[Drug Output and Aerosol Characteristics of Different Jet Nebulisers for Adults While Simulating the Nebulisation of Salbutamol]. / Aerosolcharakteristika ausgewählter Druckluftvernebler für Erwachsene in Simulationsmodellen und Verneblung von Salbutamol.

AIM: Successful inhalation therapy with nebulisers depends on the amount and quality of the aerosol. Choosing a nebuliser requires knowledge of relevant aerosol characteristics. METHODS: We analysed the aerosol performance of 9 commercially available jet nebulisers in 2 in vitro simulation models by assessing the aerosol delivery of albuterol (Sultanol forte® Inhalation Solution 2.5 mg/2.5 ml; GSK) over 4 minutes. The output parameters were analysed with PARI Compas II breath simulator mimicking an adult breathing pattern (Ph.Eur.9.0; n = 5/6 nebulisation), and the aerodynamic particle size distribution was determined by the Next Generation Impactor (Ph.Eur.9.0, Copley Scientific; n = 3 nebulisation). RESULTS: The aerosol performance of the devices differed considerably. The DDR varied from 196 µg/min (PARI LC Sprint (blue)) to 67 µg/min (MIDINEB). The Respirable Drug Delivery Rate (RDDR), calculated from the DDR and the Fine Particle Fraction ≤ 5 µm, varied by a factor of 3.5 between the nebulisers tested. CONCLUSION: The results of the in vitro simulation studies can be utilised to select an appropriate nebuliser for the individual patient. In order to enhance therapeutic efficacy and patient compliance, a nebuliser with a high RDDR should be selected.

Assessment of the effect of pharmacotherapy in common cold/acute bronchitis - the Bronchitis Severity Scale (BSS).

BACKGROUND: Acute bronchitis (AB) is a highly contagious infection of the airways, presenting mostly in connection with common cold (CC). There is a high variance in duration and course of symptoms which, sooner or later, also may disappear spontaneously and change during the course of the disease. Therefore, assessment of treatment outcome is difficult. METHODS: Composite outcome measures are commonly used to examine the effects of pharmacotherapy in complex diseases. We discuss the features of the Bronchitis Severity Scale (BSS) on the basis of the available literature. RESULTS: For the BSS the five most important symptoms of AB are rated by the patient and the physician. Since its introduction in 1996, the BSS has been used in many clinical trials evaluating treatment effects of AB. Its score correlates well with clinical findings. As thorough validation analyses revealed, this applies even more to the BSS subscales "cough domain" and "sputum domain". CONCLUSION: The validated BSS appears to be a reliable tool to assess therapeutic effects in CC/AB. The BSS and its subscales are recommended as outcome measures for future drug trials in CC/AB, but also help physicians to focus their consultation in patients with CC/AB.

Physicochemical compatibility of nebulizable drug admixtures containing colistimethate and tobramycin.

Inhalation therapy with nebulizable antibiotic drugs is a mainstay in treating Pseudomonas aeruginosa infections in cystic fibrosis patients. The combination of tobramycin and colistin was found to be superior to monotherapy in killing P. aeruginosa in biofilms. The simultaneous inhalation of tobramycin and colistin might be an option to increase the compliance of patients. The objective of this in-vitro study was to determine whether admixtures of inhalation solutions containing colistin methanesulfonate (CMS) and tobramycin are physicochemically compatible. Physical compatibility was determined by measuring pH and osmolality. Chemical compatibility was determined by testing the antibiotic activity of the mixtures by the pharmacopoeial microbiological assay and comparing the results to those of standard solutions. Samples were analyzed immediately after mixing and after 24 h. Values of pH and osmolality remained unchanged and in physiologically acceptable ranges. Neither for colistin methanesulfonate (CMS) nor for tobramycin losses of antibiotic potency were registered at any time. Admixtures of nebulizer solutions containing CMS and tobramycin were shown to be physicochemically compatible. Further investigations are needed to determine whether drug delivery is affected by mixing the nebulizer solutions to ensure that simultaneous inhalation is recommendable.

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

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.

The natural history of allergic rhinitis in childhood.

The distinction between 'seasonal' and 'perennial' allergic rhinitis (AR) is not always adequate. The 'Allergic Rhinitis and its Impact on Asthma' (ARIA) work group suggested a new classification for AR based on severity and duration of symptoms. Our primary aim was to describe the natural history and burden of AR according to the new ARIA criteria in a population-based birth cohort study of children up to 13 yr. We defined symptoms as 'severe' (impairment of daily activities) or 'mild' (no impairment) and 'persistent' (duration > 1 month) or 'intermittent' (

Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis - a randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots.

