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As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs.

The Respimat®Soft Mist™ Inhaler (SMI) is a hand-held device that generates an aerosol with a high fine-particle fraction, enabling efficient lung deposition. Inhalation therapy for children should be safe and effective. This study aimed to assess the success and the quality of inhalation maneuvers among children using the Respimat SMI. This single-center study was conducted at Mainz University Hospital, Germany, between March 2006 and August 2006. Ninety-nine children, aged 4–12 years, with asthma bronchiale or other atopic diseases, and their healthy siblings were included. Children with serious respiratory conditions such as cystic fibrosis or any chronic destructive or severe lung disease were excluded. Each child performed three inhalation maneuvers using the Respimat SMI. Inspiratory flow rate, inhaled volume, and timing of actuation for each inhalation maneuver were recorded using a pneumotachograph. Successful use and quality of inhalation maneuvers (inspiratory flow rate, theoretical inhaled dose fraction, and estimated lung deposition of the aerosol cloud) were assessed. Results were compared with respect to prior experience of inhaler use and between two age groups (4–8 years and 9–12 years). Ninety of 99 children achieved one or more successful maneuver. Overall, 75.1 % of inhalation maneuvers performed with the Respimat SMI were successful; the greatest success was seen in older versus younger children. Overall median estimated lung deposition was 67 %. Median inspiratory flow was 41.5 L/min, with slower rates noted in the younger children. Fifty-two percent of children inhaled faster than 40.0 L/min. Prior inhaler experience imparted no benefit in terms of success of inhalation maneuvers, overall, but was associated with some group differences in inhalation flow rate. Children can perform a successful inhalation maneuver with the Respimat SMI, with the greatest success rate in children aged >5 years.

Objectives:The aim of this in vitrostudy was to determine the delivered dose of budesonide 200µg via a chlorofluorocarbon-free pressurized metered dose inhaler (pMDI) when administered through different spacers in tidal breathing patterns of young children.

The rational choice of an inhalation device is a cornerstone in the effective management of asthma and COPD. In this publication, we describe the development of a new system, the Inhalation Manager, which, for the first time, offers the possibility to assess the entire inhalation maneuver of patients using original devices under everyday conditions. So far the Inhalation Manager allows the measurement of inspiratory maneuvers of patients through placebo inhalation devices of the most common breath-actuated CFC-free inhalers in the market for the three main glucocorticosteroids Budesonide [Turbohaler® (TH), dry powder inhaler (DPI)], Beclomethasone dipropionate [Autohaler® (AH), breath-actuated pressurized metered dose inhaler (pMDI)], and Fluticasone propionate [Diskus® (DI), DPI] by means of a pneumotachometer. In addition, it allows allocation of the individual maneuver to the expected drug delivery values (mass output and particle size distribution) of these three devices. In a field trial, the inhalation technique of 628 (TH), 794 (AH), and 795 (DI) patients, respectively, was tested in 72 pulmonologist practices with the Inhalation Manager. For patients in the 18-59-year-old group, the Inhalation Manager detected the following percentages needing improvement: 1.5% for the Autohaler® device, 16.7% for the Diskus®, and 38.9% for the Turbohaler®. In the 60-99-year-old group, percentages needing improvement were 1.5%, 31.5%, and 66.1% for the Autohaler®, Diskus®, and Turbohaler®, respectively. Therefore, the Inhalation Manager could become an essential tool in asthma management by finding the most suitable inhaler for an individual patient and by training the optimal inhalation technique.

Background: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16)gene maps to this region. CC16is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16gene (A38G)was previously associated with asthma. Objective: We evaluated the role of the CC16SNP in pediatric asthma and asthma severity in 2 German study populations. Methods: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the pres-ent study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. Results: No association of the CC16*38Aallele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC20FEV1values were significantly lower in individuals homozygous or heterozygous for the CC16*38Aallele compared with those in subjects with the CC16*38GGgenotype (P< .05 and P< .03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1after exercise when homozygous for the CC16*38Aallele compared with that seen in asthmatic patients with the *38AGor *38GGgenotype (P< .04 and P= .006, respectively). Conclusion: We conclude that the CC16*A38GSNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children. (J Allergy Clin Immunol 2003;111:515-9.)

Background: Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. Objective: We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Methods: Ninety-two children (age range, 6-17 years) with sensitization to birch andgrass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Results: Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P= .012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P= .03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P= .001; 2489 ng/L [1-5670 ng/L], P= .001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P= .001; birch SIT: 2792 ng/L [154-5839 ng/L], P= .04]. Conclusion: Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used. (J Allergy Clin Immunol 2002;110:728-35.)

Background:Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE antibody have complementary modes of action. Objective:The purpose of this study was to determine whether combined therapy could provide better efficacy than either treatment alone. Methods:We conducted a randomized, double-blinded trial to assess the efficacy and safety of subcutaneously administered anti-IgE (omalizumab) or placebo in children and adolescents with seasonal allergic rhinitis in both a birch pollen season and a grass pollen season (sequential seasons together lasting an average of 84 days). There were 4 treatment arms. Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was started before and maintained during the anticipated pollen seasons (a total of 24 weeks). The primary efficacy variable was symptom load, the sum of daily symptom severity score plus rescue medication use. Results:A total of 221 subjects (intent-to-treat population) aged 6 to 17 years were analyzed for efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by 48% (P< .001) over SIT alone. When analyzed separately by season, the 2 groups receiving unrelated SIT were considered placebo controls. In the grass season, symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61 (-32%); SIT-grass + anti-IgE, 0.26 (-71%). Conclusion:Anti-IgE therapy conferred a protective effect independent of the type of allergen. Additional clinical benefit was demonstrated in both pollen seasons, whether there was coverage by SIT or not. This combination might prove useful for the treatment of allergic rhinitis, particularly for polysensitized patients. (J Allergy Clin Immunol 2002;109:274-80.)