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Biomedical subjects

C J Cates

Publications and source records attributed to C J Cates.

At least 19 recordsLinked to original sources

PubMed2006

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 in COPD is to try and prevent these exacerbations, thereby reducing disease morbidity and associated healthcare costs. Pneumococcal vaccinations are considered to be one strategy for reducing the risk of infective exacerbations. OBJECTIVES: To determine the safety and efficacy of pneumococcal vaccination in COPD. The primary outcome assessed was acute exacerbations. Secondary outcomes of interest included episodes of pneumonia, 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 using pre-specified terms. We also conducted additional handsearches of conference abstracts. The last round of searches were performed in April 2006. SELECTION CRITERIA: Only 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: Although 10 studies cited in 11 publications were identified that met the inclusion criteria for this review, only four of these provided data on participants with COPD. The studies which did provide data for this review consisted of two trials using a 14-valent vaccine, and two using a 23-valent injectable vaccine. Data for the primary outcome, acute exacerbation of COPD, was available from only one of the four studies. The odds ratio of 1.43 (95% confidence interval (CI) 0.31 to 6.69) between interventions was not statistically significant. Of the secondary outcomes for which data were available and could be extracted, none reached statistical significance. Three studies provided dichotomous data for persons who developed pneumonia (OR 0.89, 95% CI 0.58 to 1.37, n = 748). Rates of hospital admissions and emergency department visits came from a single study. There was no significant reduction in the odds of all-cause mortality 1 to 48 months post-vaccination (Peto odds ratio 0.94, 95% CI 0.67 to 1.33, n = 888), or for death from cardiorespiratory causes (OR 1.07, 95% CI 0.69 to 1.66). AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials that injectable pneumococcal vaccination in persons with COPD has a significant impact on morbidity or mortality. Further large randomised controlled trials would be needed to ascertain if the small benefits suggested by individual studies are real.

Humans↗

PubMed2006

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.

Adrenal Cortex Hormones↗

PubMed2006

Continuous positive airways pressure for obstructive sleep apnoea in adults.

BACKGROUND: Obstructive sleep apnoea is the periodic reduction (hypopnoea) or cessation (apnoea) of breathing due to narrowing or occlusion of the upper airway during sleep. The main symptom is daytime sleepiness and it has been suggested it is linked to premature death, hypertension, ischaemic heart disease, stroke and road traffic accidents. OBJECTIVES: The main treatment for sleep apnoea is with the use of continuous positive airways pressure (CPAP), which requires a flow generator and mask. These are used at night to prevent apnoea, hypoxia and sleep disturbance. The objective was to assess the effects of CPAP in the treatment of obstructive sleep apnoea in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register and reference lists of articles. We consulted experts in the field. Searches were current to July 2005. SELECTION CRITERIA: We included randomised trials comparing nocturnal CPAP with an inactive control or oral appliances in adults with obstructive sleep apnoea (an apnoea and hypopnoea index greater than five per hour). Trials had a minimum intervention period of two weeks. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two review authors extracted data independently. Study authors were contacted for missing information. Parallel and crossover group trials were analysed separately. MAIN RESULTS: Thirty-six trials involving 1718 people met the inclusion criteria. Study quality was mixed. Compared with control, CPAP showed significant improvements in certain objective and subjective sleepiness, measures of quality of life and cognitive function (parallel-group studies: Epworth sleepiness scale (ESS) -3.83 units, 95% CI -4.57 to -3.09; crossover studies: ESS -1.84 units, 95% CI -2.57 to -1.11). Twenty-four hour systolic and diastolic blood pressures were lower with CPAP compared with control (parallel-group trials). Compared with oral appliances, CPAP significantly reduced the apnoea and hypopnoea index (crossover studies: -7.97 events/hr, 95% CI -9.56 to -6.38) and improved sleep efficiency (crossover studies: 2.31%, 95% CI 0.02 to 4.6) and minimum oxygen saturation (4.14%, 95% CI 3.25 to 5.03). Responders to both treatments expressed a strong preference for the oral appliance. However, participants were more likely to withdraw on OA than on CPAP therapy. AUTHORS' CONCLUSIONS: CPAP is effective in reducing symptoms of sleepiness and improving quality of life measures in people with moderate and severe obstructive sleep apnoea (OSA). It is more effective than oral appliances in reducing respiratory disturbances in these people but subjective outcomes are more equivocal. Certain people tend to prefer oral appliances to CPAP where both are effective. This could be because they offer a more convenient way of controlling OSA. Short-term data indicate that CPAP leads to lower blood pressure than control. Long-term data are required for all outcomes in order to determine whether the initial benefits seen in short-term clinical trials persist.

