Marina Mauro

Sant'Anna Hospital, Torino, Piedmont, Italy

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Publications (40)96.55 Total impact

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    ABSTRACT: Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13 % of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment.
    No preview · Article · Jan 2016 · Current Allergy and Asthma Reports
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    ABSTRACT: Introduction: Sublingual immunotherapy (SLIT) for house dust mite (HDM) allergy has an evidence of efficacy demonstrated by meta-analyses, but marked differences are reported between the various SLIT products. The standardized quality (SQ) HDM sublingual tablet containing Dermatophagoides pteronyssinus and Dermatophagoides farinae in a 1:1 ratio (MK-8237) is a qualitative advance for SLIT products. Areas covered: The rationale for developing the HDM tablets is discussed against the other available SLIT products, analyzing the clinical data on efficacy and safety obtained by controlled trials. Expert opinion: Following preliminary Phase I and II studies, a double-blind, placebo-controlled trial on 604 patients with mite-induced asthma, aged more than 14 years and treated by inhaled budesonide, was performed using one of three active doses (1, 3 or 6 SQ) or placebo. The results showed a significant mean difference between 6 SQ-HDM and placebo in the reduction in daily budesonide dose of 81 µg (p = 0.004), with relative mean and median reductions of 42 and 50% for 6 SQ-HDM and 15 and 25% for placebo, respectively. Safety was very good, with no report of anaphylactic reaction. These findings suggest a role to the HDM SLIT tablets in the treatment of patients with mite-induced asthma.
    No preview · Article · Nov 2015 · Expert Opinion on Drug Metabolism & Toxicology
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    ABSTRACT: Sublingual immunotherapy (SLIT) was introduced in the 1980s as a safer option to subcutaneous immunotherapy and in the latest decade achieved significant advances. Its efficacy in allergic rhinitis is supported by a number of meta-analyses. The development of SLIT preparations in tablets to fulfill the requirements of regulatory agencies for quality of allergen extracts made available optimal products for grass-pollen-induced allergic rhinitis. Preparations of other allergens based on the same production methods are currently in progress. A notable outcome of SLIT, that is shared with subcutaneous immunotherapy, is the evident cost-effectiveness, showing significant cost savings as early as 3 months from starting the treatment, that become as high as 80% compared with drug treatment in the ensuing years.
    No preview · Article · Oct 2015 · Immunotherapy
  • Cristoforo Incorvaia · Marina Mauro
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    ABSTRACT: Cellular and Molecular Immunology aims to report the dynamic progress being made in China and abroad in immunological research, and welcomes high-quality Research Articles, Reviews and Brief Reports across a broad range of topics including, but not limited to, clinical immunology, comparative immunology, immunobiology, immunogenetics, immunological techniques, immunopathology, immunopharmacology, infection immunology, neuroimmunology, transplantation immunology, tumor immunology, and veterinary immunology.
    No preview · Article · Mar 2015 · Cellular & molecular immunology
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    ABSTRACT: 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 © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014
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    ABSTRACT: Background Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18–45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. Conclusions These findings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed.
    Full-text · Article · Nov 2014 · Medical science monitor: international medical journal of experimental and clinical research
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    ABSTRACT: A large number of trials show that the anti-immunoglobulin (Ig) E antibody omalizumab is very effective in patients with severe allergic asthma. This is acknowledged in consensus documents. The drug also has a good safety profile and a pharmacoeconomic advantage due to a reduction in the number of hospitalizations for asthma attacks. In recent years, some studies have shown that omalizumab is effective also in nonallergic asthma. Effects on the complex signaling mechanisms leading to activation of effector cells and to mediator release may account for this outcome. Indeed, omalizumab has been reported to be effective in a number of IgE-mediated and non-IgE-mediated disorders. Concerning the former, clinical efficacy has been observed in rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, and anaphylaxis. In addition, omalizumab has been demonstrated to be able to prevent systemic reactions to allergen immunotherapy, thus enabling completion of treatment in patients who otherwise would have to stop it. Concerning non-IgE-mediated disorders, omalizumab has been reported to be effective in nasal polyposis, autoimmune urticaria, chronic idiopathic urticaria, physical urticaria, idiopathic angioedema, and mastocytosis. Current indications for treatment with omalizumab are confined to severe allergic asthma. Consequently, any other prescription can only be off-label. However, it is reasonable to expect that the use of omalizumab will be approved for particularly important indications, such as anaphylaxis, in the near future.
