Purpose of review Non-T2 asthma is currently defined by missing parameters, such as low blood eosinophils and FeNO, rather than positively identifiable mechanistic features. This definition overlaps with paucigranulocytic asthma (PGA). However, T2-biomarkers fluctuate over time, especially during glucocorticoid therapy, leading to potential over-diagnosis of T2-low asthma. Advancing beyond traditional endotyping is required for precision medicine. Recent findings Alarmin-driven asthma [interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), IL-25] can drive inflammation even without high T2-markers, but these are difficult to measure clinically. Genetic testing, such as the rs7216389 SNP (17q21 locus, GSDMB/ORMDL3), offers a stable alternative. The T allele is linked to childhood-onset asthma, viral-induced alarmin release, and epithelial dysfunction. Notably, carriers of the T allele are more likely to respond to allergen immunotherapy (AIT). This genetic marker is not subjected to treatment-dependent modification and segregates with both T2-driven and alarmin-driven asthma. Summary We propose that rs7216389 genotyping could be explored, within a treatable trait framework, to improve the mechanistic characterization of paucigranulocytic or low-biomarker asthma. While current data are associative, this one-time genetic assessment might contribute to research-driven stratification of “hidden” T2- or alarmin-leaning endotypes, potentially guiding the use of AIT and upstream biologics like anti-TSLP.

ObjectivesThis study aimed to evaluate periostin serum levels and skin expression in patients with systemic sclerosis (SSc).MethodsWe enrolled 35 patients with diffuse (d-SSc) or limited (l-SSc) SSc, 15 patients with very early diagnosis of systemic sclerosis (VEDOSS), and 30 sex-matched healthy controls. Periostin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA). Periostin skin expression was determined by immunohistochemistry (IHC) on paired involved and uninvolved 5-mm skin biopsy samples in a subgroup of 10 d-SSc and 10 L-SSc patients. A 12-month follow-up was considered.ResultsWe included 50 patients (mean age 53.1 ± 16.1 years; women 94%; mean disease duration 38.2 ± 45.1 months; anti-centromere 50%; anti-Scl70 40%), 35 of them with a definite SSc (68.8% l-SSc; 31.4% d-SSc; mean mRSS 9.0 ± 7.2) and 15 with VEDOSS; 30 controls were also included in this study. Periostin serum levels were higher in SSc patients compared to controls (32.7 ± 8.0 ng/mL vs. 27.7 ± 7.3 ng/mL; p < 0.001), while these levels were comparable among different groups of patients (29.7 ± 6.9 ng/mL in VEDOSS, 33.4 ± 7.8 ng/mL in lc-SSc; and 34.0 ± 8.5 in dc-SSc; p = ns). SSc patients with digital ulcers had higher periostin serum levels (36.2 ± 7.9 ng/mL vs. 30.6 ± 7.3 ng/mL, p < 0.02). Samples from the involved skin of l-SSc and d-SSc patients showed a significant dermal expression of periostin; an identical periostin expression was evident in the uninvolved skin of patients with d-SSc. In 7 out of 10 L-SSc patients, periostin expression was absent on uninvolved skin. In the remaining three l-SSc patients, a mild periostin expression on IHC was detectable on uninvolved skin and all of these three l-SSc patients presented a dramatic skin progression.ConclusionPeriostin skin expression may be a useful biomarker to indicate the presence of a disease at a higher risk of rapid cutaneous involvement.

Prevalence of birch pollen allergy is up to 30% in industrialized countries. Birch is a member of the order Fagales, which includes other potent elicitors of spring pollinosis, such as alder, hazel and oak. The high IgE cross-reactivity within Fagales due to PR-10-like proteins is well known. Therefore, to develop a successful anti-allergen antibody therapy for birch pollen and related allergies it becomes important to target as many PR-10 proteins as possible. Mabylon has developed a human antibody discovery platform that allowed us to clone and express Bet v 1-specific recombinant human antibodies from allergic patients. Upon screening our human-derived anti-birch antibody library, we selected the most potent antibody cocktail, MY010, as anti-allergen antibody immunotherapy for the treatment of birch-related pollen allergies. The selected antibodies are binding Bet v 1 with high affinity and targeting disease-relevant proteins and epitopes. MY010 shows broad cross-reactivity within the PR-10 protein family. It prevents patients' IgE binding to the allergens and effector cell degranulation upon stimulation with multiple Fagales extracts such as oak, hazel and alder in addition to birch. MY010 is efficacious in patient samples originating from different geographical regions. In conclusion, MY010 holds great promise as a novel therapy for birch and related pollen allergies, with a predicted immediate onset of protection and good safety profile. It shows significant cross-reactivity to the different PR-10 pollen allergens and efficacy in patient samples from different geographical regions and to multiple birch-related extracts.

