Search

Background and Objectives: The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify rhinitis as "intermittent" or "persistent" and "mild" or "moderate-severe". To assess ARIA classes in a real-world study in terms of phenotypic differences and their association with asthma., Methods: We performed a cross-sectional real-world study based on users of the MASK-air® app who reported data for at least 3 different months. We assessed the frequency of users according to the ARIA classes and compared these classes in terms of rhinitis symptoms, use of comedication, frequency of comorbid asthma, and the association between comorbid asthma and rhinitis control., Results: A total of 2273 users (180 796 days) were assessed. Most users had moderate-severe rhinitis (n=2003; 88.1%) and persistent rhinitis (n=1144; 50.3%). The frequency of patients with probable asthma was 35.7% (95%CI, 34.5%-37.0%) for intermittent rhinitis and 48.5% (95%CI, 47.1%-49.9%) for persistent rhinitis. The maximum values on the visual analog scale (VAS) for rhinitis symptoms and the combined symptom medication score were lower in patients with mild rhinitis than in those with moderate-severe rhinitis (irrespective of whether they had persistent or intermittent rhinitis). In most ARIA classes, VAS nose and VAS eye and rhinitis comedication were more frequent in patients with rhinitis+asthma than in those with rhinitis alone., Conclusion: This study suggests that the presence of asthma is more closely related to persistence of rhinitis than to severity and that the presence of comorbid asthma may be associated with poorer control of rhinitis across the different ARIA classes.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders. The percentage of CD2 - , CD25 + and/or CD30 + MC was considerably lower in patients with indolent SM compared to patients with advanced SM, including aggressive SM and MC leukemia. Whereas CD25 and CD30 expression in MC could not be associated with prognosis, we found that lack of CD2 expression in MC is associated with a significantly reduced overall survival (OS) in patients with SM (p < 0.0001). Lack of CD2 was also associated with the presence of extramedullary involvement affecting the spleen, liver, and/or lymph nodes (odds ratio 2.63 compared to SM with CD2 + MC). Together, lack of CD2 expression in MC is a prognostic marker and indicator of reduced OS and extramedullary disease expansion in patients with SM., Competing Interests: Competing interests: Conflicts of interest declared by the co-autors: Axel Rüfer: Advisory boards: Blueprint Medicines; Oliver Hermine: Research funding support from AB science and Novartis. Advisory board of AB science; Patrizia Bonadonna: Honoraria: Blueprint Medicines; Karin Hartmann: Lectures/consultancy: ALK, Allergopharma, BioCryst, Blueprint Medicines, Cogent, KalVista, Leo, Menarini, Novartis, Pfizer, Sanofi, Takeda, Thermo Fisher; Vito Sabato: Advisory boards: Blueprint Medicines, Cogent, Novartis, Telios. Honoraria: Thermo Fisher; Knut Brockow: Advisory board and honoraria: Blueprint Medicines; Nikolas von Bubnoff: Honoraria Novartis, Takeda, Astra Zeneca, Janssen-Cilag; Paul van Daele: Lectures/consultancy: Novartis, involved in clinical trials for Cogent Biosciences and Blueprint Medicines; Ingunn Dybedal: Advisory board and honoraria: Blueprint Medicines; Chiara Elena: Advisory board and honoraria: Blueprint Medicines, Gilead; Marc Heizmann: Advisory board and honoraria: Novartis; Jens Panse: Advisory board and honoraria: Blueprint Medicines, Novartis, Deciphera; Friederike Wortmann: Advisory board and honoraria: Blueprint Medicines, Novartis, Pierre Fabre, Abbvie; Jason Gotlib: Research Grant (funds for administration of clinical trials): Novartis, Blueprint Medicines, Deciphera, Cogent Biosciences; Advisory Board and Honoraria: Blueprint Medicines, Novartis, Deciphera, Cogent Biosciences; Reimbursement of travel expenses: Novartis, Blueprint Medicines; Andreas Reiter: Honoraria: Novartis, Blueprint Medicines, Incyte, Celgene/Bristol Myers Squibb, AOP Orphan Pharmaceuticals, GlaxoSmithKline, AbbVie; Consulting or Advisory Role: Novartis, Blueprint Medicines, Incyte, Celgene/Bristol Myers Squibb, AOP Orphan Pharmaceuticals, AbbVie; Massimo Triggiani: Advisory Board and Honoraria: Blueprint Medicines, Novartis; Wolfgang R. Sperr: Honoraria from AbbVie, Astellas, Blueprint, BMS-Celgene, Daiichi Sankyo, Deciphera, Incyte, Jazz Pharmaceuticals, Laboratoires Delbert, Novartis, Otsuka, Pfizer, Servier, Stemline, Thermo Fisher; Peter Valent: 1. Advisory board - honoraria: AOP Orphan, Blueprint, Cogent, Delbert, Incyte, Novartis, PentaBase, Pfizer, Stemline. 2. Research grant: AOP Orphan, Pfizer. The remaining co-authors declared no conflict of interest. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations. The ECNM registry study was approved by the responsible local ethics committee of each participating ECNM center. Written informed consent was obtained from all patients included in the ECNM registry., (© 2025. The Author(s).)

