β2-受体激动剂联合吸入糖皮质激素治疗持续性哮喘的临床疗效分析

目的：探讨β2-受体激动剂联合吸入糖皮质激素治疗持续性哮喘的临床疗效。方法选取本院2011年10月～2013年10月诊治的持续性哮喘患者134例,采用随机数字法分为两组,67例患者采用福莫特罗治疗为对照组,67例患者采用布地奈德联合福莫特罗治疗为观察组,采用哮喘控制测试评分和哮喘控制问卷评分评定患者的病症控制情况,比较两组患者的治疗情况与不良反应情况。结果治疗后,两组患者缓解药物用量均显著减少,而病情评估达标率、FEV1.0占预计值百分比、PEF 占预计值百分比均显著提升。观察组患者缓解药物用量明显少于对照组,观察组患者病情评估达标率、FEV1.0占预计值百分比、PEF 占预计值百分比、哮喘控制测试评分均明显高于对照组,观察组患者病症控制情况明显好于对照组,观察组患者哮喘控制问卷评分、不良反应发生率均明显低于对照组,差异均有统计学意义（P ＜0.05）。结论β2-受体激动剂联合吸入糖皮质激素治疗持续性哮喘的临床疗效显著,可明显改善患者的临床病症,不良反应少且安全性高,值得临床推广使用。     

The clinical implications of triple therapy in fixed-dose combination in COPD: from the trial to the patient

The emergence of a fixed-dose combination (FDC) of a long-acting ß₂-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled corticosteroid (ICS) in a single inhalation device has changed the approach to inhaled therapy. Although clinical trials describe the efficacy and safety of these FDCs, their use in daily clinical practice can present challenges for the clinician in two specific scenarios. In patients who are already receiving triple therapy via different devices, switching to FDCs could confer benefits by reducing critical errors in the management of inhalers, improving therapeutic adherence, and lowering costs, while maintaining the same clinical efficacy. In patients who are not receiving triple therapy in different devices and who require a change in treatment, triple therapy FDC has shown benefits in clinical trials. Although methodological differences among the trials advise against direct comparison, clinical results show good efficacy, but also considerable variability, and a number of clinical outcomes have yet to be explored. In the future, trials must be developed to complete clinical efficacy data. Real-world efficacy trials are needed, and studies must be designed to determine the profile of patients who present a greater therapeutic response to each FDC in order to pave the way towards more personalized treatment.     

A safety review of long-acting beta2-agonists in patients with asthma

Inhaled corticosteroids are the mainstay of asthma therapy; however, inhaled long-acting beta2-agonists (LABAs) are frequently used in the treatment of patients with asthma. LABAs are combined with high-dose inhaled corticosteroids (ICSs) for patients with severe persistent asthma, and they are combined with low-dose ICSs for patients older than 5 years with moderate persistent asthma. Recent safety concerns raised by data from the Salmeterol Multi-Center Research Trial (SMART) have indicated that use of LABAs in some populations may contribute to increased mortality. These concerns are warranted when LABAs are used as monotherapy in the treatment of patients with asthma in whom they may cause increased exacerbations, blunting of rescue-medication effect, and worsening symptoms. However, when used in combination with an ICS, they decrease both rescue-medication use and symptoms, increase lung function, and act as steroid-sparing agents.     

Safety of long-acting β agonists for the treatment of asthma: clearing the air

Concerns about the safety of long-acting β2-agonist (LABA) therapy, has led to the appearance of multiple publications and recommendations. This review critically examines the available clinical evidence and safety requirements for LABA use. On the basis of nearly 20 systematic reviews and databases, the authors conclude that LABA monotherapy significantly increases the risk of asthma-related adverse effects. We also conclude that the use of LABAs concomitantly with inhaled corticosteroids (ICS) significantly reduces asthma hospitalisations and is not associated with life-threatening events and asthma-related deaths, especially when concurrent use of LABAs and ICS can be reasonably assured (use of a single inhaler device). An appropriate clinical study would require an extremely large sample, making it impractical. Finally, some of the new US Food and Drug Administration (FDA) recommendations have caused confusion and do not appear to be fully evidence based. Although limited by low statistical power, the evidence supports the use of LABAs plus ICS in a single inhaler device (to increase adherence and reduce the potential use of LABA monotherapy) for all patients (not only children) with moderate to severe asthma.     

