Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry.

BACKGROUND: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. METHODS: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years). RESULTS: Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up. CONCLUSIONS: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.

Clinical Application of In Vitro Tests for COVID-19 Vaccine Delayed Hypersensitivity Diagnostics.

Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study.

A Challenge for Allergologist: Application of Allergy Diagnostic Methods in Mast Cell Disorders.

Primary and secondary mast cell activation syndromes (MCAS) can occur in patients with mastocytosis. During the past few years our knowledge about the pathogenesis and disease-triggering mechanisms in MCAS and mastocytosis have increased substantially. Whereas mastocytosis is characterized by an accumulation of neoplastic (clonal) mast cells (MC) in various organ systems, MCAS is defined by a massive and systemic activation of these cells. Mast cells are crucial effector cells in allergic diseases, thus their elevated number and activation can cause severe anaphylactic reactions and MCAS in patients with mastocytosis. However, these cells may also degranulate spontaneously or degranulate in response to non-allergic triggers leading to clinical symptoms. In mastocytosis patients, such symptoms may lead to the diagnosis of a primary MCAS. The diagnosis of a concomitant allergy in mastocytosis patients is challenging. In these patients, a mixed form (primary and secondary) of MCAS may be diagnosed. These patients may also suffer from life-threatening anaphylactic reactions when exposed to allergens. In these cases, the possibility of severe side effects of in vivo provocations can sometimes also limit diagnostic evaluations. In the current article, we discuss the diagnosis and management of patients suffering from mastocytosis and concomitant MCAS, with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies.

IFNG, FCER1A, PCDHB10 expression as a new potential marker of efficacy in grass pollen allergen-specific immunotherapy.

INTRODUCTION: Allergen-specific immunotherapy (AIT) is the core treatment in allergic rhinitis and asthma. Although widely used, some patients do not benefit from treatment and there is no efficacy objective marker. AIM: To define the profile of gene transcripts during the build-up phase of AIT and their comparison to the control group and then search for a viable efficacy marker in relation to patient symptoms. MATERIAL AND METHODS: AIT was administered in 22 patients allergic to grass pollen. Analysis of 15 selected transcript expression was performed in whole blood samples taken before AIT (sample A) and after reaching the maintenance dose (sample B). The control group included 25 healthy volunteers (sample C). The primary endpoint was Relative Quantification. The gene expression analysis was followed by clinical evaluation with the use of Allergy Control Score (ACS). RESULTS: Comparison between samples A and B of gene expression showed a significant increase in IFNG expression (p = 0.03). In relation to the control group, pretreatment samples from patients showed higher levels of AFAP1L1 (p = 0.006), COMMD8 (p = 0.001), PIK3CD (p = 0.027) and TWIST2 (p = 0.0003) in univariate analysis. A generalized linear regression model was built according to the Bayesian Information Criterion based on the IFNG, FCER1A and PCDHB10 expression pattern for prediction of the AIT outcome. The model showed a correlation in predicted and observed changes in ACS. CONCLUSIONS: There is a significant change in the expression of IFNG during the build-up phase of AIT. The authors propose an in vitro model of AIT efficacy prediction for further validation.

COMMD8 changes expression during initial phase of wasp venom immunotherapy.

BACKGROUND: Hymenoptera venom allergy (HVA) is of great concern because of the possibility of anaphylaxis, which may be fatal. Venom immunotherapy (VIT) is the only disease-modifying treatment in HVA and, although efficient, its mechanism remains partially unknown. Gene expression analysis may be helpful for establishing a proper model of tolerance induction during the build-up phase of VIT. The present study aimed to analyze how the start of VIT changes the expression of 15 selected genes. METHODS: Forty-five patients starting VIT with a wasp venom allergy were enrolled. The diagnosis was established based on anaphylaxis history (third or fourth grade on the Mueller scale) and positive soluble immunoglobulin E and/or skin tests. Two blood collections were performed in the patient group: before and after 3 months of VIT. One sample was taken in the control group. Gene expression analysis was performed using a reverse transcriptase-polymerase chain reaction with microfluidic cards and normalized to the 18S housekeeping gene. RESULTS: Commd8 was the only gene that changed expression significantly after the start of VIT (p = 0.012). Its expression decreased towards the levels observed in the healthy controls. Twelve out of 15 genes (commd8, cldn1, cngb3, fads1, hes6, hla-drb5, htr3b, prlr, slc16a4, snx33, socs3 and twist2) revealed a significantly different expression compared to the healthy controls. CONCLUSIONS: The present study shows that commd8 changes significantly its expression during initial phase of VIT. This gene might be a candidate for VIT biomarker in future studies.

Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine.

Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT-mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT-mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT-mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.

Genetic and Epigenetic Aspects of Atopic Dermatitis.

