W Czarlewski

Hôpital Armand-Trousseau (Hôpitaux Universitaires Est Parisien), Lutetia Parisorum, Île-de-France, France

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Publications (17)68.03 Total impact

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    ABSTRACT: Given the morbidity and mortality of asthma and the recent dramatic increase in its prevalence, pharmacologic prophylaxis of this disease in children at risk would represent a major medical advance. The Preventia I Study was designed to evaluate the efficacy and long-term safety of loratadine in reducing the number of respiratory infections in children at 24 months. A secondary objective was to investigate the benefit of loratadine treatment in preventing the onset of respiratory exacerbations. Preventia I was a randomized placebo-controlled study involving 22 countries worldwide. The children were 12-30 months of age at enrollment and had experienced at least five episodes of ENT infections, and no more than two episodes of wheezing during the previous 12 months. Phase I was a 12-month double-blind period during which the children were treated with loratadine 5 mg/day (2.5 mg/day for children</=24 months of age) or placebo. Phase II was a double-blind follow-up period without study medication. Of the 412 children enrolled, 342 and 310 completed Phase I and Phase II, respectively. The results showed a significant decrease in the number of infections in the whole population of children. However, no difference was observed between the loratadine and placebo group. When considering secondary end-points, loratadine was shown to reduce the number of respiratory exacerbations during the treatment phase. None of the 204 children who received loratadine discontinued the study because of drug-related events. Loratadine treatment was not more sedative than placebo and was not associated with cardiovascular events. The strong decrease in the rate of infections in the children at risk of recurrent infections, while not being influenced by loratadine treatment, should encourage future reflection in terms of prophylactic management. This study also confirms the long-term safety of loratadine and its metabolites in young children.
    Clinical & Experimental Allergy 11/2004; 34(11):1665-72. · 4.79 Impact Factor
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    ABSTRACT: Recent studies have demonstrated that some antihistamines can attenuate histamine-induced release of inflammatory mediators from bronchial epithelial cells. The purpose of study was to test the hypothesis that loratadine may influence pollution-induced inflammation of the airways by modulating epithelial membrane integrity and the synthesis and/or release of inflammatory mediators from airway epithelial cells. We have cultured human bronchial epithelial cell (HBEC) cultures from surgical explants and investigated the effect of loratadine on NO2-induced changes in both electrical resistance of HBEC cultures and release of IL-8, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells after exposure for 6 hours to either air or 400 ppb NO2. Exposure for 6 hours to NO2 significantly decreased the electrical resistance of HBEC cultures by 18.1% from baseline (P <.05). Incubation with 0.25 to 25 micromol/L loratadine did not alter the NO2-induced decrease in the electrical resistance of HBEC cultures. NO2 also significantly increased the release of IL-8 from a control value of 52.5 pg/microgram cellular protein to 81.9 pg/microgram cellular protein (P <.05), RANTES from a control value of 0.023 pg/microgram cellular protein to 0.062 pg/microgram cellular protein (P <.05), and sICAM-1 from a control value of 7.7 pg/microgram cellular protein to 16.3 pg/microgram cellular protein (P <.05). The NO2-induced release of all 3 mediators was significantly attenuated by incubation of HBECs with 25 micromol/L loratadine. Incubation with 2.5 micromol/L loratadine also significantly attenuated the NO2-induced release of RANTES and sICAM-1, but not IL-8. These results suggest that loratadine has the potential to reduce airway inflammation by modulating the release of inflammatory cytokines from airway epithelial cells.
    Journal of Allergy and Clinical Immunology 08/1999; 104(1):93-9. · 12.05 Impact Factor
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    ABSTRACT: New-generation H1-blockers may possess antiallergic properties, and their effect may differ, depending on the target organ. A double-blind, placebo-controlled, parallel-group study was carried out during the pollen season to compare the clinical effect on nasal and conjunctival symptoms of astemizole (10 mg o.d.) and loratadine (10 mg o.d.) with their effect on skin-test reactivity to allergen and histamine. Thirty-eight patients (12-56 years of age) were studied. Nasal and ocular symptoms were recorded daily from days 4 to 7. Skin prick tests with serial concentrations of allergens and one concentration of histamine were carried out before and at the end of the 7-day treatment period. Parallel-line bioassay, analysis of variance, and covariance were used to analyze skin test data. Loratadine and astemizole significantly decreased symptoms from baseline (P < 0.004 and P < 0.006). Skin-test reactivity to allergen and histamine was more profoundly decreased by astemizole than loratadine. The histamine covariant was more important in the allergen effect of astemizole than in that of loratadine. Two H1-blockers having the same clinical effect on nasal and ocular symptoms during the pollen season have totally different effects on skin-test reactivity. Skin-test reactivity to allergen or histamine is not predictive of the clinical efficacy of H1-blockers during seasonal allergic rhinitis.
