Pranlukast: a review of its use in the management of asthma

Pranlukast (Onon, Azlaire), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C(4), LTD(4) and LTE(4). It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225 mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. CONCLUSIONS: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting beta(2)-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.     

Cost effectiveness of leukotriene modifiers in adults with asthma

Asthma is the most common chronic disorder in industrialised nations, with over 100 million people worldwide affected. Leukotrienes are chemical mediators released from mast cells, eosinophils and basophils. They cause bronchoconstriction, an increase in mucous secretions and activation of inflammatory cells. Leukotriene modifiers are a long-term controller medication used to treat asthma. They function by selectively competing for the leukotriene receptor sites, thereby blocking their action, or by inhibiting 5-lipoxygenase and thus preventing leukotriene formation. Both current US and Global Initiative for Asthma treatment guidelines have clarified the role of leukotriene modifiers in the management of asthma in adults and children. Leukotriene modifiers have two distinct roles: to replace inhaled corticosteroids in milder asthma and as an add-on therapy to inhaled corticosteroids in more severe asthma.While efficacy is certainly an important issue, economic considerations are also important in a disease such as asthma where there are a variety of treatment options and the severity of the disease varies widely. This review examined published studies to better understand the cost effectiveness of leukotriene modifiers in adults with asthma. Fifteen articles were found that analysed the cost effectiveness of leukotriene modifiers, with almost all performed in the US. The vast majority of the studies were retrospective claims analyses, but three randomised controlled trials incorporating economic outcomes have been reported. The majority of the articles found that for both monotherapy in mild persistent asthma and add-on therapy in moderate persistent asthma, leukotriene modifiers were less cost effective than inhaled corticosteroids with or without a long-acting beta2-adrenoceptor agonist. However, these results must be viewed cautiously as in several studies there were methodological issues such as comparisons of unequal treatment groups or inappropriate use of leukotriene modifiers in stepwise treatment.     

Inhaled fluticasone propionate. A pharmacoeconomic review of its use in the management of asthma

Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to. Fluticasone propionate is one of several inhaled corticosteroids used for the treatment of asthma. Like other agents of its class, its efficacy is backed by extensive clinical data. More recently, the quality of life of recipients of fluticasone propionate and its relative cost effectiveness have been investigated. A series of comparative analyses show that inhaled fluticasone propionate is more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. Analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures and were generally conducted from the perspective of the third-party payer. When administered at a microgram dose of half or less than budesonide (as is therapeutically appropriate), the cost effectiveness of fluticasone propionate was similar to or better than that of budesonide. In children, fluticasone propionate was more cost effective per treatment success compared with inhaled sodium cromoglycate. Quality-of-life assessments in patients with mild to moderate disease show that inhaled fluticasone propionate achieved improvements which were deemed to be clinically meaningful in patients with mild to moderate asthma; these changes were significantly greater than those achieved with oral zafirlukast, inhaled triamcinolone acetonide or placebo. Greater improvements were evident with inhaled fluticasone propionate in patients with severe disease. CONCLUSIONS: In addition to the considerable body of clinical evidence supporting the use of inhaled fluticasone propionate in patients with asthma, accumulating short term cost-effectiveness data also suggest that this agent can be administered for a similar or lower cost per outcome than other inhaled corticosteroids or oral zafirlukast. Importantly, the clinical benefits offered by fluticasone propionate in patients with persistent asthma are accompanied by clinically significant improvements in quality of life.     

