Publications (37)96.99 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Sublingual immunotherapy with monomeric carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergen-driven Th1, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time of the inclusion and after 6 and 12 months of treatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After 1-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-gamma secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.
- [Show abstract] [Hide abstract] ABSTRACT: In asthmatics, a rapid decline in pulmonary function is observed, likely as a consequence of airways remodeling. Persistence of allergen exposure in patients with occupational asthma (OA) maintains chronic bronchial inflammation, resulting in a more severe lung function decline. Few studies were performed on the effects of allergen exposure cessation. This study aims at evaluating the influence of allergen exposure cessation on respiratory decline in allergic asthmatic workers. Two groups of workers with allergic OA were selected. The first group (30 workers) changed job after the diagnosis and was no more exposed to sensitizing allergens, and the second group (28 subjects) did not and, as a consequence of preventive measures in the work place, was exposed to a lower level of allergens. All were treated with conventional therapy, according to GINA protocols. FEV1 changes during a 12-year period were evaluated. Despite pharmacological therapy, the pulmonary function decay slope was steeper in workers continuously exposed to the sensitizing agent (even at reduced level) than in those with a complete cessation of exposure: final FEV1 loss was 512.5 ± 180 ml versus 332.5 ± 108 ml, respectively. The difference became significant after 4 years from the cessation of the exposure. The study shows that the cessation of the exposure to allergen in the work place appears the most effective measure in limiting pulmonary function decline in asthmatic workers and underlines the importance of allergic risk assessment and control in the management of occupational asthma.
Article: T regulatory cells in allergy[Show abstract] [Hide abstract] ABSTRACT: The progressive understanding of the nature and mechanisms of T regulatory (Treg) cells in the last decade has changed the concept of immune tolerance, that is no longer considered as a mere lack of immune reactivity but as a finely regulated process that requires specific activity of cells, adhesion and secreted molecules. Tregs play a key role in maintenance of self-tolerance and induction of tolerance against ubiquitous innocuous non-self antigens, so preventing the onset of autoimmune diseases and allergies. This review will focus on the Treg response in allergy that is characterized by a down-regulation of allergen specific T cell proliferation and inhibition of both Th1 and Th2 cytokines production. Hence, Treg cells suppress allergen-specific Th1 and Th2 cell responses playing an important role in the physiological immune response to allergens. Further, Treg cells are able to suppress IgE production by B lymphocytes and directly or indirectly inhibit the activity of allergic inflammation effector cells, namely eosinophils, basophils and mastcells. Finally, increasing evidence suggests that Treg cells are also implicated in chronicity development of inflammatory diseases. This appears to happen through a fine interaction they entertain with resident tissue cells and has been particularly highlighted in the study of airways remodeling in asthma. The understanding of the mechanisms underlying allergen tolerance has brought new interest in the development of new allergy treatment, able to target Treg cells, both in allergy prevention and in the therapy of established allergy.
Article: Environmental pollution and asthma[Show abstract] [Hide abstract] ABSTRACT: Clinical evidences and epidemiological studies show that allergic pathologies of the respiratory tract are increasing in the world areas with high pollution impact, demonstrating how many polluting substances favor both allergic sensitization and the bronchial inflammatory changes characteristic of asthma. It has been shown that asthma, as many other diseases, is a complex interaction between genetic predisposition and environmental stimuli that results in clinical expression of various phenotypes of asthma: allergic, intrinsic etc. Many pollutants have such a potential. Diesel exhaust particles (DEP) can favor allergic sensitization, induce acute asthma attacks and increase bronchial reactivity, acting both on allergen, on bronchial mucosa and on immune cells. In fact, DEP can favor B lymphocytes to shift to a production of IgE and T cells to produce Th2 cytokines. Asthma can be also induced by high exposure to many other substances as NO2 and first of all ozone (O3): strong oxidizing substance that is synthesized, in absence of ventilation, by photochemical reaction due to the combination of ultraviolet sun radiation on exhaust gases as NO2 and hydrocarbons. Ozone is abundant in cities with minimal concentration in the morning gradually increasing during the day until maximal levels in the afternoon and then decreasing during the night. Epidemiological studies show that the number of access to hospital for acute asthma and even the use of bronchodilator by asthmatics increase during the high level periods when Ozone constitute almost 90 percent of the total oxidants in the environment. Particulate matter of very small diameter have a crucial role in favoring asthma attacks, and smaller the substance deeper the penetration in the bronchial tree, with an inflammatory reaction in the peripheral bronchial mucosa characterized by increased vessel permeability, mucosal edema, inflammatory mediator production by damaged epithelium and inflammatory cells that determines acutely a high narrowing of the bronchial lumen and in a long period favor airways remodeling and a rapid decline of respiratory function.
- [Show abstract] [Hide abstract] ABSTRACT: The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries.
- [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVES: Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. METHODS: We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. RESULTS: Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. CONCLUSION: These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers.