    Allergy 06/1998; 53(6):579-85. · 5.88 Impact Factor
  • C Amsellem, W Czarlewski, M Lagarde, Y Pachéco
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    ABSTRACT: Leukotriene B4 (LTB4), an inflammatory mediator, is a potent chemoattractant for neutrophils (PMN) that plays an important role in the late reaction in asthma. Human airway epithelial cells (HAEC) can interact with PMN to increase LTB4 production. The aim of this study was to determine the influence of loratadine, an antihistaminic drug, on the production of LTB4 by PMN either alone or during interaction with transformed HAEC. The effect of tumour necrosis factor-alpha (TNF-alpha) was also examined. LTB4 production was measured by RP-HPLC after cell stimulation with calcium ionophore. Loratadine (0.25-25 microM) induced a significant and dose-dependent decrease of LTB4 production by PMN alone whereas it was up-regulated by TNF-alpha. As reported by others, we confirmed the increase of LTB4 release when PMN were cocultured with HAEC as compared to PMN alone. Addition of loratadine to HAEC before co-culture with PMN induced a significant decrease of LTB4 formation by cell interaction. This effect was noted when HAEC were washed following incubation with loratadine, demonstrating a direct action of the drug on this cell type. Moreover, the TNF-alpha-induced stimulation of LTB4 release that we demonstrated in PMN-HAEC interaction was also inhibited by loratadine. These results indicate that loratadine might reduce inflammatory reaction by a direct effect on PMN LTB4 production but also through an influence on HAEC during interaction with PMN.
    Pulmonary Pharmacology &amp Therapeutics 02/1998; 11(4):245-52. · 2.54 Impact Factor
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    ABSTRACT: Although new antihistamines exert additional antiallergic properties besides blocking histamine1 (H1) receptors, their potential for prophylactic treatment of asthma has not been thoroughly investigated. This study compared the efficacy and tolerability of loratadine with those of cromolyn sodium, the nonsteroidal prophylactic treatment of choice for mild-to-moderate childhood perennial allergic asthma. A total of 122 children (mean age, 10 ± 2 years) with mild-to-moderate perennial allergic asthma were enrolled in a multicenter, double-masked, double-dummy, randomized, parallel-group study. They received either cromolyn sodium (two 5-mg puffs four times daily) or loratadine (10 mg if body weight was ⩽30 kg or 20 mg if >30 kg) for 8 weeks. The efficacy was assessed by wheezing, cough, and asthma symptom scores, overall assessment of asthma severity, peak expiratory flow recordings, forced expiratory volume in 1 second (FEV1) measurements, and use of inhaled beta2-agonists. Tolerability was assessed by recording possible adverse reactions and blood test results. Wheezing decreased significantly in patients in both groups from day 0 to day 56; cough decreased significantly only in the loratadine group. Similarly, asthma score decreased significantly only in the loratadine group. Physicians and parents reported a highly significant reduction in asthma severity and in the number of patients using beta2-agonists in both groups. Peak-flow and FEV1 values remained constant in both groups throughout the study. No statistically significant difference was observed between the treatment groups in any variable. In addition, tolerability was similar and satisfactory for both groups. Results of this study suggest that loratadine could be an alternative to cromolyn sodium in the treatment of mild-to-moderate childhood perennial allergic asthma.