Inhaled salmeterol/fluticasone propionate combination: a pharmacoeconomic review of its use in the management of asthma

Asthma guidelines recommend an inhaled corticosteroid plus a long-acting inhaled beta(2)-agonist (beta(2)-adrenoceptor agonist) as the preferred maintenance therapy for moderate and severe persistent asthma. Advair/Seretide Diskus also registered as Accuhaler is fixed-dose salmeterol (a long-acting inhaled beta(2)-agonist) and fluticasone propionate (a corticosteroid) administered via a single powder inhalation device. The clinical effectiveness of salmeterol/fluticasone propionate in patients with persistent asthma symptoms has been established in comparative clinical trials. Pharmacoeconomic analyses, based on data from these clinical trials, have been conducted from a healthcare payer perspective in various countries. In patients with asthma not controlled with inhaled corticosteroids, salmeterol/fluticasone propionate was associated with more favourable (lower) cost-effectiveness ratios than fluticasone propionate monotherapy, oral montelukast plus inhaled fluticasone propionate, inhaled budesonide, and inhaled formoterol plus budesonide. As the initial maintenance therapy in patients with persistent asthma symptoms while receiving short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate was cost effective relative to montelukast monotherapy. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with fluticasone propionate or montelukast monotherapy, salmeterol/fluticasone propionate consistently had a more favourable cost-effectiveness ratio in terms of per successfully treated week or symptom-free day and/or was associated with small incremental costs to achieve significant additional clinical benefits. In clinical practice, salmeterol plus fluticasone propionate was associated with lower asthma-related costs than treatment with other maintenance therapies.In patients with asthma symptoms despite treatment with inhaled corticosteroids, salmeterol/fluticasone propionate produced clinically meaningful improvements in overall Asthma Quality of Life Questionnaire (AQLQ) scores relative to salmeterol or placebo monotherapy, in emotional function domain scores relative to fluticasone propionate or budesonide, and in asthma symptoms domain scores relative to budesonide. In patients with persistent asthma symptoms while receiving short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate produced clinically meaningful improvements in overall AQLQ scores compared with fluticasone propionate or montelukast. CONCLUSIONS: Pharmacoeconomic analyses indicate that salmeterol/fluticasone propionate administered via a single inhaler represents a cost-effective treatment option (relative to fluticasone propionate at the same nominal dosage, budesonide, formoterol plus budesonide and montelukast plus fluticasone propionate) in patients with asthma not controlled with inhaled corticosteroid therapy. In patients with asthma not controlled with short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate is a cost effective treatment relative to monotherapy with montelukast. Importantly, salmeterol/fluticasone propionate is also associated with improvements in health-related quality of life.     

Cost–utility analysis of reslizumab for patients with severe eosinophilic asthma inadequately controlled with high-dose inhaled corticosteroids and long-acting β2-agonists in South Korea

Objectives: We aimed to assess the cost-utility of reslizumab for patients with severe eosinophilic asthma uncontrolled with high-dose inhaled corticosteroids and long-acting β₂-agonists (ICS/LABAs) in Korea.

Methods: A Markov model with limited societal perspective was used to compare the costs and quality-adjusted life years (QALYs) of reslizumab add-on therapy with standard-of-care (high-dose ICS/LABA) and standard-of-care alone. The model adopted a 4?week cycle with the following six health states over a lifetime (60?years): controlled asthma, uncontrolled asthma, moderate exacerbation, severe exacerbation, all-cause death and asthma-related death. The population comprised adult patients (age ≥18?years) with severe eosinophilic asthma (eosinophils ≥400 cells/μL) at Global Initiative for Asthma (GINA) step 4 or 5 who had experienced at least three exacerbations in the preceding year. Model inputs were sourced from individual patient-level data from two 52?week randomized controlled trials of reslizumab (NCT01287039, NCT01285323). The model included discontinuation rules where patients uncontrolled with reslizumab add-on therapy were transitioned to the standard-of-care arm. Costs and QALYs were annually discounted at 5%. Deterministic and probabilistic sensitivity analyses were performed.

Results: Reslizumab add-on therapy was associated with increased cost (US$119,394) and improved QALYs (5.17) compared with standard-of-care alone, resulting in an incremental cost-effectiveness ratio of US$23,081 per QALY gained. Body weight, time horizon and discount rate were influential factors in the model.

Conclusions: The addition of reslizumab to high-dose ICS/LABA was cost-effective in Korean patients with severe eosinophilic asthma uncontrolled with high-dose ICS/LABA, based on the threshold of 1 gross domestic product in Korea.     