Metabolic acidosis in a context of acute severe asthma

In a context of asthma, lactic acidosis may occur during beta2-agonist therapy. Several cases have been reported during its administration by intravenous and/or inhaled route. This side-effect seems rather unknown and the mechanism for compensation of metabolic acidosis by hyperventilation may worsen dyspnoea and mislead clinicians. Other causes of lactic acidosis such as a major hypoxemia, a cardiovascular collapse or sepsis may also be experienced in this context and must be ruled out before attributing the lactic acidosis to beta2-agonist treatment. We report the case of a 50-year-old man hospitalized for an acute major asthma, who received a salbutamol continuous infusion associated with inhaled terbutaline. A serum lactate level of 13 mmol/l was noted eight hours after the introduction of the bronchodilator treatment. After reducing doses of beta2-agonists, the evolution was favourable, regarding both respiratory and metabolic aspects, with a rapid decrease of the serum lactate level, which finally returned to normal level after 32 hours of hospitalization.     

Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years

BACKGROUND: Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment. METHODS: Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism. RESULTS: Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck. CONCLUSION: In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.     

Nocturnal asthma

Nocturnal asthma is one of the difficult form of asthma. It is associated with significant decline in pulmonary function and increase of airway inflammation at night. The pathophysiological mechanisms underlying the nocturnal aggravation of asthma are intricate. The most important seem to be: nocturnal environmental allergens, exacerbation of airflows and circadian variations of bronchial hyperreactivity, beta adrenergic receptors polymorphism, increased vagal tone. Home PEF monitoring will allow an objective assessment of nocturnal asthma. The physician-patient partnership is important in educating the patient to manage nocturnal episodes. The chrono-therapeutic approach will usually include inhaled or oral corticosteroids with the addition of theophylline, long-acting beta agonists with timing of therapy to give adequate effect during the night.     

Randomised trial of an inhaled β2 agonist, inhaled corticosteroid and their combination in the treatment of asthma

BACKGROUND: Although many asthmatic patients are treated with a combination of beta2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken. METHODS: Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 microg twice daily), terbutaline (500-1000 microg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment. RESULTS: Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness. CONCLUSIONS: In this group of mild to moderate asthmatic subjects the combination of beta2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta2 agonist treatment impaired the beneficial effect of inhaled corticosteroid.     

Written action plans for asthma: an evidence-based review of the key components

BACKGROUND: Written action plans for asthma facilitate the early detection and treatment of an asthma exacerbation. Several versions of action plans have been published but the key components have not been determined. A study was undertaken to determine the impact of individual components of written action plans on asthma health outcomes. METHODS: Randomised controlled trials (n=26) that evaluated asthma action plans as part of asthma self-management education were identified. Action plans were classified as being individualised and complete if they specified when and how to increase treatment (n=17), and as incomplete (n=4) or non-specific (n=5) if they did not include these instructions. RESULTS: For individualised complete written action plans the use of 2-4 action points and the use of both inhaled (ICS) and oral (OCS) corticosteroid consistently improved asthma outcomes. Action points based on personal best peak expiratory flow (PEF) consistently improved health outcomes while those based on percentage predicted PEF did not. The efficacy of incomplete action plans was inconclusive because of insufficient data. Non-specific action plans led to improvements in knowledge and symptoms. CONCLUSION: Individualised written action plans based on personal best PEF, using 2-4 action points, and recommending both ICS and OCS for treatment of exacerbations consistently improve asthma health outcomes. Other variations appear less beneficial or require further study. These observations provide a guide to the types of variations possible with written action plans, and strongly support the use of individualised complete written action plans.     

Impact of Preventive Treatment With Long-Acting β2-Adrenergic Agonists and Inhaled Corticosteroids on the Morbidity and Mortality of Severe Asthma Exacerbations in 1543 Patients