Adult↗

PubMed2006

Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma.

BACKGROUND: In acute asthma inhaled beta2-agonists are often administered to relieve bronchospasm by wet nebulisation, but some have argued that metered-dose inhalers with a holding chamber (spacer) can be equally effective. Nebulisers require a power source and need regular maintenance, and are more expensive in the community setting. OBJECTIVES: To assess the effects of holding chambers (spacers) compared to nebulisers for the delivery of beta2-agonists for acute asthma. SEARCH STRATEGY: We last searched the Cochrane Airways Group trials register in January 2006 and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2005). SELECTION CRITERIA: Randomised trials in adults and children (from two years of age) with asthma, where spacer beta2-agonist delivery was compared with wet nebulisation. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied study inclusion criteria (one reviewer for the first version of the review), extracted the data and assessed trial quality. Missing data were obtained from the authors or estimated. Results are reported with 95% confidence intervals (CI). MAIN RESULTS: This review has been updated in January 2006 and four new trials have been added. 2066 children and 614 adults are now included in 25 trials from emergency room and community settings. In addition, six trials on in-patients with acute asthma (213 children and 28 adults) have been reviewed. Method of delivery of beta2-agonist did not appear to affect hospital admission rates. In adults, the relative risk of admission for spacer versus nebuliser was 0.97 (95% CI 0.63 to 1.49). The relative risk for children was 0.65 (95% CI: 0.4 to 1.06). In children, length of stay in the emergency department was significantly shorter when the spacer was used, with a mean difference of -0.47 hours (95% CI: -0.58 to -0.37). Length of stay in the emergency department for adults was similar for the two delivery methods. Peak flow and forced expiratory volume were also similar for the two delivery methods. Pulse rate was lower for spacer in children, mean difference -7.6% baseline (95% CI: -9.9 to -5.3% baseline). AUTHORS' CONCLUSIONS: Metered-dose inhalers with spacer produced outcomes that were at least equivalent to nebuliser delivery. Spacers may have some advantages compared to nebulisers for children with acute asthma.

Acute Disease↗

PubMed2006

Continuous positive airways pressure for obstructive sleep apnoea in adults.

BACKGROUND: Obstructive sleep apnoea is the periodic reduction (hypopnoea) or cessation (apnoea) of breathing due to narrowing or occlusion of the upper airway during sleep. The main symptom is daytime sleepiness and it has been suggested it is linked to premature death, hypertension, ischaemic heart disease, stroke and road traffic accidents. OBJECTIVES: The main treatment for sleep apnoea is with the use of continuous positive airways pressure (CPAP), which requires a flow generator and mask. These are used at night to prevent apnoea, hypoxia and sleep disturbance. The objective was to assess the effects of CPAP in the treatment of obstructive sleep apnoea in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register and reference lists of articles. We consulted experts in the field. Searches were current to July 2005. SELECTION CRITERIA: We included randomised trials comparing nocturnal CPAP with an inactive control or oral appliances in adults with obstructive sleep apnoea (an apnoea and hypopnoea index greater than five per hour). Trials had a minimum intervention period of two weeks. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two review authors extracted data independently. Study authors were contacted for missing information. Parallel and crossover group trials were analysed separately. MAIN RESULTS: Thirty-six trials involving 1718 people met the inclusion criteria. Study quality was mixed. Compared with control, CPAP showed significant improvements in objective and subjective sleepiness and several quality of life, cognitive function and depression measures (parallel-group studies: Epworth sleepiness scale (ESS) -3.83 units, 95% CI -4.57 to -3.09; crossover studies: ESS -1.84 units, 95% CI -2.57 to -1.11). Twenty-four hour systolic and diastolic blood pressures were lower with CPAP compared with control (parallel-group trials). Compared with oral appliances, CPAP significantly reduced the apnoea and hypopnoea index (crossover studies: -7.97 events/hr, 95% CI -9.56 to -6.38) and improved sleep efficiency (crossover studies: 2.31%, 95% CI 0.02 to 4.6) and minimum oxygen saturation (4.14%, 95% CI 3.25 to 5.03). Responders to both treatments expressed a strong preference for the oral appliance. However, participants were more likely to withdraw on OA than on CPAP therapy. AUTHORS' CONCLUSIONS: CPAP is effective in reducing symptoms of sleepiness and improving quality of life measures in people with moderate and severe obstructive sleep apnoea (OSA). It is more effective than oral appliances in reducing respiratory disturbances in these people but subjective outcomes are more equivocal. Certain people tend to prefer oral appliances to CPAP where both are effective. This could be because they offer a more convenient way of controlling OSA. Short-term data indicate that CPAP leads to lower blood pressure than in controls. Long-term data are required for all outcomes in order to determine whether the initial benefits seen in short-term clinical trials persist.