OBJECTIVE: The study aim was to demonstrate the efficacy and to investigate the tolerability of EPs 7630, a herbal drug preparation from Pelargonium sidoides roots, in the treatment of patients (1 - 18 years) with acute bronchitis outside the strict indication for antibiotics. MATERIALS AND METHODS: A total of 200 patients were randomized to receive either active drug containing EPs 7630 (1 - 6 years: 3 x 10 drops/d; > 6 - 12 years: 3 x 20 drops/d; > 12 - 18 years: 3 x 30 drops/d) or placebo for 7 consecutive days. PRIMARY OUTCOME MEASURE: change in the total score of bronchitis-specific symptoms (BSS) from Day 0 to Day 7. Main secondary outcome measures: treatment outcome, patients' satisfaction with treatment, onset of effect, bed rest. RESULTS: From baseline to Day 7, the mean BSS score improved significantly more for EPs 7630 compared with placebo (3.4 +/- 1.8 vs. 1.2 +/- 1.8 points, p < 0.0001). On Day 7, treatment outcome was significantly better (p < 0.0001), satisfaction with treatment more pronounced (77.6% vs. 25.8%, p < 0.0001), onset of effect faster, and time of bed rest shorter as compared with placebo. Tolerability was similarly good in both groups. All adverse events were assessed as non-serious. CONCLUSION: EPs 7630 was shown to be efficacious and safe in the treatment of acute bronchitis in children and adolescents outside the strict indication for antibiotics with patients treated with EPs 7630 perceiving a more favorable course of the disease and a good tolerability as compared with placebo.

Efficacy and tolerability of EPs 7630 in patients (aged 6-18 years old) with acute bronchitis.

AIM: For EPs-7630, a herbal drug preparation from Pelargonium sidoides roots, therapeutic effects in respiratory tract infections outside the strict indication for antibiotics have already been demonstrated in adults. Now, a dose-finding study for EPs-7630 was performed in children and adolescents. METHODS: A total of 400 patients (aged 6-18 years) were randomized to receive either 30 mg, 60 mg or 90 mg EPs-7630 or placebo daily. Primary outcome criterion was the change in the Bronchitis Severity Score (BSS) from day 0 to day 7. RESULTS: After 7 days of treatment, the change in the BSS total score was significantly better in the 60 mg and 90 mg groups compared with placebo that of the without relevant differences between these two dosages. Especially 'coughing', 'sputum' and 'rales at auscultation' improved under EPs-7630. Onset of effect was faster, time of bed rest shorter and treatment outcome and satisfaction with treatment were rated better. Tolerability was comparable with placebo in all treatment groups. CONCLUSION: EPs-7630 is effective in acute bronchitis outside the strict indication for antibiotics in 6-18 years old patients, with a dose of 60 mg or 90 mg daily offering the best benefit/risk ratio. EPs-7630 significantly reduces the severity of symptoms, leads to a more favourable course of the disease and a faster recovery from acute bronchitis compared with the placebo, and is well tolerated.

Multidisciplinary management of Hunter syndrome.

Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes of many tissues and organs and contribute to the multisystem, progressive pathologies seen in Hunter syndrome. The nervous, cardiovascular, respiratory, and musculoskeletal systems can be involved in individuals with Hunter syndrome. Although the management of some clinical problems associated with the disease may seem routine, the management is typically complex and requires the physician to be aware of the special issues surrounding the patient with Hunter syndrome, and a multidisciplinary approach should be taken. Subspecialties such as otorhinolaryngology, neurosurgery, orthopedics, cardiology, anesthesiology, pulmonology, and neurodevelopment will all have a role in management, as will specialty areas such as physiotherapy, audiology, and others. The important management topics are discussed in this review, and the use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome is presented.

Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma.