Background and objectivesRecent systematic reviews and meta-analyses examining long-acting β₂-adrenergic agonists (LABA) as maintenance treatment for asthma have shown surprisingly conflicting results. The aim of the present study was to determine the impact, in terms of efficacy and safety, of previous maintenance treatment on severe asthma exacerbations.Patients and methodsWe retrospectively evaluated the clinical characteristics of exacerbations experienced by 1543 patients with moderate persistent and severe persistent asthma. Drug therapy was as follows: a combination of inhaled LABAs and corticosteroids (493 patients), an inhaled corticosteroid only (456 patients), and no maintenance treatment (594 patients).ResultsAsthmatic patients taking LABAs did not show higher mortality, longer stay in the intensive care unit, longer hospital stay, lower pH, or worse airflow obstruction than the other 2 groups. On the contrary, they had a higher mean (SD) forced expiratory volume in 1 second at discharge (54% [16%]) than patients taking inhaled corticosteroids (48% [19%]) and patients taking no maintenance treatment (48% [20%]) (P=.009). Patients taking no maintenance treatment also had lower mean (SD) pH values (7.37 [0.11]) than patients taking LABAs (7.39 [0.09]) and patients taking inhaled corticosteroids (7.39 [0.08]) (P=.002), and more admissions to the intensive care unit (11.1% vs 6.5% and 7.7%; P=.002 and P=.018, respectively).ConclusionsThis study did not reveal higher morbidity or mortality in severe asthma exacerbations in patients with moderate persistent or severe persistent asthma who had received inhaled LABAs combined with inhaled corticosteroids. On the contrary, asthma patients who did not use maintenance treatment experienced more severe asthma exacerbations.     

Nedocromil sodium in adults with asthma dependent on inhaled corticosteroids: a double blind, placebo controlled study.

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids.     

Key observations from the NHLBI Asthma Clinical Research Network

The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed, its stated mission was to perform multiple controlled clinical trials for treating patients with asthma by dispassionately examining new and existing therapies, and to rapidly communicate its findings to the medical community. The ACRN conducted 15 major clinical trials. In addition, clinical data, manual of operations, protocols and template informed consents from all ACRN trials are available via NHLBI BioLINCC (https://biolincc.nhlbi.nih.gov/studies/). This network contributed major insights into the use of inhaled corticosteroids, short-acting and long-acting ?-adrenergic agonists, leukotriene receptor antagonists, and novel agents (tiotropium, colchicine and macrolide antibiotics). They also pioneered studies of the variability in drug response, predictors of treatment response and pharmacogenetics. This review highlights the major research observations from the ACRN that have impacted the current management of asthma.     

Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis

BACKGROUND: Current guidelines recommend the use of a combination of inhaled beta(2) agonists and anticholinergics, particularly for patients with acute severe or life threatening asthma in the emergency setting. However, this statement is based on a relatively small number of randomised controlled trials and related systematic reviews. A review was undertaken to incorporate the more recent evidence available about the effectiveness of treatment with a combination of beta(2) agonists and anticholinergics compared with beta(2) agonists alone in the treatment of acute asthma. METHODS: A search was conducted of all randomised controlled trials published before April 2005. RESULTS: Data from 32 randomised controlled trials (n = 3611 subjects) showed significant reductions in hospital admissions in both children (RR = 0.73; 95% CI 0.63 to 0.85, p = 0.0001) and adults (RR = 0.68; 95% CI 0.53 to 0.86, p = 0.002) treated with inhaled anticholinergic agents. Combined treatment also produced a significant increase in spirometric parameters 60-120 minutes after the last treatment in both children (SMD = -0.54; 95% CI -0.28 to -0.81, p = 0.0001) and adults (SMD = -0.36; 95% CI -0.23 to -0.49, p = 0.00001). CONCLUSIONS: This review strongly suggests that the addition of multiple doses of inhaled ipratropium bromide to beta(2) agonists is indicated as the standard treatment in children, adolescents, and adults with moderate to severe exacerbations of asthma in the emergency setting.     

Major reduction in asthma morbidity and continued reduction in asthma mortality in New Zealand: what lessons have been learned?

Increasing financial barriers to primary health care against a background of social and economic decline are likely to have contributed to asthma morbidity and mortality in New Zealand. Although there would not have been a sufficient increase in asthma prevalence to have accounted for the threefold increase in mortality rates, whether or not there was an increase in asthma severity in the late 1970s remains open to debate. Misuse or poor use of newly available and potent bronchodilator medications by those with the most severe asthma may simply have contributed to further delays in obtaining appropriate care and therefore to an increase in frequency of severe attacks in the community. Despite substantial increases in the use of bronchodilator therapy in New Zealand, there was no immediate improvement in indices of either asthma morbidity or mortality. The initial reduction in mortality rates in the 1980s happened at a time when first admissions for asthma were still increasing and seems to be best explained by an improvement in utilisation of hospital services (which were free until 1992) rather than a reduction in asthma severity. However, the recent reductions in all measures of asthma morbidity and further reduction in asthma mortality since 1989 does now suggest a reduction in asthma severity and would be best explained by the substantial increase in medium and high dose inhaled corticosteroid use, and to the endorsement of the current management strategies for asthma which are being promoted internationally and which were given considerable publicity in New Zealand in 1989 and 1990. Whilst sales of inhaled beta agonists were higher in 1991 than 1989, this may not reflect their pattern of use by individual patients since the need for an increase in inhaled beta agonist treatment has been accepted as indicating a lack of control and the need for either starting or increasing the dose of inhaled steroid treatment.     

