Vito Ditta

Randomized placebo‐controlled trial comparing fluticasone aqueous nasal spray in mono‐therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis

Background Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first‐line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms.

Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy.

BACKGROUND To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. OBJECTIVE We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. METHODS We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patients) or sublingual immunotherapy (203 patients) routes. Serum t-IgE and s-IgE levels, blood eosinophil counts, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to ASI. Receiver operating characteristic curves were determined. Predicted probabilities and predictive areas under the curve were calculated. RESULTS The clinical response to ASI was effective in 145 (52.0%) of 279 total patients, 42 (55.2%) of 76 patients treated with subcutaneous immunotherapy, and 103 (50.7%) of 203 patients treated with sublingual immunotherapy. A significant correlation was found between the serum s-IgE/t-IgE ratio and the clinical response to ASI, with high ratios (>16.2) associated with an effective response. The sensitivity and specificity of the area under the curve of the ratio were higher than those of serum s-IgE and t-IgE alone. CONCLUSION The calculation of the serum s-IgE/t-IgE ratio for predicting the clinical response to ASI offers an advantage over measuring t-IgE and s-IgE levels in monosensitized patients for the following allergens: grass, Parietaria judaica, Olea europea, and house dust mite.

Food-additive-induced urticaria : A survey of 838 patients with recurrent chronic idiopathic urticaria

Background: Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1–3% of the population in the USA and Europe and accounts for nearly 75% of all ‘ordinary’ chronic urticaria (CU) cases. Methods: We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. Results: The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. Conclusions: Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.

Zinc and Inflammatory/Immune Response in Aging

Abstract:  Life‐long antigenic burden determines a condition of chronic inflammation, with increased lymphocyte activation and proinflammatory cytokine production. A large number of studies have documented changes in zinc metabolism in experimental animal models of acute and chronic inflammation and in human chronic inflammatory conditions. In particular, modification of zinc plasma concentration, as well as intracellular disturbance of antioxidant intracellular pathways, has been found in aging and in some age‐related diseases. Zinc deficiency is diffused in aged individuals in order to avoid meat and other high zinc content foods due to fear of cholesterol. Rather, they increase the consumption of refined wheat products that lack zinc and other critical nutrients as a consequence of the refining process. On the other hand, plasma zinc concentration is influenced by proinflammatory cytokines (IL‐6 and TNF‐α) and by metallothioneins (MT) homeostasis, which is in turn affected by proinflammatory cytokines. MT increase in aging and chronic inflammation allowing a continuous sequestration of intracellular zinc with subsequent low zinc ion availability against stressor agents and inflammation. This phenomenon leads to an impaired inflammatory/immune response in the elderly. A major target of zinc is NF‐κB, a transcription factor critical for the expression of proinflammatory cytokines whose production is regulated by extra‐ and intracellular activating and inhibiting factors interacting with the regulatory elements on cytokine genes. Effects of zinc on translocation of NF‐κB have been attributed to the suppression of phosphorylation and degradation of the inhibitory proteins (A20) that normally sequester it in the cytoplasm. Moreover, this factor and A20 are regulated by specific genes involved in inflammation and by intracellular zinc ion availability. So, it is not so surprising that zinc deficiency is constantly observed in chronic inflammation, such as in old individuals. On the other hand, cytokine genes are highly polymorphic and some of these polymorphisms are associated with atherosclerosis and diabetes type 2. Therefore, zinc turnover, via MT homeostasis, in individuals genetically predisposed to a dysregulation of the inflammatory/immune response may play a crucial role in causing possible adverse events with the appearance of age‐related diseases.

Differences and Similarities between Allergic and Nonallergic Rhinitis in a Large Sample of Adult Patients with Rhinitis Symptoms

