Marina Mauro

Sant'Anna Hospital, Torino, Piedmont, Italy

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Publications (26)43 Total impact

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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.
    Drug Design, Development and Therapy 01/2014; 8:197-207. · 3.49 Impact Factor
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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.
    Recenti progressi in medicina 03/2013; 104(3):116-9.
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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.
    Panminerva medica 12/2012; 54(4):305-12. · 2.28 Impact Factor
  • C Incorvaia, M Mauro
    Allergy 07/2012; 67(7):966; author reply 966-7. · 5.88 Impact Factor
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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.
    PLoS ONE 01/2012; 7(6):e37980. · 3.53 Impact Factor
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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.
    Expert Opinion on Pharmacotherapy 09/2011; 12(16):2527-32. · 2.86 Impact Factor
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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.
    International Archives of Allergy and Immunology 08/2011; 156(4):416-22. · 2.25 Impact Factor
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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.
    Recent Patents on Inflammation & Allergy Drug Discovery 03/2011; 5(2):128-35.
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2011; 127(2).
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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.
    Recent Patents on Inflammation & Allergy Drug Discovery 06/2010; 4(2):124-9.
  • Cristoforo Incorvaia, Marina Mauro
    The Journal of allergy and clinical immunology 01/2010; 125(1):277; author reply 277-8. · 12.05 Impact Factor
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    Allergy 04/2009; 64(8):1229-30. · 5.88 Impact Factor
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    ABSTRACT: Specific immunotherapy is the only treatment targeting the causes, and not only the symptoms, of allergic diseases. Sublingual immunotherapy (SLIT) was introduced and developed to solve the problem of the adverse reactions, uncommon but possibly severe and rarely fatal, to the traditional subcutaneous immunotherapy (SCIT). The evidence of SLIT efficacy concerns rhinitis and asthma caused by sensitization to pollens and to house dust mites, but there are increasing data suggesting that SLIT could be applied in forms of allergy hardly feasible for SCIT because of its poor safety (this is true for food allergy and latex allergy) or could be considered for new applications, such as atopic dermatitis or baker's asthma. In particular, there are placebo-controlled trials indicating good efficacy and safety of SLIT in patients allergic to latex and to foods and in children with atopic dermatitis, that indicate SLIT as a real treatment option in such clinical entities. This article also discusses some patent related to the field.
    Recent Patents on Inflammation & Allergy Drug Discovery 02/2009; 3(2):113-7.
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    ABSTRACT: The anti-IgE antibody omalizumab is currently indicated in severe asthma not controlled by standard drug therapy. Recently, new indications for omalizumab were suggested, which include atopic dermatitis (AD), a skin disorder characterized by elevated levels of IgE. We report the case of a 39-year old woman with severe asthma and severe AD, both resistant to conventional drug treatment. The patient had a IgE level of 1304 kU/L, which exceeded the recommended maximum level for treating asthma with omalizumab (stated in 700 Ku/L) but was far lower than previously reported in cases of AD treated with anti-IgE. The treatment consisted of a dose of omalizumab 375 mg every two weeks, and induced a rapid improvement of asthma, with no need of other drugs after three months, along with a progressive decline of severity of AD, which after five months was completely cured. These findings suggest the usefulness of omalizumab in patients with concomitant severe asthma and AD, also considering the pharmaco-economic balance obtained by withdrawing the multiple drugs used to treat both diseases.
    Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 07/2008; 69(2):78-80.
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    ABSTRACT: IgE antibodies are a pivotal factor in pathophysiology of allergic diseases, and the possibility of reducing their level by anti-IgE has long been envisioned. Following several attempts, an effective biologic agent was obtained with the recombinant humanized mono-clonal antibody (rhuMAb)-E25, known as omalizumab. A number of controlled clinical trials demonstrated its efficacy and safety in the treatment of severe allergic asthma uncontrolled by standard drug treatment with maximal recommended doses, and treatment with omalizumab is currently included in international guidelines on asthma management. Other studies reported a clear effectiveness also in allergic rhinitis, but the cost of the anti-IgE treatment suggests its use in patients with rhinitis concomitant with asthma. Other indications to be further investigated are skin disorders such as atopic dermatitis and IgE-mediated urticaria, as well as adverse reactions to foods, with a particularly important role in preventing food-induced anaphylaxis. Finally, there are data indicating the usefulness of omalizumab when used in combination with allergen specific immunotherapy, in terms of reducing the adverse reactions to treatment and increasing the clinical efficacy.