Mastocytosis is a rare neoplastic disease of the bone marrow. Common symptoms like urticaria, diarrhea, bronchspasm and flushing are caused by mast cell degranulation and are mostly based on mast cell mediator release and Th2 type inflammation that occurs frequently in these patients. Psychological disorders are more prevalent in patients with systemic mastocytosis, though little is known about the mechanism behind this. The aim of the study was to investigate the Th2 cytokine (IL-4, TSLP, IL-31 and IL-33) profile in patients with mastocytosis in relation to classic degranulation symptoms and the psychometric measures of cognition and distress symptoms.In total, 115 patients diagnosed with mastocytosis were enrolled. Mini-Mental State Examination (MMSE) was performed for all subjects. Other variables: Quality of life in mastocytosis, a mood assessment commonly used in systemic mastocytosis by a certified rater-the Hamilton-17 Depression Scale, Pruritus Visual Analog Score, serum tryptase concentration and bone marrow biopsy results (archival) were also analyzed/included. Serum concentrations of IL-4, TSLP, IL-33 and IL-31 were analyzed as primary outcomes. For comparison with continuous variables linear regression was used. The mean MMSE result was 27.9. Regression analysis did not reveal significant correlation between the IL-4 ( p = 0.82), IL-31 ( p = 0.24) and TSLP ( p = 0.37) serum concentrations and MMSE. The IL-33 concentration analysis resulted in 0 for all patients (was not detected). No significant effect was observed with other endpoints as well. One in four patients with mastocytosis presents cognitive decline. This impairment does not correlate with Il-4, TSLP, nor IL-31 serum protein concentrations.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease, characterized by impaired wound repair, tissue remodeling and fibrosis. Immune system may participate in the development and progression of the disease as indicated by altered activity in IPF sufferers. This study investigates the immune response to the BNT162b2 COVID-19 vaccine in patients with IPF compared to healthy controls, with a particular focus on evaluation of antibody responses, interferon-gamma release, cytokine profiling and a broad panel of immune cell subpopulations. IPF patients without prior exposure to SARS-CoV-2 had undetectable levels of anti-N IgG antibodies, highlighting their lack of previous infection. After vaccination, IPF patients showed a significant increase in anti-S1 IgG and IgA antibodies, though their levels were lower compared to healthy controls and convalescent IPF patients. Additionally, IPF patients exhibited altered proportions of regulatory T cells (Tregs) and effector T lymphocytes (Teffs) before and after vaccination. Specifically, IPF patients had higher percentages of Tregs with a Th2 phenotype and Th17 Tregs, along with reduced proportions of Th1/17 Tregs. Teffs in IPF patients showed a decrease in Th1-like and Th2-like populations after vaccination. Moreover, IPF patients demonstrated elevated populations of cytotoxic T lymphocytes (Tc) before vaccination and increased levels of γδ Tc cells throughout the study. Alterations in cytokine profiles were also observed, IPF patients showed higher levels of IL-6 and IL-22 compared to healthy controls. These findings suggest a distinct immune response in IPF patients to the COVID-19 vaccine, characterized by differences in antibody production, T cell differentiation and cytokine secretion compared to healthy individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Maciejewska, Czernia, Piotrowska-Mieczkowska, Wajda, Słomiński, Romantowski, Sudoł, Dąbrowska, Górska, Smiatacz, Niedoszytko, Jassem, Skrzypkowska and Trzonkowski.)

Mastocytosis is a heterogeneous group of disorders, characterized by accumulation of clonal mast cells which can infiltrate several organs, most often spine (70%). The pathogenesis of mastocytosis bone disease is poorly understood. The main aim of the study was to investigate whether neoplastic mast cells may be the source of sclerostin and whether there is an association between sclerostin and selected bone remodeling markers with mastocytosis related bone disease. We assessed sclerostin, bioactive sclerostin, and SOST gene expression in HMC-1.2 human mast cell culture supernatants and plasma of SM patients (n = 39). We showed that human mast cells can secrete sclerostin, and after their stimulation with IL-6, there is a significant increase in SOST gene expression. We observed significantly higher levels of sclerostin in patients diagnosed with more advanced disease. We observed a statistically significant correlation between concentations of sclerostin and its bioactive form and the concentration of alkaline phosphatase (ALP), and between sclerostin and interleukin-6 (IL-6). We observed that significantly higher sclerostin concentrations are present in patients with increased sclerosis of the spongy bone. Sclerostin may serve as a marker of more advanced disease and bone disease in mastocytosis. Further studies are justified to evaluate its role in mastocytosis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki. Local ethical approval was obtained from the Bioethical Committee at the Medical University of Lublin (protocol code KE-0254/238/2021). All patients had given informed consent., (© 2024. The Author(s).)