Adult↗

PubMed2006

Holding chambers versus nebulisers for inhaled steroids in chronic asthma.

BACKGROUND: Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear. OBJECTIVES: To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). Date of last search August 2005. SELECTION CRITERIA: Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1. MAIN RESULTS: Two studies were selected for inclusion (63 subjects), both concerned adults. An additional small study including 14 children was identified for the 2005 update. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery. AUTHORS' CONCLUSIONS: Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that still require further assessment. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Administration, Topical↗

PubMed2006

Influenza vaccine for patients with chronic obstructive pulmonary disease.

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective. OBJECTIVES: To evaluate the evidence from RCTs for a treatment effect of influenza vaccination in COPD subjects. Outcomes of interest were exacerbation rates, hospitalisations, mortality, lung function and adverse effects. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials, and reference lists of articles. References were also provided by a number of drug companies we contacted. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine in persons with COPD. Studies of people with asthma were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. All entries were double checked. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Eleven trials were included but only six of these were specifically performed in COPD patients. The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Inactivated vaccine in COPD patients resulted in a significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo (weighted mean difference (WMD) -0.37, 95% confidence interval -0.64 to -0.11, P = 0.006). This was due to the reduction in "late" exacerbations occurring after three or four weeks (WMD -0.39, 95% CI -0.61 to -0.18, P = 0.0004). In Howells 1961, the number of patients experiencing late exacerbations was also significantly less (odds ratio 0.13, 95% CI 0.04 to 0.45, P = 0.002). Both Howells 1961 and Wongsurakiat 2004 found that inactivated influenza vaccination reduced influenza -related respiratory infections (WMD 0.19, 95% CI 0.07 to 0.48, P = 0.0005). In both COPD patient and in elderly patients (only a minority of whom had COPD), there was a significant increase in the occurrence of local adverse reactions in vaccinees, but the effects were generally mild and transient. There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination. The studies are too small to have detected any effect on mortality. An updated search conducted in September 2001 did not yield any further studies. A search in 2003 yielded two further reports of the same eligible study Gorse 2003. A search in 2004 yielded two reports of the another eligible study Wongsurakiat 2004. The author informed us of another report of the same study Wongsurakiat 2004/2. AUTHORS' CONCLUSIONS: It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.

Aged↗

PubMed2005

Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults and children.

BACKGROUND: The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant. OBJECTIVES: To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of March 2005. SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity. MAIN RESULTS: Seven studies (1230 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event. AUTHORS' CONCLUSIONS: There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Administration, Inhalation↗

PubMed2005

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 beta2-agonists (LABA) agents may both be considered as add-on therapy to inhaled corticosteroids (ICS). OBJECTIVES: We compare the efficacy and safety profile of adding either daily LABA or LTRA in asthmatic patients with asthma who remained symptomatic on ICS. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL databases were searched for randomised controlled trials up to and including January 2004. 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 beta2-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: Twelve randomised controlled trials met the inclusion criteria; only eight trials including 5,895 patients, provided data in sufficient details to allow aggregation. All eight trials pertained to adults with moderate airway obstruction (% predicted FEV1 66-76%) at baseline. Montelukast (n=6) or Zafirlukast (n=2) was compared to Salmeterol (n=7) or Formoterol (n=1) 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%; 4 to 14), symptom-free days (6%; 2 to 11), rescue beta2-agonists (-0.4 puffs/day; -0.2 to -0.5), 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 (Relative Risk 0.84, 95% CI 0.74 to 0.96). 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 use of rescue beta2-agonists.

Adrenal Cortex Hormones↗

PubMed2004

Vaccines for preventing influenza in people with asthma.