Background: Allergic rhinitis (AR) and nonallergic rhinitis (NAR) may present with different clinical and laboratory characteristics. Methods: A total of 1,511 consecutive patients, aged 18–81 years, diagnosed with rhinitis, 56% females and 44% males, underwent complete allergic evaluation including skin prick test, blood eosinophil counts, nasal eosinophil counts, peak nasal inspiratory flow (PNIF) measurement and evaluation of nasal symptoms using a visual analog scale (VAS). Results: A total of 1,107 patients (73%)had AR, whereas 404 (27%) had NAR. Patients with NAR were older and predominantly female. A higher nasal eosinophils count was associated with AR and a lack of clinical response to antihistamines. AR patients had more sneezing and nasal pruritus, whereas NAR was characterized mainly by nasal obstruction and rhinorrhea. AR patients had more severe symptoms and recurrent conjunctivitis, whereas NAR patients had slightly more frequent episodes of recurring headaches as well as olfactory dysfunction. PNIF, blood eosinophil counts and VAS of nasal symptoms were higher in patients with AR. In a final logistic regression model, 10 variables were statistically different between AR and NAR: age [OR 0.97 (95% CI 0.96–0.98)], sneezing [OR 4.09 (95% CI 2.78–6.00)], nasal pruritus [OR 3.84 (95% CI 2.60–5.67)], mild symptoms [OR 0.21 (95% CI 0.09–0.49)], intermittent/severe nasal symptoms [OR 3.66 (95% CI 2.06–6.50)], VAS [OR 1.06 (95% CI 1.04–1.08)], clinical response to antihistamines [OR 22.59 (95% CI 13.79–37.00)], conjunctivitis [OR 4.49 (95% CI 2.86–7.05)], PNIF [OR 1.01 (95% CI 1.00–1.01)] and nasal eosinophil counts [OR 1.14 (95% CI 1.10–1.18)]. Receiver operating characteristic analysis showed high predictive accuracy for a model including these variables independently of the diagnosis of AR/NAR (cutoff <0.74). Conclusions: We showed that the several clinical and laboratory parameters reported above may help to reinforce or exclude the diagnosis of AR obtained with skin prick test.

Leukotriene receptor antagonists in monotherapy or in combination with antihistamines in the treatment of chronic urticaria: a systematic review

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST)]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis.

Is there a role for antileukotrienes in urticaria

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, i.e. leukotriene receptor antagonists and synthesis inhibitors, are a new class of anti‐inflammatory drugs that have shown clinical efficacy in the management of asthma. We searched the MedLine database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin or food additive hypersensitivity or with autoreactivity to intradermal serum injection when taken with an antihistamine but not in moderate chronic idiopathic urticaria. Evidence for the effectiveness of zafirlukast and the 5‐lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angio‐oedema, and exercise‐induced anaphylaxis.

A study of age-related IgE pathophysiological changes

The literature on immunosenescence has focused mainly on T cell impairment. However, it is well known that B function is also profoundly affected. In particular, several studies have shown age-related changes in immunoglobulin serum levels. Concerning allergic diseases, the incidence of onset of allergic symptoms, as well as their severity, seems to decrease with age. So, the decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total IgE due to an unbalance of cytokines and soluble factors involved in its production. To gain insight into the mechanisms of age related incidence of onset of allergic symptoms, as well as their severity, in this study we have evaluated in a sample of young (12 females and 15 males, range 20-64 years) and old (42 females and 20, males range 70-93 years) individuals serum values of IgE and sCD23 and in vitro Type 2 cytokine production. Total serum IgE levels were quantified by CAP-system fluorescence enzyme immunoassay. Serum CD23 levels were measured by a sandwich enzyme-linked immunoassay. Enzyme immunoassay tests have been used to quantify IL-4, IL-10 and IL-13 on mitogen-stimulated cultures. Serum total IgE and sCD23 in the two groups of young and old subjects were not significantly different. No detectable levels of IL-4, IL-10 and IL-13 were observed in supernatants from unstimulated cultures in all the subjects tested. After 48 h stimulation with PHA, cytokine amounts became detectable in all subjects. However, the values of the cytokines under study were not significantly different between young and old subjects. In our study, we have not been able to show no impairment in the afferent (type 2 cytokine production) and in the central (serum IgE and sCD23 levels) branch of allergic responses. Previous studies have shown that the efferent branch, at least studied as basophil releasability and bronchial responsiveness, is not impaired in elderly. In conclusion, as suggested from the present and previous papers it is questionable whether there is sufficient information to validate the statement that the incidence of allergic diseases decreases with age.

Clinical importance of eosinophil count in nasal fluid in patients with allergic and non-allergic rhinitis.

Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver Operating Characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNFs accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNFs median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNFs median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNFs median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNFs median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was ≤ 5.0, AUC = 0.94. ECNFs median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was ≤ 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNFs performance was moderately accurate in distinguish patients with AR and NAR.

Allergic Asthma and Aging

Gabriele Di Lorenzo1, Danilo Di Bona2,3, Simona La Piana2, Vito Ditta4 and Maria Stefania Leto-Barone1 1Dipartimento di Medicina Interna e Specialistica (DIMIS), Universita degli Studi di Palermo 2Dipartimento di Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Universita degli Studi di Palermo 3Unita Operativa di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera, Universitaria Policlinico di Palermo 4Centro Trasfusionale ASPPalermo. P.O. San Raffaele G. Giglio Cefalu, Palermo Italia