Francesco Castello

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.

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.

Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma

The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics.

Increased responsiveness to histamine after propranolol in subjects with asthma nonresponsive to the bronchoconstrictive effect of propranolol

Eight nonsmoking subjects with asthma, nonresponsive to the bronchoconstrictive effect of oral propranolol, were studied. The airway response to increasing concentrations of histamine aerosol was assessed by measuring FEV1. The threshold provocative dose of histamine needed to cause a 20% fall in starting FEV1 (PD20) was measured by log dose-response curve. Histamine challenge was performed in duplicate after premedication with placebo or 40 mg of propranolol on separate days. The mean starting FEV1 did not change significantly after placebo and after propranolol administration. The mean PD20 values after propranolol (0.37 mg/ml and 0.32 mg/ml, respectively, for the first and the second challenge) were significantly lower (p less than 0.01) than mean control PD20 values (1.36 mg/ml and 1.48 mg/ml, respectively, for the first and the second challenge). These results indicate that propranolol increases airway responsiveness to histamine, even in those subjects with asthma in whom propranolol has little bronchoconstrictive effect.

Effect of Ketotifen on the Bronchodilatation Induced by Salbutamol

Twelve subjects with stable asthma each inhaled two puffs (200 μg) of salbutamol on 2 separate days 3 h after double-blind oral administration of ketotifen (two 1-mg capsules) or identical placebo. FE

A pilot study demonstrating how inhaled furosemide enhances the bronchodilator effect of salbutamol

Abstract To investigate whether inhaled furosemide can improve the bronchodilator effect of salbutamol, a single-blind crossover study in 10 subjects with stable asthma was designed. Each subject inhaled two puffs of salbutamol (200 μg) 1 hour after premedication with an aerosol preparation of either furosemide or placebo. Forced expiratory volume in 1 second (FEV 1 ) was measured before premedication, again before inhalation of salbutamol, and again 30, 60, and 90 minutes after, and 2, 3, 4, and 5 hours after inhalation of salbutamol. The FEV 1 at each time interval was greater on furosemide days but the difference was significant at 1, 4, and 5 hours after salbutamol inhalation. The areas under the curves on furosemide days were greater than on placebo days. The study suggests that pretreatment with inhaled furosemide enhances and prolongs the bronchodilator effect of salbutamol.

Effect Throughout the Day of Inhaled Fenoterol on the Bronchial Responsiveness to Histamine in Asthmatic Patients

The effect throughout the day of inhaled fenoterol on the bronchial responsiveness to inhaled histamine was evaluated in 8 asthmatic patients. The airway response to increasing concentration of histamine aerosol was assessed by measurement of forced expiratory volume in one second (FEV1). The provocative dose of histamine needed to cause a 20% fall in starting FEV1 was calculated from the cumulative log dose response curves. Histamine challenges were performed in duplicate, on separate days, after premedication with placebo or fenoterol given by metered dose inhalers in the morning and in the afternoon. The mean starting FEV1 in the morning and in the afternoon did not change significantly after placebo inhaler, but fenoterol caused a mean increase in FEV1 of 11.11% in the morning and 4.92% in the afternoon. Geometric mean histamine PC20 was significantly higher after fenoterol than after placebo. After fenoterol there was no significant difference between morning and afternoon geometric mean histamine PC20. No relation was found between bronchodilatation achieved by fenoterol and increase in the geometric mean histamine PC20 (p greater than 0.05). There was instead a significant relationship between starting FEV1 and histamine PC20 in the morning and in the afternoon both after placebo and fenoterol.