Mastocytosis is a clonal myeloid disorder defined by an increase and accumulation of mast cells (MCs) in one or multiple organ systems. The complex pathology of mastocytosis results in variable clinical presentations, courses, and outcomes. The World Health Organization (WHO) divides the disease into cutaneous mastocytosis (CM), several forms of systemic mastocytosis (SM), and MC sarcoma. In most patients with SM, a somatic KIT mutation, usually D816V, is identified. Patients diagnosed with CM or nonadvanced SM, including indolent SM, have a near-normal life expectancy, whereas those with advanced SM, including aggressive SM and MC leukemia, have limited life expectancy. Since 2001, a multidisciplinary consensus group consisting of experts from the European Competence Network on Mastocytosis and the American Initiative in Mast Cell Diseases has supported the field by developing diagnostic criteria for mastocytosis. These criteria served as the basis for the WHO classification of mastocytosis over 2 decades. More recently, an International Consensus Classification group proposed slightly modified diagnostic criteria and a slightly revised classification. In this article, these changes are discussed. Furthermore, we propose harmonization among the proposals of the American Initiative in Mast Cell Diseases/European Competence Network on Mastocytosis consensus group, WHO, and the International Consensus Classification Group. Such harmonization will facilitate comparisons of retrospective study results and the conduct of prospective trials., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 post-vaccination 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 characterized 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., Conclusion: The risk of serious cardiac adverse drug reactions to COVID-19 vaccines is low and the benefit of active immunization against that disease seems to outweigh the potential risk of serious post-vaccination cardiac adverse drug reactions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care. 1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Patient-reported outcome measures (PROMs) are used to assess a patient's health status at a particular point in time. They are essential in the development of person-centred care. This paper reviews studies performed on PROMs for assessing AR and asthma control, in particular VAS scales that are included in the app MASK-air ® (Mobile Airways Sentinel networK) for asthma and rhinitis. VASs were initially developed on paper and pencil and tested for their criterion validity, cut-offs and responsiveness. Then, a multicentric, multinational, double-blind, placebo-controlled, randomised control trial (DB-PC-RCT) using an electronic VAS form was carried out. Finally, with the development of MASK-air ® in 2015, previously validated VAS questions were adapted to the digital format and further methodologic evaluations were performed. VAS for asthma, rhinitis, conjunctivitis, work and EQ-5D are included in the app. Additionally, two control-medication scores for allergic symptoms of asthma (e-DASTHMA) were validated for their criterion validity, cut-offs and responsiveness., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

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., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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.

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, β2-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 β2-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., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

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., (© 2024 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

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.

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.

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., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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 <10 6 . 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., (© 2024 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

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., (© 2024 S. Karger AG, Basel.)

