Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease.

BACKGROUND: Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic antagonists (LAMA). LABA and LAMA bronchodilators are now available in single-combination inhalers. In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used with combination LABA and LAMA inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers as a triple therapy remain unclear. OBJECTIVES: To assess the effects of adding an ICS to combination LABA/LAMA inhalers for the treatment of stable COPD. SEARCH METHODS: We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to 30 November 2022. We also searched ClinicalTrials.gov and the WHO ICTRP up to 30 November 2022. SELECTION CRITERIA: We included parallel-group randomised controlled trials of three weeks' duration or longer that compared the treatment of stable COPD with ICS in addition to combination LABA/LAMA inhalers against combination LABA/LAMA inhalers alone. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcomes were acute exacerbations of COPD, respiratory health-related quality of life, pneumonia and other serious adverse events. The secondary outcomes were symptom scores, lung function, physical capacity, and mortality. We used GRADE to assess certainty of evidence for studies that contributed data to our prespecified outcomes. MAIN RESULTS: Four studies with a total of 15,412 participants met the inclusion criteria. The mean age of study participants ranged from 64.4 to 65.3 years; the proportion of female participants ranged from 28% to 40%. Most participants had symptomatic COPD (COPD Assessment Test Score ≥ 10) with severe to very severe airflow limitation (forced expiratory volume in one second (FEV1) < 50% predicted) and one or more moderate-to-severe COPD exacerbations in the last 12 months. Trial medications differed amongst studies. The duration of follow-up was 52 weeks in three studies and 24 weeks in one study. We assessed the risk of selection, performance, and detection bias to be low in the included studies; one study was at high risk of attrition bias, and one study was at high risk of reporting bias. Triple therapy may reduce rates of moderate-to-severe COPD exacerbations compared to combination LABA/LAMA inhalers (rate ratio (RR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; n = 15,397; low-certainty evidence). Subgroup analysis stratifying by blood eosinophil counts showed there may be a greater reduction in rate of moderate-to-severe COPD exacerbations with triple therapy in participants with high-eosinophils (RR 0.67, 95% CI 0.60 to 0.75) compared to low-eosinophils (RR 0.87, 95% CI 0.81 to 0.93) (test for subgroup differences: P < 0.01) (high/low cut-offs: 150 eosinophils/µL in three studies; 200 eosinophils/µL in one study). However, moderate-to-substantial heterogeneity was observed in both high- and low-eosinophil subgroups. These subgroup analyses are observational by nature and thus results should be interpreted with caution. Triple therapy may be associated with reduced rates of severe COPD exacerbations (RR 0.75, 95% CI 0.67 to 0.84; n = 14,131; low-certainty evidence). Triple therapy improved health-related quality of life assessed using the St George's Respiratory Questionnaire (SGRQ) by the minimal clinically important difference (MCID) threshold (4-point decrease) (35.3% versus 42.4%, odds ratio (OR) 1.35, 95% CI 1.26 to 1.45; n = 14,070; high-certainty evidence). Triple therapy may result in fewer symptoms measured using the Transition Dyspnoea Index (TDI) (OR 1.33, 95% CI 1.13 to 1.57; n = 3044; moderate-certainty evidence) and improved lung function as measured by change in trough FEV1 (mean difference 38.68 mL, 95% CI 22.58 to 54.77; n = 11,352; low-certainty evidence). However, these benefits fell below MCID thresholds for TDI (1-unit decrease) and trough FEV1 (100 mL), respectively. Triple therapy is probably associated with a higher risk of pneumonia as a serious adverse event compared to combination LABA/LAMA inhalers (3.3% versus 1.9%, OR 1.74, 95% CI 1.39 to 2.18; n = 15,412; moderate-certainty evidence). In contrast, all-cause serious adverse events may be similar between groups (19.7% versus 19.7%, OR 0.95, 95% CI 0.87 to 1.03; n = 15,412; low-certainty evidence). All-cause mortality may be lower with triple therapy (1.4% versus 2.0%, OR 0.70, 95% CI 0.54 to 0.90; n = 15,397; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that triple therapy may reduce rates of COPD exacerbations (low-certainty evidence) and results in an improvement in health-related quality of life (high-certainty evidence) compared to combination LABA/LAMA inhalers, but probably confers an increased pneumonia risk as a serious adverse event (moderate-certainty evidence). Triple therapy probably improves respiratory symptoms and may improve lung function (moderate- and low-certainty evidence, respectively); however, these benefits do not appear to be clinically significant. Triple therapy may reduce the risk of all-cause mortality compared to combination LABA/LAMA inhalers (low-certainty evidence). The certainty of the evidence was downgraded most frequently for inconsistency or indirectness. Across the four included studies, there were important differences in inclusion criteria, trial medications, and duration of follow-up. Investigation of heterogeneity was limited due to the small number of included studies. We found limited data on the effects of triple therapy compared to combination LABA/LAMA inhalers in patients with mild-moderate COPD and those without a recent exacerbation history.