    Current Therapeutic Research 01/1998; 59(8):567-578. · 0.45 Impact Factor
  • Allergy 01/1998; 53(6):579-585. · 5.88 Impact Factor
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    ABSTRACT: The allergic inflammatory reaction is characterized by leucocyte adherence and infiltration processes which are controlled by the expression of adhesion molecules on the surface of vascular endothelium. One of the main mediators implicated in allergic reactions is represented by histamine. Histamine is a potent activator of endothelial cells (EC): it induces the expression of P-selectin on the surface of endothelium and the secretion of IL-6 and IL-8. Loratadine (L), a histamine H1-antagonist, and one of its active metabolites, descarboxyethoxyloratadine (DCL), were studied at different concentrations for their ability to reduce the histamine-induced activation of human umbilical vein EC (HUVEC). HUVEC were stimulated in the presence of histamine at 10(-6) M, 10(-5) M and 10(-4) M. We assessed by ELISA the expression of P-selectin on EC surface, as well as cytokine production in EC supernatants of 24 h culture. Our results showed that for a 10(-4) M-histamine stimulation, L and DCL have a similar inhibitory effect on P-selectin expression (IC50 = 13 x 10[-9] M and 23 x 10[-9] M, respectively). L and DCL inhibited significantly IL-6 and IL-8 secretion induced by histamine with a more powerful efficiency of the active metabolite. For the dose of 10(-4) M histamine, a 50% inhibition of IL-6 secretion was obtained for a dose of DCL equal to 2.6 x 10(-12) M whereas the same magnitude of effects were only reached for a higher concentration of L (0.3 x 10[-6] M). Similar results were obtained for IL-8 (IC50 = 0.2 x 10[-6] M for L and 10[-9] M for DCL). Analysis of IL-8 mRNA expression by RT-PCR was in accordance with these data. These results demonstrate that both L and DCL are active to reduce the histamine-induced activation of EC. Interestingly, DCL seems to be effective at lesser concentrations especially to inhibit cytokine secretion.
    Clinical & Experimental Allergy 11/1997; 27(10):1167-74. · 4.79 Impact Factor
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    ABSTRACT: ICAM-1, a transmembrane glycoprotein promoting adhesion in immunologic and inflammatory reactions, was found to be increased on nasal epithelial cells of patients with allergic rhinitis. Loratadine, an H1-blocker, was found to reduce in vitro the expression of ICAM-1 on nasal epithelial cells. A double-blind, parallel-group study was carried out during the pollen season to compare the effect of two H1-blockers, cetirizine (10 mg OD) and loratadine (10 mg OD), on the release of soluble ICAM-1 in nasal secretions. A group of untreated patients was used as a control group. sICAM-1 was measured by enzyme immunoassay before and after 2 weeks of treatment. Symptoms were significantly decreased in the actively treated groups. sICAM-1 levels were unchanged in the control group but were significantly reduced in the two treated groups (P < 0.015, Wilcoxon's W test). This study shows that two H1-blockers, loratadine and cetirizine, have a similar effect on sICAM-1 released in nasal secretions during the pollen season.
    Allergy 10/1997; 52(10):1022-5. · 5.88 Impact Factor
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    ABSTRACT: H1-blockers are often added to the standard treatment of acute sinusitis, but this is not supported by a controlled study. A multicentric, randomized, double-blind, placebo-controlled, parallel-group study was done in 139 allergic patients (15-65 years) to assess the adjunct efficacy of loratadine in acute exacerbation of rhinosinusitis. Sinusitis was diagnosed by symptoms and confirmed by rhinoscopy and sinus radiograph. Allergy was characterized by skin tests, RAST, and history. Patients were treated with antibiotics (14 days), oral corticosteroids (10 days), and loratadine (10 mg OD) or placebo (28 days). Treatment efficacy was assessed over 28 days by symptom scores quoted daily by patients. Physicians also rated total symptom scores at entry and at day 28. At entry, both groups had similar symptoms. Placebo-treated patients improved significantly, but patients who received loratadine had a significantly greater improvement in sneezing (P = 0.003) after 14 days, and in nasal obstruction (P = 0.002) after 28 days. Physicians found that patients receiving loratadine were significantly improved compared to placebo patients (P = 0.0125). Loratadine in addition to standard therapy was found to improve the control of some symptoms of sinusitis.