Does nedocromil sodium have a steroid sparing effect in adult asthmatic patients requiring maintenance oral corticosteroids?

A randomised, double blind, placebo controlled trial of nedocromil sodium was undertaken to assess its corticosteroid sparing effect in 50 adults with asthma who had required an oral corticosteroid dose of (or equivalent to) at least 5 mg prednisolone a day continuously during the preceding year, in addition to inhaled beclomethasone dipropionate and bronchodilators. Patients having corticosteroids other than prednisolone were changed to prednisolone. A four week baseline period was followed by 20 weeks of inhaled nedocromil sodium (16 mg daily) or placebo. After four weeks of the treatment phase an attempt was made to reduce the oral prednisolone maintenance dose by 2.5 mg a fortnight until a dose of 5 mg daily was reached and thereafter by 1 mg a fortnight, provided that there was no significant clinical deterioration as judged by clinic assessments and daily diary cards. Of 50 patients recruited, 47 entered the treatment phase (age range 16-64 years), 24 receiving nedocromil sodium and 23 placebo. The total steroid reduction achieved was 2.5 mg in the nedocromil group and 3 mg in the placebo group, which did not differ significantly. There was no significant change in symptoms, lung function or inhaler use in either group during the study. The number of patient requiring short term upward adjustment of booster doses of oral prednisolone for exacerbations of asthma was similar in the two groups (26 with placebo, 28 with nedocromil). Thus nedocromil sodium does not appear to provide an oral corticosteroid sparing effect in chronic steroid dependent asthma.     

Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma

BACKGROUND: Cigarette smokers with asthma are insensitive to short term inhaled corticosteroid therapy, but efficacy when given for a longer duration at different doses is unknown. METHODS: Ninety five individuals with mild asthma were recruited to a multicentre, randomised, double blind, parallel group study comparing inhaled beclomethasone in doses of 400 microg or 2000 microg daily for 12 weeks in smokers and non-smokers. The primary end point was the change in morning peak expiratory flow (PEF). Secondary end points included evening PEF, use of reliever inhaler, number of asthma exacerbations, spirometric parameters, and asthma control score. RESULTS: After 12 weeks of inhaled beclomethasone there was a considerable difference between the morning PEF measurements of smokers and non-smokers with asthma (-18 (95% CI -35 to -1), adjusted p = 0.035). Among those receiving 400 microg daily there was a difference between the mean (95% CI) morning PEF (l/min) in smokers and non-smokers (-25 (95% CI -45 to -4), adjusted p = 0.019) and in the number of asthma exacerbations (6 v 1 in smokers and non-smokers, respectively, p = 0.007). These differences were reduced between smokers and non-smokers receiving 2000 microg inhaled beclomethasone daily. CONCLUSIONS: Compared with non-smokers, smokers with mild persistent asthma are insensitive to the therapeutic effect of low dose inhaled corticosteroid treatment administered for a 12 week period. The disparity of the response between smokers and non-smokers appears to be reduced with high dose inhaled corticosteroid. These findings have important implications for the management of individuals with mild asthma who smoke.     

Risk of severe life threatening asthma and beta agonist type: an example of confounding by severity.

