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Objective: Pelargonium sidoides preparation EPs 7630 has been proven safe and effective in acute respiratory tract infections (aRTIs), but data for young children have not been presented separately. This study reviewed clinical studies and presents an overview of known and newly analyzed data from children <6 years.Methods: MEDLINE and EMBASE were searched for interventional and non-interventional studies which investigated the effects of EPs 7630 in aRTIs and included children <6 years of age. Sub-group analyses for this age range were performed for symptom scales, global efficacy or effectiveness assessments, and safety outcomes.Results: Seven studies with 1067 children <6 years exposed to EPs 7630 were identified. Efficacy of EPs 7630 was significantly superior to placebo in reducing symptom intensity and time until complete recovery in two randomized, double-blind trials in patients with acute bronchitis (AB). Similar symptom time courses were observed in two non-comparative observational studies in AB. One non-comparative, open-label study was identified in acute tonsillopharyngitis (ATP), and one in acute rhinosinusitis (ARS). In both indications, nearly all children showed complete recovery or major symptom improvements during the treatment period, with changes that were similar to those observed in controlled trials investigating older patient populations. The results were supported by an additional observational study including children with various diagnoses of aRTIs. EPs 7630 was safe and well-tolerated.Conclusions: EPs 7630 is efficacious in children <6 years suffering from AB. The analyses also support the effectiveness of the product in ATP and in ARS. No safety concerns were identified. [ABSTRACT FROM AUTHOR]

Background: Aerosol therapy in young children can be difficult. A realistic model based on handling studies and in vitro investigations can complement clinical deposition studies and be used to enable dose-to-the-lung (DTL) predictions. Methods: Predictions on dose delivery to the lung were based on (1) representative inhalation flow profiles from children enrolled in a Respimat® handling study, (2) in vitro measurement of the fine-particle DTL using mouth-throat models derived from nuclear magnetic resonance/computed tomography (NMR/CT) scans of children, and (3) a mathematical model to predict the tiotropium DTL. Accuracy of the prediction was confirmed using pharmacokinetic (PK) data from children with cystic fibrosis enrolled in a phase 3 clinical trial of tiotropium Respimat with valved holding chamber (VHC). Results: Representative inhalation flow profiles for each age group were obtained from 56 children who successfully inhaled a volume >0.15 L from the Respimat with VHC. Average dimensions of the mouth±throat region for 38 children aged 1± < 2 years, 2± < 3 years, 3± < 4 years, and 4± < 5 years were determined from NMR/CT scans. The DTL from the Respimat plus VHC were determined by in vitro measurement and were 5.1 ± 1.1%, 15.6% ± 1.4%, 17.9% ± 1.5%, and 37.1% ± 1.8% of the delivered dose for child models 0± < 2 years, 2± < 3 years, 3± < 4 years, and 4± < 5 years, respectively. This provides a possible explanation for the age dependence of clinical PK data obtained from the phase 3 tiotropium trial. Calculated in vitro DTL per body mass (lg/kg [ ± SD]) were 0.031 ± 0.014, 0.066 ± 0.031, 0.058 ± 0.024, and 0.059 ± 0.029, respectively, compared to 0.046 in adults. Therefore, efficacy of the treatment was not negatively impacted in spite of the seemingly low percentages of the DTL. Conclusions: We conclude that the combination of real-life inhalation profiles with respective mouth±throat models and in vitro determination of delivered DTL is a good predictor of the drug delivery to children via the Respimat with VHC. The data provided can be used to support data from appropriate clinical trials. [ABSTRACT FROM AUTHOR]

Background Recently, we showed that combination of omalizumab with specific immunotherapy ( SIT) for treatment of patients with seasonal allergic rhinitis ( SAR) and comorbid seasonal allergic asthma ( SAA) is safe and reduced the symptom load in a statistically significant and clinically meaningful manner during the first pollen season. Objective The aim of this study was to investigate long-lasting effects of an initial combination treatment with SIT+omalizumab, a monoclonal anti-IgE antibody, in a follow-up period with SIT treatment only in patients with SAR and comorbid SAA incompletely controlled by conventional pharmacotherapy. Methods A randomized, double-blind, placebo-controlled, multicenter trial was performed to assess the efficacy and safety of omalizumab (Xolair®) vs. placebo in combination with SIT (depigmented allergoid vaccine, Depigoid®) during the first grass pollen season. Omalizumab or placebo therapy was started 2 wk before SIT; the whole treatment lasted 18 wk. After the first pollen season, SIT was given for two subsequent years without omalizumab. Primary end-point was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use in the second and third year. Results A total of 140 patients (age 11-46 yr) were randomized; 130, 128, and 114 patients finished the study after 1, 2, and 3 yr, respectively. The main efficacy variable was the mean daily symptom load as assessed in the patients' diary. No systematic differences between both analysis groups were detected in the findings from symptom load, symptom severity score, or rescue medication score. Further subjective data did not show differences between both groups in the quality-of-life data as assessed with the ACQ, AQLQ, and the RQLQ. Investigators' assessment of treatment effectiveness in the first and second year of study extension showed more patients with favorable long-term treatment outcome ('excellent' and 'good') in the SIT plus omalizumab group than in the SIT plus placebo group. In line with these findings, FEV1 improved at the end of both years in the group which was treated with the combination therapy in the double-blind study compared with the Depigoid plus placebo group. Conclusion Eighteen weeks' treatment of omalizumab in combination with SIT in patients with SAR and comorbid SAA reduced the symptom load during the treatment period but showed no prolonged effect during treatment with SIT only. A slight increase in lung function ( FEV1) in patients formerly treated with the omalizumab/ SIT combination therapy should encourage further evaluation of long-term effects of omalizumab. [ABSTRACT FROM AUTHOR]