Exposure to the Mus m 1 aeroallergen is a significant risk factor for laboratory animal allergy. This allergen, primarily expressed in mouse urine where it is characterized by a marked and dynamic polymorphism, is also present in epithelium and dander. Considering the relevance of sequence/structure assessment in protein antigenic reactivity, we compared the sequence of the variant Mus m 1.0102 to other members of the Mus m 1 allergen, and used Discotope 2.0 to predict conformational epitopes based on its 3D-structure. Conventional diagnosis of mouse allergy is based on serum IgE testing, using an epithelial extract as the antigen source. Given the heterogeneous and variable composition of extracts, we developed an indirect ELISA assay based on the recombinant component Mus m 1.0102. The assay performed with adequate precision and reasonable diagnostic accuracy (AUC = 0.87) compared to a routine clinical diagnostic test that exploits the native allergen. Recombinant Mus m 1.0102 turned out to be a valuable tool to study the fine epitope mapping of specific IgE reactivity to the major allergen responsible for mouse allergy. We believe that advancing in its functional characterization will lead to the standardization of murine lipocalins and to the development of allergen-specific immunotherapy.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a heterogeneous, multiorgan and potentially life-threatening drug-hypersensitivity reaction (DHR) that occurs several days or weeks after drug initiation or discontinuation. DHRs constitute an emerging issue for public health, due to population aging, growing multi-organ morbidity, and subsequent enhanced drug prescriptions. DRESS has more consistently been associated with anticonvulsants, allopurinol and antibiotics, such as sulphonamides and vancomycin, although new drugs are increasingly reported as culprit agents. Reactivation of latent infectious agents such as viruses (especially Herpesviridae) plays a key role in prompting and sustaining aberrant T-cell and eosinophil responses to drugs and pathogens, ultimately causing organ damage. However, the boundaries of the impact of viral agents in the pathophysiology of DRESS are still ill-defined. Along with growing awareness of the multifaceted aspects of immune perturbation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing SARS-CoV-2-related disease (COVID-19) pandemic, novel interest has been sparked towards DRESS and the potential interactions among antiviral and anti-drug inflammatory responses. In this review, we summarised the most recent evidence on pathophysiological mechanisms, diagnostic approaches, and clinical management of DRESS with the aim of increasing awareness on this syndrome and possibly suggesting clues for future research in this field.

Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.

Background. Allergies to house dust mite (HDM) and to crustaceans are clinically and pathogenically linked. Several homologous allergenic proteins have been identified, among which tropomyosin is the prototype, expressing epitopes endowed with variable levels of immunoglobulin E (IgE) cross-reactivity. Component-resolved diagnosis (CRD) does not allow a thorough characterization of all relevant IgE reactivities to these allergen sources. Objectives. We studied 1 patient allergic to shrimp with positive skin prick test to HDM and negative scores for IgE to HDM allergen components routinely used in CRD (group 1 and 2 allergens, Der p 23 and tropomyosin). Materials and methods. In order to identify the allergen(s) involved in IgE reactivity, we used serological proteome analysis (SERPA), which utilizes two-dimensional gel electrophoresis (2DE), immunoblotting and mass spectrometry (MS). The identified allergenic proteins were tested with sera from 20 crustacean-allergic patients and 19 grass-allergic patients serving as controls. Results. Der p 14 and myosin heavy chain type 1 (MHC1) were identified as the components recognized by patient's IgE in the proteome of Dermatophagoides pteronyssinus and Penaeus monodon, respectively. The MHC1 protein shows about 30% sequence identity with Der p 14 in specific domains, and cross-reactivity against epitopes shared by the 2 proteins was demonstrated by reduced reactivity to shrimp extract following pre-incubation with Der p 14. Serum IgE from 5 out of 20 patients allergic to crustaceans reacted with MHC1, compared to none among 19 controls (p < 0.05). Conclusions. We identified MHC1 as a relevant allergic component in the proteome of Penaeus monodon, the prototypic allergen source used in diagnosis of allergy to crustaceans. Our data demonstrate MHC1 cross-reactivity between MHC1 and Der p 14 from Dermatophagoides pteronyssinus.