Diferente duración del tratamiento con corticosteroides para las exacerbaciones de la enfermedad pulmonar obstructiva crónica / Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease

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Exercise for reducing falls in people living with and beyond cancer.

BACKGROUND: Current treatment modalities for cancer have been successful in achieving improved survivorship; however, they come with a number of long-term adverse effects. Accidental falls are a common and clinically significant adverse event in people living with and beyond cancer and rates are higher than in the rest of the population. OBJECTIVES: To assess the effects of prescribed or provided exercise for reducing accidental falls, and falls risk factors of strength, flexibility and balance, in people living with and beyond cancer. SEARCH METHODS: We searched the following electronic databases from inception to 10 July 2018, with no restrictions: CENTRAL, MEDLINE, Embase, and seven other databases. We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) for ongoing trials, and reference lists of reviews and retrieved articles for additional studies. SELECTION CRITERIA: We included all randomised controlled trials investigating exercise interventions versus no treatment, usual care or non-exercise interventions on falls incidence or falls risk factors in adults living with and beyond cancer (18 years of age or older at diagnosis). We excluded cross-over studies and studies in acute or inpatient hospice care. DATA COLLECTION AND ANALYSIS: At least two review authors independently completed data extraction for included papers. We used Covidence software to manage screening, data collection and extraction. We assessed evidence using GRADE and presented results in a 'Summary of findings' table. MAIN RESULTS: Eleven studies (835 participants) compared exercise to usual care. No studies compared exercise with no treatment or non-exercise interventions. The quality of the evidence was very low for the primary outcome rates of falls, and very low to low for the secondary outcomes. We downgraded the evidence due to study limitations (risk of bias), and issues of imprecision due to small sample sizes, inconsistency and indirectness. All studies were at high risk of bias for blinding of participants and personnel due to inability to blind participants to an exercise intervention. Risk of bias was generally low or unclear for other categories.There was generally little information on the important outcomes comparing exercise to usual care.Rates of falls and number of fallers: one study (223 participants) measured accidental falls, but reported neither the rate of falls or the number of fallers; there was no difference in the number of falls between exercise and usual care (very low-quality evidence).Strength: 10 studies (813 participants) reported on strength outcomes. Two analyses favoured exercise over usual care: quadriceps strength (2 studies, 72 participants; mean difference (MD) 8.99 kg, 95% confidence interval (CI) 1.29 to 16.70; low-quality evidence), and leg press (4 studies, 388 participants; MD 21.1 kg, 95% CI 8.47 to 33.74; low-quality evidence). In one analysis of the Sit-to-Stand Test, there was no difference between exercise and usual care (4 studies, 214 participants; standardised mean difference (SMD) -0.45, 95% CI -1.05 to 0.14; very low-quality evidence).Flexibility: one study (21 participants) reported on flexibility for Sit-and-Reach Distance (MD 2.05 cm, 95% CI 0.59 to 3.51; very low-quality evidence).Balance: five studies (350 participants) measured three different balance outcomes. Two analyses favoured exercise over usual care: postural balance (4 studies, 127 participants; standardised mean difference (SMD) 0.44, 95% CI 0.08 to 0.79; very low-quality evidence), and Backward Walk Test (2 studies, 280 participants; SMD -0.24, 95% CI -0.48 to -0.01; low-quality evidence). There was no difference between exercise and usual care for the Timed Up-and-Go Test (1 study, 15 participants; MD -0.35 seconds, 95% CI -1.47 to 0.77; low-quality evidence).Number of people sustaining a fall-related fracture: the quality of the evidence for exercise reducing fall-related fractures was very low.Adverse events: a single study (223 participants) noted some temporary muscle soreness on initiation of exercise or when there was an increase in the weight lifted. As no occurrence data were reported, we could not assess this variable further. No studies reported musculoskeletal injury. Analysis indicated that there was very low-quality evidence that exercise did not increase fatigue. AUTHORS' CONCLUSIONS: There is a paucity of evidence for exercise training to reduce fall rates in people living with and beyond cancer. Exercise training may improve strength, flexibility and balance for people in this population, but the evidence is very low quality.

Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Current guidelines recommend that patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) should be treated with systemic corticosteroid for seven to 14 days. Intermittent systemic corticosteroid use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could reduce adverse effects. OBJECTIVES: To compare the efficacy of short-duration (seven or fewer days) and conventional longer-duration (longer than seven days) systemic corticosteroid treatment of adults with acute exacerbations of COPD. SEARCH METHODS: Searches were carried out using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials) and ongoing trials registers up to March 2017. SELECTION CRITERIA: Randomised controlled trials comparing different durations of systemic corticosteroid defined as short (i.e. seven or fewer days) or longer (i.e. longer than seven days). Other interventions-bronchodilators and antibiotics-were standardised. Studies with participants requiring assisted ventilation were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: Eight studies with 582 participants met the inclusion criteria, of which five studies conducted in hospitals with 519 participants (range 28 to 296) contributed to the meta-analysis. Mean ages of study participants were 65 to 73 years, the proportion of male participants varied (58% to 84%) and COPD was classified as severe or very severe. Corticosteroid treatment was given at equivalent daily doses for three to seven days for short-duration treatment and for 10 to 15 days for longer-duration treatment. Five studies administered oral prednisolone (30 mg in four, tapered in one), and two studies provided intravenous corticosteroid treatment. Studies contributing to the meta-analysis were at low risk of selection, performance, detection and attrition bias. In four studies we did not find a difference in risk of treatment failure between short-duration and longer-duration systemic corticosteroid treatment (n = 457; odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46)), which was equivalent to 22 fewer per 1000 for short-duration treatment (95% CI 51 fewer to 34 more). No difference in risk of relapse (a new event) was observed between short-duration and longer-duration systemic corticosteroid treatment (n = 457; OR 1.04, 95% CI 0.70 to 1.56), which was equivalent to nine fewer per 1000 for short-duration treatment (95% CI 68 fewer to 100 more). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non-inferiority and compared five days versus 14 days of systemic corticosteroid treatment (n = 311; hazard ratio 0.95, 95% CI 0.66 to 1.37). In five studies no difference in the likelihood of an adverse event was found between short-duration and longer-duration systemic corticosteroid treatment (n = 503; OR 0.89, 95% CI 0.46 to 1.69, or nine fewer per 1000 (95% CI 44 fewer to 51 more)). Length of hospital stay (n = 421; mean difference (MD) -0.61 days, 95% CI -1.51 to 0.28) and lung function at the end of treatment (n = 185; MD FEV1 -0.04 L; 95% CI -0.19 to 0.10) did not differ between short-duration and longer-duration treatment. AUTHORS' CONCLUSIONS: Information from a new large study has increased our confidence that five days of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 days) courses. We graded most available evidence as moderate in quality because of imprecision; further research may have an important impact on our confidence in the estimates of effect or may change the estimates. The studies in this review did not include people with mild or moderate COPD; further studies comparing short-duration systemic corticosteroid versus conventional longer-duration systemic corticosteroid for treatment of adults with acute exacerbations of COPD are required.

Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are at increased risk of pneumococcal disease, especially pneumonia, as well as acute exacerbations with associated morbidity and healthcare costs. OBJECTIVES: To determine the efficacy of injectable pneumococcal vaccination for preventing pneumonia in persons with COPD. SEARCH METHODS: We searched the Cochrane Airways COPD Trials Register and the databases CENTRAL, MEDLINE and Embase, using prespecified terms. Searches are current to November 2016. SELECTION CRITERIA: We included randomised controlled trials (RCT) comparing injectable pneumococcal polysaccharide vaccine (PPV) or pneumococcal conjugated vaccine (PCV) versus a control or alternative vaccine type in people with COPD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. For meta-analyses, we subgrouped studies by vaccine type. MAIN RESULTS: For this update, we added five studies (606 participants), meaning that the review now includes a total of 12 RCTs involving 2171 participants with COPD. Average age of participants was 66 years, male participants accounted for 67% and mean forced expiratory volume in one second (FEV1) was 1.2 L (five studies), 54% predicted (four studies). We assessed risks of selection, attrition and reporting bias as low, and risks of performance and detection bias as moderate.Compared with control, the vaccine group had a lower likelihood of developing community-acquired pneumonia (CAP) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.43 to 0.89; six studies, n = 1372; GRADE: moderate), but findings did not differ specifically for pneumococcal pneumonia (Peto OR 0.26, 95% CI 0.05 to 1.31; three studies, n = 1158; GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) (preventing one episode of CAP) was 21 (95% CI 15 to 74). Mortality from cardiorespiratory causes did not differ between vaccine and control groups (OR 1.07, 95% CI 0.69 to 1.66; three studies, n = 888; GRADE: moderate), nor did all-cause mortality differ (OR 1.00, 95% CI 0.72 to 1.40; five studies, n = 1053; GRADE: moderate). The likelihood of hospital admission for any cause, or for cardiorespiratory causes, did not differ between vaccine and control groups. Vaccination significantly reduced the likelihood of a COPD exacerbation (OR 0.60, 95% CI 0.39 to 0.93; four studies, n = 446; GRADE: moderate). The NNTB to prevent a patient from experiencing an acute exacerbation was 8 (95% CI 5 to 58). Only one study (n = 181) compared the efficacy of different vaccine types - 23-valent PPV versus 7-valent PCV - and reported no differences for CAP, all-cause mortality, hospital admission or likelihood of a COPD exacerbation, but investigators described a greater likelihood of some mild adverse effects of vaccination with PPV-23. AUTHORS' CONCLUSIONS: Injectable polyvalent pneumococcal vaccination provides significant protection against community-acquired pneumonia, although no evidence indicates that vaccination reduced the risk of confirmed pneumococcal pneumonia, which was a relatively rare event. Vaccination reduced the likelihood of a COPD exacerbation, and moderate-quality evidence suggests the benefits of pneumococcal vaccination in people with COPD. Evidence was insufficient for comparison of different pneumococcal vaccine types.

Action plans with brief patient education for exacerbations in chronic obstructive pulmonary disease.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a major driver of decline in health status and impose high costs on healthcare systems. Action plans offer a form of self-management that can be delivered in the outpatient setting to help individuals recognise and initiate early treatment for exacerbations, thereby reducing their impact. OBJECTIVES: To compare effects of an action plan for COPD exacerbations provided with a single short patient education component and without a comprehensive self-management programme versus usual care. Primary outcomes were healthcare utilisation, mortality and medication use. Secondary outcomes were health-related quality of life, psychological morbidity, lung function and cost-effectiveness. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register along with CENTRAL, MEDLINE, Embase and clinical trials registers. Searches are current to November 2015. We handsearched bibliographic lists and contacted study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCT) and quasi-RCTs comparing use of an action plan versus usual care for patients with a clinical diagnosis of COPD. We permitted inclusion of a single short education component that would allow individualisation of action plans according to management needs and symptoms of people with COPD, as well as ongoing support directed at use of the action plan. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. For meta-analyses, we subgrouped studies via phone call follow-up directed at facilitating use of the action plan. MAIN RESULTS: This updated review includes two additional studies (and 976 additional participants), for a total of seven parallel-group RCTs and 1550 participants, 66% of whom were male. Participants' mean age was 68 years and was similar among studies. Airflow obstruction was moderately severe in three studies and severe in four studies; mean post bronchodilator forced expiratory volume in one second (FEV1) was 54% predicted, and 27% of participants were current smokers. Four studies prepared individualised action plans, one study an oral plan and two studies standard written action plans. All studies provided short educational input on COPD, and two studies supplied ongoing support for action plan use. Follow-up was 12 months in four studies and six months in three studies.When compared with usual care, an action plan with phone call follow-up significantly reduced the combined rate of hospitalisations and emergency department (ED) visits for COPD over 12 months in one study with 743 participants (rate ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.79; high-quality evidence), but the rate of hospitalisations alone in this study failed to achieve statistical significance (RR 0.69, 95% CI 0.47 to 1.01; moderate-quality evidence). Over 12 months, action plans significantly decreased the likelihood of hospital admission (odds ratio (OR) 0.69, 95% CI 0.49 to 0.97; n = 897; two RCTs; moderate-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) 19 (11 to 201)) and the likelihood of an ED visit (OR 0.55, 95% CI 0.38 to 0.78; n = 897; two RCTs; moderate-quality evidence; NNTB over 12 months 12 (9 to 26)) compared with usual care.Results showed no significant difference in all-cause mortality during 12 months (OR 0.88, 95% CI 0.59 to 1.31; n = 1134; four RCTs; moderate-quality evidence due to wide confidence interval). Over 12 months, use of oral corticosteroids was increased with action plans compared with usual care (mean difference (MD) 0.74 courses, 95% CI 0.12 to 1.35; n = 200; two RCTs; moderate-quality evidence), and the cumulative prednisolone dose was significantly higher (MD 779.0 mg, 95% CI 533.2 to 10248; n = 743; one RCT; high-quality evidence). Use of antibiotics was greater in the intervention group than in the usual care group (subgrouped by phone call follow-up) over 12 months (MD 2.3 courses, 95% CI 1.8 to 2.7; n = 943; three RCTs; moderate-quality evidence).Subgroup analysis by ongoing support for action plan use was limited; review authors noted no subgroup differences in the likelihood of hospital admission or ED visits or all-cause mortality over 12 months. Antibiotic use over 12 months showed a significant difference between subgroups in studies without and with ongoing support.Overall quality of life score on St George's Respiratory Questionnaire (SGRQ) showed a small improvement with action plans compared with usual care over 12 months (MD -2.8, 95% CI -0.8 to -4.8; n = 1009; three RCTs; moderate-quality evidence). Low-quality evidence showed no benefit for psychological morbidity as measured with the Hospital Anxiety and Depression Scale (HADS). AUTHORS' CONCLUSIONS: Use of COPD exacerbation action plans with a single short educational component along with ongoing support directed at use of the action plan, but without a comprehensive self-management programme, reduces in-hospital healthcare utilisation and increases treatment of COPD exacerbations with corticosteroids and antibiotics. Use of COPD action plans in this context is unlikely to increase or decrease mortality. Whether additional benefit is derived from periodic ongoing support directed at use of an action plan cannot be determined from the results of this review.

Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease.

BACKGROUND: Management of chronic obstructive pulmonary disease (COPD) commonly involves long-acting bronchodilators including beta-agonists (LABA) and muscarinic antagonists (LAMA). In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used. LABA and LAMA bronchodilators are now available in single combination inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers remains unclear. OBJECTIVES: To assess the effect of adding an inhaled corticosteroid (ICS) to combination long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) inhalers for the treatment of stable COPD. SEARCH METHODS: We carried out searches using the Cochrane Airways Group Specialised Register of Trials (searched 20 September 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 15 December 2015) and MEDLINE (searched 15 December 2015). We also searched ClinicalTrials.gov, World Health Organisation (WHO) trials portal and pharmaceutical company clinical trials' databases up to 7 Janurary 2016. SELECTION CRITERIA: We included parallel-group, randomised controlled trials (RCTs) of three weeks' duration or longer which compared treatment of stable COPD with ICS in addition to combination LABA/LAMA inhalers against combination LABA/LAMA inhalers alone. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified a total of 586 records in our search. Following removal of duplicates, 386 abstracts were assessed for inclusion. Six studies were identified as potentially relevant; however, all failed to meet the inclusion criteria on full-text assessment or after contacting the corresponding author to clarify study characteristics. AUTHORS' CONCLUSIONS: There are currently no studies published assessing the effect of ICS in addition to combination LABA/LAMA inhalers for the treatment of stable COPD. As combination LABA/LAMA inhalers are now widely available, there is a need for well-designed RCTs to investigate whether ICS provides any added therapeutic benefit.

Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Current guidelines recommend that acute exacerbations of chronic obstructive pulmonary disease (COPD) be treated with systemic corticosteroids (SCs) for seven to 14 days. Intermittent SC use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could therefore reduce the risk of adverse effects. OBJECTIVES: To compare the efficacy of short-duration (seven days or fewer) and longer-duration (more than seven days) SC treatment of acute COPD exacerbations in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Register of Trials (to April 2011) Cochrane Central Register of Controlled Trials (to April 2011), MEDLINE (from 1950 to October 2010), EMBASE (from 1980 to October 2010) and the reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing different durations of SC (seven days or fewer or more than seven days). Other interventions, e.g. bronchodilators and antibiotics, were standardised; studies in other lung diseases were excluded, unless data on participants with COPD were available. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data that were pooled them using Review Manager 5. We sought missing data from authors of studies published as abstracts only. MAIN RESULTS: We identified seven studies including 288 participants; two studies were fully published and five were published as abstracts. We obtained data for two studies published as abstracts from authors; these two abstracts and the two full papers contributed to meta-analysis. No study specified COPD diagnostic criteria and only one specified exacerbation criteria. Short course treatment varied between three and seven days and longer duration 10 to 15 days, at equivalent daily doses of corticosteroids; five studies used oral prednisolone (dose 30 mg, four studies, one tapered dose) and two studies used intravenous corticosteroid treatment. Mean ages of participants ranged from 64 to 73 years. We assessed the risk of allocation and blinding bias as low for these studies. PRIMARY OUTCOMES: risk of treatment failure did not differ significantly by treatment duration, but the confidence interval (CI) was too wide to conclude equivalence (Peto odds ratio (OR) 0.82; 95% CI 0.24 to 2.79) (three studies, n = 146). Forced expiratory volume in 1 second (FEV1) did not differ significantly when measured up to seven days (mean difference (MD) -0.07 L; 95% CI -0.19 to 0.05) or after seven days (MD -0.02 L;95% CI -0.10 to 0.06) in four studies (n = 187). The likelihood of an adverse event (four studies, n = 192) did not differ significantly by treatment duration, but again the CI was wide (OR 0.58, 95% CI 0.14 to 2.40). AUTHORS' CONCLUSIONS: We based assessment of the efficacy of short (seven days or less) compared to longer duration (more than seven days) systemic corticosteroid therapy for acute exacerbations of COPD in this review on four of the seven included studies for which data were available. Two studies were fully published and two were published as conference abstracts but trialists were able to supply data requested for the review.The finding in this review that there is no significant increase in treatment failure with shorter systemic corticosteroid treatment for seven days or less for acute exacerbations of COPD, does not give conclusive evidence to recommend change in clinical practice due to a wide confidence interval around the estimate of effect. The four studies which contributed to the meta-analysis were of relatively low quality and five of the seven studies were not published as full articles. Thus there are insufficient data to allow firm conclusions concerning the optimal duration of corticosteroid therapy of acute exacerbations of COPD to be drawn.

Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease.

BACKGROUND: As chronic obstructive pulmonary disease (COPD) progresses, exacerbations can occur with increasing frequency. One goal of therapy is to prevent these exacerbations, thereby reducing morbidity and associated healthcare costs. Pneumococcal vaccinations are one strategy for reducing the risk of infective exacerbations. OBJECTIVES: To determine the safety and efficacy of pneumococcal vaccination in COPD. The primary outcomes assessed were episodes of pneumonia and acute exacerbations. Secondary outcomes of interest included hospital admissions, adverse events related to treatment, disability, change in lung function, mortality, and cost effectiveness. SEARCH STRATEGY: We searched the Cochrane Airways Group COPD trials register and the databases CENTRAL, MEDLINE and EMBASE using pre-specified terms. The latest searches were performed in March 2010. SELECTION CRITERIA: Randomised controlled trials assessing the effects of injectable pneumococcal vaccine in people with COPD were included. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and three review authors independently assessed trial quality. MAIN RESULTS: Seven studies were identified that met the inclusion criteria for this review and were included in the 2010 review update. Two older trials used a 14-valent vaccine and five more recent trials used a 23-valent injectable vaccine.In six studies involving 1372 people, the reduction in likelihood of developing pneumonia with pneumococcal vaccination compared to control did not achieve statistical significance, the odds ratio (OR) was 0.72 (95% confidence interval (CI) 0.51 to 1.01), with moderate heterogeneity present between studies. The reduction in likelihood of acute exacerbations of COPD from two studies involving 216 people was not statistically significant (Peto OR 0.58; 95% CI 0.30 to 1.13).Of the secondary outcomes for which data were available there was no statistically significant effect for reduction in hospital admissions (two studies) or emergency department visits (one study). There was no significant reduction in pooled results from three studies involving 888 people for odds of all-cause mortality for periods up to 48 months post-vaccination (OR 0.94; 95% CI 0.67 to 1.33), or for death from cardiorespiratory causes (OR 1.07; 95% CI 0.69 to 1.66). AUTHORS' CONCLUSIONS: The limited evidence from randomised controlled trials (RCTs) included in this review suggests that, while it is possible that injectable polyvalent pneumococcal vaccines may provide some protection against morbidity in persons with COPD, no significant effect on any of the outcomes was shown. Further large RCTs in this population would be needed to confirm effectiveness of the vaccine suggested by results from longitudinal studies.