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.

Smoking history is negatively associated with allergen specific immunotherapy efficacy: a retrospective analysis.

INTRODUCTION: Allergen specific immunotherapy (AIT) is the only treatment modifying the course of the disease in patients allergic to airborne allergens. It has been proven to be effective in allergic populations, however individual patients vary in terms of response to the therapy. AIM: To assess the factors that might affect the efficacy of AIT. MATERIAL AND METHODS: Patients treated with AIT for grass pollen or house dust mites were included. The efficacy of AIT was assessed with the use of Allergy Control Score (ACS), performed before and at least 1 year after AIT. The following variables were assessed as potential risk factors for a worse response to AIT: age, gender, type of allergy, type of allergen, type of vaccine, type of AIT and smoking history. RESULTS: The study group consisted of 145 subjects.AIT was effective in the entire group; the mean ACS results decreased from 21.14 to 14.41 points (p< 0.0001). No differences in efficacy in terms of assessed risk factors were found, except for smoking history (ACS change in the smoking group was smaller: from 21.8 to 18.1 points; p = 0.09, OR = 0.323; 95% CI: 0.11-0.88; p = 0.02). CONCLUSIONS: Smoking history may affect AIT outcomes.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part I: Treg properties and functions.

Regulatory T cells (Treg) can be divided into two types: the natural cells (tTreg), which arise in the thymus, and the induced cells (iTreg), which are produced in peripheral tissues during immune response. The most recently published studies indicate that the supervisory functions of these cells are weakened in the pathogenesis of autoimmune and neoplastic diseases of the skin. This may be a result of the domination of other immune cells in the skin, such as Th1/Th17/Th22 and Tc1 type in psoriasis and Th2 in atopic dermatitis. The excessive activity of Treg cells can lead to immunosuppression and decrease in the number of Th1 cells, which promote the development and progression of skin cancers. In the case of cutaneous T-cell lymphomas, there are suggestions that tumor progression is associated with the acquisition of the suppressor phenotype of malignant cells. There is genetic background of Treg dysfunction in skin disorders. This article describes the types and functions of Treg cells.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part III: Polymorphisms of genes involved in Tregs' activation and function.

Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of several skin diseases like psoriasis, atopic dermatitis, systemic lupus erythematosus, cutaneous T-cell lymphomas, and skin cancer and is also important in rheumatoid arthritis, diabetes and other autoimmune diseases. In this review, we will summarize the role of mutations and/or polymorphisms of genes involved in Tregs development, and functions in the pathogenesis of selected skin diseases.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis.

Regulatory FOXP3+ T cells (Tregs) constitute 5% to 10% of T cells in the normal human skin. They play an important role in the induction and maintenance of immunological tolerance. The suppressive effects of these cells are exerted by various mechanisms including the direct cytotoxic effect, anti-inflammatory cytokines, metabolic disruption, and modulation of the dendritic cells function. The deficiency of Treg cells number or function are one of the basic elements of the pathogenesis of many skin diseases, such as psoriasis, atopic dermatitis, bacterial and viral infections. They also play a role in the pathogenesis of T cell lymphomas of the skin (cutaneous T cell lymphomas - CTCL), skin tumors and mastocytosis. Here, in the second part of the cycle, we describe dysfunctions of Tregs in selected skin diseases.

Asthma prevalence and risk factors analysis in Tricity university students' group.

INTRODUCTION: Asthma is the most prevalent chronic disease in a young and middle age population worldwide. It is also one of the main reasons for the lost working days and lost days at school. Several epidemiological surveys have evidenced an increase in the prevalence of asthma in Poland. This trend is further evident in urban areas such as Tricity (Gdansk, Sopot, Gdynia). The aim of the study was to assess the prevalence of the disease as well as the risk factors affecting the university student population. MATERIAL AND METHODS: Two surveys were distributed electronically to students of the four major universities in Tricity. The first survey contained nine questions concerning asthma diagnoses and symptoms. The second survey, which evaluated the occurrence of identified risk factors, was sent to students who answered the first survey. Asthmatics also received an Asthma Control Test (ACT). The results were analyzed using the Statistica 10 software. Study group consisted of 1380 students: 1031 (75%) women and 349 (25%) men; the average age was 22.2. RESULTS: Asthma was diagnosed in 138 students (9.6%), additionally 76 students (5.5%) reported asthmatic symptoms; however, these students had no previous diagnoses. Asthma tended to occur more frequently in students living in poorly maintained houses (19%) (p = 0.06), in contrast to those living in a normal environment (10%). According to their ACTs, 81% of diagnosed patients reported that their asthma was well-controlled. CONCLUSIONS: Asthma is becoming an important issue for Tricity students. Educational activities aimed at raising university students' awareness regarding asthma treatment and control should be implemented.