梅州市儿童支气管哮喘临床用药调查分析

目的了解梅州市目前治疗儿童哮喘过程中全球哮喘防治的创议（GINA）的虚用情况，分析原因并提出相应对策，以便更好地开展哮喘防治工作。方法对410名被确诊为支气管哮喘的门诊患儿及家属进行有关该患儿哮喘的治疗方式及其他相关情况的问卷调查。结果哮喘急性发作期采用吸人型糖皮质激素加β受体激动剂吸入的占39．8％，采用静脉滴注激素加氨茶碱的占41．5％；临床缓解期规则应川吸入到糖皮质激素吸入的仅占7．1％，不治疗的占53．2％。结论我地区医生在哮喘急性发作期治疗中已经执行了GINA方案，但对方案的理解、认识不充分，在医疗实践中仍有不合理用药；而GINA方案在哮喘临床缓解期治疗中采用率非常低今后哮喘防治工作府该琳续椎广GINA．做好儿童哮喘防治指南普及工作。     

Medications prescribed to asthmatic children: an historical cohort study comparing clinical practice with NIH recommendations

Purpose — NIH guidelines recommend maintenance treatment of persistent moderate or severe childhood asthma with preventive anti‐inflammatory medication (inhaled corticosteroids, cromolyn or nedocromil). The objective was to determine if the NIH guidelines for the treatment of childhood asthma were implemented by examining the prevalence of prescribing preventive medication. Methods — This was a non‐concurrent cohort study of 311 children (aged 2 to 19 years) who were treated for asthma between January and December 1994 by nine Medicaid managed care plans in the northeastern USA. Results — Preventive medications were prescribed at least once to 61.1% of the children with moderate or severe asthma and to 27.1% of the children with mild asthma. Logistic regression analyses indicated prescribing preventive medication was associated with moderate or severe asthma (aOR 5.34, 95% CI 3.22 – 8.83) and age 5 to 19 years (aOR 2.11, 95% CI 1.19 – 3.72). Prescribing preventive medication was also associated with a prior emergency department visit (aOR 2.27, 95% CI 1.24 – 4.16), after adjusting for age. Conclusions — Prescribing preventive medications is related to sentinel clinical events and the NIH recommendations are not routinely implemented for all children with moderate or severe asthma during this study period. Copyright © 2000 John Wiley & Sons, Ltd.     

Non-corticosteroid therapy for the long-term control of asthma

The non-corticosteroids approved for the maintenance therapy of persistent asthma include the long-acting inhaled beta(2) agonists (LABAs), leukotriene modifiers, chromones, theophylline and omalizumab. This review assesses the benefits and risks of each in relation to the inhaled corticosteroids and each other. Neither the LABAs nor omalizumab should be used as monotherapy for persistent asthma. There is no evidence of clinically significant differences in efficacy between the chromones, theophylline and leukotriene modifiers as monotherapy in mild-moderate persistent asthma; thus the choice of one therapy over the other is a clinical decision based upon differences in safety, acceptability to the patient and ease of use. Although there is significant variability in response to various therapies, non response to one therapy is not predictive of response to another. Neither studies of phenotypes nor genotypes have provided acceptable determinants of response as yet. As adjunctive therapy to the inhaled corticosteroids for moderate-severe persistent asthma, the LABAs provide superior improvement in lung function and reduction in exacerbations relative to higher doses of inhaled corticosteroids and the other noncorticosteroids used as adjunctive therapy. Thus, LABAs remain the adjunctive therapy of choice in patients not adequately controlled on low-medium dose inhaled corticosteroids. Omalizumab has not been compared with the other adjunctive therapies, so its relative efficacy is unknown. However, it is the only adjunctive therapy added to the combination of an inhaled corticosteroid plus LABA to demonstrate further improvement in a controlled clinical trial.     