Action plans with limited patient education only for exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterised by exacerbations, usually infective in origin, which affect symptoms and quality of life. Action plans may help individuals recognise a deterioration in their symptoms and initiate changes to treatment early, thereby reducing the impact of the exacerbation. OBJECTIVES: To assess the efficacy of action plans in the management of COPD. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register (7 July 2009), CENTRAL, MEDLINE , CINAHL and ongoing trials registers (last searched July 2009). SELECTION CRITERIA: Randomised controlled trials of an individual action plan with minimal or no self management education, compared to control in patients with COPD were included. Studies in asthma and in multi-faceted interventions in which an action plan was combined with other elements such as education programme, exercise programme or outreach visits were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We contacted investigators for additional information when necessary. MAIN RESULTS: Five studies enrolling 574 participants with moderate or severe COPD, with follow-up from six to twelve months, were included. There was no evidence that action plans reduced health care utilisation; assessed by hospital admission (mean difference (MD) 0.23; 95% CI -0.03 to 0.49), emergency department visits (MD 0.37; 95% CI -0.50 to 1.24) or GP visits (MD 0.53; -0.45, 1.50). Use of action plans was associated with increased initiation of treatment for acute exacerbations. Oral corticosteroid use was increased over 12 months (MD 0.74; 95% CI 0.14 to 1.35) with a significant increase in odds of being treated with antibiotics over 12 months (odds ratio 1.65; 95% CI 1.01 to 2.69). Self management knowledge and intention to initiate appropriate actions were improved in one study; recognition of a severe exacerbation (MD 2.50; 95% CI 1.04 to 3.96) and self initiating action in a severe exacerbation (MD 1.50; 95% CI 0.62 to 2.38). Health-related quality of life data were limited. AUTHORS' CONCLUSIONS: There is evidence that action plans with limited COPD education aid recognition of, and response to, an exacerbation with initiation of antibiotics and corticosteroids. Only one study measured patients' self health appropriate behaviour (decision making and taking action). There is no evidence of reduced healthcare resources utilisation or improved health-related quality of life.The practice of giving patients an action plan and limited self-management education for the management of COPD exacerbations, without a multi-faceted self-management program or ongoing case management cannot be recommended as the standard of care in COPD.

Erythropoiesis-stimulating agents for anaemia in chronic heart failure patients.

BACKGROUND: Chronic heart failure (CHF) is a leading cause of morbidity and mortality worldwide. Anaemia is a common (12-55%) co-morbid condition and is associated with worsening symptoms and increased mortality. Anaemia is treatable and can be targeted in the treatment of patients with CHF. Erythropoiesis-stimulating agents (ESA), supplemented by iron therapy, are used to treat anaemia in chronic kidney disease and cancer, however safety concerns have been raised in these patients. The clinical benefit and safety of these agents in CHF remains unclear. OBJECTIVES: To assess the benefits and risks of ESA for CHF patients with anaemia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to October 2008), EMBASE (1980 to October 2008) and reference lists of articles. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of any ESA, with or without iron therapy, in CHF patients were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed study quality and extracted data. Original authors were contacted for additional information. The outcomes of interest were: exercise tolerance, haemoglobin level, New York Heart Association (NYHA) functional class, quality of life, left-ventricular ejection fraction, B-type natriuretic peptide, CHF-related hospitalisations, all-cause mortality and adverse effects. Risk ratios (RR) were calculated for dichotomous data and weighted mean difference (WMD) for continuous data. MAIN RESULTS: Eleven studies (794 participants) were included. Overall quality of studies was moderate with nine studies being placebo-controlled but only five double-blinded. Compared to control, ESA treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2 to 188.4, p=0.04) and 6-minute walk distance by 69.3 metres (95% CI 17.0 to 121.7, p=0.009). Benefit was also noted in terms of peak VO2 (+2.29 mL/kg/min, p=0.007), NYHA class (-0.73, p<0.001), ejection fraction (+5.8%, p<0.001), B-type natriuretic peptide (-226.99 pg/mL, p<0.001) and quality-of-life indicators, with a mean increase in haemoglobin of 1.98 g/dL (p<0.0001). There was also a significantly lower rate of heart failure related hospitalisations (RR 0.62, 95% CI 0.44 to 0.87) and lower all-cause mortality (RR 0.61, 95% CI 0.37 to 0.99). No increase in adverse events with ESA therapy was observed, however studies were of small sample sizes and limited duration. AUTHORS' CONCLUSIONS: Meta-analysis of small RCTs suggests that ESA treatment in patients with symptomatic CHF and mild anaemia (haemoglobin more than 10g/dL) can improve anaemia and exercise tolerance, reduce symptoms and have benefits on clinical outcomes. Confirmation requires well-designed studies with careful attention to dose, haemoglobin treatment target and associated iron therapy.

