A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils).

Asthma severity and control can be measured both subjectively and objectively. Traditionally asthma treatments have been individualised using symptoms and spirometry/peak flow. Increasingly treatment tailored in accordance with inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) data) is advocated as an alternative strategy. The objective of this review was to evaluate the efficacy of tailoring asthma interventions based on inflammatory markers (sputum analysis and FeNO) in comparison with clinical symptoms (with or without spirometry/peak flow) for asthma-related outcomes in children and adults. Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles were searched. The last searches were in February 2009. All randomised controlled comparisons of adjustment of asthma treatment based on sputum analysis or FeNO compared with traditional methods (primarily clinical symptoms and spirometry/peak flow) were selected. Results of searches were reviewed against predetermined criteria for inclusion. Relevant studies were selected, assessed and data extracted independently by at least two people. The trial authors were contacted for further information. Data were analysed as 'intervention received' and sensitivity analyses performed. Six (2 adults and 4 children/adolescent) studies utilising FeNO and three adult studies utilising sputum eosinophils were included. These studies had a degree of clinical heterogeneity including definition of asthma exacerbations, duration of study and variations in cut-off levels for percentage of sputum eosinophils and FeNO to alter management in each study. Adults who had treatment adjusted according to sputum eosinophils had a reduced number of exacerbations compared with the control group (52 vs. 77 patients with ≥1 exacerbation in the study period; p=0.0006). There was no significant difference in exacerbations between groups for FeNO compared with controls. The daily dose of inhaled corticosteroids at the end of the study was decreased in adults whose treatment was based on FeNO in comparison with the control group (mean difference -450.03 µg, 95% CI -676.73 to -223.34; p<0.0001). However, children who had treatment adjusted according to FeNO had an increase in their mean daily dose of inhaled corticosteroids (mean difference 140.18 µg, 95% CI 28.94 to 251.42; p=0.014). It was concluded that tailoring of asthma treatment based on sputum eosinophils is effective in decreasing asthma exacerbations. However, tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes in children and adults. At present, there is insufficient justification to advocate the routine use of either sputum analysis (due to technical expertise required) or FeNO in everyday clinical practice.

Ciclesonide versus placebo for chronic asthma in adults and children.

BACKGROUND: Inhaled corticosteroids are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that has efficient distribution and release properties that mean it can be taken once daily, making it potentially useful in ongoing asthma management. OBJECTIVES: To assess the efficacy of inhaled ciclesonide in adults and children with chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of CENTRAL and PubMed were undertaken. The literature searches for this review are current up to June 2007. SELECTION CRITERIA: Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with placebo, and we also included studies comparing ciclesonide at different doses. DATA COLLECTION AND ANALYSIS: Two authors assessed studies for inclusion in the review, extracted data independently and checked each others' work. We contacted study investigators in order to obtain additional data. Extracted data were entered into RevMan 4.2 and analysed as fixed effect mean differences for continuous data, and fixed effect risk ratios for dichotomous data. MAIN RESULTS: Eighteen trials (reporting 20 study comparisons) met the review entry criteria. We report findings from 18 group comparisons where data were available (6343 participants, of whom 1692 were children). Ciclesonide versus placebo: The short duration of the included studies means that there is a lack of data with respect to the impact of ciclesonide on asthma exacerbations. At doses of 100 mcg/d or less up to 400 mcg/d in mild to moderate asthma, ciclesonide improved lung function, asthma symptoms and rescue inhaler use, compared with placebo.Dose response outcomes: Comparisons of 100 versus 200 mcg/d, 100 versus 400 mcg/d and 400 versus 800 mcg/d did not yield significant differences in lung function outcomes. Adverse event data were not available in sufficient detail to permit assessment of the safety profile of this drug. AUTHORS' CONCLUSIONS: Ciclesonide was more effective than placebo, in the short term, in improving lung function in patients with mild to moderate asthma previously treated with inhaled corticosteroids. There remain questions as to dose response, and the lack of data on the longer term impact on exacerbations and safety profile should be addressed in future studies.

Ciclesonide versus other inhaled steroids for chronic asthma in children and adults.

