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.

Basophil Activation Test Is Inferior to Provocation Test in Diagnosing Aspirin Hypersensitivity.

INTRODUCTION: Diagnostic of aspirin (ASA) hypersensitivity is largely based on provocation tests. However, they have significant limitations including influence of medications, necessity of hospitalization, and safety issues. Basophil activation test (BAT) seems to be a promising in vitro alternative. It has already proven to be a useful tool for diagnosing IgE-mediated allergy to certain food and airborne allergens as well as insects venoms. The aim of the study was to assess performance of BAT in diagnosing aspirin hypersensitivity in comparison with current golden standard (oral provocation test, OPT). METHODS: The study group comprised 148 adult patients with suspicion of aspirin hypersensitivity, including 51 (36%) with chronic urticaria, 73 (51%) with asthma, and 55 (39%) with chronic sinusitis. The control group was 10 healthy adult patients who used NSAIDs during preceding year with good tolerance. BAT with ASA was conducted in all the participants. Additionally, in the study group, OPT was performed with cumulative dose of 1,000 mg of ASA. RESULTS: Out of 148 study group participants, 114 underwent BAT and ASA provocation with conclusive results acquired in both tests. In this group, the threshold for positive BAT was 4.9%. Sensitivity and specificity of BAT were found to be 55.9% and 75%, respectively, with a positive predictive value of 77% and a negative predictive value of 54%. The highest sensitivity (78%) was found in subgroup patients with chronic urticaria, while specificity was highest in the subgroup with chronic respiratory diseases (87%). CONCLUSION: Despite significant advantages of BAT such as safety, no influence of drugs, and objectivity, its performance makes it inferior to current standard in ASA hypersensitivity.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

The Role of Exhaled Breath Condensate in Chronic Inflammatory and Neoplastic Diseases of the Respiratory Tract.

Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic respiratory diseases. Chronic inflammation of the airways leads to an increased production of inflammatory markers by the effector cells of the respiratory tract and lung tissue. These biomarkers allow the assessment of physiological and pathological processes and responses to therapeutic interventions. Lung cancer, which is characterized by high mortality, is one of the most frequently diagnosed cancers worldwide. Current screening methods and tissue biopsies have limitations that highlight the need for rapid diagnosis, patient differentiation, and effective management and monitoring. One promising non-invasive diagnostic method for respiratory diseases is the assessment of exhaled breath condensate (EBC). EBC contains a mixture of volatile and non-volatile biomarkers such as cytokines, leukotrienes, oxidative stress markers, and molecular biomarkers, providing significant information about inflammatory and neoplastic states in the lungs. This article summarizes the research on the application and development of EBC assessment in diagnosing and monitoring respiratory diseases, focusing on asthma, COPD, and lung cancer. The process of collecting condensate, potential issues, and selected groups of markers for detailed disease assessment in the future are discussed. Further research may contribute to the development of more precise and personalized diagnostic and treatment methods.

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.

The influence of nutritional habits, body mass index and intestinal microbiota in mastocytosis on clinical symptoms using conventional culture and next generation sequencing.

BACKGROUND: Mastocytosis is a rare neoplastic disease of the bone marrow associated with the proliferation and accumulation of mast cells in various internal organs, including the gastrointestinal tract. There are few studies describing the gut microbiome of patients with mastocytosis using next generation sequencing supported using traditional culture methods. The aims of the study were, firstly, the determination of nutrition habits, composition of the intestinal microflora and BMI in mastocytosis, and secondly, analysis of mastocytosis severity and symptoms depending on the composition of the intestinal microflora. METHODS: The study included 47 patients with indolent systemic mastocytosis and 18 healthy controls. All participants gave their informed consent to participate in the study. The study consisted of 3 parts: I-clinical assessment, II - examination of the intestinal microflora using the biochemical method, III - 16S rRNA sequencing. RESULTS: The nutrition habits and BMI of mastocytosis patients were similar to controls; however, most patients with mastocytosis had a low dietary vitamin and mineral content. As many as 94.5% of patients had too little fiber intake and mineral content. The most common cause of the abnormal stool test result with traditional culture was a titer of E. coli <106 . The low richness of microbiota species indicated by the Simpson index was observed in mastocytosis, p = 0.04. There were no significant differences in the composition of the intestinal microflora depending on the type of mastocytosis; however, the tryptase level correlated with the amount of Suterella, Barnesiellaceae, Eubacterium, Odoribacter, and Anaerostipes. CONCLUSIONS: The nutritional habits and BMI of mastocytosis patients are similar to the general population, except for too little fiber intake and mineral content. The gastrointestinal symptoms of mastocytosis patients may be related to the low richness of microbiota species and the amount of Suterella, Barnesiellaceae, Eubacterium, Odoribacter, Anaerostipes, which correlated with tryptase levels.

Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

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.

Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM.

ABSTRACT: Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, ß2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308µg/L vs 146µg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to ß2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.