Background: EQ-5D-5L (EuroQOL, 5 Domains, 5 Levels) is a widely used health-related quality-of-life instrument, comprising 5 domains. However, it is not known how each domain is impacted by rhinitis or asthma control., Objective: To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app., Methods: In this cross-sectional study, we assessed data from all MASK-air users (2015-2021; 24 countries). For the levels of each EQ-5D-5L domain, we assessed rhinitis and asthma visual analog scales (VASs) and the combined symptom-medication score (CSMS). We built ordinal multivariable models assessing the adjusted association between VAS/CSMS values and the levels of each EQ-5D-5L domain. Finally, we compared EQ-5D-5L data from users with rhinitis and self-reported asthma with data from users with rhinitis alone., Results: We assessed 5354 days from 3092 users. We observed an association between worse control of rhinitis or asthma (higher VASs and CSMS) and worse EQ-5D-5L levels. In multivariable models, all VASs and the CSMS were associated with higher levels of pain/discomfort and daily activities. For anxiety/depression, the association was mostly observed for rhinitis-related tools (VAS nose, VAS global, and CSMS), although the presence of self-reported asthma was also associated with worse anxiety/depression. Worse mobility ("walking around") was particularly associated with VAS asthma and with the presence of asthma., Conclusions: A worse rhinitis control and a worse asthma control are associated with higher EQ-5D-5L levels, particularly regarding pain/discomfort and activity impairment. Worse rhinitis control is associated with worse anxiety/depression, and poor asthma control with worse mobility., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: COVID-19 vaccines became a relevant element of prevention during COVID-19 pandemic. It is worth highlighting the importance of severe allergic post-vaccination reactions., Aim: To evaluate the usability of skin reaction tests using skin prick tests with Comirnaty (Pfizer, USA) vaccine in risk detection of the post-vaccine immediate hypersensitivity reaction (anaphylaxis) after administration of this vaccine [PvIHR(A)]., Material and Methods: The analysis embraces 102 people, 85 women and 17 men with a history of immediate hypersensitivity (anaphylaxis) [IHR(A)]. Detailed medical history was collected and skin prick tests were made among participants. The positive and negative test results were illustrated in Figure 1., Results: As it stands in Table 1, considering all participants of the study, a positive result of the skin prick tests was obtained only in 2 cases, a negative result in 99 and 1 result was questionable. The two positive results were found in participants from a group with a previous PvIHR(A) in their past medical history and they decided not to get vaccinated. The one questionable result was of a person that had PvIHR(A) after administration of the first dose of Comirnaty vaccine (Pfizer, USA). This person decided to get vaccinated again and there was no PvIHR(A) observed., Conclusions: COVID-19 vaccination involves a low risk of anaphylaxis. Purposefulness of providing the skin prick tests using the mRNA vaccine is questionable, due to their low sensitivity and low specificity., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Physiological levels of basal serum tryptase vary among healthy individuals, depending on the numbers of mast cells, basal secretion rate, copy numbers of the TPSAB1 gene encoding alpha tryptase, and renal function. Recently, there has been a growing debate about the normal range of tryptase because individuals with the hereditary alpha tryptasemia (HαT) trait may or may not be symptomatic, and if symptomatic, uncertainty exists as to whether this trait directly causes clinical phenotypes or aggravates certain conditions. In fact, most HαT-positive cases are regarded as asymptomatic concerning mast cell activation. To address this point, experts of the European Competence Network on Mastocytosis (ECNM) and the American Initiative in Mast Cell Diseases met at the 2022 Annual ECNM meeting and discussed the physiological tryptase range. Based on this discussion, our faculty concluded that the normal serum tryptase range should be defined in asymptomatic controls, inclusive of individuals with HαT, and based on 2 SDs covering the 95% confidence interval. By applying this definition in a literature screen, the normal basal tryptase in asymptomatic controls (HαT-positive persons included) ranges between 1 and 15 ng/mL. This definition should avoid overinterpretation, unnecessary referrals, and unnecessary anxiety or anticipatory fear of illness in healthy individuals., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mastocytosis is a clinically heterogenous, usually acquired disease of the mast cells with a survival time that depends on the time of onset. It ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The presence of the oncogenic KIT p. D816V gene somatic mutation is a crucial element in the pathogenesis. However, further epigenetic regulation may also affect the expression of genes that are relevant to the pathology. Epigenetic alterations are responsible for regulating the expression of genes that do not modify the DNA sequence. In general, it is accepted that DNA methylation inhibits the binding of transcription factors, thereby down-regulating gene expression. However, so far, little is known about the epigenetic factors leading to the clinical onset of mastocytosis. Therefore, it is essential to identify possible epigenetic predictors, indicators of disease progression, and their link to the clinical picture to establish appropriate management and a therapeutic strategy. The aim of this study was to analyze genome-wide methylation profiles to identify differentially methylated regions (DMRs) in patients with mastocytosis compared to healthy individuals, as well as the genes located in those regulatory regions. Genome-wide DNA methylation profiling was performed in peripheral blood collected from 80 adult patients with indolent systemic mastocytosis (ISM), the most prevalent subvariant of mastocytosis, and 40 healthy adult volunteers. A total of 117 DNA samples met the criteria for the bisulfide conversion step and microarray analysis. Genome-wide DNA methylation analysis was performed using a MethylationEPIC BeadChip kit. Further analysis was focused on the genomic regions rather than individual CpG sites. Co-methylated regions (CMRs) were assigned via the CoMeBack method. To identify DMRs between the groups, a linear regression model with age as the covariate on CMRs was performed using Limma. Using the available data for cases only, an association analysis was performed between methylation status and tryptase levels, as well as the context of allergy, and anaphylaxis. KEGG pathway mapping was used to identify genes differentially expressed in anaphylaxis. Based on the DNA methylation results, the expression of 18 genes was then analyzed via real-time PCR in 20 patients with mastocytosis and 20 healthy adults. A comparison of the genome-wide DNA methylation profile between the mastocytosis patients and healthy controls revealed significant differences in the methylation levels of 85 selected CMRs. Among those, the most intriguing CMRs are 31 genes located within the regulatory regions. In addition, among the 10 CMRs located in the promoter regions, 4 and 6 regions were found to be either hypo- or hypermethylated, respectively. Importantly, three oncogenes- FOXQ1 , TWIST1 , and ERG -were identified as differentially methylated in mastocytosis patients, for the first time. Functional annotation revealed the most important biological processes in which the differentially methylated genes were involved as transcription, multicellular development, and signal transduction. The biological process related to histone H2A monoubiquitination (GO:0035518) was found to be enriched in association with higher tryptase levels, which may be associated with more aberrant mast cells and, therefore, more atypical mast cell disease. The signal in the BAIAP2 gene was detected in the context of anaphylaxis, but no significant differential methylation was found in the context of allergy. Furthermore, increased expression of genes encoding integral membrane components ( GRM2 and KRTCAP3 ) was found in mastocytosis patients. This study confirms that patients with mastocytosis differ significantly in terms of methylation levels in selected CMRs of genes involved in specific molecular processes. The results of gene expression profiling indicate the increased expression of genes belonging to the integral component of the membrane in mastocytosis patients ( GRM2 and KRTCAP3 ). Further work is warranted, especially in relation to the disease subvariants, to identify links between the methylation status and the symptoms and novel therapeutic targets.

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.