BACKGROUND: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusion was not based on a systematic search of the literature. OBJECTIVES: Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the efficacy of influenza vaccination in children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and checked reference lists of articles. The last search was carried out in February 2003. SELECTION CRITERIA: Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. DATA COLLECTION AND ANALYSIS: Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Nine trials were initially included. Four of these trials were of high quality. Five further articles have been included in two updates (Bueving 2002; Castro 2001; Redding 2002; Reid 1998). The included studies covered a wide diversity of people, settings and types of influenza vaccination, but data from the more recent studies that used similar vaccines have been pooled. The pooled results of two trials involving 2306 people with asthma did not demonstrate a significant increase in asthma exacerbations in the two weeks following influenza vaccination (Risk Difference 0.00; 95% confidence interval -0.02 to 0.02). A recent study on 696 children with asthma did not demonstrate a significant reduction in influenza related asthma exacerbations (Risk Difference 0.01; 95% confidence interval -0.02 to 0.04). REVIEWERS' CONCLUSIONS: Evidence from recently published trials indicates that there is no significant increase in asthma exacerbations immediately after vaccination (at least with inactivated influenza vaccination); however, uncertainty remains about the degree of protection vaccination affords against asthma exacerbations that are related to influenza infection.

Adult↗

PubMed2004

Combined corticosteroid and long acting beta-agonist in one inhaler 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. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to placebo or the individual components, in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD) trials register. Date of last search April 2004. 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 either component preparation or placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The primary outcome was exacerbations. MAIN RESULTS: Six randomised trials with 4118 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were used. Combination treatment was more effective than placebo for mean exacerbation rates, quality of life and lung function. No trials were found comparing the combination of drugs in a single inhaler with the same drugs both given in separate inhalers. Exacerbations: Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments in one large study. There was no significant difference when budesonide/formoterol was compared with budesonide. Budesonide/formoterol was more effective than formoterol in reducing exacerbations (Rate ratio: 0.78 [0.68 to 0.90], two studies). A pooled analysis of both combination therapies indicated that exacerbations were less frequent when compared with either placebo or long-acting beta-agonist (versus placebo Rate ratio: 0.76 [0.68, 0.84], three studies, versus beta-agonist, Rate ratio: 0.85 [0.77, 0.95], three studies), but not when compared with steroid. The clinical impact of this effect depends on the frequency of exacerbations experienced by patients. One full exacerbation was prevented for every two to four years of treatment in the type of patients included in the trials. Quality of Life: There were conflicting findings in quality of life and symptoms when fluticasone/salmeterol was compared with inhaled steroids alone (three studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist in quality of life scores (three studies). Budesonide/formoterol improved symptoms when compared with budesonide but not with formoterol. There were conflicting findings in quality of life scores when budesonide/formoterol was compared with component inhaled corticosteroid or beta-agonist. These may be accounted for by different study design. Lung Function: Treatment with either combination led to small, significant differences in lung function compared with component steroid medication. Fluticasone/salmeterol led to small improvements in FEV1 compared with salmeterol, but budesonide/formoterol treatment did not increase FEV1 significantly when compared with formoterol. REVIEWERS' CONCLUSIONS: Compared with placebo, combination therapy led to clinically meaningful differences in quality of life, symptoms and exacerbations. However, there were conflicting results when the different combination therapies were compared with the mono-components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.

Adrenergic beta-Agonists↗

PubMed2003

Educational interventions for asthma in children.

BACKGROUND: Self-management education programs have been developed for children with asthma, but it is unclear whether such programs improve outcomes. OBJECTIVES: To determine the efficacy of asthma self-management education on health outcomes in children. SEARCH STRATEGY: Systematic search of the Cochrane Airways Group's and Cochrane Schizophrenia Group's Special Registers of Controlled Trials and hand searches of the reference lists of relevant review articles. SELECTION CRITERIA: Randomized and controlled clinical trials of asthma self-management education programs in children and adolescents aged 2 -18 years. DATA COLLECTION AND ANALYSIS: All studies were assessed independently by two reviewers. Disagreements were settled by consensus. Study authors were contacted for missing data or to verify methods. Subgroup analyses examined the impact of type and intensity of educational intervention, self-management strategy, trial type, asthma severity, adequacy of follow-up, and study quality. MAIN RESULTS: Of 45 trials identified, 32 studies involving 3706 patients were eligible. Asthma education programs were associated with moderate improvement in measures of airflow (standardized mean difference [SMD] 0.50, 95% confidence interval [CI] 0.25 to 0.75) and self-efficacy scales (SMD 0.36, 95% CI 0.15 to 0.57). Education programs were associated with modest reductions in days of school absence (SMD -0.14, 95% CI -0.23 to -0.04), days of restricted activity (SMD -0.29, 95% CI -0.49 to -0.08), and emergency room visits (SMD -0.21, 95% CI -0.33 to -0.09). There was a reduction in nights disturbed by asthma when pooled using a fixed-effects but not a random-effects model. Effects of education were greater for most outcomes in moderate-severe, compared with mild-moderate asthma, and among studies employing peak flow versus symptom-based strategies. Effects were evident within the first 6 months, but for measures of morbidity and health care utilization, were more evident by 12 months. REVIEWER'S CONCLUSIONS: Asthma self-management education programs in children improve a wide range of measures of outcome. Self-management education directed to prevention and management of attacks should be be incorporated into routine asthma care. Conclusions about the relative effectiveness of the various components are limited by the lack of direct comparisons. Future trials of asthma education programs should focus on morbidity and functional status outcomes, including quality of life, and involve direct comparisons of the various components of interventions.

