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Cristoforo Incorvaia,1 Marcello Montagni,2 Elena Makri,1 Gian Galeazzo Riario-Sforza,1 Erminia Ridolo21Allergy/Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento Hospital, Milan, Italy; 2Department of Clinical and Experimental Medicine, University of Parma, Parma, ItalyAbstract: β2-agonists were introduced in the 1940s as bronchodilators to be used in obstructive respiratory diseases. Long-acting β2-agonists have been a mainstay of bronchodilating treatment for decades. Recently, agents extending their effect to 24 hours and thus allowing the once-daily administration were introduced, defined as very-long-acting β2-agonists. Olodaterol is a new very-long-acting β2-agonist that has been shown, in controlled trials, to improve lung function as well as clinical outcomes and quality of life. Most of these trials included patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD). Olodaterol has a rapid onset of action (comparable to formoterol) and provides bronchodilation over 24 hours. In controlled trials, olodaterol was shown to be as effective as formoterol twice daily, but significantly superior in terms of quality of life in patients with COPD. The safety profile of olodaterol was very good, with a rate of adverse events, including the cardiac events that are particularly important for β2-agonists, comparable to placebo. Also, the efficiency of the Respimat® device concurs to the effectiveness of treatment.Keywords: bronchodilators, β2-agonists, very long acting, olodaterol, efficacy, safety, COPD

Cristoforo Incorvaia,1 Marcello Montagni,2 Elena Makri,1 Erminia Ridolo21Allergy/Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento Hospital, Milan, 2Department of Clinical and Experimental Medicine, University of Parma, Parma, ItalyAbstract: The current guidelines on chronic obstructive pulmonary disease (COPD) recommend the prominent use of bronchodilators, including long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), while inhaled corticosteroids are recommended only in patients with severe disease or frequent exacerbations. LABA–LAMA combinations are indicated when single bronchodilators are insufficient to control COPD. A number of LABA–LAMA combinations are available, based on twice-daily or once-daily administration according to the 12- or 24-hour duration of action, respectively. The aclidinium–formoterol combination is based on the new LAMA aclidinium bromide, which has a high selectivity for M3 muscarinic receptors and a fast onset of action, and the well-known LABA formoterol. Both drugs require twice-daily administration. The fixed-dose combination of aclidinium 400 µg/formoterol 12 µg has shown in randomized controlled trials fast and sustained bronchodilation that was greater than either monotherapy and provided clinically significant improvements in dyspnea and health status compared with placebo, also reducing the use of rescue medications. The overall incidence of adverse events was low and comparable to placebo. These data define the aclidinium–formoterol fixed-dose combination as a new treatment option for patients with COPD. The need for twice-daily administration could be an apparent disadvantage compared to the available once-daily LABA–LAMA combinations, but the immediately perceived benefit in reducing dyspnea due to the fast onset of action, as well as reported correct patient use and satisfaction with the Genuair inhaler might prove useful in favoring adherence.Keywords: bronchodilators, COPD, LABA, LAMA, combination, efficacy, safety, inhalation device

Erminia Ridolo,1 Marcello Montagni,1 Elisa Olivieri,1 Gian Galeazzo Riario-Sforza,2 Cristoforo Incorvaia2 1Department of Clinical and Experimental Medicine, University of Parma, Parma, 2Pulmonary Rehabilitation Unit, ICP Hospital, Milan, Italy Abstract: Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far. Keywords: chronic obstructive pulmonary disease, bronchodilators, very long-acting β2-agonists

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-specific lipid transfer proteins (nsLTPs) are a family of plant pan-allergens that represent the primary cause of food allergies in the Mediterranean area, characterized by a wide range of clinical manifestations, ranging from the total absence of symptoms up to anaphylaxis. This wide variety of symptoms is related to the intrinsic capacity of nsLTPs to cause an allergic reaction in a specific subject, but also to the presence of co-factors exacerbating (i.e., exercise, NSAIDs, PPIs, alcohol, cannabis, prolonged fasting, menstruation, acute infections, sleep deprivation, chronic urticaria) or protecting from (i.e., co-sensitization to PR10, profilin or polcalcin) severe reactions. In this picture, recognizing some nsLTPs-related peculiarities (i.e., route, type and number of sensitizations, concentration of the allergen, cross-reactions) and eventual co-factors may help the allergist to define the risk profile of the single patient, in order to promote the appropriate management of the allergy from dietary advices up to the prescription of life-saving epinephrine autoinjector., 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., (© 2023 Ridolo, Barone, Ottoni, Peveri, Montagni and Nicoletta.)