BACKGROUND: Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects. OBJECTIVES: To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007. SELECTION CRITERIA: Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01). AUTHORS' CONCLUSIONS: The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Herbal interventions for chronic asthma in adults and children.

BACKGROUND: Herb and plant based preparations are a popular treatment for asthma, although there remain concerns as to their efficacy and safety. In Western societies, motivations for using such treatments may be both positive and negative, with their perceived safety and dissatisfaction with conventional medicine among them. In China such treatments are more commonly used and many compounds considered 'conventional' are derived from herbs or plants. OBJECTIVES: To assess the efficacy and safety of herb and plant extracts in the management of chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group Trials Register, CENTRAL, MEDLINE, EMBASE and AMED were searched with pre-defined terms. Searches are current as of February 2007. SELECTION CRITERIA: Randomised placebo controlled trials of any herb or plant extract were eligible. Study participants had to have a primary diagnosis of asthma. Studies in both adults and children were eligible for the review. DATA COLLECTION AND ANALYSIS: Two reviewers assessed studies for suitability. Data were extracted and double-checked. MAIN RESULTS: Twenty-seven studies (29 experimental groups) met the review entry criteria, randomising a total of 1925 participants. The studies identified assessed the effects of 21 different herbal preparations. Study quality varied considerably, and the sample sizes were often small. For primary outcomes (exacerbations, steroids use and lung function measurements): Two out of six studies reporting change in FEV1 were positive, with very few data available on the frequency of exacerbations. One study which did report these data was negative. Health-related quality of life was only measured in one trial. AUTHORS' CONCLUSIONS: The evidence base for the effects of herbal treatments is hampered by the variety of treatments assessed, poor reporting quality of the studies and lack of available data. The data that are available from the studies provide only a small insight into the long-term efficacy and harm profiles of these treatments. The absence of common endpoint measurements limits the validity of our findings further. Positive findings in this review warrant additional well-designed trials in this area.

Education interventions for adults who attend the emergency room for acute asthma.

BACKGROUND: The use of educational and behavioural interventions in the management of chronic asthma have a strong evidence base. There may be a role for educative interventions following presentation in an emergency setting in adults. OBJECTIVES: To assess the effectiveness of educational interventions administered following an acute exacerbation of asthma leading to presentation in the emergency department. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register. Study authors were contacted for additional information. Searches are current to November 2006. SELECTION CRITERIA: Randomised, parallel group trials were eligible if they recruited adults (> 17 years) who had presented at an emergency department with an acute asthma exacerbation. The intervention of interest was any educational intervention (for example, written asthma management plan). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Twelve studies involving 1954 adults were included. Education significantly reduced subsequent admission to hospital (relative risk 0.50; 95% confidence interval 0.27 to 0.91); however, did not significantly reduce the risk of re-presentation at emergency departments (ED) the study follow up (relative risk 0.69; 95% confidence interval 0.40 to 1.21). The lack of statistically significant differences between asthma education and control groups in terms of peak flow, quality of life, study withdrawal and days lost were hard to interpret given the low number of studies contributing to these outcomes. One study from the early 1990s measured cost and found no difference for total costs and costs related to physician visits and admissions to hospital. If data were restricted to emergency department treatment, education led to lower costs than control. AUTHORS' CONCLUSIONS: This review found that educational interventions applied in the emergency department reduce subsequent asthma admissions to hospital. The interventions did not significantly reduce ED re-presentations; while the trend in effect favours educational interventions, the pooled results were not statistically significant. The impact of educational intervention in this context on longer term outcomes relating to asthma morbidity is unclear. Priorities for additional research in this area include assessment of health-related quality of life, lung function assessment, exploration of the relationship between socio-economic status and asthma morbidity, and better description of the intervention assessed.

Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction.