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: COPD is a common condition, mainly related to smoking. Acute exacerbations of COPD, usually related to superimposed infection, occur commonly and systemic corticosteroids are widely used in their management in combination with other treatments including antibiotics, oxygen supplementation and bronchodilators. OBJECTIVES: To determine the efficacy of corticosteroids, administered either parenterally or orally, on the outcomes of acute exacerbations of COPD. SEARCH STRATEGY: Searches were carried out using the Cochrane Airways Group COPD RCT register with additional studies sought in the bibliographies of randomised controlled trials and review articles. Authors of identified randomised controlled trials were contacted for other published and unpublished studies. The last search was carried out in August 2008. SELECTION CRITERIA: Randomised controlled trials comparing corticosteroids, administered either parenterally or orally, with appropriate placebo control. Other interventions e.g. bronchodilators and antibiotics were standardised. Clinical studies of acute asthma were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Data measured but not reported were sought from authors of included studies. Trials were combined using Review Manager for analyses. MAIN RESULTS: Eleven studies (n=1081) fulfilled the inclusion criteria and 10 studies contributed data for analyses (n=1051). There were significantly fewer treatment failures within thirty days in patients given corticosteroid treatment, Odds Ratio (OR) 0.50; 95% confidence interval (CI) 0.36 to 0.69 and Hazard Ratio 0.78; 95% CI 0.63 to 0.97. It would have been necessary to treat 10 patients (95%CI 7 to 16) with corticosteroids to avoid one treatment failure in this time period. Duration of hospitalisation was significantly shorter with corticosteroid treatment, mean difference -1.22 days; 95% CI -2.26 to -0.18. For FEV1 there were significant treatment benefits with mean differences at the early time point (to 72 hours), 140 ml; 95% CI 90 to 190 ml and at end of treatment (up to 15 days) 80 ml; 95% confidence interval 10 to 160. There was a significant improvement in breathlessness and blood gases at both time points. There was no significant effect on mortality but an increased likelihood of an adverse event associated with corticosteroid treatment, OR 2.33; 95% CI 1.60 to 3.40. Overall one extra adverse effect occurred for every 5 people treated (95% CI 4 to 9). The risk of hyperglycaemia was significantly increased, OR 4.95; 95% CI 2.47 to 9.91. AUTHORS' CONCLUSIONS: Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment and shortens hospital stay. It increases the rate of improvement in lung function and dyspnoea and the improvement continues during treatment, but there is a significantly increase in the risk of an adverse drug event occurring. The optimal dose and length of treatment regime needs to be better defined.

Anti-IgE and chemotherapy: a critical appraisal of treatment options for severe asthma.

In this narrative review the scientific rationale for the development of a therapeutic modality for asthma based on decreasing the circulating and cell-bound levels of immunoglobulin-E (IgE) is outlined. The one drug that has so far entered clinical practice to do this is a humanised monoclonal antibody to the Fc portion of the IgE molecule, omalizumab. It is highly effective in reducing IgE blood levels and its established mode of delivery is by subcutaneous injection. The clinical trial development of omalizumab is reviewed and the published data and claims for its efficacy and role in clinical practice is critically appraised. The target group of omalizumab has become focused on severe asthmatics who are still symptomatic after being administered with high-dose inhaled corticosteroids plus long-acting beta-agonists. The strongest evidence for effect is in those with frequent severe exacerbations.