Wouter H van Geffen, W R Douma, Dirk Jan Slebos, Huib AM Kerstjens

Bronchodilators are a central component for treating exacerbations of chronic obstructive pulmonary disease (COPD) all over the world. Clinicians often use nebulisers as a mode of delivery, especially in the acute setting, and many patients seem to benefit from them. However, evidence supporting this choice from systematic analysis is sparse, and available data are frequently biased by the inclusion of asthma patients. Therefore, there is little or no formal guidance regarding the mode of delivery, which has led to a wide variation in practice between and within countries and even among doctors in the same hospital. We assessed the available randomised controlled trials (RCTs) to help guide practice in a more uniform way. To compare the effects of nebulisers versus pressurised metered dose inhalers (pMDI) plus spacer or dry powder inhalers (DPI) in bronchodilator therapy for exacerbations of COPD. We searched the Cochrane Airways Group Trial Register and reference lists of articles up to 1 July 2016. RCTs of both parallel and cross-over designs. We included RCTs during COPD exacerbations, whether measured during hospitalisation or in an outpatient setting. We excluded RCTs involving mechanically ventilated patients due to the different condition of both patients and airways in this setting. Two review authors independently assessed studies for inclusion, extracted data and assessed the risk of bias. We report results with 95% confidence intervals (CIs). This review includes eight studies with a total of 250 participants comparing nebuliser versus pMDI plus spacer treatment. We identified no studies comparing DPI with nebulisers. We found two studies assessing the primary outcome of 'change in forced expiratory volume in one second (FEV1) one hour after dosing'. We could not pool these studies, but both showed a non-significant difference in favour of the nebuliser group, with similar frequencies of serious adverse events. For the secondary outcome, 'change in FEV1 closest to one hour after dosing': we found a significant difference of 83 ml (95% CI 10 to 156, P = 0.03) in favour of nebuliser treatment. For the secondary outcome of adverse events, we found a non-significant odds ratio of 1.65 (95% CI 0.42 to 6.48) in favour of the pMDI plus spacer group. There is a lack of evidence in favour of one mode of delivery over another for bronchodilators during exacerbations of COPD. We found no difference between nebulisers versus pMDI plus spacer regarding the primary outcomes of FEV1 at one hour and safety. For the secondary outcome 'change in FEV1 closest to one hour after dosing' during an exacerbation of COPD, we found a greater improvement in FEV1 when treating with nebulisers than with pMDI plus spacers.A limited amount of data are available (eight studies involving 250 participants). These studies were difficult to pool, of low quality and did not provide enough evidence to favour one mode of delivery over another. No data of sufficient quality have been published comparing nebulisers versus DPIs in this setting. More studies are required to assess the optimal mode of delivery during exacerbations of COPD.