BACKGROUND: The pathogenesis of exercise induced bronchoconstriction is likely multifactorial and is not completely understood. Inflammation plays an important role in the pathogenesis of exercise induced bronchoconstriction in asthmatic subjects but the evidence seems less strong in non-asthmatic subjects. The management of exercise induced bronchoconstriction focuses on prevention, through both pharmacologic and non-pharmacologic interventions. OBJECTIVES: The objectives of this review were to evaluate the use of inhaled corticosteroids in the treatment of exercise induced bronchoconstriction in a systematic way. Specifically, the review was designed to: determine whether inhaled corticosteroids (compared to placebo) has an attenuating effect on exercise induced bronchoconstriction in adult and pediatric asthmatic patients; estimate the magnitude of the attenuating effect. SEARCH STRATEGY: We searched the Cochrane Airways Review Group Specialised Register of trials, the Cochrane Central Register of Controlled Trials, review articles, textbooks and reference list of articles. SELECTION CRITERIA: Randomised trials in adults or children comparing inhaled corticosteroids with placebo to prevent bronchoconstriction in patients with exercise induced bronchoconstriction. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were conducted independently by two reviewers. MAIN RESULTS: The results from six randomised controlled trials involving 123 participants were analyzed (two trials involving adults and four involving children). Combining results from the two parallel studies with at least 4 weeks duration of inhaled corticosteroids, the use of inhaled corticosteroids significantly attenuated the percent fall index in forced expiratory volume in 1 second (WMD = 14.07%; 95% CI: 11.62% to 16.52%). The result from one crossover study with duration of inhaled corticosteroids of 4 weeks revealed significant attenuation of percent fall in forced expiratory volume in 1 second ( WMD = 6.90%; 95% CI: 1.40% to 12.40%) and the percent fall in peak expiratory flow ( WMD =11.50%; 95% CI: 6.31% to 16.69%). The small amount of data from placebo-controlled trials using a single treatment do not currently allow conclusions to be drawn. AUTHORS' CONCLUSIONS: Inhaled corticosteroids used for 4 weeks or more before exercise testing significantly attenuated exercise-induced bronchoconstriction. The relative benefits of inhaled corticosteroids compared to other forms of exercise induced bronchoconstriction treatment (sodium cromoglycate, nedocromil sodium, salbutamol, and other anti-inflammatory agents) remains unclear.

Fluticasone versus beclomethasone or budesonide for chronic asthma in adults and children.

BACKGROUND: Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays. OBJECTIVES: To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register (January 2007) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2006). SELECTION CRITERIA: Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1. MAIN RESULTS: Seventy-one studies (14,602 participants) representing 74 randomised comparisons met the inclusion criteria. Methodological quality was fair. Dose ratio 1:2: FP produced a significantly greater end of treatment FEV1 (0.04 litres (95% CI 0 to 0.07 litres), end of treatment and change in morning PEF, but not change in FEV1 or evening PEF. This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. FP led to fewer symptoms and less rescue medication use. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in morning PEF, evening PEF, and FEV1 over BDP or BUD. The effects on exacerbations were mixed. There were no significant differences incidence of hoarseness, pharyngitis, candidiasis, or cough. AUTHORS' CONCLUSIONS: Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing sore throat and when given at the same daily dose leads to increased hoarseness. There are concerns about adrenal suppression with Fluticasone given to children at doses greater than 400 mcg/day, but the randomised trials included in this review did not provide sufficient data to address this issue.

Combined corticosteroid and long-acting beta-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler may facilitate adherence to medication regimens, and improve efficacy. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to placebo, in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. SELECTION CRITERIA: Studies were included if they were randomised and double-blind. Studies could compare any combined inhaled corticosteroids and long-acting beta-agonist preparation with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. One author entered the data. MAIN RESULTS: Eleven studies met the inclusion criteria (6427 participants randomised). Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were used. Study quality was good. Fluticasone/salmeterol and budesonide/formoterol both reduced the rate of exacerbations. Pooled analysis of both combination therapies indicated that exacerbations were less frequent when compared with placebo, Rate Ratio: 0.74 (95% CI 0.7 to 0.8). The clinical impact of this effect depends on the frequency of exacerbations experienced by patients. The patients included in these trials had on average 1-2 exacerbations per year which means that treatment with combination therapy would lead to a reduction of one exacerbation every two to four years in these individuals. There is an overall reduction in mortality, but this outcome is dominated by the results of TORCH and further studies on budesonide/formoterol are required. The three year number needed to treat to prevent one extra death is 36 (95% CI 21 to 258), using a baseline risk of 15.2% from the placebo arm of TORCH. Both treatments led to statistically significant improvement in health status measurements, although the clinical importance of the differences observed is open to interpretation. Symptoms and lung function assessments favoured combination treatments. There was an increase in the risk of pneumonia with combined inhalers. The three year number needed to treat for one extra case of pneumonia is 13 (95% CI 9 to 20), using a baseline risk of 12.3% from the placebo arm of TORCH. Fewer participants withdrew from studies assessing combined inhalers due to adverse events and lack of efficacy. AUTHORS' CONCLUSIONS: Compared with placebo, combination therapy led to a significant reduction of a quarter in exacerbation rates. There was a significant reduction in all-cause mortality with the addition of data from the TORCH trial. The increased risk of pneumonia is a concern, and better reporting of this outcome in future studies would be helpful. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, particularly in relation to the profile of adverse events and benefits in relation to different doses of inhaled corticosteroids.

