Wolfgang Kamin

Transient impact of omalizumab in pollen allergic patients undergoing specific immunotherapy

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.

Positioning of the Bronchitis Severity Score (BSS) for standardised use in clinical studies

Abstract Objective: Diagnosis and assessment of response to treatment in acute bronchitis depends on clinical findings. We evaluated published data on the Bronchitis Severity Score (BSS) used to diagnose acute bronchitis and to evaluate the impact of treatment in clinical studies. Methods: We conducted a literature search using PubMed (search terms: acute bronchitis, treatment, score, and BSS; publication date April 2012 or earlier) and asked the manufacturer for relevant publications. Articles were reviewed and relevant studies were classified according to author, study design, measurements made and duration of study, study drug(s), outcome, and statistical significance. Results: The medication most frequently evaluated by the BSS is a herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630). The BSS consistently demonstrated statistically significant differences between active treatments and placebo as well as between different doses of active treatment. The proportion of responders was considerably higher in the EPs 7630 group than in the placebo group. Because of the subjective components of the BSS, inter-individual differences in results may exist. However, the BSS outcome was supported by the results of secondary outcome measures, such as the Integrated Medicine Patient Satisfaction Scale (IMPSS), documenting that patients were more often ‘satisfied’ or ‘very satisfied’ with EPs 7630 than placebo. Conclusions: We recommend further use of the BSS as a reliable and convenient clinical trial tool for selecting and evaluating patients in studies of acute bronchitis. Improvement in the BSS correlates with outcomes reported by these patients.

Physicochemical compatibility and stability of nebulizable drug admixtures containing Dornase alfa and tobramycin.

The objective of this in-vitro study was to determine whether admixtures of the inhalation solutions Pulmozyme(®) (Dornase alfa) and either Bramitob(®) or Tobi(®) (both containing Tobramycin) are physicochemically compatible and to analyze the aerodynamic parameters of these admixtures. After mixing, test solutions were stored at room temperature and under ambient light conditions over a period of 24 h. Tobramycin concentrations were determined by using a fluorescence immunoassay. Stability of dornase alfa was determined by size-exclusion high performance liquid chromatography, ultraviolet spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis and tentacle strong cation-exchange chromatography. In addition, pH values and osmolality of the admixtures were measured and test solutions were visually examined for any changes up to 24 h. Aerosols of Pulmozyme(®)/Bramitob(®) or Pulmozyme(®)/TOBI(®) admixtures were generated with the PARI eFlow(®) rapid and aerodynamic particle sizing was performed via cascade impaction with the Next Generation Pharmaceutical Impactor. The stability tests revealed that neither the stability of tobramycin nor the stability of dornase alfa was affected by mixing the inhalation products. Cascade impaction showed no relevant changes in particle size distribution, Mass Median Aerodynamic Diameter, Geometric Standard Deviation and Fine Particle Fraction in comparison to aerodynamic parameters of the unmixed solutions. Thus, admixtures of Pulmozyme(®) and either Bramitob(®) or TOBI(®) can be designated as compatible for a 24 h period and simultaneous inhalation is feasible.

Inhalation solutions — Which ones may be mixed? Physico-chemical compatibility of drug solutions in nebulizers — Update 2013

Many patients suffering from chronic respiratory diseases rely on inhalation therapy with nebulizers. About 25% of patients who need to inhale several different drugs per day save time by mixing them for simultaneous inhalation. This review presents a comprehensive overview of the available data concerning physico-chemical compatibility of commonly mixed nebulizer solutions and suspensions. Information is based on our in vitro studies and a thorough literature search. Results indicate that many nebulizer solutions/suspensions are mixable without provoking incompatibilities. However, certain excipients contained in some of the tested drug products could be identified as a reason for incompatibilities, e.g. impaired activity of dornase alfa. Studies assessing the aerosol characteristics of compatible mixtures nebulized with commonly used nebulizers are limited and should be encouraged. The clinical efficacy of simultaneous inhalation of duplicate, tripartite or quadripartite mixtures must be evaluated in clinical studies before final recommendations for the inhalation regimens can be made.