    Full-text · Article · Feb 2014 · Drug Design, Development and Therapy
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    Preview · Article · Feb 2014 · World Allergy Organization Journal
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    ABSTRACT: Allergic rhinitis may appear of little value but at present its high and still increasing prevalence, its socio-economic burden, the frequent association with asthma and the significant impairment of quality of life in affected patients make it a disease of general importance. The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines allow to properly recognize the mild forms and the moderate/severe forms, and, based on the duration of symptoms, the intermittent and persistent forms. Etiologic diagnosis can be suspected by history data but the certainty can be achieved only by allergy testing. The treatment is mainly based on oral or nasal topical antihistamines and topical corticosteroids, that ensure in most cases a satisfactory control of symptoms. However, there are patients who have an insufficient response to drugs, event at high doses. Recent studies showed that patients not controlled by drug treatment achieve a significant benefit from allergen specific immunotherapy, currently available by the subcutaneous and sublingual route. This should be considered as a criterion to choose patients for specific immunotherapy, who must be referred to the allergy specialist.
    No preview · Article · Mar 2013 · Recenti progressi in medicina
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    ABSTRACT: The immunoglobulin E (IgE) are a key factor in the pathophysiology of allergic diseases and the important therapeutic role of an anti-IgE antibody was long envisioned. It took time and efforts to solve the safety problems related to the anaphylactogen capacity of anti-IgE, finally crowned by the introduction of the humanized, monoclonal anti-IgE antibody omalizumab. Currently, omalizumab is indicated, based on clear evidence of efficacy, only in severe allergic asthma not controlled by conventional treatment. However, a continuously increasing amount of literature shows that omalizumab is efficacious in a number of disorders concerning the upper and lower airway and the skin, and, most importantly, in anaphylaxis. The latter application was demonstrated successful in placebo-controlled trials and warrants for a new, life-saving, indication for omalizumab. Also, the systemic reactions precluding the performance of allergen immunotherapy, especially concerning Hymenoptera venom, were prevented by omalizumab treatment. The most surprising success of omalizumab regards clinical conditions thus far considered unrelated to IgE antibodies. This is true for intrinsic asthma and for idiopathic urticaria (demonstrated by a placebo-controlled trial), and angioedema, suggesting in these condition a pathophysiologic role of IgE. These observations support a off-label use of omalizumab in patients suffering from IgE-related pathologies other than asthma who are at risk of fatal events or are uncontrolled by the optimal standard treatment.
    No preview · Article · Dec 2012 · Panminerva medica
  • C Incorvaia · M Mauro

    No preview · Article · Jul 2012 · Allergy
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    ABSTRACT: Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is involved in the activation pathways of T lymphocytes. It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy. to assess the effects on CTLA-4 of venom immunotherapy, given with different induction protocols: conventional (6 weeks), rush (3 days) or ultra rush (1 day). Sera from patients with hymenoptera allergy were collected at baseline and at the end of the induction phase. CTLA-4 and IL-10 were assayed in the same samples. A subset of patients were assayed also after 12 months of VIT maintenance. Ninety-four patients were studied. Of them, 50 underwent the conventional induction, 20 the rush and 24 the ultra-rush. Soluble CTLA-4 was detectable in all patients at baseline, and significantly decreased at the end of the induction, irrespective of its duration. Of note, a significant decrease of sCTLA-4 could be seen already at 24 hours. In parallel, IL-10 significantly increased at the end of the induction. At 12 months, sCTLA-4 remained low, whereas IL-10 returned to the baseline values. Serum CTLA4 is an early marker of the immunological effects of venom immunotherapy, and its changes persist after one year of maintenance treatment.
