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BackgroundPoor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success. AimTo determine whether treatment with a single inhaler containing a long-acting β 2 -agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids. Design of studyRandomised, parallel group, open-label trial. SettingForty-four general practices in Nottinghamshire. MethodParticipants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 µg one puff twice daily plus their own short-acting β 2 -agonist as required (control group), or budesonide/formoterol 200/6 µg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose. ResultsSeventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 µg/day, mean difference 196 µg, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified. ConclusionUsing a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.

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The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. In patients with asthma, salmeterol and formoterol increase lung function, reduce asthmatic symptoms and improve quality of life when compared with placebo. Both drugs protect against exercise-induced asthma, although some tolerance develops with regular use. Tolerance to the bronchodilator effects of formoterol has also been seen, although this is small and most of the beneficial effects are maintained long-term. Both drugs have been shown to reduce asthma exacerbations but only in studies in which most patients were taking an inhaled corticosteroid. Adding a long-acting beta2-agonist provided better control than increasing the dose of inhaled corticosteroid in several studies. Long-acting beta2-agonists also provide better asthma control than use of regular short-acting beta2-agonists and theophylline. Their relative efficacy compared with leukotriene antagonists is uncertain as yet. Formoterol appears to be at least as safe and effective as a short-acting beta2-agonist when used on an 'as required' basis. In patients with COPD, both salmeterol and formoterol offer improved lung function and reduced COPD symptoms compared with placebo, and quality of life has been improved in some studies. Some tolerance to the bronchodilating effect of salmeterol was seen in one study. Most studies have not found a significant reduction in exacerbations in COPD. Both drugs have provided greater benefit than ipratropium bromide or theophylline; there are limited data on tiotropium bromide. The long-acting beta2-agonists cause predictable adverse effects including headache, tremor, palpitations, muscle cramps and a fall in serum potassium concentration. Salmeterol can also cause paradoxical bronchospasm. There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.

IntroductionAcute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used.MethodsConsecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally non-invasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD recommendations.ResultsDerivation cohort, n=489, in-hospital mortality 25.4%; validation cohort, n=733, in-hospital mortality 20.1%. Using 6 simple categorised variables; extended Medical Research Council Dyspnoea score (eMRCD)1–4/5a/5b, time from admission to acidaemia >12 h, pH<7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant NIVO score had area under the receiver operated curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort.DiscussionThe NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism, and comparing risk-adjusted outcomes across centres.

BACKGROUND: Transcutaneous carbon dioxide (P tcCO 2 ) monitoring is rarely used in the acute hospital setting, where serial samples of arterial blood are instead taken to measure carbon dioxide tension (P aCO 2 ). In this pilot observational study, we assessed the potential of P tcCO 2 monitoring to calculate pH and guide management of acute noninvasive ventilation (NIV). METHODS: Ten subjects with acute hypercapnic respiratory failure were recruited. All had arterial lines placed to guide acute NIV. P tcCO 2 was monitored for 12 h (TOSCA TCM4) and compared with P aCO 2 . Noninvasive transcutaneous pH was determined from P tcCO 2 and calculated bicarbonate and then compared with true arterial pH. Agreements between P CO 2 and pH methods were assessed using Bland-Altman analysis of limits of agreement and Pearson correlation coefficients. Hypothetical adjustments to acute NIV settings were based on transcutaneous data alone and evaluated in comparison with true management. Pain scores for each method were compared using the Wilcoxon signed-rank test. RESULTS: P CO 2 time trends were concordant. Mean P CO 2 bias was ؊2.33 (95% limits of agreement of ؊9.60 to 5.03) mm Hg, and r ‫؍‬ 0.89 (P < .001). Mean pH bias was 0.012 (95% limits of agreement of ؊0.070 to 0.094), and r ‫؍‬ 0.84 (P < .001). Hypothetical clinical decisions based on transcutaneous data alone matched true management on 85% of 34 occasions. Initiation of transcutaneous monitoring was less painful than the arterial equivalent (P ‫؍‬ .008). CONCLUSIONS: This pilot study demonstrates that P tcCO 2 monitoring provides a continuous and reliable trend and also allows pH prediction. This patient-friendly approach is a promising alternative to repeated arterial blood gas sampling in patients requiring NIV for acute hypercapnic respiratory failure.

Unlike general anaesthesia, neuraxial anaesthesia (NA) reduces the burden and risk of respiratory adverse events in the post-operative period. However, both patients affected by chronic obstructive pulmonary disease (COPD) and chest wall disorders and/or neuromuscular diseases may experience the development or the worsening of respiratory failure, even during surgery performed under NA; this latter negatively affects the function of accessory respiratory muscles, resulting in a blunted central response to hypercapnia and possibly in an exacerbation of cardiac dysfunction (NA-induced relative hypovolemia). According to European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, non-invasive ventilation (NIV) is effective in the post-operative period for the treatment of both impaired pulmonary gas exchange and ventilation, while the intra-operative use of NIV in association with NA is just anecdotally reported in the literature. Whilst NIV does not assure a protected patent airway and requires the patient's cooperation, it is a handy tool during surgery under NA: NIV is reported to be successful for treatment of acute respiratory failure; it may be delivered through the patient's home ventilator, may reverse hypoventilation induced by sedatives or inadvertent spread of anaesthetic up to cervical dermatomes, and allow the avoidance of intubation in patients affected by chronic respiratory failure, prolonging the time of non-invasiveness of respiratory support (i.e., neuromuscular patients needing surgery). All these advantages could make NIV preferable to oxygen in carefully selected patients.