Summary:Eosinophil-associated diseases (EADs) refer to heterogeneous conditions in which eosinophils are believed to play critical pathological roles. They encompass common respiratory conditions, such as asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), less common primary eosinophilic disorders of gastrointestinal tract, and rare conditions including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). A literature search was carried out in January 2024 in the MEDLINE and Scopus databases using the PubMed search engine (PubMed, National Library of Medicine, Bethesda, MD). We focused on blood eosinophilia and hypereosinophilia. A diagnostic workup is proposed. From allergist's point of view, we focused the review on 4 groups of eosinophilic disorders of specific interest. Our increased understanding of type 2 inflammation and biology has recently led to development of highly effective precision targeted therapies that are now approved for a growing number of eosinophilic disorders. Novel targeted biologics have a major impact on treatment strategies and have resulted in major advances in our understanding of the pathogenesis of these disorders. In the context of EADs, according to the heterogeneity of eosinophilic disorders a multidisciplinary approach should be adopted. Allergists and Clinical Immunologists play an important role as they have a clear understanding of the eosinophilic inflammation and the role of cytokines and are trained to recognize and characterize type 2 (T2) inflammation and its associated pathologies.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses.CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma.CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13.Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease.Methods: As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immunoallergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results: Two hundred and fifty-five experts and specialists participated in the survey. Conclusions:The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn.The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated.Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Summary:The aim of this contribution was to highlight the "favorable" and "unfavorable" roles of domestic and non-domestic animals on airway sensitization processes and on the type/severity of the clinical symptoms induced by their exposure. We performed a literature research in MEDLINE for allergic manifestations and animals. Pets can be "allergy friends" through mechanisms related to hygiene hypothesis and translational aspects, the dual role of IgG4 antibodies for pets, and their promising role as healthcare service animals (dogs). On the contrary, animals can be "allergy enemies" when inducing allergic sensitization and  respiratory symptoms (sometimes leading to severe reactions), and also due to cross reactivity with other pets allergens, indirect exposure and ubiquity of their allergens, cross reactivity between Can f 5 and human prostate-specific antigen (PSA). Moreover, in some cases they can trigger anaphylaxis, induce occupational asthma, and act as pests. Finally, we must outline the modest efficacy of allergen immunotherapy (AIT) for their allergens. From a strictly allergological perspective, it is evident that the "negative" aspects resulting from exposure to domestic / non-domestic animals outweigh the "positive" aspects. As a consequence, it is up to humans to seek new ways to balance the pros and cons by exploring research areas that can allow the best possible coexistence with subjects at risk of allergy with domestic and non-domestic animals.

Abstract A 22–year–old man, without prior cardiological history, was waiting for a concert to start many hours in summer heat. Suddenly he started to feel chest pain, dyspnea, and palpitations. Electrocardiogram (EKG), registered from first aid responders, showed a ST elevation in V1–V3 leads and ventricular repolarization alterations in inferior leads. The patient was brought to Emergency department (ED) where a new EKG resulted normalized, blood test samples showed High Sensitive Troponin T (HsTn) 35 ng/L (at plateau in three seriate measures), serum creatinine 2.0 mg/dL, total Creatine Kinase 646U/L, Ck–MB 10.6 ng/mL, Reactive C Protein (RCP) 1.2 mg/dl. The toxicological evaluation was negative. Transthoracic Echocardiography (TTE) did not show any regional ventricular kinesis alterations nor valvular defects, global systolic function was preserved. A Coronary Computed Tomography (CT) scan showed an intramyocardial bridge on Anterior Descending (DA) Coronary Artery associated to 7 mm pericardial effusion without coronary stenosis. A Cardiac Magnetic Resonance (CMR) with gadolinium was performed, which did not show (in T2 mapping sequences) oedema nor Late Gadolinium Enhancement (LGE). Considering a coexistence of Brugada syndrome pattern at EKG, an Ajmaline testing was performed, which resulted negative. Discussion: Dehydration due to any intake of water after standing many hours in summer heat could have been the trigger for a vasospasm of DA that in this patient has a partially intramyocardial course. This anatomical finding was not known until CT scan was performed. Our diagnostic hypothesis of a vasospasm on DA is supported by EKG alterations and elevation enzymes of myocardionecrosis, in absence of any coronary stenosis. Elevated creatinine values in the absence of other renal concomitant comorbidities were suggestive for acute dehydration too. Differential diagnosis took also into consideration myo–pericarditis, especially for the pericardial effusion finding revealed by CT scan: this diagnosis was not confirmed through CMR but also by the evolution of clinical conditions of our patient. We discharged the patient, asymptomatic with normalized renal function after some intravenous hydration and we prescribed a calcium channel blocker. At a follow up visit, three months after the acute event, our patient was in good clinical condition and denied occurrence of any other similar events.

To the Editor, Hymenoptera venom allergy (HVA), characterized by hypersensitivity reactions to stings from insects such as bees and wasps, poses a significant health concern worldwide.Besides the pathophysiological aspects of HVA, there is a growing recognition of its significant impact on Health-Related Quality of Life (HRQoL), comparable to other chronic conditions including allergic diseases (1,2).In addition to generic questionnaires, the Vespid Quality of Life Questionnaire (VQLQ) has been developed as a disease-specific instrument to assess the multidimensional impact of HVA on HRQoL (3), and it has been already validated in several languages (3-9).