    Full-text · Article · Jun 2012 · PLoS ONE
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    ABSTRACT: INTRODUCTION: The efficacy of venom immunotherapy (VIT) in patients with insect sting allergy is not questioned. However, its safety, especially when honeybee is used, is a matter of concern. AREAS COVERED: A systematic review of the literature on VIT was done, with both aqueous and depot extracts, to compare the frequency of systemic reactions to honeybee and vespid venoms. A Medline search was performed using the keywords 'venom immunotherapy', 'safety' and 'tolerability'. The articles obtained were analyzed regarding the total number of patients treated with either honeybee or vespid VIT, the number and severity of systemic reactions during therapy, the type of extract used (aqueous or depot) and the administration regimen. EXPERT OPINION: The incidence of systemic reactions to VIT was 25.1% for honeybee venom and 5.8% for vespid venom (p < 0.0001), while it was similar with aqueous and depot extracts in the whole population of patients. This confirms that during VIT systemic reactions are significantly more frequent with honeybee venom compared with vespid venom, while there are no significant overall differences in systemic reactions between aqueous and depot extracts.
    No preview · Article · Sep 2011 · Expert Opinion on Pharmacotherapy
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    ABSTRACT: The most common pollen-fruit cross-reaction is the birch-apple syndrome. Allergen immunotherapy (IT) is clearly effective for birch allergy, but its efficacy on apple allergy is controversial. We performed a randomized study on patients with birch-apple syndrome to evaluate the outcome of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Forty patients underwent IT with a birch extract (Staloral; Stallergenes, Antony, France), 20 by SCIT and 20 by SLIT. After 1 year of treatment, 15 patients (8 for SCIT and 7 for SLIT) accepted to undergo an oral apple challenge. Measurements of specific IgE to Bet v 1 and Mal d 1 and related allergens Api g 1 and Dau c 1 were obtained in 10 patients, at baseline and after IT. Two of 8 SCIT-treated patients (25%) and 1 of 7 SLIT-treated patients (14.2%) developed complete tolerance to apple. In the remaining patients, an increase in the provocative dose was found in 3 of the SCIT-treated (37.5%) and 2 of the SLIT-treated patients (28.6%). Changes in the levels of specific IgE to Mal d 1 were unrelated to clinical results. These findings suggest that different doses of birch extract may be needed in different patients to improve the associated apple allergy and that a finer diagnostic work-up in selecting patients with birch-apple syndrome who are candidates to respond to birch pollen IT also concerning apple allergy is required.
    No preview · Article · Aug 2011 · International Archives of Allergy and Immunology
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    ABSTRACT: Diagnosis and treatment of hypersensitivity to Hymenoptera venom took a landmark step forward in the late 1970s with the introduction of venom as an adequate material instead of whole body extracts. Since then, venom immunotherapy (VIT) has provided allergic subjects with a complete protection from fatal anaphylaxis and prevented about 90% of all reactions to stings. The cross-reactivity among some venom components, particularly important in the case of cross-reacting carbohydrate determinants, has often made it difficult to recognize the true causative venom to be used in VIT. Recently, the introduction of purified and recombinant allergens, such as Api m 1 from honeybee venom, Ves v 5 from yellow jacket venom, and Pol d 5 from wasp venom, have allowed a more precise diagnosis with identification of the causative venom component. This paves the way for a patient-tailored VIT in the near future. Another issue which needs to be addressed is the improvement in the safety of VIT with honeybee venom, which is significantly less favourable in comparison to vespid venom. A number of molecular approaches are under investigation in order to achieve this objective. Alternative routes of administration, such as the sublingual and the intralymphatic, have also been proposed, but there are not yet sufficient data available to demonstrate their feasibility. This review also presents patents on new trends in therapies for the management of hypersensitivity to hymenoptera venom.