Background: Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment. Methods: We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3–10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment. Results: A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3–10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33–60%) when compared to patients with low DAO (40%, IQR = 20–60%; p = 0.045) or high DAO (33%, IQR = 0–50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels. Conclusions: HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.

The presented data were obtained with the lipocalin allergen Mus m 1.0102 and its cysteine mutants MM-C138A, MM-C157A and MM-C138,157A, whose structural features and unfold reversibility investigations are presented in the research article entitled "The allergen Mus m 1.0102: cysteine residues and molecular allergology" [1]. The data were obtained by means of a Dynamic Light Scattering-based thermal stability assay, a Fluorescence-based ligand-binding assay and a basophil degranulation test, and describe proteins' fold stability, ligand binding ability and allergenic potential, respectively. Analysis of the collected data produced the temperatures corresponding to the onset of the protein unfolding, the dissociation constants for N-Phenyl-1-naphthylamine ligand and the profiles of beta-hexosaminidase release from RBL SX-38 cells, sensitized with the serum of selected allergic patients and incubated with increasing antigens concentrations. These data allow for comparison of the lipocalin allergen Mus m 1.0102 with its conserved cysteines mutants and, with regard to their potential application in allergy diagnostics and immunotherapy, they contribute to the process of recombinant allergen characterization and standardization. (C) 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Mus m 1.0102 is a member of the mouse Major Urinary Protein family, belonging to the Lipocalins superfamily. Major Urinary Proteins (MUPs) are characterized by highly conserved structural motifs. These include a disulphide bond, involved in protein oxidative folding and protein structure stabilization, and a free cysteine residue, substituted by serine only in the pheromonal protein Darcin (MUP20). The free cysteine is recognized as responsible for the onset of inter- or intramolecular thiol/disulphide exchange, an event that favours protein aggregation. Here we show that the substitution of selected cysteine residues modulates Mus m 1.0102 protein folding, fold stability and unfolding reversibility, while maintaining its allergenic potency. Recombinant allergens used for immunotherapy or employed in allergy diagnostic kits require, as essential features, conformational stability, sample homogeneity and proper immunogenicity. In this perspective, recombinant Mus m 1.0102 might appear reasonably adequate as lead molecule because of its allergenic potential and thermal stability. However, its modest resistance to aggregation renders the protein unsuitable for pharmacological preparations. Point mutation is considered a winning strategy. We report that, among the tested mutants, C138A mutant acquires a structure more resistant to thermal stress and less prone to aggregation, two events that act positively on the protein shelf life. Those features make that MUP variant an attractive lead molecule for the development of a diagnostic kit and/or a vaccine.

Introduction: Diamine oxidase (DAO) catabolizes and inactivates histamine, a key player in a wide range of invalidating conditions, such as migraine and chronic spontaneous urticaria (CSU). The highest expression of DAO occurs in the gastrointestinal tract, possibly to control the burden of histamine intake from food. Methods: Here, we tested the hypothesis that a 30-day oral supplementation with DAO (1 capsule b.i.d., 15 min before a meal) could reduce the severity of CSU as estimated by the 7-Day Urticaria Activity Score (UAS-7). The study was designed as a double-blind, placebo-controlled, crossover investigation of 22 patients with CSU incompletely controlled by first-line antihistamine therapy. Results: Twenty patients completed the study. Supplemental therapy with DAO caused a 3.8 ± 1.2 point mean ± SEM UAS-7 score reduction in patients with low serum DAO levels at time 0 (p = 0.041 compared to placebo). The degree of UAS-7 improvement was inversely correlated with the levels of basal DAO (p = 0.019). Patients receiving DAO supplementation were able to slightly reduce their daily antihistamine dose (p = 0.049). Conclusion: These data suggest that DAO may be involved in the pathogenic cascade of CSU and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.

Component-resolved diagnosis (CRD) of IgE-mediated hypersensitivities is challenged by the possibility that single patients are sensitized to components not commercially available to the clinical lab.Here, we studied a patient with positive extract-based diagnosis of house dust mite (HDM) allergy based on routine in vivo (prick test) and in vitro (serum specific IgE) tests, whose serum scored negative for" IgE to the three recombinant allergens routinely used in CRD (group 1 allergens, group 2 allergens and tropomyosin).By means of serological proteome analysis via two-dimensional gel electrophoresis combined with immunoblotting and mass spectrometry, paramyosin (group 11 allergen: Der f 11 and Der p 11) was identified as the allergen component recognized by serum IgE from this patient in a raw allergen extract. Nine patients (64%) had IgE to Der p 11 in a group of 14 HDM allergic patients.Biological significance: Our results add up to previous reports indicating that paramyosin is a clinically relevant HDM allergen and highlight that it can represent, in some patients, the first sensitizing component of this allergen source. This suggests that, at the moment, the use of allergen extract for the purpose of measuring IgE reactivity cannot be replaced by component resolved diagnosis and that group 11 allergens should be included among allergen components routinely tested in the clinical laboratory. (C) 2017 Elsevier B.V. All rights reserved.