Combined corticosteroid and long-acting beta-agonist in one inhaler versus inhaled steroids for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy. Two preparations are currently available, fluticasone/salmeterol (FPS) and budesonide/formoterol (BDF). OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to inhaled corticosteroids, in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. SELECTION CRITERIA: Studies were included if they were randomised and double-blind. Studies compared combined inhaled corticosteroids and long-acting beta-agonist preparations with the inhaled corticosteroid component. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The primary outcome were exacerbations, mortality and pneumonia. Health-related quality of life (measured by validated scales), lung function and side-effects were secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios (OR), and continuous data as mean differences and 95% confidence intervals (CI). MAIN RESULTS: Seven studies of good methodological quality met the inclusion criteria randomising 5708 participants with predominantly poorly reversible, severe COPD. Exacerbation rates were significantly reduced with combination therapies (Rate ratio 0.91; 95% confidence interval 0.85 to 0.97, P = 0.0008). Data from two FPS studies indicated that exacerbations requiring oral steroids were reduced with combination therapy. Data from one large study suggest that there is no significant difference in the rate of hospitalisations. Mortality was also lower with combined treatment (odds ratio 0.77; 95% confidence interval 0.63 to 0.94). Quality of life, lung function and withdrawals due to lack of efficacy favoured combination treatment. Adverse event profiles were similar between the two treatments. No significant differences were found between FPS and BDP in the primary outcomes, but the confidence intervals for the BDP results were wide as smaller numbers of patients have been studied. AUTHORS' CONCLUSIONS: Combination ICS and LABA significantly reduces morbidity and mortality in COPD when compared with mono component steroid. Adverse events were not significantly different between treatments, although evidence from other sources indicates that inhaled corticosteroids are associated with increased risk of pneumonia. Assessment of BDF in larger, long-term trials is required. Dose response data would provide valuable evidence on whether efficacy and safety outcomes are affected by different steroid loads.

Combined corticosteroid and long-acting beta-agonist in one inhaler versus long-acting beta-agonists for chronic obstructive pulmonary disease.

BACKGROUND: The co-administration of inhaled corticosteroids and long-acting beta-agonists in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy in COPD. In this review they are compared with mono component long-acting beta-agonists. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroids and long-acting beta-agonists preparations with mono component long-acting beta-agonists in adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. SELECTION CRITERIA: Studies were included if they were randomised and double-blind. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with component long-acting beta-agonist preparation. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The primary outcomes were exacerbations, mortality and pneumonia, with health-related quality of life (measured by validated scales), lung function and side-effects as secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios (OR), and continuous data as mean differences and 95% confidence intervals (CI). Sensitivity analysis was performed by combining data with a random effects model. MAIN RESULTS: Ten studies of good methodological quality met the inclusion criteria, randomising 7598 participants with severe chronic obstructive pulmonary disease. Eight studies assessed fluticasone/salmeterol, and two studies budesonide/formoterol. The exacerbation rates with combined inhalers were reduced in comparison to long-acting beta-agonists alone (Rate Ratio 0.82, 95% CI 0.78 to 0.88). There was no significant difference in mortality between combined inhalers and long-acting beta-agonists alone. Pneumonia occurred more commonly with combined inhalers (OR 1.62; 95% CI 1.35 to 1.94). There was no significant difference in terms of hospitalisations, although the two studies contributing data to this outcome may have been drawn from differing populations. Combination was more effective than LABA in improving quality of life measured by the St George Respiratory Questionnaire, and the Chronic Respiratory Questionnaire, and predose and post dose FEV1. AUTHORS' CONCLUSIONS: Combination therapy was more effective than long-acting beta-agonists in reducing exacerbation rates, although the evidence for the effects on hospitalisations was mixed, and requires further exploration. No significant impact on mortality was found even with additional information from the TORCH trial. The superiority of combination inhalers should be viewed against the increased risk of side-effects, particularly pneumonia. Additional studies on BDF are required and more information would be useful of the relative benefits and adverse event rates with different doses of inhaled corticosteroids.

Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid.

BACKGROUND: Asthma is a common respiratory disease among both adults and children and short acting inhaled beta-2 agonists are used widely for 'reliever' bronchodilator therapy. Long acting beta-2 agonists (LABA) were introduced as prospective 'symptom controllers' in addition to inhaled corticosteroid 'preventer' therapy (ICS). In this updated review we have included studies in which patients were either not on ICS as a group, or in which some patients, but not all, were on ICS to complement previous systematic reviews of studies where LABA was given in patients uniformly receiving ICS. We have focussed particularly on serious adverse events, given previous concerns about potential risks, especially of death, from regular beta-2 agonist use. OBJECTIVES: This review aimed to determine the benefit or detriment on the primary outcome of asthma control with the regular use of LABA compared with placebo, in mixed populations in which only some were taking ICS and in populations not using ICS therapy. SEARCH STRATEGY: We carried out searches using the Cochrane Airways Group trial register, most recently in October 2005. We searched bibliographies of identified RCTs for additional relevant RCTs and contacted authors of identified RCTs for other published and unpublished studies. SELECTION CRITERIA: All randomised studies of at least four weeks duration, comparing a LABA given twice daily with a placebo, in chronic asthma. Selection criteria to this updated review have been altered to accommodate recently published Cochrane reviews on combination and addition of LABA to ICS therapy. Studies in which all individuals were uniformly taking ICS were excluded from this review. DATA COLLECTION AND ANALYSIS: Two reviewers performed data extraction and study quality assessment independently. We contacted authors of studies for missing data. MAIN RESULTS: Sixty-seven studies (representing 68 experimental comparisons) randomising 42,333 participants met the inclusion criteria. Salmeterol was used as long-acting agent in 50 studies and formoterol fumarate in 17. The treatment period was four to nine weeks in 29 studies, and 12 to 52 weeks in 38 studies. Twenty-four studies did not permit the use of ICS, and forty permitted either inhaled corticosteroid or cromones (in three studies this was unclear). In these studies between 22% and 92% were taking ICS, with a median of 62%. There were significant advantages to LABA treatment compared to placebo for a variety of measurements of airway calibre including morning peak expiratory flow (PEF), evening PEF and FEV1. They were associated with significantly fewer symptoms, less use of rescue medication and higher quality of life scores. This was true whether patients were taking LABA in combination with ICS or not. Findings from SMART (a recently published surveillance study) indicated significant increases in asthma related deaths, respiratory related deaths and combined asthma related deaths and life threatening experiences. The absolute increase in asthma-related mortality was consistent with an increase of around one per 1250 patients treated with LABA for six months, but the confidence intervals are wide (from 700 to 10,000). Post-hoc exploratory subgroups suggested that African-Americans and those not on inhaled corticosteroids were at particular risk for the primary end-point of death or life-threatening asthma event. There was also a suggestion of an increase in exacerbation rate in children. Pharmacologically predicted side effects such as headache, throat irritation, tremor and nervousness were more frequent with LABA treatment. AUTHORS' CONCLUSIONS: LABA are effective in the control of chronic asthma in the "real-life" subject groups included. However there are potential safety issues which call into question the safety of LABA, particularly in those asthmatics who are not taking ICS, and it is not clear why African-Americans were found to have significant differences in comparison to Caucasians for combined respiratory-related death and life threatening experiences, but not for asthma-related death.