Safety and Tolerability of EPs 7630 in Clinical Trials

Herbal medicines play an increasingly important role in the perception of physicians and patients looking for equally effective, albeit safer approaches to conventional management of certain diseases. The controversy surrounding effective management regimes for respiratory tract infections (RTI) has made many healthcare providers reconsider current therapeutic strategies. This review presenting the available evidence from clinical trials and non-interventional studies on the safety and tolerability profile of EPs 7630 is based on publications and study reports of 29 clinical trials and post-marketing surveillance studies completed by February 2010. It includes study data from 10,026 adults and children suffering from acute or chronic RTI such as acute tonsillopharyngitis, rhinopharyngitis, sinusitis, bronchitis, or COPD and from 31 healthy subjects. In 19 double-blind, placebo-controlled trials, the type and incidence rate of adverse events under EPs 7630 were similar to those in patients treated with placebo. For gastrointestinal complaints and epistaxis, event rate differences of 2.9% and of 0.6% against EPs 7630 were determined; hypersensitivity reactions and all other system groups showed rate differences <0.5%. For liver associated events, rate differences of 0.0% for all events and of 0.1% for potentially related events were observed. Patients treated with EPs 7630 did not exhibit increased liver enzyme or bilirubin values – neither in terms of a shift in the mean, nor according to individual deviations from the reference ranges. These findings were fully supported by the data from the post-marketing surveillance studies reviewed. EPs 7630 appears to be a well-tolerated herbal medicine in the management of RTI in adults and children alike. Evidence for hepatotoxic effects in humans during routine administration was neither provided in the literature, nor by our own analyses.

EPs 7630 is effective and safe in children under 6 years with acute respiratory tract infections: clinical studies revisited

Abstract 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.

Physicochemical compatibility of nebuliser solution admixtures containing colistimethate and hypertonic saline or colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate

Objectives For practical reasons, patients with cystic fibrosis (CF) tend to mix different inhalation solutions for concomitant inhalation instead of inhaling the different medications consecutively. A study was undertaken to examine the compatibility of colistimethate dissolved in 5.85% hypertonic sodium chloride (NaCl) solution and the quadripartite mixtures of colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate. Methods The test solutions were prepared by mixing ordinary doses of the inhalation products and analysed immediately. Microbiological assays of antibiotics and high-performance liquid chromatography assays were used to determine chemical compatibility and visual inspection, pH and osmolality measurements were used to determine physical compatibility. Mixtures of colistimethate with NaCl solutions were stored in a refrigerator at 2–8°C for 48 h and retested. Results The antimicrobial activity of colistimethate dissolved in 5.85% NaCl solution did not differ from the activity of colistimethate dissolved in 0.9% NaCl solution and remained unchanged over a period of 48 h. In the quadripartite admixtures the activity of colistimethate and the concentrations of ipratropium bromide, salbutamol sulfate and fluticasone-17-propionate amounted to ≥ 100% of the nominal concentrations. Chemical and physical compatibility was shown. Conclusions When colistimethate is dissolved in 5.85% NaCl solution for inhalation, the antimicrobial activity remains unchanged over a period of 48 h. With regard to in vitro compatibility, simultaneous inhalation of quadripartite mixtures of colistimethate, fluticasone-17-propionate, salbutamol sulfate and ipratropium bromide or colistimethate in 5.85% NaCl solution is feasible but needs to be clinically confirmed.

Krupp oder Epiglottitis

ZusammenfassungEin Elternpaar kommt mit seinem zweijährigen Kind, das unter akuter Luftnot mit inspiratorischem Stridor und bellendem Husten leidet, in die Praxis. Sie berichten über eine leichte Temperaturerhöhung in den letzten 48 Stunden und etwas Schnupfen.