Non-corticosteroid therapy for the long-term control of asthma

The non-corticosteroids approved for the maintenance therapy of persistent asthma include the long-acting inhaled β₂ agonists (LABAs), leukotriene modifiers, chromones, theophylline and omalizumab. This review assesses the benefits and risks of each in relation to the inhaled corticosteroids and each other. Neither the LABAs nor omalizumab should be used as monotherapy for persistent asthma. There is no evidence of clinically significant differences in efficacy between the chromones, theophylline and leukotriene modifiers as monotherapy in mild-moderate persistent asthma; thus the choice of one therapy over the other is a clinical decision based upon differences in safety, acceptability to the patient and ease of use. Although there is significant variability in response to various therapies, non response to one therapy is not predictive of response to another. Neither studies of phenotypes nor genotypes have provided acceptable determinants of response as yet. As adjunctive therapy to the inhaled corticosteroids for moderate-severe persistent asthma, the LABAs provide superior improvement in lung function and reduction in exacerbations relative to higher doses of inhaled corticosteroids and the other noncorticosteroids used as adjunctive therapy. Thus, LABAs remain the adjunctive therapy of choice in patients not adequately controlled on low-medium dose inhaled corticosteroids. Omalizumab has not been compared with the other adjunctive therapies, so its relative efficacy is unknown. However, it is the only adjunctive therapy added to the combination of an inhaled corticosteroid plus LABA to demonstrate further improvement in a controlled clinical trial.     

Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma

ABSTRACT

Background: Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma.

Scope: Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms ‘mometasone furoate AND pharmacology’ and ‘mometasone furoate AND asthma AND clinical trial’. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed.

Findings: In clinical studies, MF, administered by dry powder inhaler (MF-DPI), was effective in treating all severities of persistent asthma, improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids. Once-daily dosing of MF-DPI was effective in patients with mild or moderate persistent asthma previously taking twice-daily regimens of inhaled corticosteroids (ICSs), and in patients taking only inhaled β₂?agonists for symptom relief. Once-daily dosing in the evening with MF-DPI 200?µg conferred a greater benefit than morning dosing with MF-DPI 200?µg. Patients with severe asthma who were dependent on oral corticosteroids (OCSs) and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate OCSs when switched to MF-DPI. In trials of up to 1 year in duration, MF-DPI was well tolerated, with the majority of adverse events considered mild or moderate in intensity. MF had low systemic bioavailability and no clinically significant hypothalamic–pituitary–adrenal-axis suppression at therapeutic doses. The DPI device is a multiple-dose inhaler with a counter containing agglomerates of MF and lactose. Patients of all severities of persistent asthma were able to generate and maintain airflow profiles necessary to provide a uniform and accurate dose.

Limitations: Only one study evaluated both morning and evening administration of once-daily doses, and one of the comparative clinical trials was an open-label study.

Conclusion: Once-daily administration of MF-DPI 200–400?µg in patients with mild to moderate persistent asthma effectively improved lung function and asthma control. In patients with severe persistent asthma dependent on oral corticosteroids, treatment with MF-DPI 400?µg BID permitted substantial reduction of oral corticosteroid use. All MF-DPI treatments were well tolerated and had minimal systemic effects.     

Inhaled corticosteroid therapy in newly detected mild asthma

Inhaled corticosteroids are the most effective medications currently available to treat symptomatic asthma, and are free of clinically relevant unwanted effects, when used at the doses needed to provide optimal control in most patients with asthma. Inhaled corticosteroids also improve the physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness that characterise asthma. Inhaled corticosteroids are also cost-beneficial when compared with other treatments, even in patients with milder asthma who are treated in primary care. For these reasons, inhaled corticosteroids are now being considered as first-line therapy for patients with regular daily asthma symptoms. Inhaled corticosteroids are, however, often not utilised until other treatments have been demonstrated not to provide optimal asthma control. Available evidence from both children and adults with asthma suggests that the benefits achieved from inhaled corticosteroids are reduced when their introduction as therapy is delayed for several years after persistent symptoms develop. For this reason, corticosteroids should be started soon after a diagnosis is made and persistent symptoms develop. It is not yet known, however, whether inhaled corticosteroids should be used in asthmatic patients who have very mild and infrequent symptoms and who have normal airway calibre most of the time. The current consensus statements do not recommend regular treatment in such patients. Airway biopsies from these asthmatic patients do show evidence of airway inflammation and structural changes; however, we do not yet know whether they lose lung function more rapidly than individuals without asthma, or whether the morbidity associated with very mild asthma warrants the use of regular treatment. This issue is being addressed in a large, multinational, placebo-controlled trial. The results of this study (available in 3 more years) will resolve this persisting question about inhaled corticosteroid use in mild asthma.     