BACKGROUND: The treatment of allergic asthma by specific immunotherapy (SIT) is hampered by potential side-effects. OBJECTIVE: The aim of this study was to study the effect of omalizumab, a monoclonal anti-IgE antibody, in combination with SIT in patients with seasonal allergic rhinoconjunctivitis (SAR) and co-morbid seasonal allergic asthma (SAA) incompletely controlled by conventional pharmacotherapy. METHODS: A randomized, double-blind, placebo-controlled, multi-centre trial was performed to assess the efficacy and safety of omalizumab (Xolair) vs. placebo in combination with depigmented SIT (Depigoid) during the grass pollen season. Omalizumab or placebo was started 2 weeks before SIT; the whole treatment lasted 18 weeks. Primary endpoint was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use. RESULTS: A total of 140 patients (age 11-46 years) were randomized; and a total of 130 finished the study. Combination therapy reduced the symptom load by 39% (P=0.0464, Wilcoxon test) over SIT monotherapy. This difference was mainly due to reduced symptom severity (P=0.0044), while rescue medication use did not change significantly. Combination therapy also improved asthma control (Asthma Control Questionnaire, P=0.0295) and quality of life in the case of asthma (Asthma Quality of Life Questionnaire, P=0.0293) and rhinoconjunctivitis (Rhinoconjunctivitis Quality of Life Questionnaire, P=0.0537). Numbers of patients with 'excellent or good' treatment efficacy according to ratings of investigators (75.0% vs. 36.9%) or patients (78.5% vs. 46.1%) were markedly higher in the combination group than under SIT alone. CONCLUSION: Combination of omalizumab with SIT for treatment of patients with SAR and co-morbid SAA was safe and reduced the symptom load in a statistically significant and clinically meaningful manner.

[Postnatally acquired pulmonary cyst: differential diagnosis of pediatric cystic pulmonary lesions]. / Postnatal erworbene Lungenzyste. Differenzialdiagnosen zystischer Lungenläsionen im Kindesalter.

BACKGROUND: Differential diagnosis of infantile pulmonary cysts comprises congenital cystic lesions (including foregut cysts) and pneumatoceles (i.e., pulmonary cysts of acquired, inflammatory or traumatic origin). CASE: We report the resection of a subpleural air-filled lung cyst of 4 cm in a former preterm (33rd week of pregnancy) at the age of 8 months that was first diagnosed 7 days postnatally by chest X-ray. Pneumatocele was diagnosed pathomorphologically. CONCLUSION: In children, most pneumatoceles are caused by trauma or pneumonia. In the case described, disruption of subpleural alveolar walls due to high pressure ventilation is the likely cause. Differential diagnoses are discussed.

[Teaching the inhalation manoeuvre to asthmatic children by means of visual feedback]. / Schulung des Inhalationsmanövers bei Kindern mit Asthma bronchiale mittels optischem Feedback.

BACKGROUND: For inhalation as a mainstay of asthma therapy, the correct inhalation technique is of utmost importance. This comprises not only the correct handling of the device but also specific device-dependent requirements concerning the inhalation manoeuvre itself. METHODS: We examined whether totally different inhalation manoeuvres can be educated in parallel in asthmatic children. As target manoeuvres we defined: 1) an inhalation as fast as possible (peak inspiratory flow >or= 60 l/min) with high acceleration in the starting phase as it is normally required for dry powder inhalers. 2) A constant inhalation at a flow between 40 and 90 l/min with a long duration as it is regarded to be optimal for propellant driven systems. As models for dry powder inhalers the Diskus (Accuhaler, a medium resistance device) and the Turbuhaler (high resistance) were chosen. As an example of a propellant-driven we used the Autohaler (breath-actuated MDI). A total of 52 outpatients (age 4 to 14 years) with asthma were educated two times. We measured peak inspiratory flow (PIF), duration of inspiration with inspiratory flow >or= 30 l/min (Ti30), inspiratory volume (Vol) and acceleration of inspiratory flow (mPIF) through the devices in random order before and after each training session. Measurements were performed using the inhalation manager, a computer based spirometry system, which allows recording of inspiratory manoeuvres through Placebo inhalers by means of a pneumotachometer. Results are immediately visualized (optical feedback) and evaluated. RESULTS: Training children simultaneously with different inhalation systems appeared to be difficult. Only for the DPIs a significant increase of children inhaling in the pre-given target area could be reached. With Diskus, the rate of correct manoeuvres increased from initially 57.7 % to 88.5 % after training and with Turbohaler from 32.7 % to 65.4 %, respectively. With MDI, this rate increased only from 32.7 % to 42.3 %. This indicates that a high inspiratory flow may be easier to be learned than a constant slow inhalation, at least when training is done simultaneously in children. CONCLUSIONS: Thus, training of the different inhalation manoeuvres for DPI and MDI should be performed separately. When prescribing inhaled drugs for reliever treatment and maintenance therapy for any individual patient, prescribers should select inhalation devices, which can be used in a similar way without clinical disadvantage.

Pelargonium sidoides preparation (EPs 7630) in the treatment of acute bronchitis in adults and children.