    Targets & therapy 04/2008; 2(1):67-73.
  • Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Cu rrent Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 01/2008; 7(1):52-57.
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    ABSTRACT: Allergen immunotherapy (IT) is an effective treatment of respiratory allergy, but requires strict rules of performance. This makes compliance particularly relevant, but thus far only a few studies have investigated this issue. We reviewed all the available articles on compliance and adherence with IT in its different forms of administration, ie, subcutaneous (SCIT), sublingual (SLIT), and local nasal (LNIT). Early studies, when only SCIT was available, reported a low compliance, ranging from 45% to 60%, but the demanding schedules used, with very frequent injections, accounted for this outcome, as shown by patients' recognition of inconvenience as the major cause of noncompliance. The most recent studies reported a good compliance, estimated in 75% to 90%, to both SCIT and SLIT, inconvenience remaining the major cause of noncompliance, followed by cost of the treatment. The only study addressing LNIT found a very poor compliance (27%), the major cause being the side effects, with repeated nasal reactions to the allergen extract. Adequate education of patients and optimization of administration schedules, with fine balancing between dose effectiveness and cost, are the factors most likely to achieve further improvement of compliance with IT.
    Patient Preference and Adherence 01/2008; 2:247-51. · 1.33 Impact Factor
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    ABSTRACT: Sublingual immunotherapy (SLIT) is currently considered a valid option to subcutaneous immunotherapy (SCIT), but only a few studies made a direct comparison of their effectiveness. The aim of this study was to compare the clinical and immunological effects of SCIT and SLIT in pollinosis induced by Betulaceae. Forty-seven adult patients were randomized to receive SCIT or SLIT, performed by Betulaceae (alder, birch, and hazel) extracts from Stallergenes (Antony, France) standardized in index of reactivity (IR) with the treatment schedules proposed by the producer. The clinical effects were established by symptom-medication scores recorded during the month of March. Side effects were reported directly by the physicians for SCIT and were registered in diary cards by the patients for SLIT. Immunologic evaluation was done by measuring specific IgE and IgG4 to Bet v 1. Thirty-four patients (19 for SCIT and 15 for SLIT) completed the registration of symptoms and drug consumption during pollen period of Betulaceae. Mean cumulative doses of respectively 50.65 IR by SCIT and 4653.1 IR by SLIT were administered, with a SLIT/SCIT ratio of 92. There was no significant difference in mean symptom-medication score between SCIT and SLIT. Systemic reactions occurred in 16% of SCIT treated but in none of SLIT treated. As to immunologic evaluation, Bet v 1 specific IgE did not rise after the pollen season in SCIT treated, while increased non significantly in SLIT treated. Bet v 1 specific IgG4 increased in both treatment, buy only the increase with SCIT was significant (p = 0.001). SLIT and SCIT with a ratio of about 100 are equally effective in controlling rhinoconjunctivitis caused by tree pollen allergy. SLIT is safer than SCIT, but does not show the same immunologic effects on serum specific IgE and lgG4 antibodies.
    European annals of allergy and clinical immunology 05/2007; 39(4):119-22.
  • World Allergy Organization Journal. 01/2007;
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    ABSTRACT: Venom immunotherapy is an effective method for the treatment of Hymenoptera venom allergy. Different extracts and treatment schedules are available. To compare the safety and efficacy of immunotherapy in 3 cohorts of patients sensitized to Vespula species. In this open study, 43 patients were treated with a subcutaneous aqueous extract for induction and maintenance (AA), 34 with a subcutaneous depot extract for induction and maintenance (DD), and 29 with subcutaneous aqueous and subcutaneous depot extracts for induction and maintenance, respectively (AD). Cluster schedules were followed to reach maintenance, and adverse effects during treatment and after naturally occurring stings were recorded. Depot immunotherapy was better tolerated mainly owing to the lower frequency of local adverse effects in the induction phase (5.9% vs 42.5% and 1.3% vs 5.1% on a per patient and per dose basis, respectively; P < .001 for both) and for effects occurring within 60 minutes after vaccination (2.9% vs 19.2% and 0.2% vs 2.8% on a per patient and per dose basis; P = .03 and P < .001, respectively). Furthermore, 19 of 20 AA, 9 of 9 AD, and 10 of 10 DD patients who were restung experienced only minor local effects. Venom immunotherapy is efficacious. Although there was no decrease in systemic reactions, depot immunotherapy to Vespula venom induced fewer early local adverse effects. Patients undergoing an induction phase with an aqueous extract can benefit from switching to a depot extract during maintenance. Increasing the flexibility of the immunization schedules may improve compliance with this potentially lifesaving treatment.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2006; 97(1):92-7. · 3.45 Impact Factor