Christopher J Cates

British guideline on the management of asthma: A national clinical guideline

These guidelines have been replaced by British Guideline on the Management of Asthma. A national clinical guideline. Superseded By 2012 Revision Of 2008 Guideline: British Guideline on the Management of Asthma. Thorax 2008 May; 63(Suppl 4): 1–121.

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

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

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.

Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma

Abstract Objective: To determine the clinical effectiveness of pressurised metered dose inhalers (with or without spacer) compared with other hand held inhaler devices for the delivery of corticosteroids in stable asthma. Design: Systematic review of randomised controlled trials. Data sources: Cochrane Airways Group trials database (Medline, Embase, Cochrane controlled clinical trials register, and hand searching of 18 relevant journals), pharmaceutical companies, and bibliographies of included trials. Trials: All trials in children or adults with stable asthma that compared a pressurised metered dose inhaler with any other hand held inhaler device delivering the same inhaled corticosteroid. Results: 24 randomised controlled trials were included. Significant differences were found for forced expiratory volume in one second, morning peak expiratory flow rate, and use of drugs for additional relief with dry powder inhalers. However, either these were within clinically equivalent limits or the differences were not apparent once baseline characteristics had been taken into account. No significant differences were found between pressurised metered dose inhalers and any other hand held inhaler device for the following outcomes: lung function, symptoms, bronchial hyper-reactivity, systemic bioavailability, and use of additional relief bronchodilators. Conclusions: No evidence was found that alternative inhaler devices (dry powder inhalers, breath actuated pressurised metered dose inhalers, or hydrofluoroalkane pressurised metered dose inhalers) are more effective than the pressurised metered dose inhalers for delivery of inhaled corticosteroids. Pressurised metered dose inhalers remain the most cost effective first line delivery devices. What is already known on this topic Many inhaler devices are available for administering inhaled corticosteroids Current guidelines for their use are inconsistent and not evidence based What this study adds This systematic review found no evidence that alternative inhaler devices are more effective than pressurised metered dose inhalers for giving inhaled corticosteroids. Pressurised metered dose inhalers (or the cheapest device) should be first line treatment in all patients with stable asthma

Spacers and nebulisers for the delivery of beta-agonists in non-life-threatening acute asthma

BACKGROUND In asthma exacerbations, higher doses of inhaled beta-agonists are used to overcome acute bronchoconstriction. Traditionally, wet nebulisation has been used, but metered-dose inhaler with a spacer device is an alternative delivery method. OBJECTIVE To compare the clinical outcomes in adults and children with acute asthma, presenting in emergency departments or in the community, who have been randomised to beta-agonists given by two different delivery. METHODS a metered-dose inhaler with spacer or a nebuliser. RESULTS A Cochrane review has found no important differences between the two delivery methods in adults. Children may suffer fewer side effects with spacer delivery. CONCLUSIONS Individual response to treatment cannot be predicted, but many studies overcame this problem by using frequent repeated doses of beta-agonists (one respule via nebuliser or four separate actuations of a metered-dose inhaler through a spacer) every 10-15 min, titrated against the clinical response of the patients. This approach is advocated in clinical practice.

Safety of tiotropium

Indirect evidence suggests the Respimat inhaler is riskier than the Handihaler

Cochrane Airways Group reviews were prioritized for updating using a pragmatic approach.

OBJECTIVES Cochrane Reviews should address the most important questions for guideline writers, clinicians, and the public. It is not possible to keep all reviews up-to-date, so the Cochrane Airways Group (CAG) decided to prioritize updates and new reviews without requesting additional resources. The aim of the objective was to develop pragmatic and transparent prioritization techniques to identify 25 to 35 high-priority updates from a total of 270 CAG Reviews and become more selective over which new reviews we publish. STUDY DESIGN AND SETTING We used elements from existing prioritization processes, including existing health care uncertainties, expert opinion, and a decision tool. We did not conduct a full face-to-face workshop or an iterative group decision-making process. RESULTS We prioritized 30 reviews in need of updating and aimed to update these within 2 years. Within the first 18 months, nine of these have been published. CONCLUSION A pragmatic approach to prioritization can indicate priority reviews without an excessive drain on time and resources. The steps provide us with better control over the reviews in our scope and can be built on in the future.