Adolescent↗

PubMed2003

Ionisers for chronic asthma.

BACKGROUND: Previous reports have shown that ion content in the air may have an effect on respiratory function. Results from studies which test the efficacy of air ionisers to reduce asthma symptoms are often inconclusive and their use as a treatment for asthma remains debatable. OBJECTIVES: We conducted a systematic review of the available evidence to determine the effectiveness of positive and negative ion generators in people with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register (January 1966 to March 2003), Cochrane Central Register of Controlled Trials (Cochrane Library issue 2, 2003) as well as The Alternative Medicine Database AMED (1985 to March 2003). SELECTION CRITERIA: Randomised controlled trials (parallel or crossover design studies) comparing ionisers with dummy ionisers (being negative or positive ion emitters), in children or adults with chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed titles and abstracts of studies and assessed trial quality. Study quality was determined using two methods:The Cochrane approach to allocation concealment and the five point Jadad scale. MAIN RESULTS: Six studies were selected for inclusion (106 participants). No results were combined as the studies were all of a crossover design. EFFECTS OF NEGATIVE ION GENERATORS (five studies)No study reported a significant difference in lung function between ionised and control air (morning Peak expiratory flow (PEF) - three studies; forced expiratory flow in one second (FEV1) - one study). There were no significant differences in symptoms or beta-2 agonist usage between ionised and control air in three studies. EFFECTS OF POSITIVE ION GENERATORS (one study)This study demonstrated that although positively ionised air was associated with a larger fall in FEV1 with exercise, this did not reach statistical significance. Baseline FEV1 was not demonstrated to be significantly different between treatment groups. REVIEWER'S CONCLUSIONS: Based on the evidence currently available from randomised controlled trials, a recommendation cannot be given for the use of room air ionisers to reduce symptoms in patients with chronic asthma.

Adult↗

PubMed2003

Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis.

Beta-blocker therapy has a mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. Comprehensive searches were performed of the EMBASE, MEDLINE and CINAHL databases from 1966 to May 2001, and identified articles and related reviews were scanned. Randomised, blinded, controlled trials that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 s (FEV1) or symptoms in patients with COPD were included in the analysis. Interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. Outcomes measured were the change in FEV1 from baseline and the number of patients with respiratory symptoms. Eleven studies of single-dose treatment and 8 of continued treatment were included. Cardioselective beta-blockers produced no significant change in FEV1 or respiratory symptoms compared to placebo, given as a single dose (-2.05% [95% CI, -6.05% to 1.96%]) or for longer duration (-2.55% [CI, -5.94% to 0.84]), and did not significantly affect the FEV1 treatment response to beta2-agonists. Subgroup analyses revealed no significant change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. In conclusion, cardioselective beta-blockers given to patients with COPD do not produce a significant reduction in airway function or increase the incidence of COPD exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should be considered for patients with COPD.

Adrenergic beta-1 Receptor Antagonists↗

PubMed2001

Holding chambers versus nebulisers for inhaled steroids in chronic asthma.

BACKGROUND: Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear. OBJECTIVES: To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). SELECTION CRITERIA: Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1. MAIN RESULTS: Two studies were selected for inclusion (63 subjects), both concerned adults. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery. REVIEWER'S CONCLUSIONS: Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that have not been assessed. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Administration, Topical↗

PubMed2000

Holding chambers versus nebulisers for beta-agonist treatment of acute asthma.