Inhaled corticosteroids for stable chronic obstructive pulmonary disease.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much controversy. Major international guidelines recommend selective use of ICS. Recently published meta-analyses have reported conflicting findings on the effects of inhaled steroid therapy in COPD. OBJECTIVES: The objective of the review is to determine the efficacy of regular use of inhaled corticosteroids in patients with stable COPD. SEARCH STRATEGY: A pre-defined search strategy was used to search the Cochrane Airways Group specialised register for relevant literature. Searches are current as of October 2006. SELECTION CRITERIA: We selected randomised trials comparing any dose of any type of inhaled steroid with a placebo control in patients with COPD. Acute bronchodilator reversibility to short term beta2-agonists and bronchial hyperresponsiveness were not exclusion criteria. The a priori primary outcome was change in lung function. Data on mortality, exacerbations, quality of life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and safety were also analysed. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Forty-seven primary studies with 13,139 participants met the inclusion criteria. Medium term use of ICS (> two months and up to six months) resulted in a small improvement in FEV1 in some studies. Long term use of ICS (> six months) did not significantly reduce the rate of decline in FEV1 in COPD patients (weighted mean difference (WMD) 5.80 ml/year with ICS over placebo, 95% CI -0.28 to 11.88, 2333 participants). There was no statistically significant effect on mortality in COPD patients (OR 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (WMD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (WMD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.49, 95% CI 1.78 to 3.49, 4380 participants) and hoarseness. The few long term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over 3 years. AUTHORS' CONCLUSIONS: Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life), against the known increase in local side effects (oropharyngeal candidiasis and hoarseness). The risk of long term adverse effects is unknown.

Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma.

BACKGROUND: Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. OBJECTIVES: To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006. SELECTION CRITERIA: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist. DATA COLLECTION AND ANALYSIS: In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information. MAIN RESULTS: Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86, Risk Difference -0.07; 95% CI -0.12 to -0.02, NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55, Risk Difference -0.11; 95% CI -0.16 to -0.06, NNT 9; 95% CI 6 to 16). AUTHORS' CONCLUSIONS: Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults.

BACKGROUND: Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Interventions for asthma therapies have been traditionally based on symptoms and spirometry. OBJECTIVES: To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was on 31 October 2006. SELECTION CRITERIA: All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Three sets of reviewers selected relevant studies. Two review authors independently assessed trial quality extracted data. Authors were contacted for further information but none were received. Data was analysed as "treatment received" and sensitivity analyses performed. MAIN RESULTS: Three adult studies were included; these studies were clinically and methodologically heterogenous (use of medications, cut off for percentage of sputum eosinophils and definition of asthma exacerbation). There were no eligible paediatric studies. Of 246 participants randomised, 221 completed the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms; pooled odds ratio (OR) was 0.49 (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4 to 32). There were also differences between groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids but the reduction in hospitalisations was not statistically significant. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was similar in both groups and no adverse events were reported. However sputum induction was not always possible. AUTHORS' CONCLUSIONS: Tailored asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. This review supports the use of sputum eosinophils to tailor asthma therapy for adults with frequent exacerbations and severe asthma. Further studies need to be undertaken to strengthen these results and no conclusion can be drawn for children with asthma.

Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. METHODS: We identified randomized controlled trials (RCTs) from the Cochrane Airways Group Specialised Register. We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or exercise capacity were measured. Rehabilitation was defined as exercise training for at least 4 weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. RESULTS: A total of 31 RCTs met the inclusion criteria. We found statistically significant improvements for all the outcomes. In 4 important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference. For exercise capacity, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 m; 95% CI: 32 to 65; n = 16 trials). CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Immunosuppressive and cytotoxic therapy for pulmonary sarcoidosis.