Omalizumab: the evidence for its place in the treatment of allergic asthma

Introduction:

Asthma is a chronic inflammatory airways disease associated with reversible airflow obstruction and bronchial hyperresponsiveness. Asthma is prevalent worldwide and results in significant morbidity, mortality, and healthcare costs, the majority of which arise from those with severe disease. Omalizumab is a monoclonal antibody to immunoglobulin E (IgE) that has been developed for the treatment of severe persistent allergic (IgE mediated) asthma.

Aims:

The aim of this review is to evaluate the available clinical evidence on omalizumab to determine the role it has to play in the treatment of persistent allergic asthma.

Evidence review:

There is clear evidence to show that omalizumab is effective in reducing the rate of asthma exacerbations, inhaled corticosteroid dose, and the need for rescue medication in patients with allergic asthma. Clinical data indicate beneficial effects on patient-reported symptoms and perceived quality of life, as well as a reduction in unscheduled healthcare visits. There is little evidence to suggest omalizumab may enhance lung function or reduce the requirement for oral corticosteroids. Omalizumab has a favorable safety profile, although anaphylaxis has occurred. A study in children showed similar results to those achieved in adults and adolescents, with fewer asthma exacerbations and school days missed. Omalizumab may be cost effective in patients when used as add-on therapy to inhaled corticosteroids and long-acting beta₂ agonists (LABA).

Place in therapy:

Omalizumab is an effective add-on therapy to inhaled corticosteroids and LABAs in adults and adolescents with severe persistent allergic asthma. Currently there is insufficient evidence to support the use of omalizumab in children.     

Emerging oligonucleotide therapies for asthma and chronic obstructive pulmonary disease

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are disorders of the airways largely related to the presence of persistent inflammation. The approval of inhaled corticosteroids in the early 1970s pioneered a new age of therapy in treating chronic inflammatory airway diseases. This was the first time that an anti-inflammatory product was available to reduce the characteristic lung inflammation in airways and the associated obstruction, inflammation and hyper-responsiveness. Fast forward 40 years: corticosteroids are still an important therapeutic intervention; however, they exhibit limited use in moderate to severe asthma and COPD. Oligonucleotide therapies are an emerging class which include the antisense, the RNAi (siRNA and miRNA), the immunomodulatory, the aptamer and the decoy approaches. As these approaches are rather recent in the respiratory field, most are still early in development. Nevertheless, with limitations of current small molecule therapies and the hurdles faced with biologics, the use of oligonucleotides is relevant and the door is open to the development of this category of therapeutics. This review focuses on the major classes of oligonucleotides that are currently in late stage preclinical or clinical development for the treatment of asthma and COPD, and discusses the implications for their use as therapies for respiratory diseases.     

Omalizumab: a recombinant humanized anti-IgE antibody for allergic asthma.

PURPOSE: The pharmacology, efficacy, dosage, adverse events, and economics of omalizumab are discussed. SUMMARY: Omalizumab, a recombinant DNA-derived humanized monoclonal antibody, binds to the C epsilon3 domain of immunoglobulin E (IgE) and forms complexes that inhibit the immune system's response to allergens by averting IgE-mediated inflammatory changes. Omalizumab exhibits a similar pharmacokinetic profile in adults, adolescents, and children. Omalizumab is indicated for adults and adolescents with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. Because of the limited data regarding the safety and effectiveness of omalizumab in children, the drug is indicated for patients 12 years of age or older. The recommended starting dosage is 150-375 mg s.c. every two or four weeks. Dosages and frequency of dose administration are determined by total serum IgE level, measured before the start of treatment, and body weight. Omalizumab is generally well tolerated in adults and children with allergic asthma. Adverse events most commonly observed are injection-site reaction, viral infection, upper-respiratory-tract infection, sinusitis, headache, and pharyngitis. Three large phase III clinical trials demonstrated that omalizumab is more effective than placebo in controlling moderate to severe allergic asthma in patients who have poor disease control or exacerbations despite recommended therapy. Currently, there are no clinical comparisons of omalizumab with other standard treatments for asthma; therefore, it is difficult to determine its overall place in therapy. CONCLUSION: Omalizumab should be considered as a second-line therapy for patients with moderate to severe persistent allergic asthma.     