- [Show abstract] [Hide abstract] ABSTRACT: Hymenoptera venom immunotherapy (VIT) is a safe and effective approach to insect sting allergy. However, after discontinuation, relapses can occur in some patients, especially those with a high occupational risk, and they may need to prolong VIT indefinitely. In order to improve adherence, we propose extending the interval between injections of maintenance VIT (MVIT). To evaluate the safety, efficacy, and patient acceptance of a 3-month interval between MVIT injections in a group of Hymenoptera-allergic patients who are occupationally exposed to insect stings. We included 72 patients with severe systemic reactions to Hymenoptera stings. MVIT was administered for 4 years at intervals increasing up to 3 months and then continued for a further 2 years. Patients were informed of the risk of relapse after discontinuation and of the need for indefinite treatment at 3-month intervals. During the 3-month interval maintenance phase, only 235 local reactions (17.8%) were observed in 17 patients. Sixty patients experienced 125 field re-stings and only 1 experienced a systemic reaction with generalized urticaria. The study confirms that the conventional MVIT interval of 4 to 6 weeks can be extended to 3 months in most patients with no adverse events, while maintaining safety and efficacy, improving adherence, and guaranteeing safe continuation of professional activity.
- [Show abstract] [Hide abstract] ABSTRACT: Extrinsic allergic alveolitis in farmers may be caused by exposures to many organic substances. Potentially inhalable particulate material of biologic origin are collectively referred to as organic dust, whose composition includes also molds and other microorganisms. Organic dust may evoke immuno-allergic reactions and cause an acute, subacute or chronic form of the disease, depending on the entity and type of exposure as well as the individual immunological response. The agricultural work environment represents a risk factor for extrinsic allergic alveolitis, whose occupational origins are often overlooked by clinicians. Prevalence studies of extrinsic allergic alveolitis among farmers are advocated for the development of prevention strategies.
- [Show abstract] [Hide abstract] ABSTRACT: The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.
- [Show abstract] [Hide abstract] ABSTRACT: Nickel is the metal that most frequently causes allergic reactions since it is an ubiquitous metal that can be found in many objects and foods. The major manifestations of nickel allergy are Allergic contact dermatitis and Systemic Nickel Allergy Syndrome (also called Systemic Contact Dermatitis - SCD). Clinically Systemic Nickel Allergy Syndrome is characterized by eczema, urticaria, flare up of previous positive patch tests and other skin manifestations, abdominal pain, diarrhoea or constipation, and other minor symptoms appearing after ingestion of nickel with food. The syndrome can be observed in vivo after oral provocation test. Many Authors administer for this purpose 0.3 to 10 mg Ni and the subsequent syndrome seems correlated to the amount of nickel administered. There are no specific laboratory data so the oral challenge is the gold standard in the diagnosis. The patho-physiology of Systemic Nickel Allergy Syndrome is quite different from the Ni-allergic contact dermatitis. In fact, Systemic Nickel Allergy Syndrome is characterized by a significant increase of IL-5 and IL-2 serum levels after challenges. It has been observed also modification in the CD expression in lymphocytes of Systemic Nickel Allergy Syndrome patients respect to the Allergic contact dermatitis patients and healthy controls both in the blood and in the gastrointestinal mucosa. All findings suggest a role of the Th2-type immune response in this syndrome.
- [Show abstract] [Hide abstract] ABSTRACT: Few cytological studies have investigated the morphologic changes occurring during lymphocyte differentiation in the nose. The aim of the study is to investigate lymphocyte and plasma cell morphology in patients with allergic rhinitis. Nasal cytology was performed in 110 patients (61 men, 49 women) of ages ranging from 12 to 47 years (mean age, 27), 72 of whom were affected by pollen allergic rhinitis (32 allergic to olive, 21 to Parietaria, 13 to grasses, and 6 to cypress) and 38 by perennial allergic rhinitis (allergy to house dust mites). Cytological samples were obtained by scraping with Rhino-Probe™. The samples were collected from the inferior middle turbinate. After fixing and drying, the samples were stained and counted. Cells belonging to the lymphocyte-plasma cell lineage were analyzed. Within this population, 5 different cellular types were identified displaying particular morphologic features of the nucleus and the cytoplasm. These morphological variants constitute various functional stages of B lymphocytes. In allergic inflammation, antigen stimulation induces B lymphocytes to differentiate and become plasma cells. The findings from this strictly morphological study will need to be confirmed by immunohistochemical and immunophenotypic studies.
