Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry.

BACKGROUND: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach. OBJECTIVE: This study aimed to evaluate the phenotype and risk factors of VIA. METHODS: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]). RESULTS: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis. CONCLUSION: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving ß-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA.

The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs.

CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary glands, stomach, liver, pancreas, intestines, and kidneys). We focus on the importance of CXCL1 on implantation and placentation as well as on human pluripotent stem cells. We also show the significance of CXCL1 in selected diseases of the abdominal organs, including the gastrointestinal tract and oral cavity (periodontal diseases, periodontitis, Sjögren syndrome, Helicobacter pylori infection, diabetes, liver cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), HBV and HCV infection, liver ischemia and reperfusion injury, inflammatory bowel disease (Crohn's disease and ulcerative colitis), obesity and overweight, kidney transplantation and ischemic-reperfusion injury, endometriosis and adenomyosis).

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).

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.

BACKGROUND: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. METHODS: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. RESULTS: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. CONCLUSIONS: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

Rhinitis as a cause of respiratory disorders during pregnancy.

Rhinitis is a common disease of women during pregnancy. It can start in almost any gestational week and disappears after delivery. The main symptoms are sneezing, nasal congestion or running nose. The diagnosis is usually based on history, physical examination, blood tests, and exclusion of the other more common types of rhinitis. The etiology remains to be clarified. The rhinitis may be caused by numerous substances and hormones secreted during pregnancy (PGH, VIP, estrogen, progesterone). They lead to changes in the nasal mucosa in the form of increased activity of serous-mucous glands and increase of their vasculature. The best treatment is using saline irrigations, exercise, and mechanical alar dilators. The nasal decongestants provide only temporary relief. The aim of this study was to evaluate the prevalence of pregnancy rhinitis. The study was conducted on 117 pregnant women in the province of the West Pomerania in 2009-2010. The information was obtained from interviews, questionnaires, and data contained in pregnancy records. About 39% of pregnant women suffered from pregnancy rhinitis. Most such ailments were found during 13th and 21st week of gestation. Doctors should pay more attention to symptoms which result from pregnancy rhinitis, which are reported by their patients. The quality of prenatal care understood as an education of pregnant women as far as pregnancy rhinitis is concerned, is much insufficient. Pregnancy rhinitis significantly affects quality of life of pregnant women and, as a result, it may affect fetal development.

Idiopathic Anaphylaxis? Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland.

The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature where as many as 41% of all cases are idiopathic anaphylaxis. Since the introduction of new diagnostic methods such as molecular diagnostics (MD) in our centre, the percentage of idiopathic anaphylaxis in the Anaphylaxis Register has significantly decreased. The purpose of this study was to identify possible causes of idiopathic anaphylaxis in patients with a history of moderate to severe anaphylactic reactions. After using MD, the causative agent was found in another 29 people. The proportion of people with idiopathic anaphylaxis in the Registry decreased from 9.2% to 3.5%. There were no significant differences in the incidence, although men appear to be slightly more common in primary idiopathic anaphylaxis. The mean age of primary idiopathic anaphylaxis was 40 years, but this was as high as 51 for anaphylaxis with alpha-gal allergy. Exercise may or may not be present as a cofactor despite its established role, e.g., in wheat-dependent exercise-induced anaphylaxis (WDEIA). In most of the analyzed cases, i.e., 70%, the reaction took place within an hour. The longest time interval from exposure to the development of symptoms is in the case of alpha-gal allergy; in this analysis, it was at least 5 h after ingestion of the so-called "red meat". Patients are not aware of the disease, or further attacks cannot be prevented. As many as 80% had idiopathic anaphylaxis prior to visiting the centre, and 80% developed anaphylaxis after visiting the centre, which emphasizes the need to not stop the medical team in their search for the causes. As many as 93% of cases required medical intervention, of which adrenaline was used only in 34.5%, antihistamines in 86%, systemic glucocorticosteroids (sCS) in 75%, and fluids in 62% of cases. A total of 83% of patients received an emergency kit for self-administration. Idiopathic anaphylaxis can be resolved as known-cause anaphylaxis after a thorough medical history and, if possible, without exposing the patient after using appropriate, modern in vitro diagnostic methods, including molecular diagnostics. The diagnosis of idiopathic anaphylaxis should extend the diagnosis to include alpha-gal syndrome, LTP syndrome and WDEIA.