    Allergy 07/1997; 52(6):650-5. · 5.88 Impact Factor
  • Allergy 01/1997; 52(10):1022-1025. · 5.88 Impact Factor
  • J L Menardo, F Horak, M R Danzig, W Czarlewski
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    ABSTRACT: Patients with seasonal or allergic bronchial asthma experience an immediate allergic response caused by allergen-specific immunoglobulin E-mediated histamine release. The release of histamine and other chemical mediators may trigger airway hyperresponsiveness and exaggerated bronchoconstriction, characteristic features of allergic bronchial asthma. Traditional antihistamines have demonstrated only moderate activity of short duration against this disease. In contrast, loratadine, a potent, nonsedating, histamine-1-receptor antagonist with activity in seasonal and perennial allergic rhinitis, has demonstrated effective control of asthma symptoms, improved pulmonary function, and long duration of action in patients with allergic bronchial asthma. This review summarizes preclinical evidence for the antiallergic activity of loratadine and the results of clinical studies with oral loratadine in patients with allergic bronchial asthma.
    Clinical Therapeutics 01/1997; 19(6):1278-93; discussion 1523-4. · 2.23 Impact Factor
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    ABSTRACT: 1. In this study, we compared the effects of two antihistamine drugs on the production of granulocyte-macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro. 2. Cytokine production was assessed by the use of an enzyme-linked immunosorbent assay. 3. Epithelial cells spontaneously released both cytokines and tumor necrosis factor alone induced a significant increase in this production but loratadine and cetirizine had no effect at the various concentrations studied. 4. The antihistamines have no effect and this suggests that histamine plays no role in cytokine production under these conditions.
    General Pharmacology 04/1996; 27(2):269-72.
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/1996; 97(1):237-237.
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/1996; 97(1):279-279.
  • J Bousquet, I Chanal, W Czarlewski, F B Michel
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    ABSTRACT: The reproducibility of any challenge and its sensitivity to change during therapeutic interventions should always be examined before any drug trial is conducted. Conjunctival challenge has been widely used to assess objectively the efficacy of antiallergic treatments. A double-blind, placebo-controlled, crossover study was carried out in 26 patients allergic to grass pollen to test the reproducibility of a composite symptom score during placebo and control days, and to check the ability of loratadine to increase the provocative dose inducing a positive challenge. Conjunctival challenge was carried out with increasing concentrations of a standardized orchard grass pollen extract until a composite symptom score of 5 was reached. The provocative dose inducing a positive challenge was similar for the baseline (6.94 +/- 8.7 index of reactivity (IR)) and placebo days (20.0 +/- 32.5 IR) and was significantly increased (P < 0.01 and P < 0.001) when patients received loratadine (117.3 +/- 136.8 IR). This study shows that the composite score used was reproducible and sensitive to change, making it possible to use in drug trials.
    Allergy 10/1995; 50(10):841-3. · 5.88 Impact Factor
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    ABSTRACT: Nasal epithelial cells represent the first barrier against noxious agents and allergens. In allergic rhinitis, these cells are activated and histamine may be involved in this activation. Loratadine and one of its active metabolites, descarboethoxyloratadine, were studied for their ability to reduce the activation of nasal epithelial cells by histamine. Nasal turbinates or polyps were removed during surgery from 19 subjects, and nasal epithelial cells were recovered after enzymatic digestion. The in vitro activation of epithelial cells with histamine using an optimal dose (1 microM) and an optimal time (24 h) of incubation was studied, and the effect of loratadine or descarboethoxyloratadine (10 microM) was investigated. The expression of membrane markers (intercellular adhesion molecule-1 (ICAM-1) and a human leukocyte class II antigen (HLA-DR) was assessed by immunocytochemical analysis using an alkaline-antialkaline phosphatase (APAAP) system. The spontaneous expression of both markers was not significantly different in cells recovered from nasal turbinates or polyps, and there was a highly significant increase in the numbers of cells expressing ICAM-1 and HLA-DR following incubation with histamine. Loratadine or descarboethoxyloratadine significantly blocked these effects. This study shows a new possible antiallergic effect of H1-blockers and suggests that their effects on epithelial cells may be relevant in vivo.
    Allergy 04/1995; 50(3):200-3. · 5.88 Impact Factor
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    ABSTRACT: A double blind multicentre study of seasonal rhinitis (108 patients) has compared Loratadine and Cetirizine. The results of clinical scores are significantly good for both products. Only tolerance is different and in favour of Loratadine, since sleepiness was found in 9.5% of patients treated with Cetirizine, and 3.6% with Loratadine.
    Allergie et immunologie 10/1992; 24(7):270-4.