BACKGROUND: Immunosuppressive and cytotoxic agents have been used as both an alternative to oral corticosteroids, and as a means of maintaining a low dose of steroids in the treatment of pulmonary sarcoidosis. OBJECTIVES: To determine the efficacy of immunosuppressive and cytotoxic agents in the treatment of pulmonary sarcoidosis. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE and CINAHL were searched for possible randomised trials and bibliographies were checked for other potentially relevant trials. Searches were current as of April 2006. SELECTION CRITERIA: Randomised controlled trials comparing an immunosuppressive or cytotoxic therapy with a control in patients with pulmonary sarcoidosis were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data for entry in to the RevMan 4.2. Pharmaceutical companies and study investigators were contacted for unpublished trials. MAIN RESULTS: Five studies were included in the review. Trials comparing methotrexate, chloroquine, cyclosporin A and pentoxifylline were identified. No data could be combined for a meta-analysis. Data on lung function, chest x-ray scores and dyspnoea were largely inconclusive. Adverse effects were associated with methotrexate, cyclosporin A, chloroquine and pentoxifylline. In two small studies methotrexate and pentoxifylline were associated with a steroid sparing effect. In the methotrexate study this was apparent after 12 months of therapy, but no difference was observed at 6 months. AUTHORS' CONCLUSIONS: The current body of evidence supporting the use of immunosuppressive agents and cytotoxic therapies is limited. Side-effects associated with some of the therapies were severe.

Long-acting beta2-agonists versus anti-leukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma.

BACKGROUND: Patients who continue to experience asthma symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Leukotriene receptor antagonists (LTRA) and long-acting beta(2)-agonists (LABA) agents may both be considered as add-on therapy to inhaled corticosteroids (ICS). OBJECTIVES: We compared the efficacy and safety profile of adding either daily LABA or LTRA in asthmatic patients who remained symptomatic on ICS. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched for randomised controlled trials up to and including March 2006. Reference lists of all included studies and reviews were screened to identify potentially relevant citations. Inquiries regarding other published or unpublished studies supported by the authors of the included studies or pharmaceutical companies who manufacture these agents were made. Conference proceedings of major respiratory meetings were also searched. SELECTION CRITERIA: Only randomised controlled trials conducted in adults or children with recurrent asthma where a LABA (for example, salmeterol or formoterol) or LTRA (for example, montelukast, pranlukast, zafirlukast) was added to ICS for a minimum of 28 days were considered for inclusion. Inhaled short-acting beta(2)-agonists and short courses of oral steroids were permitted as rescue medications. Other daily asthma treatments were permitted, providing the dose remained constant during the intervention period. Two reviewers independently reviewed the literature searches. DATA COLLECTION AND ANALYSIS: Data extraction and trial quality assessment were conducted independently by two reviewers. Whenever possible, primary study authors were requested to confirm methodology and data extraction and to provide additional information and clarification when needed. Where necessary, expansion of graphic reproductions and estimation from other data presented in the paper was performed. MAIN RESULTS: Fifteen randomised controlled trials met the inclusion criteria; eleven trials including 6,030 participants provided data in sufficient detail to permit aggregation. All eleven trials pertained to adults with moderate airway obstruction (% predicted FEV(1) 66-76%) at baseline. Montelukast (n=9) or Zafirlukast (n=2) was compared to Salmeterol (n=9) or Formoterol (n=2) as add-on therapy to 400-565 mcg of beclomethasone or equivalent. Risk of exacerbations requiring systemic corticosteroids was significantly lower with LABA+ICS when compared to LTRA+ICS (RR= 0.83, 95% Confidence Interval (95%CI): 0.71, 0.97): the number needed to treat with LABA compared to LTRA, to prevent one exacerbation over 48 weeks, was 38 (95% CI: 23 to 247). The following outcomes also improved significantly with the addition of LABA compared to LTRA to inhaled steroids (Weighted Mean Difference; 95%CI): morning PEFR (16 L/min; 13 to 18), evening PEFR (12 L/min; 9 to 15), FEV(1) (80 mL; 60 to 100), rescue-free days (9%; 5% to 13%), symptom-free days (6%; 2 to 11), rescue beta(2)-agonists (-0.5 puffs/day; -0.2 to -1), quality of life (0.1; 0.05 to 0.2), symptom score (Standard Mean Difference -0.2; -0.1 to -0.3), night awakenings (-0.1/week; -0.06 to -0.2) and patient satisfaction (RR 1.12; 1.07 to 1.16). Risk of withdrawals due to any reason was significantly lower with LABA+ICS compared to LTRA+ICS (Risk Ratio 0.83, 95% CI 0.73 to 0.95). Withdrawals due to adverse events or due to poor asthma control, hospitalisation, osteopenia, serious adverse events, overall adverse events, headache or cardiovascular events were not significantly different between the two study groups. AUTHORS' CONCLUSIONS: In asthmatic adults inadequately controlled on low doses of inhaled steroids, the addition of LABA is superior to LTRA for preventing exacerbations requiring systemic steroids, and for improving lung function, symptoms, and the use of rescue beta(2)-agonists.