Step one for asthma treatment: Beta2-agonists or inhaled corticosteroids?

Inhaled corticosteroids have proven effectiveness in chronic persistent asthma and are now recommended as first-line therapy in this condition. In contrast, long term preventative therapy is not currently considered necessary for patients with disease that is only mild and episodic. Recently, there has been growing interest in the possible benefits of using inhaled corticosteroids at an earlier stage in asthma, as soon as the condition is diagnosed. The concept of early intervention is supported by the recognition that airway inflammation is common to all grades of asthma, including early and mild disease. A number of studies have suggested that delayed introduction of inhaled corticosteroids in asthma can result in a poorer clinical response. The precise reason for this is unknown, although it may result from persistent uncontrolled inflammation leading to airway remodelling associated with airflow obstruction that is relatively resistant to therapy. There have also been suggestions that early intervention may alter the natural history of the disease, either to induce sustained remission or to prevent long term decline in lung function, but these effects have yet to be clearly established. On the basis of present knowledge, early intervention remains controversial, particularly in children. The Steroid Treatment As Regular Therapy (START) trial is a large, placebo-controlled, multicentre study that is currently comparing early and delayed use of inhaled corticosteroids in adults and children with newly diagnosed asthma. It is hoped that this study will resolve some of the present uncertainties, and lead to a better understanding of whether an early intervention strategy in asthma can be justified.     

RETRACTED ARTICLE: Inhaled corticosteroids and long-acting beta-agonists in adult asthma: a winning combination in all?

In the recent years, considerable insight has been gained in to the optimal management of adult asthma. Most adult patients with asthma have mild intermittent and persistent disease, and it is acknowledged that many patients do not reach full control of all symptoms and signs of asthma. Those with mild persistent asthma are usually not well controlled without inhaled corticosteroids (ICS). Studies have provided firm evidence that these patients can be well controlled when receiving ICS, especially when disease is of recent onset. This treatment should be given on a daily basis at a low dose and when providing a good response should be maintained to prevent severe exacerbations and disease deterioration. Intermittent ICS treatment at the time of an exacerbation has also been suggested as a strategy for mild persistent asthma, but it is less effective than low-dose regular treatment for most outcomes. Adding a long-acting beta-agonist (LABA) to ICS appears to be unnecessary in most of these patients for optimising control of their asthma. Patients with moderate persistent asthma can be regarded as those who are not ideally controlled on low-dose ICS alone. The combination of an ICS and LABA is preferred in these patients, irrespective of the brand of medicine, and this combination is better than doubling or even quadrupling the dose of ICS to achieve better asthma control and reduce exacerbation risks. An ICS/LABA combination in a single inhaler represents a safe, effective and convenient treatment option for the management of patients with asthma unstable on inhaled steroids alone. Ideally, once asthma is under full control, the dose of inhaled steroids should be reduced, which is possible in many patients. The duration of treatment before initiating this dose reduction has, however, not been fully established. One of the combinations available to treat asthma (budesonide and formoterol) has also been assessed as both maintenance and rescue therapy with a further reduction in the risk for a severe exacerbation. Clinical effectiveness in the real world now has to be established, since this approach likely improves compliance with regular maintenance therapy.     