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly., Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods., Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro ., Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro , was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south., Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity should still rely on skin tests with fresh material. The exclusion of mollusks from shrimp allergic patients' diets should occur when clinical history, available diagnostic instruments, and/or tolerance tests support such a decision., (© 2022 The Author(s).)

Introduction: Lipid transfer proteins (nsLTPs) are ubiquitous allergens. Patients affected by nsLTP syndrome experience symptoms to various plant-derived foods, ranging from local manifestations to anaphylaxis, the critical treatment of which is represented by self-administration of adrenaline. The principle aim of this study is to assess how dietary recommendations influence the occurrence of new and severe cases and if poly-sensitization to different nsLTPs may play a role. We also investigated about the appropriate use of adrenaline auto-injector during the episodes of anaphylaxis. Moreover, we examinated how other features (ie, co-sensitization to profilin and PR-10 and the presence of risk co-factors) affect these events., Materials and Methods: We evaluated 78 patients allergic to nsLTPs, investigating adherence to diet and ability to use the adrenaline auto-injector. Number of sensitization to nsLTPs, co-sensitization to other panallergens, and presence of risk factors for new reactions were also assessed. Diagnosis was based on clinical history and positivity to in vivo and in vitro tests. During the follow-up, compliance, diet modifications, and new reactions were noted, and re-training for the use of epinephrine auto-injector was performed. At the last visit we evaluated the patients' ability to use the self-injector., Results: The whole of fruits belonging to the Rosaceae family emerged as the most frequent culprit foods (28%), followed by walnut (17%), peanut (17%), and hazelnut (10%). At the baseline visit 23% of the patients described the presence of a risk factor during the allergic reaction (mainly nonsteroidal anti-inflammatory drugs [NSAIDs] and exercise). Forty-five percent of the patients reported anaphylactic reactions; no association between the type of food and the severity of the reactions was found. The presence of sensitization to 4 or more nsLTPs was associated to more severe reactions ( p  < .05; OR 1.67). During the follow-up 38% of the patients experienced at least 1 new allergic reaction: in 79% of them the culprit food was previously tolerated, and in 69% the reaction was an anaphylaxis. Only 47% of the patients showed a proper use of adrenaline auto-injector during the final evaluation, but a significant correlation between periodic education and reduction of the probability of mistakes in the use was reported ( p  < .05; OR 0.34). Furthermore, an association between co-sensitization to PR-10 (in particular Bet v1) and profilin and less severe symptoms was found, but without a significant odds ratio., Conclusion: A careful education aimed to the prevention of new reactions, through dietary restrictions and avoidance of risk co-factors, and to the management of anaphylaxis, through the training for the correct use of adrenaline auto-injector, should be a routine practice in nsLTP syndrome., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Objective: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences., Methods: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844)., Results and Conclusion: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease., Abbreviations: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Background: Peanut allergy has not been well characterized in Italy., Objective: Our aim was to better define the clinical features of peanut allergy in Italy and to detect the peanut proteins involved in allergic reactions., Methods: A total of 22 centers participated in a prospective survey of peanut allergy over a 6-month period. Clinical histories were confirmed by in vivo and/or i n vitro diagnostic means in all cases. Potential risk factors for peanut allergy occurrence were considered. Levels of IgE to Arachis hypogea (Ara h) 1, 2, 3, 6, 8, and 9 and profilin were measured., Results: A total of 395 patients (aged 2-80 years) were enrolled. Of the participants, 35% reported local reactions, 38.2% reported systemic reactions, and 26.6% experienced anaphylaxis. The sensitization profile was dominated by Ara h 9 (77% of patients were sensitized to it), whereas 35% were sensitized to pathogenesis-related protein 10 (PR-10) and 26% were sensitized to seed storage proteins (SSPs). Sensitization to 2S albumins (Ara h 2 and Ara h 6) or lipid transfer protein (LTP) was associated with the occurrence of more severe symptoms, whereas profilin and PR-10 sensitization were associated with milder symptoms. Cosensitization to profilin reduced the risk of severe reactions in both Ara h 2- and LTP-sensitized patients. SSP sensitization prevailed in younger patients whereas LTP prevailed in older patients ( P < . 01). SSP sensitization occurred mainly in northern Italy, whereas LTP sensitization prevailed in Italy's center and south. Atopic dermatitis, frequency of peanut ingestion, peanut consumption by other family members, or use of peanut butter did not seem to be risk factors for peanut allergy onset., Conclusions: In Italy, peanut allergy is rare and dominated by LTP in the country's center and south and by SSP in the north. These 2 sensitizations seem mutually exclusive. The picture differs from that in Anglo-Saxon countries., (© 2022 The Author(s).)