Comorbidities and Cofactors of Anaphylaxis in Patients with Moderate to Severe Anaphylaxis. Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland.

Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction that is still rarely diagnosed. For safety reasons, patients should visit an allergologist to identify potential causes and cofactors of this reaction. This paper presents the analysis of data from the Anaphylaxis Registry gathered over ten years at the Allergy Clinic, Pomeranian Medical University (PMU). A questionnaire-based survey was used for patients visiting the Allergy Clinic to identify potential augmentation factors/comorbidities and/or cofactors of anaphylaxis in patients with a history of moderate to severe anaphylaxis. The registry comprised patients with grade II or higher anaphylaxis. The gathered data concerned chronic comorbidities (cardiovascular diseases, respiratory diseases, and others), recurrence of anaphylaxis, and potential cofactors in anaphylaxis. In the analyzed group, the incidence rate of anaphylaxis was the highest for women aged 19-60 years. Most common comorbidities in patients with moderate to severe anaphylaxis included: cardiovascular diseases, respiratory tract diseases, features of atopy, and thyroid diseases. More than 30% of drug-induced reactions were anaphylactic reactions due to the re-exposure to the same drug, which points to the need for educational initiatives in this area. The incidence rate of anaphylaxis induced by Hymenoptera stings was comparable in patients who had a previous generalized reaction and those who had good tolerance to the previous sting. It is important to take these cofactors into consideration when evaluating patients with anaphylaxis as they may play a role in future anaphylactic reactions.

A new formulation of fluticasone propionate/salmeterol in a metered-dose inhaler (MDI HFA) allows for the reduction of a daily dose of corticosteroid and provides optimal asthma control - A randomized, multi-center, non-inferiority, phase IV clinical study.

BACKGROUND: Improvement of the delivery method of inhaled corticosteroids and subsequent dose reduction can minimize the risk of unfavorable outcomes while providing optimal asthma control. OBJECTIVE: This randomized, multi-center, non-inferiority, phase IV clinical study compared the efficacy and safety of a new formulation of fluticasone propionate/salmeterol (250 µg/50 µg, twice daily) administered in a metered-dose inhaler hydrofluoroalkane (MDI HFA) with a dry-powder inhaler (DPI) containing fluticasone propionate/salmeterol (500 µg/50 µg, twice daily). METHODS: Adults with asthma (n = 231) were randomly assigned to either the study group (treated for 12 weeks with fluticasone propionate/salmeterol MDI HFA) or a control group (treated for 12 weeks with fluticasone propionate/salmeterol DPI). Asthma symptoms, exacerbations, short-acting ß2-agonist (SABA) use, physical activity, lung function, and general health status were assessed during four study visits. RESULTS: Compared with the reference drug, the study drug decreased the incidence of daytime and night-time asthma symptoms, asthma exacerbations, self-administration of SABA, and the limitation of physical activity. Comparable improvement in peak expiratory flow ([MDI HFA] from 6.2 ± 0.2 to 6.6 ± 0.2 l/s vs. [DPI] from 6.0 ± 0.2 to 6.9 ± 0.2 l/s; p > 0.05), forced expiratory volume in one second, and forced vital capacity were obtained in both groups. Significantly lower incidence of hoarseness was observed in the study group ([MDI HFA] 0.0% vs. [DPI] 2.8%; p = 0.0267); no major differences were found for other adverse events. CONCLUSIONS: Fluticasone propionate/salmeterol (250 µg/50 µg, twice daily) MDI HFA provides optimal asthma control and is non-inferior to fluticasone propionate/salmeterol (500 µg/50 µg, twice daily) DPI.

Wheat Anaphylaxis in Adults Differs from Reactions to Other Types of Food.