Summary:Airways hyperresponsiveness (AHR) is a pathognomonic event of asthma in which the airways are reactive to various bronchoconstrictor stimuli at 'doses' that normally have no bronchoconstrictor effect in non-asthmatics. AHR is an objective measure of clinical efficacy, and the introduction of biologics revived interest as a marker of disease and its pathophysiologic mechanism. This article aims to discuss the mechanisms of AHR, focusing on the role of epithelial damage and TSLP production, and promote its correct assessment for the evaluation of patients with severe asthma, to predict the risk of exacerbations and outcomes, and the eligibility for treatment with an anti-TSLP agent. AHR is a complex trait of asthma, induced by the concurrence of many pathophysiological factors and related to different clinical manifestations. Recent evidence demonstrates the important role of airway epithelial damage and TSLP production in many of these events. A therapeutic response based on AHR control could be considered as a condition of disease remission and seems a promising new goal for the management of patients with severe asthma.

Summary:Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

Background: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. Patients: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. Results: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. Conclusion: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Summary:It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

It is currently recognized that the airway epithelium plays a pivotal role in orches-trating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The im-pact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several path-ways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the patho-genesis of asthma. Pollutants also have a pleiotropic effect on respiratory epitheli-um. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are trig-gered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyper -reactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

An accurate clinical evaluation of asthmatics (especially those with a relevant degree of asthma severity) is recommended, before ICM administration.

Nocebo effect" and induction/aggravating bronchospasm in asthmatics

Summary:Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

SummaryBackground.The Italian Registry on Severe Asthma (IRSA) is the most recent and largest registry in Italy. Objective. To improve the knowledge on the clinical and biological features of severe asthma (SA), and to monitor its treatments. Methods. To analyze clinical, functional, inflammatory, and treatment characteristics of severe asthmatics from the IRSA registry. Results. 851 subjects were enrolled. 31.8% and 64.5% of patients were submitted to oral corticosteroids (OCS), and monoclonal antibodies (MABs), respectively. At least two comorbidities affected 77.4% patients. Asthma was uncontrolled in 62.2% patients. Uncontrolled patients had a higher frequency of exacerbations, and hospitalization, showing a higher eosinophilic phenotype, a greater use of OCS, and being treated with MAB less frequently. However, uncontrolled patients treated with MAB had a lower use of OCS and a lower rate of hospitalization. Comparing SA patients with atopy and without atopy, the latter showed a greater use of OCS, and more frequent nasal polyposis and osteoporosis. Among SA patients with atopy treated with MAB, 36% were on a treatment targeting the IL-5 pathway. Conclusions and clinical relevance. This study shows the features of the greatest Italian registry of SA patients, revealing at the time of enrollment a poor disease control, and the use of OCS and MABs in about one third and two thirds of patients, respectively. SA is a complex disease that requires a more precise phenotyping and a greater disease control.

SUMMARY:Objective. The purpose of the study was to describe the characteristics of patients experiencing hypersensitivity reactions (HRs) to iodinated contrast media (ICM) in a large Italian population and to investigate potential risks factors in order to obtain a risk stratification, helpful in the management of these patients. Methods. Data of 407 patients investigated in 9 Italian Allergy Centers for suspected HRs to ICM were analyzed and compared with a control group of 152 subjects that tolerated one or more ICM-enhanced examinations. The univariate and multivariate logistic regression model was used to evaluate associated factors. Results. The mean age of reactive patients was 61 years and 60% were female; 67% of patients reported immediate reactions and 35% experienced the reaction, more frequently with immediate onset, at the first examination in life. Iomeprol, iopromide and iodixanol were the most frequent culprit agents and 20% of patients showed a positive skin test result. Previous adverse reactions to ICM were reported by 15.6% of patients, whereas 35% of subjects experienced the reaction, more frequently immediate, after the first ICM-enhanced examination in their life. The multivariate analysis showed that male gender and age > 65 were associated with ICM reactions as protective factors [ORadja = 0.51; 95% CI: 0.33-0.77 and ORadja = 0.60; 95% CI: 0.39-0.92 respectively]. Cardio-vascular disease [ORadja = 2.06; 95% CI: 1.22-3.50)], respiratory allergy [ORadja = 2.30; 95% CI: 1.09-4.83)] and adverse drug reactions [ORadja = 1.99; 95% CI: 1.05-3.77)] were identified as risk factors for ICM reactions. Food allergy was not significantly associated with reactions [ORadja = 1.51; 5% CI: 0.41-5.56]. Conclusions. This is the largest study on Italian patients experiencing hypersensitivity reactions to ICM. Most results are in line with other studies, showing some association with factors that could influence the incidence of hypersensitivity reactions but not allowing an easy risk stratification.

Anaphylaxis is the most severe systemic hypersensitivity reaction, and it can be life-threatening or even fatal. It involves the activation of multiple immune and non immune pathways beyond IgE, thus exhibiting different phenotypes. New symptoms of hypersensitivity caused by chemotherapy drugs, monoclonal antibodies, and biological agents have been suggested to be recognized as anaphylaxis phenotypes. No biomarker has been described that allows an unequivocal diagnosis of anaphylaxis. Moreover, more biomarkers for specific endotypes are needed to stratify severity, to predict risk, and to optimaze tretament choice in the individual patient. Food, drugs and stinging insects represent the most commly identified triggers. Idiopathic anaphylaxis is a diagnosis of exclusion and it can hide a clonal mast cell disorder. Individual risk factors and co-factors may influence the severity of anaphylaxis or its onset, and they should be identified to implement the appropriate measures to prevent recurrence. Prompt recognition and treatment are critical in anaphylaxis, adrenaline being the first-line saving therapy. Individualized anaphylaxis action plan should include avoidance measures, prescription of an adrenaline autoinjector, education, optimal management of relevant comorbidities, venom specific immunotherapy, food oral immunotherapy, and drug desensitization, when appropriate. However, the quality of acute and long-term anaphylaxis management is variable influencing the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes, but they often prove challenging to implement in routine clinical care.