Background-We compared cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators from mast cells isolated from heart tissue of patients with idiopathic dilated (DCM) (nϭ24) and ischemic cardiomyopathy (ICM) (nϭ10) undergoing heart transplantation and from control subjects (nϭ10) without cardiovascular disease. Methods and Results-HHMC density in DCM (18.4Ϯ1.6 cells/mm 2 ) and ICM (18.4Ϯ1.5 cells/mm 2 ) was higher than that in control hearts (5.3Ϯ0.7 cells/mm 2 ; PϽ.01). The histamine and tryptase contents of DCM and ICM hearts were higher than those of control hearts. The histamine content of the hearts was correlated with mast cell density (r s ϭ.91; PϽ.001). Protein A/gold staining of heart tissue revealed stem cell factor (SCF), the principal growth, differentiating, and activating factor of human mast cells, in HHMC secretory granules. Histamine release from cardiac mast cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli (Ca 2ϩ ionophore A23187) was higher in patients with DCM and ICM compared with control subjects. Immunological activation of HHMC induced a significantly greater release of tryptase and LTC 4 in patients with DCM and ICM compared with control subjects. Conclusions-Histamine and tryptase content and mast cell density are higher in failing hearts than in control hearts. SCF, present in secretory granules of HHMC, might represent an autocrine factor sustaining mast cell hyperplasia in heart tissue in these patients. The increased local release of fibrogenic factors (eg, histamine, tryptase, and leukotriene C 4 ) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy. 1 Mast cells are present in human heart tissue 2,3 and in adventia and intima of coronary arteries of patients with coronary artery disease. [4][5][6] Moreover, the in vitro immunological activation of human heart tissue with anti-IgE induces the release of histamine and prostaglandin D 2 . 7,8 The concentration of histamine and the density of mast cells are increased in the arteries of cardiac patients, 4,5,9 and coronary arteries from cardiac patients are hyperresponsive in vitro to histamine. 4 Furthermore, in vivo administration of histamine and other mast cell-derived mediators (peptide LTC 4 ) in humans causes significant cardiovascular effects. 10 -12 Finally, serum IgE levels are increased in patients with coronary artery disease. 13,14 Taken together, these observations raise the possibility that local activation of cardiac mast cells might contribute, through the release of vasoactive mediators, to certain cardiovascular diseases. 15,16 Fibrosis is a hallmark of failing hearts in DCM and ICM. 17 The cells and the mediators responsible for fibroblast proliferation and collagen accumulation in failing hearts in DCM and ICM are largely unknown. Mast cells are involved in many types of inflammation and repair processes and are found in increased numbers in fibrotic tissues. For example, increased mast cell density has be...

Background The coronavirus disease 2019 (COVID‐19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. Method The scientific information on COVID‐19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet. Results Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” initiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. Conclusions This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID‐19 pandemic.

SummaryThe most dangerous and life-threatening manifestation of allergic diseases is anaphylaxis, a condition in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. The heart is both a source and a target of chemical mediators released during allergic reactions. Mast cells are abundant in the human heart, where they are located predominantly around the adventitia of large coronary arteries and in close contact with the small intramural vessels. Cardiac mast cells can be activated by a variety of stimuli including allergens, complement factors, general anesthetics and muscle relaxants. Mediators released from immunologically activated human heart mast cells strongly influence ventricular function, cardiac rhythm and coronary artery tone. Histamine, cysteinyl leukotrienes and platelet-activating factor (PAF) exert negative inotropic effects and induce myocardial depression that contribute significantly to the pathogenesis of anaphylactic shock. Moreover, cardiac mast cells release chymase and renin that activates the angiotensin system locally, which further induces arteriolar vasoconstriction. The number and density of cardiac mast cells is increased in patients with ischaemic heart disease and dilated cardiomyopathies. This observation may help explain why these conditions are major risk factors for fatal anaphylaxis. A better understanding of the mechanisms involved in cardiac mast cell activation may lead to an improvement in prevention and treatment of systemic anaphylaxis.

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Hymenoptera venom allergy is an epidemiologically underestimated condition representing an important cause of morbidity worldwide. Preventing future allergic reactions in patients who have developed a systemic reaction is based on the correct management of emergency followed by a correct diagnosis, prescription of adrenaline autoinjectors and, where indicated, specific venom immunotherapy (VIT). Some epidemiological studies highlight the poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high quality Hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and the quality of life of allergic patients. The subcutaneous VIT represents the most effective form of immunotherapy with allergen presently available, with a carry-over effect lasting up to several years after its interruption. This report on the management of children and adults allergic to Hymenoptera venom was drawn up by a panel of Italian experts. The main objective of this consensus is to review the scientific evidences related to diagnosis, therapy and management of patients allergic to Hymenoptera venom and is aimed to improve the knowledge about this disease and promote good clinical practices. Practical suggestions for a correct diagnosis, prescription of emergency therapy and immunotherapy, as well as strategies for taking care of patients´ management are included.

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Background Asthma is one of the most common non-communicable respiratory diseases, affecting about 6% of the general population. Severe asthma, even if afflicts a minority of asthmatics, drives the majority of costs of the disease. The aim of this study is to create a pharmacoeconomic model to predict the costs of corticosteroid-related adverse events in severe asthmatics and applying it to the first published epidemiologic data from the Severe Asthma Network in Italy (SANI) registry. Methods The analysis was conducted from the perspective of the Italian National Healthcare System (INHS). Model inputs, derived from literature, included: asthma epidemiology data, frequency of adverse events, percentage of severe asthma treated with OCS and adverse event cost (Diagnosis-Related Group (DRG) national tariffs). We estimated costs per different patient groups: non-asthma controls, mild/moderate and severe asthmatics. Final results report estimated direct cost per patient and total direct cost for overall target population, showing economic impact related to corticosteroid complication. Results Based on epidemiological data input, in Italy, asthmatic subjects resulted about 3,999,600, of which 199,980 with severe asthma. The number of patients with severe asthma OCS-treated was estimated at 123,988. Compared to the non-asthma control cohort and to that with moderate asthma annual cost per severe asthmatic patient resulted respectively about €892 and €606 higher, showing a corticosteroids shadow cost ranging from 45% to 30%. Applying the cost per patient to the target population identified for Italy, the budget impact model estimated a total annual cost related to OCS-related adverse events of €242.7 million for severe asthmatics. In respect with non-asthmatic and moderate population, an incremental expenditure of about € 110.6 million and €75.2, respectively, were shown. Conclusions Our study provides the first estimates of additional healthcare costs related to corticosteroid induced adverse events in severe asthma patient. Budget impact model results highlighted the relevant economic impact of OCS-related adverse events in severe asthma patients. The future extrapolation of additional data from SANI registry will support the development of a model to investigate the role of corticosteroids sparing drugs.

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