Background: Honey is a rare cause of food allergy, especially in children, but it can cause severe systemic allergic reactions. In the pediatric age group, only a few cases have been reported in the literature. Honey allergy may be caused by pollen content or bee-derived proteins. A role for Compositae has been suggested among pollen allergens. Allergology workup of a patient with suspected honey allergy is not well defined. Here we describe a rare case of anaphylaxis in a 5-year-old boy, sensitized to Compositae pollen (ragweed and mugwort), after the ingestion of artisanal honey., Case Presentation: The Slavic patient was referred to our hospital emergency department for generalized urticaria and breathing impairment. All the symptoms occurred approximately 30 minutes after the ingestion of a meal containing salmon and artisanal honey. The allergology workup revealed that a skin prick-by-prick test with the implicated artisanal honey was positive, while a variety of different commercial honey and salmon products yielded negative results. Skin prick test and serum-specific immunoglobulin E (IgE) results were also positive for Compositae pollen (ragweed and mugwort). Patients sensitized to weed pollens who ingest bee products may experience an immediate allergic reaction because of the cross-reaction between weed pollens and Compositae bee product pollen. In this case, primary sensitization may be due to airborne Compositae pollen. Commercial honey is heavily processed due to pasteurization and filtration, which removes most of the pollen. These observations highlight the role of Compositae pollen in the observed allergic reaction and suggest that the different pollen content in the artisanal honey relative to commercial honey was responsible for the allergic reaction in our patient., Conclusions: This is the first reported pediatric case of honey-induced anaphylaxis in a child under 6 years of age sensitized to Compositae pollen. Pediatricians should be aware of the potential risk of severe allergic reactions upon ingestion of honey and bee products, especially in patients sensitized to weed pollens. To diagnose honey allergy, obtaining a proper clinical history is essential. In addition, skin prick-by-prick tests are helpful, and may represent a simple method to screen for honey allergy in patients sensitized to Compositae pollen, in light of the potential risk.