Introduction: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting β2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA., Materials and Methods: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day., Results: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001)., Conclusions: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control., Competing Interests: Conflicts of interest JS reports grants and personal fees from SANOFI, personal fees from GSK, personal fees from NOVARTIS, personal fees from ASTRA ZENECA, personal fees from MUNDIPHARMA, personal fees from FAES FARMA, outside the submitted work. BS reports personal fees from Polpharma, personal fees from Viatris, grants and personal fees from AstraZeneca, personal fees from TEVA, personal fees from patient ombudsman, personal fees from Polish Allergology Society, grants from GSK, outside the submitted work. SBA reports grants from TEVA, personal fees from TEVA, personal fees from TEVA, personal fees from AstraZeneca, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Sanofi, personal fees from Mylan, personal fees from Menarini, outside the submitted work. BG reports grants from Chiesi, grants from Sandoz, grants from GSK, grants from AstraZeneca, grants from Deva, grants from Abdi İbrahim, outside the submitted work. RL reports grants and personal fees from AZ, grants and personal fees from GSK, grants from Chiesi, outside the submitted work. MK reports personal fees from Astra Zeneca, personal fees from Chiesi, personal fees from GSK, personal fees from Novartis, personal fees from Berlin Chemie, personal fees from Zentiva, personal fees from Allergopharma, personal fees from LEK-AM, personal fees from Polpharma, personal fees from Teva, personal fees from Sanofi, personal fees from Adamed, personal fees from Sandoz, personal fees from EMMA, outside the submitted work. FDB reports other from NOVARTIS, other from ALK, other from STALLERGENES, other from REGENERON, other from DBV, other from SANOFI, other from BOEHRINGER, other from ASTRAZENECA, outside the submitted work. CSU reports grants and personal fees from AZ, personal fees from GSK, personal fees from TEVA, grants and personal fees from Sanofi, grants and personal fees from BI, personal fees from Novartis, personal fees and non-financial support from Orion Pharma, personal fees from Chiesi, personal fees from TFF Pharmaceuticals, personal fees from Takeda, personal fees from Pfizer, personal fees from Covis Pharma, outside the submitted work. NP reports grants from Capricare, personal fees from Nestle, personal fees from Numil, personal fees from Vianex, outside the submitted work. FR reports personal fees from Novartis, personal fees from Sanofi, personal fees from AstraZeneca, personal fees from GSK, personal fees from Medinfar, personal fees from Azentis, outside the submitted work. TZ reports grants and personal fees from Novartis, grants and personal fees from Henkel, personal fees from Bayer, personal fees from FAES, personal fees from Astra Zeneca, personal fees from AbbVie, personal fees from ALK, personal fees from Almirall, personal fees from Astellas, personal fees from Bayer, personal fees from Bencard, personal fees from Berlin Chemie, personal fees from FAES, personal fees from Hal, personal fees from Leti, personal fees from Mesa, personal fees from Menarini, personal fees from Merck, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sanofi, personal fees from Stallergenes, personal fees from Takeda, personal fees from Teva, personal fees from UCB, personal fees from Henkel, personal fees from Kryolan, personal fees from L'Oreal, outside the submitted work; and Organizational affiliations: Commitee member: WHO-Initiative "Allergic Rhinitis and Its Impact on Asthma" (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF); President: Global Allergy and Asthma European Network (GA2LEN); Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). AP reports grants from CHIESI, ASTRAZENECA, GSK, SANOFI, personal fees from CHIESI, ASTRAZENECA, GSK, NOVARTIS, SANOFI, IQVIA, AVILLION, ELPEN PHARMACEUTICALS, personal fees from CHIESI, ASTRAZENECA, GSK, BI, MENARINI, NOVARTIS, ZAMBON, MUNDIPHARMA, TEVA, SANOFI, EDMOND PHARMA, IQVIA, MSD, AVILLION, ELPEN PHARMACEUTICALS, outside the submitted work. RB reports grants from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche, personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Sanofi, Roche and Teva, outside the submitted work. LTB reports personal fees from DIATER, personal fees from Novartis, personal fees from LETI, outside the submitted work. JF reports personal fees from Viatris/Mylan, personal fees from AstraZeneca, outside the submitted work; and being co-founder of an SME that develops mHealth technologies, such as digital biomarkers and has the copyright of the CARAT anda CARATkids PROM. VK reports non-financial support from Norameda, non-financial support from Berlin CHemie Menarini, outside the submitted work. NR reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, grants and personal fees from GSK, personal fees from AstraZeneca, personal fees from Chiesi, grants and personal fees from Pfizer, personal fees from Sanofi, personal fees from Zambon, personal fees from MSD, personal fees from Austral, outside the submitted work. SB reports personal fees from Sanofi Genzyme, personal fees from AstraZeneca, grants from Auris medical, personal fees from Allergopharma, personal fees from ALK Abello, grants, personal fees and non-financial support from Bencard Allergy, personal fees from Allergy Therapeutics, non-financial support from Smart Reporting, personal fees from Stryker, personal fees from MSD, personal fees from Mylan, personal fees from GSK, outside the submitted work. JB reports personal fees from Cipla, Menarini, Mylan, Novartis, Purina, Sanofi-Aventis, Teva, Uriach, other from KYomed-Innov, other from Mask-air-SAS, outside the submitted work. TH reports personal fees from Orion Pharma, outside the submitted work. LC reports personal fees from Thermofisher, personal fees from Novartis, personal fees from ALK, personal fees from Sanofi, personal fees from GSK, personal fees from Astra Zeneca, outside the submitted work. LPB reports grants from Time frame: past 36 months Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Sanofi-Regeneron, personal fees from Astra Zeneca, Novartis, GlaxoSmithKline, Merck, Sanofi-Regeneron, personal fees from AstraZeneca, Covis, Cipla, GlaxoSmithKline, Novartis, Merck, Sanofi, outside the submitted work. SDG reports grants and personal fees from AstraZeneca, personal fees from Chiesi, grants and personal fees from GSK, grants and personal fees from Novartis, personal fees from Guidotti, personal fees from Sanofi, outside the submitted work. PK reports personal fees from Adamed, personal fees from Berlin Chemie Menarini, personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Glenmark, personal fees from Novartis, personal fees from Polpharma, personal fees from GSK, personal fees from Sanofi, personal fees from Chiesi, personal fees from Celon Pharma, outside the submitted work. AC reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GSK, personal fees from Eurofarma, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. MS reports grants from Immune Tolerance Network, grants from Medical Research Council, grants and personal fees from Allergy Therapeutics, grants and personal fees from LETI Laboratorios, grants from Revolo biotherapeutics, grants from Angany Inc, personal fees from Bristol Myers Squibb, outside the submitted work. GB reports personal fees from Astra Zeneca, personal fees from Boehringer-Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Sanofi, grants from MerckSharp&Dohme, outside the submitted work. MJ reports personal fees from ALK-Abello, personal fees from Allergopharma, personal fees from Stallergenes, personal fees from Anergis, personal fees from Allergy Therapeutics, personal fees from Leti, personal fees from HAL, during the conduct of the study; personal fees from GSK, personal fees from Novartis, personal fees from Teva, personal fees from Takeda, personal fees from Chiesi, outside the submitted work. DLL reports personal fees from ALK, Astrazeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GSK national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot, grants from Abbvie, Bayer, Lilly, Sanofi, Astrazeneca, Lilly, Pfizer, Novartis, Circassia, UCB, GSK, Purina institute., outside the submitted work. OP reports grants and personal fees from ALK-Abelló, grants and personal fees from Allergopharma, grants and personal fees from Stallergenes Greer, grants and personal fees from HAL Allergy Holding B.V./HAL Allergie GmbH, grants from Bencard Allergie GmbH/Allergy Therapeutics, grants from Lofarma, grants and personal fees from ASIT Biotech Tools S.A., grants and personal fees from Laboratorios LETI/LETI Pharma, grants and personal fees from GlaxoSmithKline, personal fees from ROXALL Medizin, personal fees from Novartis, grants and personal fees from Sanofi-Aventis and Sanofi-Genzyme, personal fees from Med Update Europe GmbH, personal fees from streamedup! GmbH, grants from Pohl-Boskamp, grants from Inmunotek S.L., personal fees from John Wiley and Sons, AS, personal fees from Paul-Martini-Stiftung (PMS), personal fees from Regeneron Pharmaceuticals Inc., personal fees from RG Aerztefortbildung, personal fees from Institut für Disease Management, personal fees from Springer GmbH, grants and personal fees from AstraZeneca, personal fees from IQVIA Commercial, personal fees from Ingress Health, personal fees from Wort&Bild Verlag, personal fees from Verlag ME, personal fees from Procter&Gamble, personal fees from ALTAMIRA, personal fees from Meinhardt Congress GmbH, personal fees from Deutsche Forschungsgemeinschaft, personal fees from Thieme, grants from Deutsche AllergieLiga e.V., personal fees from AeDA, personal fees from Alfried-Krupp Krankenhaus, personal fees from Red Maple Trials Inc., personal fees from TU Dresden, outside the submitted work. YO reports personal fees from Torii pharmaceutical Co., LTD., personal fees from Tanabe-Mitsubishi Pharmaceutical Co., Ltd., personal fees from Kirin Holdings Co., Ltd., personal fees from Novartis Co., Ltd., personal fees from Allergologisk Laboratorium København, personal fees from Shionogi Co., Ltd., outside the submitted work. JCI reports personal fees and non-financial support from Laboratorios Casasco, personal fees from Abbott Ecuador, personal fees from Laboratorios Bago Bolvia, personal fees from Faes Farma, outside the submitted work. HK reports personal fees from Mylan/Viatris, personal fees from Sanofi, outside the submitted work. MO reports personal fees from Hycor Diagnostics, outside the submitted work; and Scientific Co-Founder, Tolerogenics SARL, Luxembourg. The other authors have no COIs to disclose, outside the submitted work., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, and to the classification, prognostication, and treatments of patients with mastocytosis and MC activation disorders. The ECNM also organized annual meetings and several working conferences, thereby supporting the development of the World Health Organization classification between 2002 and 2022. In addition, the ECNM established a robust and rapidly expanding patient registry and supported the development of new prognostic scoring systems and new treatment approaches. In all projects, ECNM representatives collaborated closely with their U.S. colleagues, various patient organizations, and other scientific networks. Finally, ECNM members have started several collaborations with industrial partners, leading to the preclinical development and clinical testing of KIT-targeting drugs in systemic mastocytosis, and some of these drugs received licensing approval in recent years. All these networking activities and collaborations have strengthened the ECNM and supported our efforts to increase awareness of MC disorders and to improve diagnosis, prognostication, and therapy in patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of interests IA is an associate editor for Allergy and Clinical and Translational Allergy journals. RAl reports personal fees from operation POCI-01–0145–36 FEDER-029130 (titled “mINSPIRE-mHealth to measure and improve adherence to medication in chronic respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies”), co-funded by European Regional Development Fund, Programa Operacional Competitividade e Internacionalização, Portugal 2020, and by Portuguese Funds through Fundação para a Ciência e a Tecnologia, outside the submitted work. SB-A reports grants from TEVA, and personal fees from Teva, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, and Mylan, outside the submitted work. L-PB reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Sanofi-Regeneron; personal fees from AstraZeneca, Novartis, GlaxoSmithKline, Merck, Sanofi-Regeneron, Covis, and Sanofi, outside the submitted work; and is a member of the Chair of Global Initiative for Asthma (GINA) Board of Directors, President of the Global Asthma Organisation (Interasma), and is a member of the Canadian Thoracic Society Respiratory Guidelines Committee and Laval University Chair on Knowledge Transfer, and Prevention and Education in Respiratory and Cardiovascular Health. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Purina, Sanofi-Aventis, Takeda, Teva, and Uriach; and other from Kyomed-Innov, outside the submitted work. GB reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Sanofi, outside the submitted work. RB reports grants to Mainz University Hospital from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche; and personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Roche, Sanofi, and Teva, all outside the submitted work. LC reports personal fees from Thermofisher, Sanofi, Novartis, and AstraZeneca, outside the submitted work. AAC reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Eurofarma, GSK, Novartis, and Sanofi, outside the submitted work. FdB reports other grants from Novartis, ALK, Stallergenes, Regeneron, DBV, Sanofi, Boehringer, and AstraZeneca, outside the submitted work. PD reports non-financial support from AstraZeneca, Boehringer Ingelheim, Stallergenes, and ALK Abelló; and personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Stallergenes, ALK Abelló, and IQVIA, outside the submitted work. JAF reports grants from Astrazeneca and Mundipharma; and personal fees from AstraZeneca, Mundipharma, Sanofi, GSK, and Teva, outside the submitted work; and is co-founder of a company that develops mobile health technologies and has the copyright of the Control of Allergic Rhinitis and Asthma Test Patient-Reported Outcome Measurement. BG reports grants from AstraZeneca, Sanofi, Deva, Abdi Ibrahim, and Sandoz, outside the submitted work. TH reports personal fees from Orion Pharma, outside the submitted work. GJ reports personal fees from AstraZeneca, GSK, Chiesi, Novartis, and Laparcon; support from GSK, outside the submitted work; and is a member of European Respiratory Society Chair of Operational Committee International Respiratory Coalition. MJ reports personal fees from ALK-Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Leti, and HAL, during the conduct of the study; and personal fees from GSK, Novartis, Teva, Takeda, and Chiesi, outside the submitted work. LK reports grants from Allergopharma, MEDA/Mylan, ALK Abelló, LETI Pharma, Stallergenes, Sanofi, ASIT biotech, Lofarma Quintiles, AstraZeneca, GSK, and Inmunotk; and personal fees from Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Sanofi, Allergy Therapeut, and Cassella Med, outside the submitted work; and is a member of Ärzteverband Deutscher Allergologen, Deutsche Gesellschaft für Hals-Nasen-Ohren, Deutsche Akademie für Allergologie und klinische Immunologie, Berufsverband der Hals-Nasen-Ohrenärzte, Gesellschaft für Pädiatrische Allergologie, andEuropean Academy of Allergy and Clinical Immunology. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, FAES, Glenmark, Novartis, Polpharma, Boehringer Ingelheim, Teva, and Zentiva, outside the submitted work. MKup reports personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Lekam, Alvogen, Emma, Nexter, Teva, Sanofi Aventis, and Berlin Chemie, outside the submitted work. VK reports non-financial support from Norameda and Berlin Chemie Menarini, outside the submitted work. DL-L reports personal fees from ALK, Allakos, Amstrong, Astrazeneca national and global, Chiesi, DBV Technologies, Grunenthal, GSK national and global, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot; and grants from Sanofi, Astrazeneca, Lilly, Pfizer, Novartis, Circassia, UCB, GSK, and Purina institute, outside the submitted work. RL reports personal fees from GSK and AZ; and grants from GSK, AZ, and Chiesi, outside the submitted work. NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, and Boehringer Ingelheim; and grants from Gerolymatos International SA and Capricare, outside the submitted work. AP reports grants from Chiesi, Astrazeneca, GSK, BI, Pfizer, Teva, and Sanofi; personal fees from CHIESI, Astrazeneca, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, BI, Menarini, Zambon, Mundipharma, Teva, Edmon Pharma, and MSD, outside the submitted work. OP reports grants from ALK Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding BV/HAL Allergie, Bencard Allergie/Allergy Therapeutics, Lofarma, Biomay, Circassia, ASIT Biotech Tools SA, Laboratorios LETI/LETI Pharma, Anergis SA, GlaxoSmithKline, Pohl-Boskamp, Inmunotek SL, and AstraZeneca; and personal fees from ALK-Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding BV/HAL Allergie, Bencard Allergie/Allergy Therapeutics, Lofarma, ASIT Biotech Tools SA, Laboratorios LETI/LETI Pharma, MEDA Pharma/MYLAN, Anergis SA, AstraZeneca, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, GlaxoSmithKline, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe, streamedup!, John Wiley and Sons, AS, Paul-Martini-Stiftung, Regeneron Pharmaceuticals, RG Aerztefortbildung, Institut für Disease Management, Springer, IQVIA Commercial, Ingress Health, Wort & Bild Verlag, Verlag ME, and Procter & Gamble, outside the submitted work; and is a member of EAACI Excom, member of external board of directors Deutsche Gesellschaft für Allergologie und klinische Immunologie; and is a coordinator, main author, or coauthor of different position papers and guidelines in rhinology, allergology, and allergen immunotherapy. FSR reports speaker and advisory fees from AstraZeneca, Novartis, Sanofi, GSK, Teva, Kedrion, Takeda, LEO Pharma, and Lusomedicamenta, all outside the submitted work. NR reports grants from Boehringer Ingelheim, Novartis, GSK, and Pfizer; and personal fees from Boehringer Ingelheim, Novartis, GSK, AstraZeneca, Chiesi, Pfizer, Sanofi, Zambon, and MSD, outside the submitted work. JS reports grants from Sanofi; and personal fees from Sanofi, GSK, Novartis, AstraZeneca, MundiPharma, and Faes Farma, outside the submitted work. CSU reports personal fees from GSK, AZ, TEVA, Novartis, BI, Chiesi, Sanofi, Orion Pharma, and Covis Pharma; and grants from AZ, Novartis, BI, Sanofi, Orion Pharma, and Covis Pharma, outside the submitted work. OV reports grants from Astrazeneca and Chiesi, outside the submitted work. TZ reports grants from Novartis and Henkel; personal fees from Bayer Health Care, FAES, Novartis, Henkel, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bencard, Berlin Chemie, HAL, Leti, Meda, Menarini, Merck, MSD, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB, Kryolan, and L'Oréal, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms., Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results., Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control., Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested., Objective: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms., Methods: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs., Results: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100)., Conclusions: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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 FEV 1 . 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Specjalski, Romantowski and Niedoszytko.)

