PubMed · 15192348
This article reviews the latest treatment of asthma and incorporates recent changes in asthma management.
Explore connections, maps & timelines
Susan Holcomb. Asthma update.. https://doi.org/10.1097/00003465-200405000-00001
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
A novel design for a study comparing two drugs (A and B), their combination (AB) and placebo (P) in a stable disease such as chronic asthma is proposed. The primary objectives of the trial are to compare A (a new drug) with placebo and AB with B (an old drug). Other between-treatment comparisons are secondary. The new design consists of the first 2 sequences of a single 4 x 4 Latin square: (A, AB, P, B|P, B, A, AB|AB, A, B, P|B, P, AB, A). The washout period between A and AB and that between P and B are eliminated based on the assumptions that there is no carry-over effect from placebo and that the effect of the combination would be approximately same at steady state either starting the 2 drugs at the same time or adding one later. Equal period effect for Periods 1 and 2, and for Periods 3 and 4 are also assumed for all treatment effects being estimable. Advantages and disadvantages of this design were evaluated and compared with other possible designs. Compared with other possible designs, the new design is more efficient. For example, the new design requires less than (1/4) of the sample size a parallel design would need and it requires (2/3) of the sample size a 4-treatment, 3-period incomplete block design would need for the same power at the same detectable difference. It has a similar efficiency to a 4-treatment, 4-period cross-over design but with a shorter duration. In this design, all between-treatment comparisons are based on direct within-subject information. The new design could also potentially decrease the probability of patient's drop-outs and use of rescue medication due to lack of efficacy during the placebo periods by reducing the number of placebo washout periods. The benefits reaped from the new design seem to outweigh its risks, which include potential bias for the secondary between-treatment comparisons if the additional assumption about period effects are not satisfied and the incapability of directly assessing the onset of action of the combination of 2 drugs.
IgE molecules play a crucial role in allergic respiratory diseases and may cause chronic airway inflammation in asthma through activation of effector cells via high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII) IgE receptors. Since the discovery of IgE antibodies our understanding of the mechanisms of allergy has improved to such an extent that we can differentiate allergic/atopic from intrinsic respiratory diseases. Therapeutic anti-IgE antibodies, able to reduce free IgE levels and to block the binding of IgE to FcepsilonRI without crosslinking IgE and triggering degranulation of IgE-sensitized cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (omalizumab) binds IgE at the same site as these antibodies bind FcepsilonRI and FcepsilonRII. Consequently, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the FcepsilonR1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma showed that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted effective in reducing asthma-related symptoms, decreasing corticosteroid use and improving quality of life of asthmatic patients. Recent studies show the benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled by optimal pharmacological therapy. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases such as allergic rhinitis, a favorable safety profile and a convenient dosing frequency.
OBJECTIVE: The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months. RESEARCH DESIGN AND METHODS: 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL tid. Follow-up was at 6 months. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and 78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in both groups. CONCLUSIONS: Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6-month follow-up.