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. OBJECTIVE: We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. METHODS: One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. RESULTS: All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. CONCLUSION: The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.

Serum levels of soluble CD23 in patients with asthma or rhinitis monosensitive to Parietaria. Its relation to total serum IgE levels and eosinophil cationic protein during and out of the pollen season.

The diagnostic value for allergies of the low affinity IgE receptor and its soluble circulating fragment (sCD23) remains unclear. In particular, little is know about seasonal influences on serum sCD23 levels in subjects with pollen allergy. In the present study, to gain insight into pathophysiological role of sCD23, we have analyzed, in blood from patients allergic to Parietaria sCD23, IgE, and eosinophil cationic protein (ECP) serum levels. IgE were assessed as atopy markers and ECP as an inflammation marker. Patients were studied during and out of pollen season, and results were compared to those obtained in nonallergic subjects. The study population included 42 nonsmoking outpatients, living in Palermo (Sicily, Italy) or in other west Sicilian towns, with a clinical diagnosis of seasonal asthma or rhinitis and monopositive skin test to Parietaria pollen. The group of asthmatic subjects consisted of 25 patients who had one or more of the usual asthma symptoms (wheezing, dyspnea, and cough) only during the pollen season. The group of rhinitis patients consisted of 17 patients, who, during pollen season, had the nasal symptoms (nasal blockage, sneezing, nasal itching, and rhinorrhoea) but no signs of asthma. As a control group, we studied 10 nonatopic subjects from laboratory staff. They had no history of seasonal or perennial rhinitis, asthma, or urticaria and had negative skin tests to a panel of allergens. Soluble CD23, IgE, and ECP were assessed in blood during and out of pollen season. Total serum IgE levels were clearly higher in atopic patients, as classically established. Concerning sCD23 serum levels, a similar pattern of results was obtained. Accordingly, significant correlations were shown between the levels of sCD23 and IgE in all groups of patients. A completely different pattern was observed by analyzing serum ECP levels because ECP levels were significantly increased only in asthmatic patients during pollen season. Accordingly, no significant correlations were observed between the levels of sCD23 and those of ECP. Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent diseases. As demonstrated by the close correlation with total serum IgE values and the lack of correlation with serum ECP values, serum levels of sCD23 appear to be an additional marker for the diagnosis of atopy but not for the follow-up of allergic diseases.

Efficacy, tolerability, and effects on quality of life of inhaled salmeterol and oral theophylline in patients with mild-to-moderate chronic obstructive pulmonary disease. SLMT02 Italian Study Group.

The aims of management in mild-to-moderate stable chronic obstructive pulmonary disease (COPD) are to improve symptoms and quality of life (QOL), reduce decline in lung function, prevent and treat complications, increase survival while maintaining QOL, and minimize the adverse effects of treatment. Bronchodilator therapy is the keystone of improving COPD symptoms and functional capacity. The primary objective of this open-label study was to compare the efficacy and tolerability of salmeterol 50 microg BID administered by metered-dose inhaler versus oral, titrated, sustained-release theophylline BID, both given for 3 months to patients with a clinical history of chronic bronchitis. The secondary objectives of the study were to evaluate the safety profile of the two drugs for an additional 9-month period and to assess changes in QOL both within and between treatment groups, using the 36-Item Short Form (SF-36) Health Survey. One hundred seventy-eight outpatients (122 men, 56 women; mean age, 56 +/- 12.9 years; mean body weight, 76.1 +/- 11.8 kg) were randomized to the two treatment groups. Patients receiving salmeterol showed significant improvement in mean morning peak expiratory flow rate (16.56 L/min) over the 3-month period compared with patients receiving theophylline (P = 0.02). Salmeterol also significantly increased the percentage of symptom-free days and nights with no additional salbutamol requirement (P < 0.01). A significant difference was found between increases in forced expiratory volume in 1 second compared with baseline for salmeterol compared with theophylline throughout the initial 3-month period (0.13, 0.16, and 0.16 L at months 1, 2, and 3, respectively) and during the additional 9 months. The incidence of adverse events was similar in the two groups (salmeterol, 49.5%; theophylline, 49.4%), with a lower percentage of pharmacologically predictable adverse events in patients receiving salmeterol (4%) compared with those receiving theophylline (14.8%). Both drugs improved QOL, as measured by effects on the eight aspects of life experience analyzed by the SF-36 questionnaire. Salmeterol therapy was effective in more aspects, and the improvements seen in each were numerically greater than those seen with theophylline therapy. Statistically different changes between the two treatment groups were reported for physical functioning, changes in health perception, and social functioning (P = 0.02, P = 0.03, and P = 0.004, respectively). These data suggest that inhaled salmeterol 50 microg BID was more effective and better tolerated than oral, titrated theophylline and allowed better long-term control of airways obstruction and symptoms with improved lung function in patients with COPD.

Allergic rhinitis to grass pollen: measurement of inflammatory mediators of mast cell and eosinophils in native nasal fluid lavage and in serum out of and during pollen season.

BACKGROUND: In allergic rhinitis, mast cells, activated by cross-linking of allergen to mast cell-bound specific IgE, release both vasoactive mediators related to the early nasal symptoms and chemotactic mediators that attract inflammatory cells, such as eosinophils, related to the late-phase response. OBJECTIVE: We have analyzed, during and out of pollen season, in blood and nasal fluid from patients allergic to grass pollen, histamine and tryptase to monitor the early phase markers and eosinophil and eosinophil cationic protein (ECP) to monitor the late phase. METHODS: Twenty patients were enrolled in the study. As a control, we studied 10 nonatopic subjects. Mediators and eosinophils were assessed in blood and nasal fluid. Histamine was tested only in nasal fluid. RESULTS: During pollen season, tryptase but not histamine increased in nasal fluids from patients (2.96 vs 0.22 U/ml, p = 0.001) and correlated with symptom scores (r(s) = 0.63, p = 0.003). Tryptase was not detected in serum. Eosinophils increased in nasal cytology (17.0% vs 2.0%, p = 0.001) and in the blood (265 vs 12.7 x 10(6) L, p = 0.001) from patients, but they did not correlate with symptom scores. ECP increased only in the nasal lavage (1633 vs 1.30 ng/ml, p = 0.001) and correlated with symptom scores (r(s) = 0.53, p = 0.016). CONCLUSIONS: Both ECP and tryptase increase in nasal secretion in natural disease. Therefore the measurement of tryptase and ECP levels in nasal fluid might be a useful clinical test for monitoring disease activity and the effects of therapeutic agents.

Blood eosinophils and serum eosinophil cationic protein in patients with acute and chronic urticaria.

We have analysed the relationship of blood eosinophil count and serum eosinophil cationic protein (ECP) levels in patients with acute and chronic idiopathic urticaria. The ECP levels and eosinophil counts were measured in the peripheral blood of 15 patients with acute urticaria, 25 with chronic idiopathic urticaria and 10 normal healthy subjects. Blood eosinophil counts and serum ECP levels increased in all patients with acute urticaria. Concerning patients affected by chronic urticaria, taking into account the recrudescence of the disease at the moment of taking the blood sample, only symptomatic patients showed increased eosinophil blood values whereas serum ECP levels were increased both in symptomatic and asymptomatic patients. Furthermore, serum ECP levels in chronic urticaria did not correlate with the peripheral eosinophil counts, as they did in acute urticaria. The results of the present study indicate that eosinophils may play a role in the inflammatory mechanisms in patients with acute and chronic urticaria showing a positive correlation between serum ECP levels and disease activity.