines and prescription behavior of allergy experts regarding the number of AAIs prescribed for a given patient. Methods A standardized questionnaire was applied to the participants of the 5th International Conference of the Network of Online Registration for Anaphylaxis (NORA e. V.). Twenty-six experts (medical doctors with at least 2 years of experience in the field of anaphylaxis) answered the questions regarding the number of autoinjectors prescribed and the reasons influencing their decisions. Results Sixty-eight percent of the experts usually prescribed one AAI, while 32% prescribed two. The pediatricians and physicians with less experience tended to prescribe two autoinjectors more frequently. The experts were more likely to prescribe two adrenaline autoinjectors if the patient was a child, had a previous severe reaction, had mastocytosis, asthma, cardiovascular disease, or high body weight, or lived far from the emergency department. Conclusion Our data confirm the lack of consensus regarding the number of AAIs to prescribe. Despite the European Medical Agency recommendation, the majority of allergy experts prescribed one autoinjector per patient. However, under distinct circumstances (e.g. mastocytosis, asthma, excess body weight, a history of severe anaphylaxis, or restricted access to immediate emergency), experts tended to prescribe more AAIs, which is in accordance with the European Academy of Allergy and Clinical Immunology guidelines

Refractory anaphylaxis: Data from the European Anaphylaxis Registry

Refractory anaphylaxis (unresponsive to treatment with at least two doses of minimum 300 μg adrenaline) is a rare and often fatal hypersensitivity reaction. Comprehensive data on its definition, prevalence, and risk factors are missing. Using the data from the European Anaphylaxis Registry (11,596 cases in total) we identified refractory anaphylaxis cases (n = 42) and analyzed these in comparison to a control group of severe anaphylaxis cases (n = 4,820). The data show that drugs more frequently elicited refractory anaphylaxis (50% of cases, p < 0.0001) compared to other severe anaphylaxis cases (19.7%). Cases elicited by insects (n = 8) were more often due to bees than wasps in refractory cases (62.5 vs. 19.4%, p = 0.009). The refractory cases occurred mostly in a perioperative setting (45.2 vs. 9.05, p < 0.0001). Intramuscular adrenaline (as a first line therapy) was administered in 16.7% of refractory cases, whereas in 83.3% of cases it was applied intravenously (significantly more often than in severe anaphylaxis cases: 12.3%, p < 0.0001). Second line treatment options (e.g., vasopression with dopamine, methylene blue, glucagon) were not used at all for the treatment of refractory cases. The mortality rate in refractory anaphylaxis was significantly higher (26.2%) than in severe cases (0.353%, p < 0.0001). Refractory anaphylaxis is associated with drug-induced anaphylaxis in particular if allergens are given intravenously. Although physicians frequently use adrenaline in cases of perioperative anaphylaxis, not all patients are responding to treatment. Whether a delay in recognition of anaphylaxis is responsible for the refractory case or whether these cases are due to an overflow with mast cell activating substances—requires further studies. Reasons for the low use of second-line medication (i.e., methylene blue or dopamine) in refractory cases are unknown, but their use might improve the outcome of severe refractory anaphylaxis cases

Foodborne transmission of bovine spongiform encephalopathy to nonhuman primates

Risk for human exposure to bovine spongiform encephalopathy (BSE)-inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received >5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7-5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7-10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown

Systematic review of measurement properties of questionnaires measuring somatization in primary care patients

Objective The aim of this review is to critically appraise the evidence on measurement properties of self-report questionnaires measuring somatization in adult primary care patients and to provide recommendations about which questionnaires are most useful for this purpose. Methods We assessed the methodological quality of included studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. To draw overall conclusions about the quality of the questionnaires, we conducted an evidence synthesis using predefined criteria for judging the measurement properties. Results We found 24 articles on 9 questionnaires. Studies on the Patient Health Questionnaire-15 (PHQ-15) and the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale prevailed and covered the broadest range of measurement properties. These questionnaires had the best internal consistency, test-retest reliability, structural validity, and construct validity. The PHQ-15 also had good criterion validity, whereas the 4DSQ somatization subscale was validated in several languages. The Bodily Distress Syndrome (BDS) checklist had good internal consistency and structural validity. Some evidence was found for good construct validity and criterion validity of the Physical Symptom Checklist (PSC-51) and good construct validity of the Symptom Check-List (SCL-90-R) somatization subscale. However, these three questionnaires were only studied in a small number of primary care studies. Conclusion Based on our findings, we recommend the use of either the PHQ-15 or 4DSQ somatization subscale for somatization in primary care. Other questionnaires, such as the BDS checklist, PSC-51 and the SCL-90-R somatization subscale show promising results but have not been studied extensively in primary care. © 2017 Elsevier Inc

Anaphylaxis in Elderly Patients—Data From the European Anaphylaxis Registry

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more.Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed.Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p &lt; 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p &lt; 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p &lt; 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p &lt; 0.001) were absent. Most strikingly, a loss of consciousness (33%, p &lt; 0.001) and preexisting cardiovascular comorbidity (59%, p &lt; 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p &lt; 0.001) and hospitalization was more often required (60 vs. 50%, p &lt; 0.001).Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome

Tolerance induction through early feeding to prevent food allergy in infants with eczema (TEFFA): rationale, study design, and methods of a randomized controlled trial

BACKGROUND: Up to 8% of all children in industrialized countries suffer from food allergies, whereas children with atopic eczema are affected considerably more frequently. In addition, the type and starting time of weaning foods seem to influence the development of food allergies. However, data from interventional studies on weaning are controversial. The aim of this randomized-controlled clinical trial is to investigate, whether an early introduction of hen's egg (HE), cow's milk (CM), peanut (PN), and hazelnut (HN) in children with atopic eczema can reduce the risk for developing food allergies in the first year of life. METHODS: This is a protocol for a randomized, placebo controlled, double blind, single-center clinical trial. One hundred fifty infants with atopic eczema at 4-8 months of age will be randomized in a 2:1 manner into an active group that will receive rusk-like biscuit powder with HE, CM, PN, and HN (initially approximately 2 mg of each food protein) for 6-8 months or a placebo group, whose participants will receive the same rusk-like biscuit powder without HE, CM, PN, and HN on a daily basis. During the interventional period, the amount of allergens in the study product will be increased three times, each after 6 weeks. All study participants who are sensitized to HE, CM, PN, or HN at the end of the interventional period will undergo an oral food challenge to the respective food in a further visit. Primary endpoint is IgE-mediated food allergy to at least one of the four foods (HE, CM, PN or HN) after 6-8 months of intervention (i.e., at around 1 year of age). Secondary endpoints include multiple food allergies, severity of eczema, wheezing, and sensitization levels against food allergens. DISCUSSION: This clinical trial will assess whether an early introduction of allergenic foods into the diet of children with atopic eczema can prevent the development of food allergies. This trial will contribute to update food allergy prevention guidelines. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016770 . Registered on 09 January 2020