Multiple ligand presentation is a powerful strategy to enhance the affinity of a probe for its corresponding target. A promising application of this concept lies in the analytical field, where surface immobilized probes interact with their corresponding targets in the context of complex biological samples. Here we investigate the effect of multiple epitope presentation (MEP) in the challenging context of IgE-detection in serum samples using peptide microarrays, and evaluate the influence of probes surface density on the assay results. Using the milk allergen alpha-lactalbumin as a model, we have synthesized three immunoreactive epitope sequences in a linear, branched and tandem form and exploited a chemoselective click strategy (CuAAC) for their immobilization on the surface of two biosensors, a microarray and an SPR chip both modified with the same clickable polymeric coating. We first demonstrated that a fine tuning of the surface peptide density plays a crucial role to fully exploit the potential of oriented and multiple peptide display. We then compared the three multiple epitope presentations in a microarray assay using sera samples from milk allergic patients, confirming that a multiple presentation, in particular that of the tandem construct, allows for a more efficient characterization of IgE-binding fingerprints at a statistically significant level. To gain insights on the binding parameters that characterize antibody/epitopes affinity, we selected the most reactive epitope of the series (LAC1) and performed a Surface Plasmon Resonance Imaging (SPRi) analysis comparing different epitope architectures (linear versus branched versus tandem). We demonstrated that the tandem peptide provides an approximately twofold increased binding capacity with respect to the linear and branched peptides, that could be attributed to a lower rate of dissociation (Kd).

INTRODUCTION:Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients.METHODS:We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated.RESULTS:We found that 10 out of 14 patients had serum DAO activity<10 U/mL, which was the threshold suggested as a cutoff for probable histamine intolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (±SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04±6.90 U/mL compared to 39.50±18.16 U/mL in 34 healthy controls (P=0.0031).CONCLUSION:In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy.

Background: The species Mus musculus experiences an obligate proteinuria: predominant are the Major Urinary Proteins (MUPs), that, collectively known as the major mouse allergen Mus m 1, are among the most important aeroallergens for mouse allergic patients. The production of a soluble and stable hypoallergenic form of Mus m 1 is essential for the development of immunotherapeutic protocols to treat allergic symptoms.Methods: We introduced the substitution C1385 in recombinant Mus m 1.0102, an allergenic isoform of Mus m 1. Solubility, conformation, stability and ability to refold after chemical denaturation were investigated with dynamic light scattering, circular dichroism, fluorescence and NMR spectroscopy. An in vitro degranulation assay was used to evaluate the protein allergenic potential, and compare it with Mus m 1.0102 and with an hypoallergenic variant bearing the substitution Y120A.Results: Mus m 1.0102-C138S retains a native-like fold revealing, however, local conformational alterations that influence some of its physical and allergenic properties: it is monodispersed, thermostable up to 56 degrees C, able to reversibly unfold and it exhibits an enhanced allergenicity.Conclusions: The unique free thiol group affects the solution structural stability of the native protein. Because the mutant C1385 does not aggregate over time it is a good lead protein to develop diagnostic and therapeutic applications.General significance: We elucidated the relationship between unfolding reversibility and sulphydryl reactivity. We ascribed the enhanced allergenicity of the mutant C1385 to an increased accessibility of its allergenic determinants, an enticing feature to further investigate the structural elements of the allergen-IgE interface. (C) 2016 Elsevier B.V. All rights reserved.