Background: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM)., Objectives: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM., Methods: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed., Results: Overall survival (OS) was adversely affected by the number of organomegalies (OS: #0 vs #1 hazard ratio [HR], 4.9; 95% CI, 3.4-7.1, P < .001; #1 vs #2 HR, 2.1, 95% CI, 1.4-3.1, P < .001; #2 vs #3 HR, 1.7, 95% CI, 1.2-2.5, P = .004). Lymphadenopathy was frequently detected in patients with smoldering SM (SSM, 18 of 60 [30%]) or advanced SM (AdvSM, 137 of 344 [40%]). Its presence confered an inferior outcome in patients with AdvSM compared with patients with AdvSM without lymphadenopathy (median OS, 3.8 vs 2.6 years; HR, 1.6; 95% CI, 1.2-2.2; P = .003). OS was not different between patients having organomegaly with either ISM or SSM (median, 25.5 years vs not reached; P = .435). At time of disease progression, a new occurrence of any organomegaly was observed in 17 of 40 (43%) patients with ISM, 4 of 10 (40%) patients with SSM, and 33 of 86 (38%) patients with AdvSM, respectively., Conclusions: Organomegalies including lymphadenopathy are often found in SSM and AdvSM. ISM with organomegaly has a similar course and prognosis compared with SSM. The number of organomegalies is adversely associated with OS. A new occurrence of organomegaly in all variants of SM may indicate disease progression., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

