The effect of stepping down combination therapy on airway hyperresponsiveness to mannitol

SummaryRationaleControversy exists about the safety of long acting beta2-agonist (LABA) treatment, in particular in children. Combination therapy with a LABA and an inhaled corticosteroid (ICS) is prescribed to children with moderate asthma and can be stepped down by withdrawal of the LABA when asthma is well controlled.ObjectiveTo analyze the effect of stepping down from LABA/ICS combination therapy to monotherapy with the same dose of ICS on the airway response to mannitol in asthmatic children.Methods17 children, aged 12–17 years, with clinically stable asthma, receiving combination therapy, were analyzed in this observational prospective open-label study. Children performed a mannitol challenge at baseline and 30±4 days after their medication was stepped down to ICS monotherapy. The changes in the provoking dose of mannitol to cause a 15% fall in FEV1 (PD15), response-dose ratio and recovery time following a short acting beta2-agonist to ≥95% of baseline FEV1 were assessed.ResultsMannitol PD15 and response-dose ratio did not significantly change after stepping down. The recovery time following a short acting beta2-agonist to ≥95% of baseline FEV1 was significantly shorter (p=0.01) after the withdrawal of the LABA.ConclusionsIn short-term follow-up, stepping down clinically stable asthmatic children from combination therapy to monotherapy with an ICS does not change airway hyperresponsiveness (AHR) to mannitol but does shorten recovery time to baseline lung function following a rescue short acting beta2-agonist

Training for the future

Aim The aim of this prospective study was to examine the association between behavioural problems and medical and psychological outcomes in clinically treated children and adolescents with asthma. Methods Patients (n=134) were recruited from two high-altitude asthma clinics in Switzerland and one asthma clinic in the Netherlands. Outcome measures were Asthma Control Test (ACT), Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)), forced expiratory volume in 1sec (FEV1) and fractional concentration of exhaled nitric oxide (FeNO). Parents completed the Child Behaviour Checklist (CBCL) (predictor variable). Data were collected at the start and end of treatment. Multiple regression analysis was used while adjusting for demographic variables, clinic and length of stay. Results More severe internalizing behavioural problems were associated with less improvement of total quality of life (t=2.26, p=0.03) and the domains symptoms (t=2.04, p=0.04) and emotions (t=2.3, p=0.02) after clinical treatment. Behavioural problems were not associated with a change of lung function measurements (FEV1 and FeNO) and asthma control (ACT) during treatment. Conclusion A focus of healthcare professionals on the treatment of internalizing behavioural problems may optimize the quality of life in clinically treated youth with asthma

Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment

SummaryBackgroundPolarization in yeast has been proposed to involve a positive feedback loop whereby the polarity regulator Cdc42p orients actin cables, which deliver vesicles carrying Cdc42p to the polarization site. Previous mathematical models treating Cdc42p traffic as a membrane-free flux suggested that directed traffic would polarize Cdc42p, but it remained unclear whether Cdc42p would become polarized without the membrane-free simplifying assumption.ResultsWe present mathematical models that explicitly consider stochastic vesicle traffic via exocytosis and endocytosis, providing several new insights. Our findings suggest that endocytic cargo influences the timing of vesicle internalization in yeast. Moreover, our models provide quantitative support for the view that integral membrane cargo proteins would become polarized by directed vesicle traffic given the experimentally determined rates of vesicle traffic and diffusion. However, such traffic cannot effectively polarize the more rapidly diffusing Cdc42p in the model without making additional assumptions that seem implausible and lack experimental support.ConclusionsOur findings suggest that actin-directed vesicle traffic would perturb, rather than reinforce, polarization in yeast

Gender differences in respiratory symptoms in 19-year-old adults born preterm

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Anti-inflammatory drug therapy in asthma

Asthma is a disease with chronic inflammation of the airways and and-inflammatory treatment is a logical treatment. Inhaled corticosteroids [ICS] remain the cornerstone of anti-inflammatory therapy in recent international guidelines. Asthma cannot be cured by any medication: if the drug is discontinued, the disease manifestations return. This has been proven at all ages. In preschool children the diagnosis of asthma is difficult to establish. In this heterogeneous group ICS or leukotriene receptor antagonists [LTRA] are just as effective as placebo; in the future it will hopefully be possible to describe characteristics of responders. LTRA are an alternative in mild asthma, especially when mono-triggered viral related wheeze is present. Theophylline is effective and also has bronchodilatory properties, which need to be balanced against the relatively frequent side effects. The working mechanisms of anti-inflammatory asthma medications including ICS, LTRA, cromones, macrolides and theophylline are described. (C) 2009 Elsevier Ltd. All rights reserved