Long-acting beta-agonists plus inhaled corticosteroids safety: a systematic review and meta-analysis of non-randomized studies

BackgroundAlthough several systematic reviews investigated the safety of long-acting beta–agonists (LABAs) in asthma, they mainly addressed randomized clinical trials while evidence from non-randomized studies has been mostly neglected. We aim to assess the risk of serious adverse events in adults and children with asthma treated with LABAs and Inhaled Corticosteroids (ICs), compared to patients treated only with ICs, from published non-randomized studies.MethodsThe protocol registration number was CRD42012003387 (http://www.crd.york.ac.uk/Prospero). Literature search for articles published since 1990 was performed in MEDLINE and EMBASE. Two authors selected studies independently for inclusion and extracted the data. A third reviewer resolved discrepancies. To assess the risk of serious adverse events, meta-analyses were performed calculating odds ratio summary estimators using random effect models when heterogeneity was found, and fixed effect models otherwise.ResultsOf 4,415 candidate articles, 1,759 abstracts were reviewed and 220 articles were fully read. Finally, 19 studies met the inclusion criteria. Most of them were retrospective observational cohorts. Sample sizes varied from 50 to 514,216. The meta-analyses performed (69,939-624,303 participants according to the outcome considered) showed that odds ratio of the LABAs and ICs combined treatment when compared with ICs alone was: 0.88 (95% CI 0.69-1.12) for asthma-related hospitalization; 0.75 (95% CI 0.66-0.84) for asthma-related emergency visits; 1.02 (95% CI 0.94-1.10) for systemic corticosteroids; and 0.95 (95% CI 0.9-1.0) for the combined outcome.ConclusionsEvidence from observational studies shows that the combined treatment of LABAs and ICs is not associated with a higher risk of serious adverse events, compared to ICs alone. Major gaps identified were prospective design, paediatric population and inclusion of mortality as a primary outcome.

Assessing the methodological quality of systematic reviews

Dear Sirs, We read with interest the paper by Ho et al,1 which used the AMSTAR tool to assess the methodological quality of systematic reviews (SRs) on chronic obstructive pulmonary disease (COPD). As staff at the Cochrane Airways Group with the responsibility of producing high-quality SRs for airway conditions, including COPD, we are always happy to hear how we could improve. However, there are some methodological issues within the study. The abstract states that the methodological quality of the reviews was disappointing and emphasises the more negative findings, neglecting the positive results (e.g., a priori design in 67% SRs, comprehensive literature search in 97% and scientific quality assessed and documented in 85%). The authors did not complete the AMSTAR ratings in duplicate; yet, duplicate data extraction is a mark of a good SR. Our experience with this tool is that the discussion between two or more people helps reach a fair judgement.2 It would have been helpful to see the AMSTAR ratings per review so that the work could be replicated and evaluated. We noted the lack of discussion about the choice to limit the study to SRs that include a meta-analysis. Choosing not to perform a meta-analysis when there is a lot of heterogeneity between studies is a valid decision. The authors highlighted that non-English databases were searched infrequently. This is not an AMSTAR criterion; have the authors suggested that this be incorporated in any update of the tool? Cochrane does not require that non-English language databases be searched and this is usually done only when we expect that this will yield additional relevant trials. We agree that multilingual SR teams are advantageous and we would be grateful if people who wish to translate the trial reports for inclusion in Cochrane reviews contact us. We take the authors’ point about being clearer about reviewers’ support, and making a statement about publication bias in the results section as well as the methods section when there are too few studies to permit a funnel plot. As highlighted in the paper, the quality of SRs has improved significantly in recent years through the development of methods and improved implementation.3,4 It would have been helpful to highlight this important point in the conclusions and abstract.

Clinical importance cannot be ruled out using mean difference alone

Christopher Cates and Charlotta Karner argue that information about individual patient responses should be included in the clinical assessment of treatments