    No preview · Article · Mar 2011 · Recent Patents on Inflammation & Allergy Drug Discovery

  • No preview · Article · Feb 2011 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: Anaphylaxis is the most concerning manifestation of hypersensitivity. Recent thorough investigations on the pathophysiology of anaphylaxis achieved important advances in its understanding, regarding in particular the emerging role of mediators such as platelet activating factor (PAF) and sphyngosine 1 phosphate (S1P) and the improved knowledge on the actors of the signaling cascade, from the contact between the specific allergen and the IgE fixed on the Fc-epsilon-RI receptor to the opening of calcium channels. These advances may provide new diagnostic and therapeutical tools. In particular, a role for PAF and S1P as laboratory markers of anaphylaxis is likely to be developed, and innovative preventive strategies able to induce a negative signaling are currently under evaluation. Also, using well known preventive treatments, such as allergen specific immunotherapy may offer new perspectives for the management of patients at risk of potentially fatal reaction to foods. In fact, controlled studies demonstrated that sublingual immunotherapy is able to significantly increase the tolerance to the causative foods, fulfilling the need and protecting the allergic subject from anaphylaxis caused by accidental ingestion of small food amounts. The article also presented some promising patents on anaphylaxis.
    No preview · Article · Jun 2010 · Recent Patents on Inflammation & Allergy Drug Discovery
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    ABSTRACT: Allergic reactions to hymenoptera stings concern about 3% of the general population and are caused by antigens occurring in venom, such phospholipase, hyaluronidase and, for vespids, antigen 5. Diagnosis is based on skin tests and in vitro tests, while the challenge with live insect is not recommended. Cross-reactivity of IgE antibodies to some allergens or to carbohydrate epitopes may result in apparent polysensitization and in difficulties in venom choice for immunotherapy. Another useful in vitro data, especially in patients with severe reactions, is measurement of tryptase, that may reveal an unrecognized mastocytosis. Management of hymenoptera venom allergy is based on pharmacological treatment of anaphylactic reactions, that absolutely requires epinephrine by intramuscular injection (also by auto-injectors for self-administration), and on prevention of further reactions. This is optimally achieved by venom immunotherapy (VIT), which demonstrated the complete capacity to prevent fatal reactions and to prevent more than 90% of reactions of any type, though with a lower efficacy if honeybee venom is used. VIT can be safely stopped after 5 years in most patients, but the occurrence of adverse reactions to treatment, of incomplete protection to stings, or of a concomitant mastocytosis indicates the need to continue VIT even life-span. Increasing the interval between venom administration up to 16 weeks favours the long-term compliance. This document updates the recent advances in diagnosis and treatment of hymenoptera venom allergy and discuss the possible future development.
    No preview · Article · Jun 2010 · Italian Journal of Allergy and Clinical Immunology
  • Cristoforo Incorvaia · Marina Mauro

    No preview · Article · Jan 2010 · The Journal of allergy and clinical immunology
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    ABSTRACT: The most common allergic diseases, such as rhinitis, asthma and atopic dermatitis, are sustained by allergic inflammation, the treatment of which requires anti-inflammatory activity. Among the available treatments, allergen immunotherapy (IT) has a documented impact on allergic inflammation which persists after its discontinuation and modifies the natural course of allergy. The anti-inflammatory effects of IT, and particularly of sublingual IT (SLIT), are based on the ability to modify the phenotype of T cells which, in allergic subjects, are characterized by a prevalence of the Th2 type, with production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines. IT-induced changes result in a Th1-type response (immune deviation) related to an increased IFN-gamma and IL-2 production or in a Th2 reduced activity, through a mechanism of anergy or tolerance. It is now known that T cell tolerance is characterized by the generation of allergen-specific Treg cells, which produce cytokines such as IL-10 and TGF-beta with immunosuppressant and/or immunoregulatory activity. Recent studies suggest that the anti-inflammatory mechanism of SLIT is similar to classical, subcutaneous IT, with a prominent role in SLIT for mucosal dendritic cells. The tolerance pattern induced by Treg accounts for the suppressed or reduced activity of inflammatory cells and for the isotypic switch of antibody synthesis from IgE to IgG, and especially to IgG4. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa plays a pivotal role in inducing tolerance to the sublingually administered allergen.
    No preview · Article · Sep 2009 · European Journal of Inflammation