Acute bronchitis, although mostly caused by viral infections, is commonly treated with antibiotics. As antibiotics should only be prescribed upon strict indication, treatment options like a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) gain more and more interest. To evaluate the efficacy and safety of treatment with EPs 7630 in patients with acute bronchitis, a multi-centre, prospective, open observational study was conducted in 440 study sites located in Germany. A total of 2099 patients aged 0-93 years with productive cough for less than six days without indication for treatment with antibiotics were given EPs 7630-solution in an age-dependent dosage for 14 days. The primary outcome criterion was the mean change of the Bronchitis Severity Score (BSS: cough, sputum, rales/rhonchi, chest pain at cough, dyspnoea) from baseline to patient's individual last observation. During treatment, the mean BSS of all patients decreased from 7.1+/-2.9 points at baseline to 1.0+/-1.9 points at patients' individual last visit. Subgroup analysis for children showed a decrease of mean BSS from 6.3+/-2.8 points to 0.9+/-1.8 points and analysis of children younger than three years showed a decrease of mean BSS from 5.2+/-2.5 points to 1.2+/-2.1 points. Adverse events occurred in 26/2099 (1.2%) patients. Serious adverse events were not reported. In conclusion, EPs 7630 is an effective and well tolerated treatment of acute bronchitis in adults, children and infants outside the strict indication for antibiotic treatment.

Physicochemical compatibility of nebulizable drug mixtures containing dornase alfa and ipratropium and/or albuterol.

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of Pulmozyme inhalation solution with Atrovent or Sultano are physicochemically compatible. Drug combinations were prepared in accordance with the product information and clinical practice by mixing the content of one respule Pulmozyme with 2 mL Atrovent LS and 0.5 mL Sultanol Inhalationslösung (inhalation solution) or with one respule of either Atrovent 500 microg/2 mL Fertiginhalat (unit dose formulation) or Sultanol forte Fertiginhalat. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity was determined by a kinetic colorimetric DNase activity assay. Ipratropium bromide and albuterol concentrations were investigated by a stability-indicating HPLC assay with ultraviolet detection. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Ipratropium bromide and albuterol concentrations were not affected by mixing the drug products. Dornase alfa activity is affected by benzalkonium chloride, used as excipient in Atrovent"LS and Sultanol'Inhalationsl6öung, and disodium edetate used as an excipient in AtroventfLS. Patients should be advised not to mix Pulmozymelwith Atrovent1LS and/or Sultanol"Inhalationsldöung, because of the incompatibility reaction. Mixtures of Pulmozyme with Atrovent 500 microg/2 mL Fertiginhalat or Sultanol forte Fertiginhalat can be designated as compatible for a limited period of time.

Easy removal of a large mucus plug with a flexible paediatric bronchoscope after administration of rhDNase (Pulmozyme).

Mucoid impaction and plastic bronchitis are relatively rare disorders affecting patients of any age. Here we report the case of mucoid impaction developing in a four-year-old child as a complication of pneumonic infection treated four weeks prior. p.a. chest X-ray and fiberoptic bronchoscopy showed atelectasis and the location of a mucus cast in the left upper lobe. After extraction of the cast via the suction channel of the bronchoscope had failed, we administered 2.5 mg of undiluted recombinant human deoxyribonuclease (rhDNase) instilled directly over the affected area of occlusion for 15 minutes. This mucolytic agent mobilized the cast by reducing viscoelasticity and adherence of mucus. Subsequent extraction of the mucus cast was easy, resulting in immediate reduction of atelectasis and discharge of the child the following day. Treatment of severe mucus plugging by direct instillation of rhDNase has been a safe and efficacious procedure for mobilising adherent mucus plugs and for facilitating bronchoscopic extraction.

[Anaphylaxis after vaccination due to hypersensitivity to gelatin]. / Anaphylaxie nach gleichzeitiger Impfung gegen Masern, Mumps, Röteln und Frühsommer-Meningoenzephalitis aufgrund einer Gelatineallergie.

Most allergic reactions after vaccination occur in patients sensitive to egg protein. Therefore this subject is well investigated, and the majority of common vaccines today contain only traces of egg protein. In contrast, there is little knowledge of hypersensitivities to other substances frequently contained in vaccines, e. g. antibiotics, phenol, gelatin and different preservatives. Here we report the case of a boy who had an anaphylactic reaction after being vaccinated against measles, mumps, rubella (MMR), and tick-born encephalitis (TBE) simultaneously. Different tests finally revealed a hypersensitivity to gelatin. This should be kept in mind especially during emergency care, since gelatin containing products like Haemaccel, Gelifundol or Gelofusin are widely used as colloid for resuscitation. If type 1 reactions after vaccination occur, gelatin should be taken into account as the causative agent. A medical alert card is recommended for such patients.