Cardiac adverse drug reactions to COVID-19 vaccines. A cross-sectional study based on the Europe-wide data.

AIMS: We aimed to analyse serious cardiac adverse drug reactions to COVID-19 vaccines from the Europe-wide EudraVigilance database. METHODS AND RESULTS: In this retrospective, cross-sectional study, the EudraVigilance database was searched to identify suspected serious cardiac postvaccination adverse drug reactions to COVID-19 vaccines. This data was coupled with the number of total vaccine doses administered in the European Economic Area for Comirnaty (Pfizer BioNTech), Spikevax (Moderna), Vaxzevria (AstraZeneca), Jcovden (Janssen), Nuvaxovid (Novavax), products, available from the European Centre for Disease Prevention and Control "Vaccine Tracker" database. The analysis included 772,228,309 administered doses of eligible vaccines from the "Vaccine Tracker" database and 86,051 eligible records of cardiac adverse drug reactions from the EudraVigilance database.The frequency of most of the investigated adverse drug reactions was very rare (<1/10,000 i.e. <100/1,000,000 doses). The lowest risk of any serious cardiac adverse drug reactions was noticed for vaccination with Comirnaty (135.5 per million doses), while Spikevax, Jcovden, Vaxzevria and Nuvaxovid were characterised by higher risk (respectively, 140.9, 194.8, 313.6 and 1065.2 per million doses). The most common complications of vaccinations included syncope, arrhythmia, tachycardia, palpitations, angina pectoris, hypertension, myocarditis, thrombosis and pulmonary embolism. CONCLUSIONS: The risk of serious cardiac adverse drug reactions to COVID-19 vaccines is low and the benefit of active immunisation against that disease seems to outweigh the potential risk of serious postvaccination cardiac adverse drug reactions.

Analysis of Allergy and Hypersensitivity Reactions to COVID-19 Vaccines According to the EudraVigilance Database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine: the development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to COVID-19 vaccines' allergic potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyze the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. METHODS: The total number of administrated vaccine doses was extracted on 5 October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines were extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. RESULTS: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta, and 3.1 for Valneva. The most prevalent reported reactions were edema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. CONCLUSIONS: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

YKL-40 as a possible marker of neutrophilic asthma.

Asthma is a heterogeneous chronic disorder of the airways, with inflammation and bronchial hyperresponsiveness as its major underlying phenomena. Asthmatics vary in terms of inflammation pattern, concomitant pathologies, and factors aggravating the course of the disease. As a result, there is a need for sensitive and specific biomarkers that could facilitate diagnosing asthma as well as phenotyping in everyday practice. Chitinases and chitinase-like proteins (CLPs) seem promising in this field. Chitinases are evolutionarily conserved hydrolases that degrade chitin. In contrast, CLPs bind chitin but do not have degrading activity. Mammalian chitinases and CLPs are produced by neutrophils, monocytes, and macrophages in response to parasitic or fungal infections. Recently, several questions have been raised about their role in chronic airway inflammation. Several studies demonstrated that overexpression of CLP YKL-40 was associated with asthma. Moreover, it correlated with exacerbation rate, therapy resistance, poor control of symptoms, and, inversely, with FEV1. YKL-40 facilitated allergen sensitization and IgE production. Its concentration was elevated in bronchoalveolar lavage fluid after an allergen challenge. It was also found to promote the proliferation of bronchial smooth muscle cells and correlate with subepithelial membrane thickness. Thus, it may be involved in bronchial remodeling. Associations between YKL-40 and particular asthma phenotypes remain unclear. Some studies showed that YKL-40 correlates with blood eosinophilia and FeNO, suggesting a role in T2-high inflammation. Quite the opposite, cluster analyses revealed the highest upregulation in severe neutrophilic asthma and obesity-associated asthma. The main limitation in the practical application of YKL-40 as a biomarker is its low specificity. High serum levels of YKL-40 were also found in COPD and several malignancies, in addition to infectious and autoimmune diseases. To conclude, the level of YKL-40 correlates with asthma and some clinical features in the whole asthmatic population. The highest levels are found in neutrophilic and obesity-related phenotypes. However, due to its low specificity, the practical application of YKL-40 remains uncertain but could be useful in phenotyping, especially when combined with other biomarkers.

Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study.

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78). INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. FUNDING: None.

miRNA profiles change during grass pollen immunotherapy irrespective of clinical outcome.