Treatment options for initial maintenance therapy of persistent asthma: a review of inhaled corticosteroids and leukotriene receptor antagonists

Inhaled corticosteroids (ICSs) are recognized as the cornerstone of asthma therapy. They are considered to be the most effective anti-inflammatory medication currently available for the treatment of persistent asthma, regardless of its severity. Leukotriene receptor antagonists (LTRAs) are also used as initial maintenance therapy in patients whose asthma is uncontrolled by bronchodilators alone. There are now sufficient data available to allow a comparison of the relative effectiveness and cost-effectiveness of LTRAs and ICSs as initial maintenance therapy. The consensus from the studies reviewed in this article demonstrates that ICSs are more effective than LTRAs as initial maintenance therapy. In particular, studies on fluticasone propionate have shown that it was more effective than LTRAs in clinical outcomes: producing greater improvements in lung function and asthma control; as measured by either forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF); by a greater reduction in daytime and night-time asthma symptoms; and short-acting beta2-agonist use. This superiority was also seen when patients were switched from an LTRA to fluticasone propionate. Similar findings have been demonstrated with beclomethasone dipropionate (BDP), showing that, in adults, this inhaled steroid also had a greater effect on pulmonary function and symptom scores than did LTRAs. Quality of life assessments showed that fluticasone propionate achieved improvements that were deemed to be clinically meaningful; these changes were significantly greater than those achieved with LTRAs. However, questionnaire-based patient preference studies comparing BDP with LTRAs showed that children and adolescents generally preferred an LTRA to BDP. A number of comparative analyses showed that inhaled fluticasone propionate is more cost-effective than either montelukast or zafirlukast; these analyses used cost per symptom-free day and cost per successfully treated patient as outcome measures, from the perspective of a third-party payer. In general, these results were supported by resource utilisation studies in real-world settings. Asthma treatment guidelines (e.g. GINA, 2002) recommend combination therapy with ICSs and a long-acting beta2-agonist as initial maintenance therapy if the disease is of sufficient severity. Studies that assessed the effectiveness, cost-effectiveness, and quality of life achieved with a salmeterol fluticasone propionate combination as initial maintenance therapy also showed it to be superior to LTRAs. In conclusion, in terms of efficacy and quality of life, fluticasone propionate is more effective than LTRAs as initial maintenance therapy and is associated with significantly lower healthcare costs and less frequent use of healthcare resources than LTRAs. There is also evidence to suggest that initial maintenance therapy with the combination of an inhaled steroid plus a long-acting beta-agonist bronchodilator may be a more effective option for the management of persistent asthma than treatment with a single-controller agent alone (ICS or LTRA).     

三元系统疗法辅助治疗哮喘儿童的生活质量分析

目的探讨三元系统疗法辅助全球哮喘防治战略倡议（GINA）方案对轻、中度慢性持续期哮喘患儿生活质量的影响。方法选择轻、中度慢性持续期哮喘患儿78例,随机分为观察组41例,对照组37例。2组均以GINA阶梯式方案为基础治疗,观察组辅以三元系统疗法,治疗前及治疗后6月对患儿生活质量进行评估,分别填写儿科哮喘生活质量量表（PAQLQ）。结果2组患儿治疗后症状、情感方面均较治疗前明显改善,治疗后症状维度、情感维度2组间差异有统计意义（P〈0．05）,而活动维度2组间差异无统计意义（P〉0．05）。结论与单纯应用GINA方案治疗相比,辅以三元系统疗法治疗轻、中度慢性持续期儿童哮喘,能改善临床症状,提高患儿的生活质量。     

Combination therapy with inhaled long-acting beta2-agonists and inhaled corticosteroids: a paradigm shift in asthma management

Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of drugs with different mechanisms of action that are commonly used to provide effective long-term control of persistent asthma. Scientific and clinical data support the complementary mechanisms of action of the inhaled corticosteroids and the long-acting beta2-agonists in achieving a superior level of asthma control. In addition, evidence supports significant reductions in exacerbations and effective control of airway inflammation with an inhaled corticosteroid and a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or combinations of other therapeutic agents with an inhaled corticosteroid. Finally, there are distinct economic advantages to combining an inhaled corticosteroid and a long-acting beta2-agonist in the treatment of asthma relative to other treatment regimens.