Background: We evaluated the ability of quercetin, a natural antioxidant formulated in a specific delivery system, to reduce skin inflammation induced by a variety of stimuli, including UV radiation, stimulation with a histamine solution, or contact with chemical irritants. In particular, we tested the soothing and anti-itch effect of Quercevita (R), 1% cream for external use, a formulation characterized by a phospholipids-based delivery system.Patients and methods: The study was a monocentric, single blind trial that enrolled a group of 30 healthy volunteers. The back of each subject was examined to identify four quadrants with no previous skin damage or naevi that were treated in order to induce a controlled and reversible form of skin stress. The areas were treated as follows: no product; Quercevita (R) 1% cream, 2 mg/cm(2); placebo; positive control (a commercially available topical formulation containing 1% dexchlorpheniramine).Results: Only quercetin phospholipids 1% and dexchlorpheniramine 1% achieved a significant reduction in erythema with comparable results: (-10.05% [P=0.00329] for quercetin phospholipids 1% vs -14.05% [P=0.00046] for the positive control). Moreover, quercetin phospholipids 1% and dexchlorpheniramine 1% were both associated with a significant decrease in mean wheal diameter: (-13.25% and -12.23% for dexchlorpheniramine 1%, respectively). Similar findings were reported for the other tested parameters.Conclusion: Quercetin has a skin protective effect against damage caused by a variety of insults, including UV radiation, histamine, or contact with toxic chemical compounds. Indeed, quercetin is able to reduce redness, itching, and inflammation of damaged skin; it may also help restore skin barrier function, increasing hydration, and reducing water loss.

Introduzione e scopo. Le allergie respiratorie, tra cui rinite allergica e asma allergico, rappresentano un costo medico ed economico gravante in tutto il mondo. In Italia, nonostante la loro dimensione e il peso economico-sociale, non sono disponibili dati sui costi associati alla gestione delle malattie allergiche respiratorie. L’obiettivo di questo studio è quello di stimare il costo medio annuo sostenuto dal Servizio Sanitario Nazionale (SSN) e dalla società italiana, causato dalle allergie respiratorie e le loro principali comorbilità. Metodi. È stato sviluppato un modello probabilistico di cost of illness in grado di stimare una misura aggregata dell’onere economico associato alle allergie respiratorie e le loro principali comorbilità, in termini di costi diretti e indiretti. È stata effettuata una revisione sistematica della letteratura per identificare sia il costo per caso (espresso in valore presente), sia il numero di nuovi pazienti colpiti, applicando un metodo di stima basato sull’incidenza. I costi diretti sono stati stimati, secondo l’approccio bottom-up, moltiplicando i dati epidemiologici italiani con i costi di ospedalizzazioni, farmaci e gestione della malattia derivanti dalla letteratura. I costi indiretti sono stati calcolati sulla base di perdita di produttività secondo l’approccio del capitale umano. Inoltre, per testare la robustezza dei risultati, sono state effettuate un’analisi di sensitività probabilistica, in grado di definire gli intervalli di confidenza (IC 95%) e un analisi di sensibilità a una via. Risultati. Nel complesso, il burden economico complessivo connesso alle allergie respiratorie e le loro principali comorbilità è € di 7,33 (IC 95%: € 5,99-€ 8,82) miliardi di euro, di cui il 27,5% è stato associato a costi indiretti (€ 2,02; IC 95%: € 1,72- € 2,34 miliardi) e il 72,5% con costi diretti (€ 5,32; IC 95%: € 4,04-€ 6,77 miliardi). Per asma allergico, rinite allergica, rinite allergica e asma combinati, ipertrofia dei turbinati e congiuntivite allergica, il modello stima una spesa media annua di € 1,35 (IC 95%: € 1,14- € 1,58) miliardi, € 1,72 (IC 95%: € 1,14-€ 2,43) miliardi, € 1,62 (€ 0,91-€ 2,53) miliardi, € 0,12 (€ 0,07-€ 0,17) miliardi, € 0,46 (€ 0,16-€ 0,92) miliardi rispettivamente. Conclusioni. A nostra conoscenza, questo è il primo studio in cui si è cercato di stimare l’onere complessivo associato alle malattie respiratorie causate dalle allergie nel nostro Paese. Di conseguenza, è risultato difficile fare confronti diretti con i risultati di altri studi pubblicati. Tuttavia, il burden economico evidenziato sembra essere in linea con altri studi che definiscono i costi economici delle malattie respiratorie rilevanti, in particolare di rinite e asma allergico. In conclusione, il presente lavoro può rappresentare un efficiente strumento di riferimento per i decisori pubblici che vogliano comprendere adeguatamente gli aspetti economici generati dalla gestione delle malattie allergiche.

Allergen immunotherapy (AIT) is the only therapeutic approach that can modify the course of allergic diseases. Atopic dermatitis (AD) has an allergic component, but studies performed to assess the efficacy of AIT in AD are not yet conclusive.