MASK-air ® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air ® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air ® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air ® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air ® results should lead to change management in rhinitis and asthma., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background: Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available., Objective: To use RWD to assess the impact of allergic rhinitis on academic performance (measured through a visual analog scale [VAS] education and the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific [WPAI+CIQ:AS] questionnaire), and to identify factors associated with the impact of allergic rhinitis on academic performance., Methods: We assessed data from the MASK-air mHealth app of users aged 13 to 29 years with allergic rhinitis. We assessed the correlation between variables measuring the impact of allergies on academic performance (VAS education, WPAI+CIQ:AS impact of allergy symptoms on academic performance, and WPAI+CIQ:AS percentage of education hours lost due to allergies) and other variables. In addition, we identified factors associated with the impact of allergic symptoms on academic productivity through multivariable mixed models., Results: A total of 13,454 days (from 1970 patients) were studied. VAS education was strongly correlated with the WPAI+CIQ:AS impact of allergy symptoms on academic productivity (Spearman correlation coefficient = 0.71 [95% confidence interval (CI) = 0.58; 0.80]), VAS global allergy symptoms (0.70 [95% CI = 0.68; 0.71]), and VAS nose (0.66 [95% CI = 0.65; 0.68]). In multivariable regression models, immunotherapy showed a strong negative association with VAS education (regression coefficient = -2.32 [95% CI = -4.04; -0.59]). Poor rhinitis control, measured by the combined symptom-medication score, was associated with worse VAS education (regression coefficient = 0.88 [95% CI = 0.88; 0.92]), higher impact on academic productivity (regression coefficient = 0.69 [95% CI = 0.49; 0.90]), and higher percentage of missed education hours due to allergy (regression coefficient = 0.44 [95% CI = 0.25; 0.63])., Conclusion: Allergy symptoms and worse rhinitis control are associated with worse academic productivity, whereas immunotherapy is associated with higher productivity., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT., Methods: We assessed the MASK-air® app data (May 2015-December 2020) by users self-reporting AR (16-90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication., Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71-0.80)., Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