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics., Competing Interests: GW Canonica received in the last three years research grants as well as lecture or advisory board fees from: A. Menarini, Alk-Abello, Allergy Therapeutics, AstraZeneca, Boehringer-Ingelheim, Chiesi Farmaceutici, Genentech, Guidotti-Malesci, Glaxo Smith Kline, Hal Allergy, Mylan, Merck, Mundipharma, Novartis, Regeneron, Sanofi-Aventis, Sanofi-Genzyme, StallergenesGreer, UCB pharma, Uriach Pharma, Valeas, ViborPharma. F Blasi received grants and/or personal fees from: AstraZeneca, Bayer, Chiesi, Guidotti, Glaxo Smith Kline, Grifols, Insmed, Menarini, Mundifarma, Novartis, Pfizer, Zambon. PL Paggiaro received grants and/or personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Guidotti, Mundipharma, Novartis, Sanofi. S Aliberti received grants and/or personal fees from Actavis UK Ltd, Aradigm Corporation, AstraZeneca, Basilea, Bayer Healthcare, Chiesi, Grifols, Horizon, INSMED, Novartis, Raptor, Zambon. L Cosmi received personal fees from Glaxo Smith Kline and Novartis. S Centanni received grants and/or personal fees from AstraZeneca, Boheringer Ingelheim, Chiesi, Glaxo Smith Kline, Guidotti, Menarini, Novartis, Valeas. ME Conte received personal fees from Glaxo Smith Kline. S D’Alò received fees for clinical trials from Glaxo Smith Kline. S Del Giacco received grants and/or personal fees from AstraZeneca, Chiesi, Glaxo Smith Kline, Menarini. Novartis. F Puggioni received personal fees from Allergy therapeutics, Almirall, AstraZeneca, Chiesi, Glaxo Smith Kline, Guidotti, Menarini, Mundipharma, Novartis, Sanofi, Valeas. FLM Ricciardolo received grants, personal fees and/or other supports from AstraZeneca, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Guidotti, Lusofarmaco, Menarini, Neopharmed, Novartis, Sanofi, Teva. L Richeldi received personal fees from Bayer, Boehringer Ingelheim, Celgene, FibroGen, Promedior, RespiVant, Roche, Sanofi-Aventis. P Santus received grants and/or personal fees from ALK Abellò, AstraZeneca, Berlin Chemie, Boheringer Ingheleim, Menarini International, Novartis, Sanofi, Valeas, Zambon. E Heffler received personal fees from AstraZeneca, Boheringer Ingheleim, Circassia, Glaxo Smith Kline, Nestlè Purina, Novartis, Sanofi, Teva, Valeas. GE Senna, G Passalacqua, A Spanevello, D Bagnasco, M Bonavia, M Bonini, L Brussino, C Bucca, MF Caiaffa, C Calabresi, G Camiciottoli, M Caminati, GE Carpagnano, C Caruso, AG Corsico, MT Costantino, N Crimi, M D'Amato, A Farsi, E Favero, MP Foschino Barbato, G Guarneri, G Guida, M Latorre, S Lo Cicero, C Lombardi, L Macchia, F Mazza, F Menzella, M Milanese, M Montagni, P Montuschi, E Nucera, R Parente, V Patella, G Pelaia, L Pini, L Ricciardi, E Ridolo, G Rolla, N Scichilone, G Spadaro, A Vianello, V Viviano, MR Yacoub, MC Zappa have nothing to disclose., (© 2020 The Authors.)

Summary: Anakinra, one of the novel biological agents, is a recombinant human IL-1 receptor antagonist. It is preferred as an alternative drug for familial Mediterranean fever cases where colchicine is not sufficient or cannot be used due to its side effects. Like all other biologics, hypersensitivity reactions to anakinra are quite rare. This is the first case which was successfully desensitized with anakinra after a severe immediate-type hypersensitivity reaction. We report a case of WDEIA in an asthmatic boy admitted to our Unit with suspected mushroom acute toxicity. The symptoms occurred during a gym session, approximately 2 hours after the ingestion of a meal based on pasta and cooked mushroom found in the family's garden. Acute toxicity due to mushroom ingestion was then excluded. Triptase serum levels resulted elevated in acute phase and normal after 24 hours. Food specific IgE showed a sensitization to lipid transfer protein Pru p 3 and to Tri a 14. This case highlights that WDEIA is underdiagnosed, especially when patients are firstly visited in Emergency Unit. Moreover, Tri a 14 is seldom described as responsible for WDEIA, compared to omega 5 gliadin.

