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- Material and methods
Background: It was the aim of the authors to compare all of the latest second-generation antihistamines and to see if there were significant differences in their efficacy. It is important for ENT specialists to know if these differences exist, as it is for general practitioners trying to choose between these drugs.
Methods: In 12 confirmed grass pollen allergic patients the authors performed nasal smears to asses eosinophilia, histamine/grass pollen skin tests, and grass pollen nasal provocation tests. All tests were performed before and after administration of one of five different antihistamines (cetirizine, loratadine, ebastine, fexofenadine, mizolastine) or placebo. The order of administration of antihistamines and placebo was randomised, and patients were not aware of which drug they were given. A decrease in nasal eosinophilia (nasal smear), or nasal or skin reactivity (provocation tests) was looked for.
Results: A significant decrease in nasal eosinophilia was observed for all antihistamines but not for placebo. For the grass pollen nasal provocation tests, the decrease was significant for nasal blockage and sneezing; for rhinorrhea there was an insignificant decrease that was true for all antihistamines. A significant reduction in histamine/grass pollen skin test reactivity was also observed for all antihistamines, during an 8 h observation period. A significant difference in efficacy between the different antihistamines could not be found with any of the tests performed.
Conclusions: For the newer nonsedating H1-antagonists there appears to be no clinically relevant differences in activities – at least not in our study. Preference of the patient may be the most important factor in making a choice between these drugs.
Oral antihistamines or H1-receptor antagonists are considered part of the first-line medical treatment of mild persistent as well as intermittent allergic rhinitis (1), and this is true for adults as well as for children (2). Histamine H1-receptor antagonists are divided into first generation drugs which often have sedating side-effects caused by blood-brain-barrier passage, and the newer second generation, nonsedating drugs.
In recent years, several new molecules have been developed, such as cetirizine, ebastine, fexofenadine, mizolastine and loratadine. All of these newer drugs seem to be safe, easy to use, and without important side-effects (3–7). Furthermore, for most of these newer drugs it is claimed that besides a strong H1-antagonist activity, they also have important anti-inflammatory properties (8, 9). For the ENT specialist and the general practitioner alike, it is not easy to make the best possible choice from these new nonsedating antihistamines, especially since little is known about the comparative efficacy of these drugs.
The purpose of this study was to evaluate any differences in efficacy of five of the newer antihistamines used for the treatment of allergic rhinitis, as compared to placebo. To compare the efficacy of these drugs intradermal histamine and grass pollen skin test reactivity, nasal grass pollen provocative concentrations, and nasal smear eosinophilia were determined before and after drug administration. Earlier studies comparing the efficacy of antihistamines were done using histamine skin tests in nonallergic patients (10, 11). In our study the drugs were compared in allergic patients using allergen as well as histamine skin testing, and also with nasal allergen provocation. By using nasal provocation as well as skin tests we tried to get a more complete picture of the effects of these drugs. We performed tests on allergic patients rather than normal test subjects, to observe drug effects in a setting that more closely resembles the situation in which the drugs are normally used. Suppression of nasal eosinophilia and nasal blockage after nasal allergen provocation also gives some insight into the clinical relevance of claims of anti-inflammatory activity of the newer antihistamines.
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- Material and methods
In our study design, for all antihistamines tested, there was a significant reduction in nasal smear eosinophilia after nasal allergen provocation as compared with placebo.
To date not many nasal provocation studies have been performed where a significant effect of antihistamines on nasal eosinophilia after nasal allergen challenge has been demonstrated. During natural allergen exposure, however, it has been suggested that certain antihistamines diminish eosinophil counts (12). There are several in vitro studies in which a reduction in eosinophil chemotaxis caused by certain antihistamines was found (13, 14). The number of local eosinophils in allergen skin tests has also been shown to be reduced by antihistamines (15).
The reduction in nasal eosinophilia after nasal allergen challenge might be an indication of the anti-inflammatory properties of these newer antihistamines. More studies are certainly necessary to show to what extent this reduction in nasal eosinophilia is clinically relevant.
For the nasal allergen provocation test, a significant reduction in nasal blockage and sneezing was found for all tested antihistamines. In this study, though the rhinorrhea induced by nasal allergen provocation tended to be reduced for all antihistamines vs placebo, this trend was not significant.
Normal exposure to grass pollen during the season is not entirely comparable to nasal challenge with grass pollen. During the season the patient is exposed continuously to grass pollen and therefore there is a constant hyperreactive state due to persistent eosinophilia (16, 17). The significant reduction of nasal blockage and sneezing is, however, a clear indication of the effectiveness of these new drugs in preventing symptoms in grass pollen allergic patients. The lack of significant reduction of rhinorrhea might be an indication that nose-blowing, as a method of collection of secretions during allergen provocation, is not sensitive enough.
Intradermal skin tests using either histamine or allergen (in an allergic patient) have long been used to assess the efficacy of antihistamines in the treatment of allergic rhinitis. Some authors doubt whether this is valid since the skin does not react completely in the same way as the shock organ in IgE-mediated allergic rhinitis (18, 19).
Also in our setting, in the histamine and the grass pollen skin test there was a significant reduction in wheal diameter caused by all antihistamines at 4 h as well as at 8 h after administration of the drug. Fexofenadine tended to be less effective after 8 h but even this trend was not significant; fexofenadine might better be administered twice a day instead of once daily.
A significant difference in action between the different antihistamines could not be found in any of the tests performed in our study (nasal smear, nasal allergen provocation, allergen/histamine skin tests), all antihistamines showed significant activity compared to placebo. By using allergic patients and allergen testing in our study we tried to make the test setting as similar as possible to the normal situation in which these drugs are used. However, the fact that the study was performed outside the grass pollen season in grass pollen allergic patients may have influenced the final results.
The authors do conclude, however, that when choosing a drug from this group of second generation histamine H1-antagonists for treatment of allergic rhinitis, the preference of the patients might be the one most important factor, because all the new histamine H1-antagonists appear to be comparable in their efficacy.