Variability of total serum immunoglobulin E levels from birth to the age of 10 years. A prospective evaluation in a large birth cohort (German Multicenter Allergy Study).

BACKGROUND: Many environmental factors influence the concentration of total serum IgE (tIgE); however, tIgE synthesis is believed to be under strong genetic influence. Multiple genetic studies on tIgE regulation have been performed. For these population-based studies tIgE was commonly determined at one time-point, assuming that tIgE phenotypes (adjusted for age and gender) are stable over time. OBJECTIVE: We assessed correlations of tIgE levels from birth to the age of 10 years in the birth cohort MAS (Multicenter Allergy Study; n=1314). MATERIALS AND METHODS: We determined cord-blood IgE levels, total and specific IgE at the age of 1, 2, 3, 5, 6, 7, and 10 years. Spearman correlation coefficients were calculated for tIgE at different time-points. All analyses were performed in the entire cohort, adjusted for gender, as well as in non-atopic children only. RESULTS: tIgE percentiles increased steadily from birth to the age of 10 years with higher values for boys than for girls at each time-point. tIgE values from birth to 3 years of age correlated poorly with tIgE levels at 10 years (r<0.5). However, good correlations (r>0.8) were observed for tIgE concentrations at 6, 7 and 10 years. The same results were observed when the analyses were limited to non-atopic children. CONCLUSION: In childhood, tIgE levels underlie remarkable variation over time even in the absence of atopy. For cross-sectional population-based genetic and epidemiologic studies, tIgE values of children <5 years should be interpreted with caution since these values correlate poorly with tIgE levels later in life.

[Acute dyspnea in childhood]. / Krupp-Fremdkörper-Asthma oder Epiglottitis? Wenn Kinder nach Luft schnappen.

Acute dyspnea is one of the most frequent pediatric emergencies in the medical practice. The severity of the condition ranges from mild and self-limiting to severe and life threatening. The primary care physician must recognize the clinical symptoms of impending respiratory distress in a child and, especially, in an infant or very young child who is not yet able to communicate verbally, so that the appropriate therapy can be initiated as quickly as possible and, therefore, to fundamentally influence the development of the condition. The most important clinical causes of dyspnea are croup, epiglottitis, foreign body aspiration, and bronchial obstruction.

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children.

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone. CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.

Effect of anti-immunoglobulin E on nasal inflammation in patients with seasonal allergic rhinoconjunctivitis.

BACKGROUND: Binding of allergens to IgE on mast cells and basophils causes release of inflammatory mediators in nasal secretions. OBJECTIVE: The combined effect of specific immunotherapy (SIT) and omalizumab, a humanized monoclonal anti-IgE antibody, on release of eosinophilic cationic protein (ECP), tryptase, IL-6, and IL-8 in nasal secretion was evaluated. METHODS: Two hundred and twenty five children (aged 6-17 years) with a history of seasonal allergic rhinoconjunctivitis induced by birch and grass pollen were randomized into four groups: either birch- or grass-pollen SIT in combination with either anti-IgE or placebo. Complete sets of nasal secretion samples before treatment Visit 1 (V1), during birch- (V2) and grass (V3)-pollen season and after the pollen season (V4) were collected from 53 patients. RESULTS: A significant reduction in tryptase only was seen in the anti-IgE-treated group at V2 (P<0.05) and V4 (P<0.05) compared with the placebo group. During the pollen season, patients with placebo showed an increase of ECP compared with baseline (V2: +30.3 microg/L; V3: +134.2 microg/L, P< 0.005; V4: +79.0 microg/L, P< 0.05), and stable levels of tryptase, IL-6 and IL-8. Treatment with anti-IgE resulted in stable ECP values and a significant decrease of tryptase compared with V1 (baseline): V2: -80.0 microg/L (P< 0.05); V3: -56.3 microg/L, which persisted after the pollen season with V4: -71.6 microg/L (P< 0.05). After the pollen season, a decrease of IL-6 was observed in both groups (V4 placebo group: -37.5 ng/L; V4 anti-IgE group: -42.9 ng/L, P< 0.01). CONCLUSION: The combination of SIT and anti-IgE is associated with prevention of nasal ECP increase and decreased tryptase levels in nasal secretions.

Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).