(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 C anis 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.

Mast cell activation (MCA) is common and occurs in a number of pathologic conditions, including IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes, and mastocytosis. In a subset of patients, no underlying disease and no known trigger of MCA are found. When the symptoms are severe, systemic, and recurrent, and accompanied by a diagnostic increase in the serum tryptase level or other mast cell mediators, an MCA syndrome (MCAS) may be diagnosed. In these patients, the symptoms typically respond to drugs suppressing MCA, mediator production in mast cells, or mediator effects. In each case, diagnostic consensus criteria must be fulfilled to diagnose MCAS. In other patients, MCA may be local, less severe, or less acute, or may be suspected but not confirmed, so that the diagnostic criteria of MCAS are not fulfilled. In these patients, it may be difficult to prove MCA, for example, by measuring multiple mast cell mediators or basophil activation, the latter as a surrogate of IgE-dependent hypersensitivity. However, validated diagnostic criteria for implicating suspected MCA behind such conditions are lacking, even if some of these conditions have recently been assigned to an International Classification of Diseases-10-Clinical Modification code (ICD-10-CM). In this article, we discuss diagnostic features and criteria and propose a ICD-10-CM-adjusted classification for disorders associated with MCA, herein referred to as MCA disorders (MCADs), with special emphasis on the delineation between confirmed MCAS, MCAD not fulfilling MCAS criteria, and suspected MCAD that is not present. In addition, we discuss the discrimination between overt MCAD and predisposing conditions, such as atopic states, mastocytosis, and hereditary alpha tryptasemia., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user's guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)