Background: Precision medicine (PM) is changing the scope of allergy diagnosis and treatment. An in vitro IgE assay, a prototype PM method, was developed in the sixties and has garnered increasing interest because of the introduction of recombinant components in the test. More recently, microarrays of allergen components have significantly improved the ability to describe the IgE profile. Aim of this study was to evaluate the characteristics of the newly developed Allergy Explorer (ALEX), a macroarray containing both extracted "whole" allergens and molecular components. This method allows the acquisition of an IgE profile comprising 282 reagents (157 allergen extracts and 125 components), resulting in the widest screening of potential allergens available., Methods: Sera from 43 patients with allergies were assayed with ALEX and then with ImmunoCAP ISAC. The results of the two tests were compared, and the consistency of the molecular results with the presence of IgE in the relevant extract was also evaluated., Results: A good correlation between ISAC and ALEX was observed. The ALEX results for second-level tests (i.e., specific IgE to complete extracted allergens) were consistent with the results obtained for the relevant components., Discussion: Despite differences in the methodology, the IgE profiles detected for molecular allergens by ALEX and ISAC were very similar. The differences were mainly related to the lower dynamic range of ALEX and to the use of a CCD inhibitor in the first incubation phase, which reduced the binding of IgE to CCD, as represented in the extracted allergens and components., Conclusion: Based on our findings, ALEX is a novel tool for describing the IgE profile in a PM setting, where the IgE assay must be performed on many allergens and components. In particular, polysensitized patients and patients with pollen-food syndrome will have a real advantage due the combination of the second and third levels of allergy diagnostics in the same chip., Competing Interests: This was a laboratory study where two methods commercially available were used to describe the IgE profile in a group of sera collected for diagnostic reasons in allergic patients. Sera were identified by a unique laboratory code and were processed in an anonymous procedure. All patients were informed of the fact that their serum could be used in a comparison with another assay and gave a verbal consent.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The introduction of highly purified natural and recombinant single allergenic molecules represented an important improvement in the diagnosis of IgE sensitization. The identification of specific IgE against cross-reacting molecules such as profilin, lipid transfer proteins, calcium binding proteins or against “genuine molecules”, represents an added value and allows to distinguish between true and false polysensitization. In vitro tests add information to recognize patients with sensitization to genuine molecules that cause allergic diseases and to evaluate in childhood the spreading of sensitization for each molecule in order to choose the best treatment and to identify the ideal patient for allergen immunotherapy. Also, in order to detect patients with sensitization to pan-allergens it is important to manage the risk of anaphylaxis for patients allergic to latex and to identify IgE to particular molecules involved in occupational allergy. In patients with negative skin prick tests (SPT), that results in a lower sensitivity compared with in vitro tests, the negative test may be caused by the lack of some important allergenic molecules in the extract used for SPT.

Objectives: Molecular diagnostic is a new therapeutic approach that - allows to valuate sensitization towards a single molecule in a allergenic source and to obtain relevant information on clinical features: sensitization towards molecules as alfa amylase of wheat or lipocalins of pets, Alt a 1 of alternaria spores and Hev b 6 of latex correlates with the risk to develop asthma - has a greater sensitivity in the serum IgE identification than the whole source., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by Aracne Editrice, Roma, Italy.)

Background: Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal., Methods: We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP)., Results: The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom., Conclusion: The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

Allergen immunotherapy (AIT) was introduced more than a century ago and is yet the only disease-modifying treatment for allergy. AIT is currently conducted with whole allergen extracts and several studies clearly support its efficacy in the treatment of respiratory allergies, however the need for a long treatment - that affects costs and patients compliance - and possible IgE-mediated adverse events are still unresolved issues. Peptide immunotherapy is based on the use of short synthetic peptides which represent major T-cell epitopes of the allergen with markedly reduced ability to cross-link IgE and activate mast cells and basophils. Data from clinical trials confirmed the efficacy and tolerability of peptide immunotherapy in patients with cat allergy, with a sustained clinical effect after a short course treatment. Peptide therapy is a promising safe and effective new specific treatment for allergy to be developed for the most important allergens causing rhinitis or asthma.