BACKGROUND: A study was undertaken to test the hypothesis that a particular inhaled beta agonist, fenoterol, increases the incidence of severe life threatening asthma. METHODS: A retrospective cohort was assembled comprising 655 patients with asthma aged 15-55 years who attended a single Auckland hospital for acute asthma between 1 January 1986 and 31 December 1987 (the "index event"). Patients were followed for the occurrence of death from asthma or admission to the intensive care unit for asthma, until death or 31 May 1989. Data on asthma medications and asthma severity were obtained from forms used specifically for managing patients with acute asthma in the emergency department and maintained as part of the hospital record and/or from the hospital record (when patients were admitted). RESULTS: Following the index event 90 admissions to the intensive care unit (ICU) and 15 asthma deaths were identified. Before adjusting for asthma severity, patients using inhaled fenoterol had a greater incidence of severe life threatening asthma than patients using inhaled salbutamol (RR = 2.1, 95% CI 1.4 to 3.1). After controlling for two markers of severe asthma used in previous studies-a hospital admission in the previous year and prescribed oral corticosteroids-the relative risk estimate declined to 1.5 (95% CI 1.0 to 2.3). After controlling further for the number of hospital admissions during the study period, continuous oral corticosteroid use rather than short courses of treatment, severity of the previous attack requiring a hospital visit, and race, fenoterol was not associated with severe life threatening asthma at the time of attendance for a previous hospital visit (RR = 1.0, 95% CI 0.6 to 1.7). CONCLUSION: Fenoterol is used more often by patients with severe asthma and, after adjusting for differences in baseline risk, it does not increase the risk of severe life threatening asthma.     

Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care.

BACKGROUND: Oral corticosteroids used in short courses for acute asthma are regarded as safe, although the frequent use of these drugs may result in patients suffering from systemic side effects. It has become common practice for patients to increase their own inhaled corticosteroid intake when their asthma goes out of control, but it has never been established whether a high dose of inhaled corticosteroid can be as effective as a short course of oral corticosteroid in the treatment of acute exacerbations. METHODS: A multicentre, randomised, double blind, double dummy, parallel group study was undertaken to determine whether the introduction of a high dose of inhaled fluticasone propionate (2 mg daily) is as effective as a short reducing course of oral prednisolone (starting at 40 mg/day and reducing by 5 mg every other day) in the treatment of acute exacerbations of asthma not considered severe enough for admission to hospital but requiring treatment with oral corticosteroid. RESULTS: Four hundred and thirteen adult asthmatic subjects who presented to their general practitioner with an acute exacerbation of asthma were recruited in 47 general practices in the United Kingdom. Treatment failures, defined as a reduction in peak expiratory flow (PEF) to below 60% of the patient's best/predicted value on two consecutive occasions or persistent symptoms with no improvement on three consecutive days, occurred in 23% of patients who received oral prednisolone and 27% who received inhaled fluticasone propionate (difference in percentage of treatment failures 4.3, 95% CI -4.1 to 12.8, p = 0.31). In each group 48% were classified as treatment successes, defined as a 10% or greater increase in percentage best/predicted morning PEF. Both treatments were equally well tolerated. CONCLUSIONS: There is no evidence of a significant difference in efficacy between a reducing dose course of oral prednisolone and high dose inhaled fluticasone propionate in mild exacerbations of asthma which do not require admission to hospital.     

Initial starting dose of inhaled corticosteroids in adults with asthma: a systematic review

BACKGROUND: Asthma guidelines vary in their recommendations for the initial dose of inhaled corticosteroid (ICS) in asthma. A systematic review of the literature was conducted to establish the optimal starting dose of ICS for asthma in adults. METHODS: Randomised controlled trials comparing two doses of the same ICS in adults with asthma and no concomitant inhaled or oral corticosteroid were assessed. Included trials were analysed according to the following ICS dose comparisons: high (> or =800 microg/day beclomethasone (BDP)) versus moderate (400<800 microg/day BDP) (n = 7); moderate versus low (<400 microg/day BDP) (n = 6); step down versus constant dose (n = 4). RESULTS: Fourteen publications describing 13 trials were included in the review. Studies (n = 4) that compared a step down approach with a constant moderate/low dose of ICS found no difference in lung function, symptoms, or rescue medications between the two treatment approaches (p>0.05). There was no difference in the change in morning peak flow after treatment with high compared with moderate dose ICS. When compared with low dose ICS, moderate dose ICS significantly improved morning peak flow (change from baseline WMD 11.14 l/min, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06). CONCLUSIONS: For patients with asthma who require ICS, starting with a moderate dose is equivalent to starting with a high dose and stepping down. The small non-significant benefits of starting with a high ICS dose are not of sufficient clinical benefit to warrant its use. Initial moderate ICS doses appear to be more effective than an initial low ICS dose.