BACKGROUND: In acute asthma inhaled beta-agonists are often administered to relieve bronchospasm by wet nebulisation, but some have argued that metered-dose inhalers with a holding chamber (spacer) can be equally effective. In the community setting nebulisers are more expensive, require a power source and need regular maintenance. OBJECTIVES: There is controversy as to whether wet nebulisers are better than metered dose inhalers with holding chambers to deliver beta2-agonist medications for acute asthma. Comparisons of hospital and home use are also of interest. The objective of this review was to assess the effects of holding chambers compared to nebulisers for the delivery of beta2-agonists for acute asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Randomised trials in adults and children (from two years of age) with asthma, where holding chamber beta2-agonist delivery was compared with wet nebulisation. DATA COLLECTION AND ANALYSIS: One reviewer applied study inclusion criteria and extracted the data. Trial quality was assessed independently by two reviewers. Missing data were obtained from the authors or estimated. MAIN RESULTS: This review analysed 686 children and 375 adults included in 16 trials. Method of delivery of beta2-agonist did not appear to affect hospital admission rates. In adults, the odds ratio of holding chamber versus nebuliser was 1.12, 95% confidence interval 0.45 to 2.76. The odds ratio for children was 0.91, 95% confidence interval 0.4 to 2.1. Children's length of stay in the emergency department was significantly shorter when the holding chamber was used, with a weighted mean difference of -0.62 hours, 95% confidence interval -0.84 to -0.40 hours. Adults' length of stay in the emergency department was similar for the two delivery methods. Peak flow and forced expiratory volume were also similar for the two delivery methods. Pulse rate was lower for holding chamber in children, weighted mean difference -8.3% baseline, 95% confidence interval -11.5 to -5.0,. REVIEWER'S CONCLUSIONS: Metered-dose inhalers with holding chamber produced outcomes that were at least equivalent to nebuliser delivery. Holding chambers may have some advantages compared to nebulisers for children with acute asthma.

Acute Disease↗

PubMed2000

Vaccines for preventing influenza in people with asthma.

BACKGROUND: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusions was not based on a systematic search of the literature. OBJECTIVES: Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the effects of influenza vaccination in children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and checked reference lists of articles. SELECTION CRITERIA: Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. DATA COLLECTION AND ANALYSIS: Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Nine trials were included. Four of these trials were of high quality. One further article has been included since the previous version of this review. Inclusion of the new trial has not altered the conclusions of this review. The included studies covered a wide diversity of people, settings and types of influenza vaccination, so data from the different trials were not pooled. In one trial, no protective effect of influenza vaccination against asthma exacerbation was demonstrated, but the incidence of influenza was low during the study period. A higher number of asthma exacerbations following killed influenza vaccination was found in one trial (risk difference 3 1%, 95% confidence interval 0.3% to 5.8%). When people with upper respiratory tract infections were excluded, this difference was no longer significant. A small trial using recombinant vaccine found no significant difference in asthma exacerbations between the vaccinated and placebo groups. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the benefits and risks of influenza vaccination for people with asthma.

Adult↗

PubMed2000

Influenza vaccine for patients with chronic obstructive pulmonary disease.

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective. OBJECTIVES: To evaluate the evidence from RCTs for a treatment effect of influenza vaccination in COPD subjects. Outcomes of interest were exacerbation rates, hospitalisations, mortality, lung function and adverse effects. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. References were also provided by a number of drug companies we contacted. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine in persons with COPD. Studies of people with asthma were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. All entries were double checked. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Nine trials were included but only four of these were specifically performed in COPD patients. The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. In one study of inactivated vaccine in COPD patients there was a significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo (weighted mean difference (WMD) -0.45, 95% confidence interval -0.75 to -0.15, p = 0.004). This difference was mainly due to the reduction in exacerbations occurring after 3 weeks (WMD -0.44, (95% CI -0.68 to -0.20, p<0.001). The number of patients experiencing late exacerbations was also significantly less (OR= 0.13, 95%CI 0.04 to 0.45, p=0.002). There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination. In studies in elderly patients (only a minority of whom had COPD), there was a significant increase in the occurrence of local adverse reactions in vaccinees, but the effects were generally mild and transient. REVIEWER'S CONCLUSIONS: It appears, from the limited number of studies performed, that inactivated vaccine may reduce exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination. In elderly, high risk patients there was an increase in adverse effects with vaccination, but these are seen early and are usually mild and transient.

Aged↗