BACKGROUND: Wheat is one of the most commonly consumed foods and a known elicitor of anaphylaxis in children and adults. Reactions in adults are often cofactor dependent and characterized by a prolonged time between food intake and the onset of symptoms making the diagnosis of wheat anaphylaxis challenging. OBJECTIVE: To characterize a cohort of patients with the history of wheat anaphylaxis to better understand this atypical phenotype of anaphylaxis. METHODS: Data from the European Anaphylaxis Registry from 2007 to 2019 (n = 10,636) including 250 patients (213 adults and 37 children) with a history of anaphylaxis caused by wheat were analyzed. RESULTS: Wheat was the most common food elicitor of anaphylaxis in adults in the registry in Central Europe. Reactions to wheat in adults were frequently associated with exercise as a cofactor (82.8%) and partially delayed (57.5%). Only 36.9% of patients had atopic comorbidities, which was uncommonly low for adult patients allergic to other kinds of foods (63.2%). Anaphylaxis to wheat presented frequently with cardiovascular symptoms (86.7%) including severe symptoms such as loss of consciousness (41%) and less often with respiratory symptoms (53.6%). The reactions to wheat were more severe than reactions to other foods (odds ratio [OR] = 4.33), venom (OR = 1.58), or drugs (OR = 2.11). CONCLUSIONS: Wheat is a relevant elicitor of anaphylaxis in adults in Central Europe. Wheat anaphylaxis is highly dependent on the presence of cofactors and less frequently associated with atopic diseases compared with other food allergies. More data on mechanisms of wheat-induced anaphylaxis are required to develop preventive measures for this potentially life-threatening disease.

Evaluation of spirometry values in relation to beta-2-adrenergic receptor gene polymorphism.

INTRODUCTION: The vagus nerve plays a special role in the control of respiratory system activity which represents the parasympathetic part of the autonomic nervous system. A small bronchial innervation by the sympathetic system also is observed, and there is a significant expression of adrenergic receptors, in particular ß⊂2 receptors, in the airways. The development of genetics and molecular biology allows for a detailed study which can clarify the essential elements in the pathogenesis of many types of lung disease, as well as the physiological phenomena - bronchial smooth muscle tone and their contractile mechanism. MATERIAL AND METHODS: The study involved 148 healthy male volunteers aged 20-26. In all subjects, gene polymorphism at nucleotide position 46 and 79 of ß⊂2-adrenergic receptor (ß⊂2-ADR) was assessed. According to the gene polymorphism data, we divided the whole examined population of males into 6 groups for further studies. Moreover, in all the subjects, we performed spirometry testing to verify their pulmonary functions. RESULTS: The basic values of spirometry tests in all subjects were in the range of normal values. The frequency of different genotypes in the gene polymorphism of the ß⊂2-adrenergic receptor at nucleotide positions 46 and 79 were typical for the Caucasian population. Analysis of the output values of spirometry, conducted in the particular groups based on their genotype, showed significant inter-group differences in the selected spirometry tests. CONCLUSIONS: Our results may be useful in explaining the differences in the measured values of spirometric indices in healthy subjects in relation to the polymorphism of ß⊂2-ADR, and may also contribute to the verification of standards for spirometric indices for this selected group of young males in the Polish population.

Clinical Manifestations and Causes of Anaphylaxis. Analysis of 382 Cases from the Anaphylaxis Registry in West Pomerania Province in Poland.

