Cinzia Gamalero

Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters

Background Levocetirizine (LCZ) has been shown to be effective in allergic rhinitis. We evaluated its clinical efficacy, antinflammatory actions and its effects on quality of life (QoL) with a specific instrument in the asthma–rhinitis comorbidity.

New insights into airway remodelling in asthma and its possible modulation.

Purpose of reviewAirway remodelling, a central feature of asthma, is characterized by an alteration in the size, mass or number of tissue components which occur in and around the trachea, bronchi and bronchioles in the airways in response to injury and/or inflammation.The present review focuses on the most recent literature on airway remodelling and on the different drugs commonly used or potentially useful in the treatment of asthma with a particular attention to the studies conducted by our group in the last few years. Recent findingsThe interaction between the epithelium and mesenchymal elements such as fibroblasts is essential for normal airway repair. An abnormal response of this epithelial–mesenchymal trophic unit has been proposed to be central to the airway pathology and physiology characteristic of asthma. Current treatments may indirectly control airway remodelling through a reduction of inflammation but such a kind of approach is only in part successful. SummaryThe clear understanding of the events that take place during remodeling and the targeting of its specific components will be helpful in the development of novel therapies that might restore lung function.

Anti-proliferative and anti-remodelling effect of beclomethasone dipropionate, formoterol and salbutamol alone or in combination in primary human bronchial fibroblasts.

Background:  Bronchial asthma is characterized by lower airway inflammation and remodelling. Anti‐inflammatory treatment with inhaled corticosteroids (ICS) provides the mainstay of asthma therapy together with bronchodilation induced by short‐ and long‐acting inhaled β2‐agonists. Lower airway fibroblasts may play a critical role in airway inflammation and remodelling, suggesting that they might represent an important target for the major anti‐asthmatic drugs. The aim of our study was to investigate the effects of beclomethasone dipropionate (BDP), salbutamol and formoterol either alone or in combination on in vitro cultures of human bronchial fibroblasts.

Levocetirizine in persistent allergic rhinitis: continuous or on-demand use? A pilot study

ABSTRACT Background: Allergic rhinitis is a high-prevalence disease that affects quality of life (QOL), sleep quality and productivity of patients. According to the ARIA initiative, it is classified as intermittent and persistent, the latter being the most troublesome. Methods: The aim of this randomized, open-label, 6-month, pilot study was to determine whether levocetirizine 5 mg administered continuously once daily in the morning was better than levocetirizine 5 mg on-demand in symptomatic subjects with persistent allergic rhinitis. Total and individual symptom scores were recorded in a diary card throughout the study. QOL, quality of sleep, nasal cytology, rate of drug intake, and safety were also assessed at pre-defined time-points. Results: In all, adult patients (31 in each group) were enrolled, of whom 22 dropped out. Both treatment regimens considerably decreased the total and individual symptoms scores from baseline and achieved similar levels up to week 14. Continuous treatment was generally better than on-demand from week 15 onwards, reaching statistical significance from weeks 17 to 21 (from week 19 to 21 for nasal pruritus). Both regimens substantially improved QOL and sleep quality. Both treatments were well tolerated, although the on-demand group reported more adverse events. Conclusion: The present open label study in 62 patients indicates that levocetirizine 5 mg reliably controls persistent rhinitis over a period of 6 months, and shows a trend to be more effective in controlling the symptoms of rhinitis, improving QOL and decreasing nasal inflammation, when administered as long-term continuous therapy rather than as on-demand therapy.

A model of allergen-driven human airway contraction: β2 pathway dysfunction without cytokine involvement

BACKGROUND In our previous in vitro model, allergen incubation of passively sensitized human airways reduced the response to salbutamol. However, whether cytokines play a role in this model is still unknown. OBJECTIVE To investigate interleukin 1beta and tumor necrosis factor a expression in allergen-challenged human airways. METHODS Nonasthmatic airways (n = 13) were passively sensitized by overnight atopic serum incubation and then challenged with allergen for 1 hour (n = 9). After repeated washouts, airways were immersed in physiologic salt solution for 6 hours and finally in formaldehyde for immunohistochemical studies. The effect of co-incubation in anti-interleukin 1beta and anti-tumor necrosis factor a specific neutralizing antibodies on salbutamol response was also studied (n = 4). RESULTS No differences were found among control, sensitized, and challenged rings in the number of inflammatory cells. The percentage of basement membrane covered by epithelium was similar in the different conditions. There was a higher percentage of degranulating to total mast cells in allergen-challenged rings than in sensitized rings (P < .001). A significant correlation was observed between allergen-induced contraction and mast cell degranulation (r = 0.88; P < .001). The sensitization procedure was validated by paired allergen-induced contractions. No expression of the 2 cytokines was detectable up to 6 hours after allergen challenge, and specific neutralizing antibodies did not attenuate the impaired response to salbutamol in allergen-challenged rings. CONCLUSION These data suggest that in our in vitro model of allergic inflammation, beta2 pathway dysfunction can occur without cytokine involvement, thus supporting previous results that suggest a role for leukotrienes.