Marcello Mincarini

Continuous versus on demand treatment with cetirizine for allergic rhinitis.

BACKGROUND Cetirizine is an antihistamine used in the treatment of allergic rhinoconjunctivitis, that has antiallergic activity. OBJECTIVE The aim of this double-blind, placebo-controlled, parallel group study was to evaluate the clinical efficacy and the antiallergic activity of cetirizine, administered either continuously or on demand over a 4-week period of natural allergen exposure. METHODS Twenty patients, with allergic rhinoconjunctivitis due to grass and/or Parietaria pollen, were enrolled. They were randomized into 2 parallel groups: one group received the standard dose of 10 mg cetirizine daily and the other received placebo, all patients were allowed to take an additional daily dose of cetirizine when needed. Variables evaluated were clinical symptoms (recorded on diary cards), number of additional on demand cetirizine doses, nasal inflammatory cells, and pollen counts. RESULTS The results of the present study show that patients treated with continuous administration of cetirizine achieved significant symptomatic relief and inflammatory control (decreases in numbers of infiltrating neutrophils and eosinophils) in comparison to patients treated on demand. CONCLUSION Continuous treatment with cetirizine is more effective than on demand treatment. Continuous treatment reduces clinical and inflammatory variables more than symptomatic treatment and the on demand therapy can determine acceptable clinical control, but does not reduce allergic inflammation.

Quantitative flow cytometric analysis of the effects of cetirizine on the expression of ICAM-1/CD54 on primary cultured nasal cells

An in vitro flow cytometric model has been developed to evaluate the effects of antiallergic drugs such as cetirizine (CTZ) on the expression of surface molecules on primary cultured normal cells. Quantitative analysis demonstrated that HLA class I and ICAM‐1/CD54 molecules are present on both epithelial and stromal cells, and that their expression is strongly enhanced by treatment with interferon‐gamma (IFN‐γ). Nevertheless, the IFN‐γ‐mediated upregulation of ICAM‐1/CD54 was inhibited by treatment with CTZ, demonstrating a direct effect on both cell types. This finding is particularly interesting because ICAM‐1/CD54 is the main rhinovirus receptor, and rhinoviruses are the principal cause of asthma exacerbation in children. Thus, according to data derived from this in vitro model, CTZ should have an important role in the reduction of infectious exacerbation of asthma in atopic patients.

Single-dose oral tolerance test with alternative compounds for the management of adverse reactions to drugs.

Background: Adverse reactions to drugs are common in the clinical practice. Many outpatients are frequently referred to allergists in order to determine which drugs they can safely take in the future. Objective: We set up an oral single-dose tolerance test procedure to find out for each patient one or more alternative drugs that can be taken when needed. Methods: 452 outpatients (130 male, 322 female) with well-documented reactions (urticaria/angioedema, respiratory symptoms, laryngeal edema, anaphylaxis, exfoliative skin diseases) underwent the challenge. All tests were preceded by a single-blind placebo: if a reaction occurred, a second placebo was administered. Otherwise, a single dose (1/10 of the therapeutic one) of an alternative drug was given blindly and the patient was then observed for 6 h. The drugs used were different in structure from those suspected of having caused the adverse reaction. The patients were followed up at 4- to 6-month intervals, in order to detect any reaction that may have occurred with the tested drugs. Results: 98 patients (89 women) had untoward reactions after the first placebo and 34 out of them reacted to the second placebo, too. During challenges the reaction rate ranged between 4.6 and 9.0%; these reactions were easily managed and none of them was severe. We followed up 407 patients: 87.2% of them were able to use one or more of the suggested drugs without reactions, 9.3% did not take the drugs and only 3.5% reported reactions to the previously tested drugs. Conclusion: The challenge procedure proved to be a simple tool for managing patients with adverse reactions to drugs. Its safety and reliability were validated by a long-term follow-up.

Aeropollinic sampling at three different heights by personal volumetric collector (Partrap FA 52)

Background: Aeropollinic sampling is usually performed by volumetric pollen traps located on the top of buildings at a height of 15–20 m. The present study aimed to determine whether pollen concentration is similar, at the same time, at different heights.

Aerobiologic particle sampling by a new personal collector (Partrap FA52) in comparison to the Hirst (Burkard) sampler

A new personal portable sampler of biologic particles (Partrap FA52, Coppa, Biella, Italy) was used for pollen sampling in comparison with Hirsts (Burkard) fixed device. The acrobiologic samplings were carried out simultaneously outdoors with the two devices coupled on the same axis, during the daytime of 10 dry, nonconsecutive spring days. The total amount and the percentages of the pollens most often trapped by the two collectors were compared by Students t‐test for paired samples. The Partrap FA52 showed a highly significant efficacy, quite comparable to that of the Burkard device, in pollen trapping for both the total number (P < 0.0001) and the percentages of Parietaria (P < 0.0001), pine (P < 0.002), and grass (P < 0.0001) pollens. Therefore, Partrap FA52 proved to be highly effective in obtaining quantitative and qualitative aerobiologic samples in comparison with the commonly used fixed samplers.