Anaphylaxis is most commonly defined as an acute, severe, potentially life-threatening systemic hypersensitivity reaction. Current expert consensus has defined anaphylaxis as a serious reaction that is rapid in onset and can be fatal, and is a severe, potentially life-threatening systemic hypersensitivity reaction that is still rarely diagnosed. For safety reasons, patients should visit an allergologist to identify potential causes of this reaction. There are no data from other health care centres in Poland presenting characteristics of anaphylactic reactions. Clinical manifestations of anaphylaxis should be analysed, because some patients (10-30%) with anaphylaxis can present without cutaneous findings. This lack of skin/mucosa involvement can lead to misdiagnosis or delayed diagnosis of anaphylaxis. Objectives-to gather epidemiological data on anaphylactic reactions, to identify clinical manifestations of anaphylaxis (organ systems involved), to present diagnostic methods useful for the identification of anaphylaxis triggers, and most importantly, to find causes of anaphylaxis. In this retrospective analysis, we used a questionnaire-based survey regarding patients visiting the Clinical Allergology Department, Pomeranian Medical University (PMU) in Szczecin, between 2006 and 2015. The registry comprised patients with grade II (Ring and Messmer classification) or higher anaphylaxis. Patients with grade I anaphylaxis (e.g., urticaria) were not included in the registry. The incidence of anaphylaxis was higher in women. Clinical manifestations included cutaneous and cardiovascular symptoms, but more than 20% of patients did not present with cutaneous symptoms, which may create difficulties for fast and correct diagnosis. Causes of anaphylaxis were identified and confirmed by means of detailed medical interview, skin tests (STs), and measurement of specific immunoglobulin E (sIgE) and tryptase levels. In the analysed group, the most common cause of anaphylaxis (allergic and nonallergic) was Hymenoptera stinging (wasp), drugs (nonsteroidal anti-inflammatory drugs, NSAIDs) and foods (peanuts, tree nuts, celery). The incidence of anaphylaxis is low, but because of its nature and potentially life-threatening consequences it requires a detailed approach. Comprehensive management of patients who have had anaphylaxis can be complex, so partnerships between allergy specialists, emergency medicine and primary care providers are necessary. Monitoring its range is very important to monitor changes in allergy development.

[Physiological and pathological consequences of a presence of germ line stem cells in adult tissues]. / Konsekwencje fizjologiczne i patologiczne wystepowania komórek linii zarodkowych w doroslych tkankach.

Various therapheutic strategies employing stem cells have been proposed as the alternative, effective methods for therapy of multitude diseases, difficult to treat using standard, well-established methods. Advancing regenerative medicine, which is becoming a novel branch of clinical medicine, has high hopes of stem cells which could be used in treatment of injuried organs such as myocardium after heart infarction, brain after stroke, spinal cord after mechanical injury as well as in treatment of diabetes and Parkinson disease. Application of embryonic stem cells, harvested from developing embryos, is highly controversial. Hence, the stem/primitive cells isolated from adult tissuses are considered to be an optimal source of cells for therapy. Recently our research team has isolated a population of very primitive stem cells from adult tissues (very small embryonic-like stem cells - VSELs) that show several embryonic-like features. These cells can become an alternative and more ethical source of the stem cells for therapy when compared to those isolated from the developing embryos.

[Bronchi reaction to the inhaled salbutamol according to the polymorphisms of beta2-adrenergic receptor]. / Reaktywnosc oskrzeli na zastosowany wziewnie salbutamol w odniesieniu do polimorfizmu genu kodujacego receptor beta2-adrenergiczny.

INTRODUCTION: The functioning of beta2-adrenergic receptor (beta2ADR) depends on its isoforms. Polymorphism of the beta2ADR gene has been described, the most frequent being g.46A --> G and g.79C --> G. The reaction of the bronchi to inhaled salbutamol has now been studied in relation to g.46A --> 4G and g.79C --> G polymorphisms. For this purpose, spirometry was done in healthy males aged 20-26 years. MATERIAL AND METHODS: The study group comprised 170 young men who were allocated to six groups according to the beta2ADR genotype determined with PCR: g.46A --> G polymorphism (g.46AA, g.46GG, g.46AG), g.79C --> G polymorphism (g.79CC, g.79GG, g.79GC). Spirometric parameters were measured before and after inhalation of salbutamol. The results of the test were compared in g.46A --> G groups and g.79C --> G groups. RESULTS: Administration of 200 microg of salbutamol significantly increased spirometrc parameters during forced expiration. However, changes were not specific for any genotype. Increase in PEF was significantly higher in g.46AA than g.46GG and in g.79CC than g.79GC genotypes. The distribution of genotypes was typical for the Caucasian population.