- [Show abstract] [Hide abstract] ABSTRACT: The decline in pulmonary function is a normal feature of aging, but in asthmatics a more rapid progression is observed. This report aims at evaluating the influence of therapeutic intervention and allergen exposure avoidance in the decline of pulmonary function in allergic asthmatic workers. To this purpose 53 patients were recruited and their pulmonary function was monitored along 12±6 years: 25 (group A) changed their work after the diagnosis of asthma. 28 (group B) continued with their occupation. All were pharmacologically treated. A significant greater reduction of FEV1 and FVC respect to the predicted values (p <0.05 and <0.0001 respectively) were observed in all subjects, with a significant greater reduction of FVC (p<0.05) and FEV1 (p<0.01) in Group B respect to Group A. FEV1 decay was significantly greater among asthmatics with baseline FEV1 < 80% predicted (ANOVA, p < 0.03) and the FEV1 decay slopes were significantly steeper in the subgroup with a disease duration > 10 years and with a FEV1 variability >15% (ANOVA, p < 0.0001). Group A experienced a great loss of FEV1 during the first 3 years and then their FEV1 decay slopes declined with a similar trend of healthy subjects, on the contrary exposed asthmatics showed a slope characterized by a great variability with a steeper decrease of values. The study shows the allergen exposure is a determinant factor favoring the decline in pulmonary function in asthmatics so underlining the importance of allergic risk assessment and control in the treatment of asthmatic workers.
- [Show abstract] [Hide abstract] ABSTRACT: Here, we report our experience on benzoate hypersensitivity. Drug and food additives are known to induce pseudo-allergic reactions such as urticaria, eczema, asthma and rhinitis. These reactions are often under-diagnosed, above all in allergic patients treated with additive containing drugs. On the contrary, attention to the additives present in some drug formulations and foods may often permit more correct diagnosis.
- [Show abstract] [Hide abstract] ABSTRACT: This study evaluates the effectiveness and safety of cyclosporine (CsA) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test (ASST), who fail to respond to conventional therapy, and requiring long-term oral steroid treatment. In a double-blind study, 40 adults were assigned randomly to receive CsA (5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks) or cetirizine (10 mg/day) and then they were followed up for 9 months. After 2 weeks, the study was opened because 16 patients (40%) had daily severe relapses requiring systemic steroids treatment. All of these patients had been receiving antihistamines and, therefore, all patients also were assigned to the CsA treatment regimen (5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks). The ASST and clinical severity score were evaluated before and after treatment. All of the 40 patients completed the 16-week CsA course without dropping out because of relevant side effects. In three patients, CsA was reduced by 0.5 mg/kg per day after the 1st month of treatment for a mild and reversible increase in serum creatinine. During CsA treatment, 20 patients had relapses resolving spontaneously (8 patients) or with antihistamines (12 patients). During the 9-month follow-up period, 22 patients had relapses resolving spontaneously (10 patients) or with antihistamines (12 patients). Only two patients failed to complete the study because of severe symptoms occurring after 4 and 7 days of follow-up and requiring long-term steroid treatment. After 9 months of follow-up, 16 patients were still in full remission. The clinical severity score of chronic idiopathic urticaria dropped significantly by the end of the 4th month of treatment (p = 0.002) as well as by the completion of follow-up (p = 0.007). The ASST was negative in 13 patients and positive in 3 of 16 patients, with total remission of symptoms. Significant score reduction also was observed in patients experiencing relapses that resolved spontaneously (p = 0.005) or with antihistamines (p = 0.03). These results show the long-term efficacy and tolerability of CsA in patients with severe chronic idiopathic urticaria, unresponsive to conventional treatments.
Conference Paper: Our experience in the rush immunotherapy for insect sting allergy
Article: Probiotics and food-allergic disease[Show abstract] [Hide abstract] ABSTRACT: The definition of probiotics is always evolving, since it includes natural live micro-organisms, cellular subfractions, as well as genetically engineered derivatives or proteins. The scope of probiotic administration is beneficial change of the intestinal microflora, and improvement of non immune or immune resistance in the intestinal tract. Very few controlled human studies have been reported, but many in vitro and experimental animal studies point to their safety and potentially useful applications. We shall review the published reports and discuss mainly the prospective uses in the field of allergic diseases, with reference to the implication of the natural (innate) immune system as regulator of the development of abnormal responses to ingested food antigens.
- [Show abstract] [Hide abstract] ABSTRACT: The association of eosinophilic fasciitis and immunological defects is rare, especially hypogammaglobulinemia. We report a case of eosinophilic fasciitis occurring in a female, 53 years old, with common variable immunodeficiency. The diagnosis of common variable immunodeficiency was established by chance observation of persistently low levels of all immunoglobulin classes unrelated to protein loss or immunosuppressive treatment, one year after the appearance of eosinophilic fasciitis, which is usually characterized by hypergammaglobulinemia. Our description may prompt the investigation of an increased rate of simultaneous occurrence of eosinophilic fasciitis and common variable immunodeficiency.
- [Show abstract] [Hide abstract] ABSTRACT: RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-1 receptor antagonists (antihistamines) (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by the mini-Wright procedure. PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p<0.001 and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p<0.01) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that the steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.
Aristotle University of ThessalonikiSaloníki, Central Macedonia, Greece
The Catholic University of AmericaWashington, Washington, D.C., United States