IL-13 and idiopathic pulmonary fibrosis: Possible links and new therapeutic strategies

The recent advances in the knowledge of immunological aspects of many pulmonary diseases, allowed to identify cells, biological functions, cytokines, and receptors that are preferentially involved in each disease. This is the case of asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The role of IL-13 is strictly related, via complex signaling pathways, to eosinophil recruitment and activation, to mucus secretion, periostin generation and to fibrogenic processes (which are part of the remodeling process). These peculiar roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary Fibrosis, and consequently of its antagonists in the treatment of such disease. We review herein the immunological roles of IL-13 in asthma and IPF, and the currently ongoing attempts to treat IPF by IL-13 antagonism strategies.

Cetirizine-induced downregulation of airway fibroblast proliferation and function: a rationale for a different approach to allergy treatment?

Recently, airway fibroblasts captured the attention of both allergists and basic scientists since they are no longer considered as mere bystanders, as far as allergic airway diseases are concerned. The aim of the present study was to assess the effects of different Cetirizine (Cet) concentrations (0.01, 0.05, 0.1 mg/ml) on human airway fibroblast proliferation and on CD54 expression. By means of flow cytometry analysis, we evaluated CD54 expression by airway fibroblasts in basal conditions or after gammaIFN stimulation in the presence of Cetirizine; we also evaluated the effect of the drug on cell proliferation by a [3H]thymidine incorporation assay. All of the tested doses of Cetirizine were able to significantly reduce CD54 upregulation induced by gammaIFN; concerning the fibroblast proliferation, we observed a dose-dependent inhibition of [3H]thymidine incorporation. These results show that Cetirizine exerts a biologic effect directly on human airway fibroblasts, suggesting a new rationale in the use of this compound.

Allergen Specific Immunotherapy in Asthma

The use of allergen Specific Immunotherapy (SIT) to treat allergic asthma is still a matter of scientific debate. Currently, there are few studies specifically designed to evaluate asthma, and few studies had a formal sample size calculation, or objective parameters of pulmonary function assessed. On the other hand, there are good quality trials with both Subcutaneous Immuno-therapy (SCIT) and Sublingual Immunotherapy (SLIT) in allergic rhinitis, where asthma symptoms were also evaluated, if present. These studies consistently reported positive results. Moreover, several favourable meta-analyses are available, although their validity is limited by the great heterogeneity of the trials included. The disease modifying effect of SIT that is the capacity of preventing asthma onset should be also taken into account. Concerning the safety, fatalities seem to be an exceptional event, and in Europe no fatality has been reported over the last two decades. Uncontrolled asthma is universally recognized as the most important risk factor for severe adverse events. In conclusion, both SLIT and SCIT can be used in asthma associated with rhinitis (which is the most common condition), provided that asthma is adequately controlled by pharmacotherapy. In such case, a measurable clinical benefit on asthma symptoms can be expected. Nonetheless, SIT cannot be presently recommended as single therapy when asthma is the unique manifestation of respiratory allergy.

The safety of monoclonal antibodies in asthma

ABSTRACT Introduction: In the last two decades the knowledge of the mechanisms of the inflammatory processes underlying asthma rapidly evolved, several key mediators (cytokines and receptors) were identified, and the laboratory techniques have allowed us to synthesize monoclonal antibodies highly specific for those target molecules. Nowadays, many biological agents are investigated in asthma (with anti IgE being the only commercially available). The clinical efficacy of some biologics was demonstrated in many cases, however, the safety issue has progressively emerged and has been recognized as a crucial aspect. Areas covered: We summarized the currently available knowledge on the safety and side effects of biologics in asthma, as derived by reviews, meta analyses and clinical trials. PubMed was searched with the terms anti IL-x [AND] safety [OR] side effects, within the categories “clinical trial”, meta-analysis” and “review”. Case reports were excluded. The authors collegially selected the relevant entries to be included. Expert opinion: Overall, the safety of most of the investigated agents seems to be satisfactory, a certain risk of side effects remains present, and is variable for the different molecules. Thus caution must be paid in evaluating the risk to benefit ratio. Specific biomarkers to predict the response to each biological are urgently needed to improve the safety profile.