Background: The aim of this trial was to investigate the efficacy and tolerability of EPs 7630, a herbal drug preparation from Pelargonium sidoides, in children and adolescents suffering from acute bronchitis, outside the strict indication for antibiotics. Methods: A total of 220 patients with acute bronchitis were randomized and given either verum containing EPs 7630 (1-6 years/>6-12 years/>12-18 years: 3 × 10/3 × 20/3 × 30 drops/day) or matching placebo for 7 days. The main outcome measure was the change in the total score of bronchitis-specific symptoms (BSS) from day 0 to day 7. Results: The decrease in the BSS total score was significantly higher for EPs 7630 compared to placebo (change day 0-day 7: 4.4 ± 1.6 vs 2.9 ± 1.4 points; P < 0.0001). Improvements were most pronounced for 'coughing' and 'rales at auscultation'. Tolerability was similarly good in both groups. Conclusions: EPs 7630 proved to be an efficacious and well-tolerated option for the treatment of acute bronchitis in children and adolescents outside the strict indication for antibiotics. [ABSTRACT FROM AUTHOR]

Introduction Seasonal allergic rhinitis (SAR) affects at least 10-25% of the Caucasian race and about 40% of patients are children. Standard treatment of SAR is specific immunotherapy (SIT), but anti-allergic drugs can significantly enhance efficacy of SIT. One candidate is the humanized monoclonal anti-IgE antibody omalizumab. Material and Methods Randomized, double-blind, placebo-controlled, multi-centre trial in Germany. A total of 221 children were randomly assigned to four different groups and treated with SIT (either grass or birch pollen), starting at least 14 wk before the local birch pollen season. After the 12- wk SIT titration phase, either anti-IgE (omalizumab) or placebo (NaCl 0.9%) therapy was added. This combination therapy with SIT and anti- IgE or placebo lasted 24 wk. To record local reactions and adverse events (AE), the injection site was examined by a clinician 20 min after application of study medication. Further, patients stated any AE and the use of rescue medication by means of a diary 3 days after every injection. Finally, any AE or serious adverse event (SAE) reported by the patients was specified on a standard form by clinicians. Overall tolerance was judged by the doctors according to the patient's diaries. To test differences between the groups, we used either the two-sided Wilcoxon rank-sum test or the two-sided chi-square test. Results Tolerability of SIT and omalizumab treatment was good (82% of patients). Only some AE with possible causal relationship to treatment occurred slightly more often in the verum groups, i.e. local reactions (16.8 vs. 12.3%) and gastrointestinal (2.7 vs. 0.9%) and ear symptoms (1.8 vs. 0%). Most AE (93.4% in omalizumab and 87.2% in placebo group) were judged by the patients as mild to moderate. SAE were restricted to four patients with asthma in the placebo group, two subjects with headache in the verum group and three patients with infections (two in verum and one in placebo group). Only the cases of asthma were judged to be possibly related to study medication. Further, redness and swelling at the SIT injection site appeared significantly more often in the placebo group which suggests a positive effect of omalizumab on local reaction induced by SIT. Conclusion Omalizumab represents an important clinical advance in the management of allergic diseases and can be considered to be safe in children [ABSTRACT FROM AUTHOR]

To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3–17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy. [ABSTRACT FROM AUTHOR]

Summary: We aimed to evaluate the efficacy and safety of fluticasone propionate (FP) in children aged 12–47 months with recurrent/persistent asthma symptoms. One hundred and sixty children (12–47 months) were randomised into this multicentre, double-blind, placebo-controlled, parallel-group study, and treated with either FP (100μg bd) or placebo (2 puffs bd), both administered by metered-dose-inhaler and Babyhaler™ for 12 weeks. The primary endpoint was percentage of symptom-free 24h periods. Over weeks 1–12, FP-treated patients had significantly more percentage symptom-free 24-h periods compared with placebo (odds ratio 0.53; 95% CI 0.29–0.95; ). Relative to baseline, where all patients were symptomatic for at least 21/28 days of the run-in, the improvement equated to one additional symptom-free 24h period per week. FP patients also had a significantly higher percentage of 24h periods with no wheeze or cough, the odds ratio for treatment difference corresponding to two additional wheeze-free and one additional cough-free periods per week. FP was well-tolerated, with similar reported adverse events in both groups. Urinary cortisol-creatinine ratio was slightly decreased among FP patients after 12 weeks, but with no clinical correlates. FP is effective for the treatment of chronic persistent asthma symptoms in very young children. [Copyright &y& Elsevier]