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. This review updates that reported in 2001. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. SEARCH STRATEGY: We identified additional RCTs from the Cochrane Airways Group Specialised Register. Searches were current as of July 2004. SELECTION CRITERIA: We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. Rehabilitation was defined as exercise training for at least four weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We calculated weighted mean differences (WMD) using a random-effects model. We requested missing data from the authors of the primary study. MAIN RESULTS: We included the 23 randomized controlled trials (RCTs) in the 2001 Cochrane review. Eight additional RCTs (for a total of 31) met the inclusion criteria. We found statistically significant improvements for all the outcomes. In four important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference of 0.5 units (for example: Dyspnoea score: WMD 1.0 units; 95% confidence interval: 0.8 to 1.3 units; n = 12 trials). Statistically significant improvements were noted in two of the three domains of the St. Georges Respiratory Questionnaire. For FEC and MEC, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 meters; 95% CI: 32 to 65; n = 16 trials). AUTHORS' CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Drug therapy for obstructive sleep apnoea in adults.

BACKGROUND: The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway. OBJECTIVES: To determine the efficacy of drug therapies in the treatment of sleep apnoea. SEARCH STRATEGY: We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005. SELECTION CRITERIA: Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre-specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI). MAIN RESULTS: Twenty-six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.

Oral appliances for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea-hypopnoea (OSAH) is a syndrome characterised by recurrent episodes of partial or complete upper airway obstruction during sleep that are usually terminated by an arousal. Nasal continuous positive airway pressure (CPAP) is the primary treatment for OSAH , but many patients are unable or unwilling to comply with this treatment. Oral appliances (OA) are an alternative treatment for OSAH. OBJECTIVES: The objective was to review the effects of OA in the treatment of OSAH in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register. Searches were current as of June 2005. Reference lists of articles were also searched. SELECTION CRITERIA: Randomised trials comparing OA with control or other treatments in adults with OSAH . DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Study authors were contacted for missing information. MAIN RESULTS: Sixteen studies (745 participants) met the inclusion criteria. All the studies had some shortcomings, such as small sample size, under-reporting of methods and data, and lack of blinding. OA versus control appliances (six studies): OA reduced daytime sleepiness in two crossover trials (WMD -1.81;95%CI -2.72 to -0.90), and improved apnoea-hypopnoea index (AHI) (-10.78; 95% CI-15.53 to -6.03 parallel group data - five studies). OA versus CPAP (nine studies): OA were less effective than CPAP in reducing apnoea-hypopnoea index (parallel group studies: WMD 13 (95% CI 7.63 to 18.36), two trials; crossover studies: WMD 7.97; (95% CI 6.38 to 9.56, seven trials). However, no significant difference was observed on symptom scores. CPAP was more effective at improving minimum arterial oxygen saturation during sleep compared with OA. In two small crossover studies, participants preferred OA therapy to CPAP. OA versus corrective upper airway surgery (one study): Symptoms of daytime sleepiness were initially lower with surgery, but this difference disappeared at 12 months. AHI did not differ significantly initially, but did so after 12 months in favour of OA. AUTHORS' CONCLUSIONS: There is increasing evidence suggesting that OA improves subjective sleepiness and sleep disordered breathing compared with a control. CPAP appears to be more effective in improving sleep disordered breathing than OA. The difference in symptomatic response between these two treatments is not significant, although it is not possible to exclude an effect in favour of either therapy. Until there is more definitive evidence on the effectiveness of OA in relation to CPAP, with regard to symptoms and long-term complications, it would appear to be appropriate to recommend OA therapy to patients with mild symptomatic OSAH, and those patients who are unwilling or unable to tolerate CPAP therapy. Future research should recruit patients with more severe symptoms of sleepiness, to establish whether the response to therapy differs between subgroups in terms of quality of life, symptoms and persistence with usage. Long-term data on cardiovascular health are required.