Objective: As confirmed by systematic reviews and meta-analyses, allergen immunotherapy is clinically effective in the treatment of allergic diseases. In particular, subcutaneous immunotherapy is a pivotal treatment in patients with severe reactions to Hymenoptera venom, whereas subcutaneous immunotherapy and sublingual immunotherapy are indicated in the treatment of allergic rhinitis and asthma by inhalant allergens. Other allergies related to animal dander (other than cat, which is the most studied), such as dog, molds, occupational allergens, and insects, have also been recognized. For these allergens, immunotherapy is poorly studied and often unavailable. Thus, use of the term orphan immunotherapies is appropriate., Data Sources: We used MEDLINE to search the medical literature for English-language articles., Study Selection: Randomized, controlled, masked studies for orphan immunotherapies were selected. In the remaining cases, the available reports were described., Results: The literature on food desensitization is abundant, but for other orphan allergens, such as mosquito, Argas reflexus, dog, or occupational allergens, there are only a few studies, and most are small studies or case reports., Conclusion: Orphan immunotherapy is associated with insufficient evidence of efficacy from controlled trials, an erroneous belief of the limited importance of some allergen sources, and the unlikelihood for producers to have a profit in making commercially available extracts (with an expensive process for registration) to be used in few patients. It should be taken into consideration that adequate preparations should be available also for orphan allergens., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Self-administered adrenaline through an auto-injector is the main out-of-hospital treatment for anaphylaxis, and patients should be trained to promptly and correctly use the device. The aim of the study was to verify the proper use of the device and the correct drug administration, and to identify possible misuse by patients. In seven Italian Allergy clinics, patients who were previously provided with self-injectable adrenaline were recruited at the follow-up visit required for the renewal of their prescription. All patients completed a questionnaire covering details of their allergic reactions, and knowledge of the device. The correct use was verified by the physician using a trainer with a four-step examination. 242 patients were included; 46 patients (18 %) did not always carry the auto-injector, and 35 patients (14 %) reported situations in which they were doubtful about whether to use adrenaline. Only 39 % of patients properly managed the device, while some patients (6 %) failed in all four steps. The majority of patients considered it appropriate to use adrenaline at the onset of respiratory symptoms (56 %). The factor most closely related to proper use of the device was the education of the patient (p = 0.03), while age and the time from first prescription did not affect the ability to properly use the auto-injector. Even though accurate training is conducted, many patients are still unable to properly use the adrenaline auto-injector in case of anaphylaxis. Allergists should review the instructions provided to the patients every time a renewal of the auto-injector is prescribed.

The introduction of new laboratory techniques to detect specific IgE antibodies against single allergen molecules rather than whole extracts represents a significant advance in allergy diagnostics. The advantages of such component-resolved diagnosis can be summarized as follows: (1) the ability to identify the truly responsible allergens in polysensitized patients, whether they be genuine (causing specific sensitization to their corresponding allergen source) or primary (the original sensitizing molecule); (2) distinguishing these allergens from simply cross-reactive components; (3) improving the appropriateness of the prescribed specific immunotherapy; and (4) identifying a risk profile for food allergens. Component-resolved diagnosis is performed using either a singleplex (1 assay per sample) platform or a multiplex (multiple assays per sample) platform. Using an immuno solid-phase allergen chip microarray that falls into the latter category--it currently tests sensitivity to 112 allergens--may lead to a pitfall: detecting IgE to unexpected allergens, such as Hymenoptera venom. In fact, testing insect venom sensitivity in individuals with no history of reactions to stings is contrary to current guidelines and presents the physician with the dilemma of how to manage this information; moreover, this may become a legal issue. Based on what is currently known about venom allergy, it remains likely that a positive sensitization test result will have no clinical significance, but the possibility of reacting to a future sting cannot be completely ruled out. Because this problem has not been previously encountered using the more common allergy tests, no indications are currently available on how to effectively manage these cases., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods - all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Bilastine is a new second generation H1-antihistamine recently approved for the symptomatic treatment of allergic rhinitis (AR) and chronic urticaria (CU). Bilastine epitomizes the evolution of research on antihistamines concerning both efficacy and safety. In AR treatment, a number of large controlled clinical trials documented its efficacy, as assessed by improvement of all nasal and ocular symptoms and quality of life. These outcomes show that bilastine meets current EAACI/ARIA criteria for medications used in the treatment of AR. Also in CU, the review of the literature indicates that once-daily treatment with bilastine 20 mg was effective in managing symptoms and improving patient's quality of life. Concerning safety and tolerability, the profile of bilastine is very similar to placebo and in particular the adverse effects on central nervous system are insignificant. The balance of efficacy and safety of bilastine is particularly helpful when dosages higher than standard are needed to control the symptoms, as frequently occurs in patients with urticaria, in whom antihistamines doses up to four times the standard dose may be administered.