Background: Subcutaneous immunotherapy (SCIT) is widely used in the treatment of allergic rhinitis (AR). This study aimed to determine the expression of 48 miRNAs in patients with AR undergoing grass pollen SCIT and investigate relations with clinical outcomes. Methodology: Expression of selected miRNAs was determined using RT-PCR in the full blood of 16 patients with AR and seven healthy controls. Results: miR-136, miR-208 and miR-190 were upregulated in the AR group. After 6 months of SCIT, significant downregulation of some proinflammatory miRNAs and upregulation of several miRNAs regulating Th1/Th2 balance were found. No differences were found between good and poor responders. Conclusion: miRNAs may play a regulatory role in SCIT, leading to tolerance induction.

Background: Subcutaneous immunotherapy is widely used in the treatment of allergic rhinitis (AR). MicroRNAs (miRNAs) are small molecules controlling gene expression. Their role in the process of immunotherapy is not yet well understood. This study aimed to investigate the expression of 48 miRNAs in patients with AR undergoing grass pollen immunotherapy and relations between miRNAs and clinical outcomes. Methodology: The expression of selected miRNAs was determined in the blood of 16 patients with AR and seven healthy people. Results: Three miRNAs were found to be overproduced in allergic patients. During immunotherapy, the production of several proinflammatory miRNAs was reduced while those responsible for allergen tolerance were produced in larger amounts. Conclusion: miRNAs may play an important role in immunotherapy, leading to better tolerance of allergens.

Atopy and Multisensitizations in Specific IgE Microarrays and Their Impact on Severe Asthma.

(1) Asthma is a chronic inflammatory airway disease. Around 3-10% of patients experience severe refractory asthma. These patients with high symptom intensity and frequent exacerbations present a challenge for allergologists. Their allergic vs. non-allergic profile might be different from the standard asthmatic group and this difference is vital in qualifying for anti-IgE biologicals. The aim of the study was to analyze multiple sensitizations in patients with severe asthma and assess their impact on the course of the disease. (2) Forty-two patients with severe asthma according to GINA were enrolled. They experienced at least two exacerbations during the past year and had uncontrolled asthma despite high inhaled steroid use. A microarray serum Alex test (allergen-specific IgE to 295 extracts and components) was performed together with Complete Blood Count tests, the Asthma Control Questionnaire (ACQ), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), and spirometry. (3) There were 29 female and 13 male patients. The patient mean age was 50.4 (22-70). In 25 (60%) patients, inhalant sensitizations were detected. In 9 (21%) cases, a new perennial allergen was discovered that might enable anti-IgE treatment in the future. In the entire studied group, 8 patients (19%) would still not qualify for anti-IgE, anti-IL4, or anti-IL5 treatment. A linear regression analysis revealed that a Canis familiaris allergen (Can f 1) correlated with worse asthma control in ACQ. An Aspergillus allergen (Asp f 6) correlated negatively with Forced Expiratory Volume in one second (FEV1). (4) The study presents the usefulness of the ALEX test in 21% of patients with severe asthma in qualification for anti-IgE treatment. It highlights the impact of canine and Aspergillus sensitizations on worse control in patients with severe asthma.

Protocol of safe vaccination against COVID-19 in patients with high risk of allergic reactions.

Background: Sars-CoV-2 infections are hazardous, especially to the elderly and patients with comorbidities. With no efficient treatment available, newly developed vaccines are the only way to change the course of the pandemic. However, reports of allergic reactions resulted in some patients and practicing physicians being concerned about the safety of vaccine administration, particularly in people with severe anaphylactic reactions to multiple or unknown factors in their medical history.This study aimed to develop an allergic work-up protocol based on skin prick tests (SPT), intradermal testing (IDT) and intramuscular provocations, and desensitisation which may contribute to diagnosis and management of anti-COVID-19 vaccine allergy. Methods: Two hundred and eighty-five patients were enrolled. Two hundred and five of them entered the study based on severe anaphylactic reaction to unknown or multiple factors in their medical history which disqualified them for standard treatment. Another 80 patients were enrolled after developing an allergic reaction to the first dose of one such vaccine. In all subjects, SPT and IDT were performed. Serum tryptase was assessed in 79 patients randomly chosen from the study group. Results: Two hundred and seventy-seven patients with negative tests were given a vaccine without complications. Seven patients had positive skin tests. In two cases, tests confirmed Comirnaty allergy, while the other five confirmed solely skin sensitisation with no exposure prior to the study. Six patients with positive tests received titrated challenge using desensitisation protocol with a reasonable tolerance. One patient did not consent to desensitisation and one patient resigned despite negative tests. Overall, 283 (99%) patients were vaccinated using this newly developed protocol. Patients with adverse reactions to the first dose of the vaccine before the study had a significantly lower basal serum tryptase concentration (p = 0.001). Conclusion: Skin tests with anti-COVID-19 vaccines are a useful tool in the vaccination protocol. This protocol enables safe immunisation of high-allergy-risk patients even in cases of positive skin tests.