Discussion
Recommendations by professional organisations, such as GOLD, Canadian Thoracic Society and Spanish Society of Pulmonology and Thoracic Surgery, on the management of COPD, have generally emphasised the need to provide education and training on inhaler device technique to patients and the need to assess a patient’s technique before modifying therapy.29–31 But in some guidelines, this consideration is not discussed,32 and in practice, it is frequently overlooked.33 A study of patients in nine countries (Brazil, Canada, France, Germany, Italy, Japan, the Netherlands, the UK and the USA) found that 29% had not had their inhaler technique checked by a healthcare professional within the last 2 years.34
Although it seems obvious that patients who do not use a device correctly will not get the full benefit of the drugs they contain, this systematic review found only weak and inconsistent evidence that making fewer mistakes using inhalers is associated with better clinical outcomes, including lung function, symptoms, health status and exacerbation rates in COPD. The prospective cohort studies did not assess changes in clinical outcomes in patients whose error rates were reduced, nor did they account for adherence.11 13 19 24 26 In the cross-sectional studies, it is impossible to separate cause and effect. For example, patients with poor health status or lung function may make more errors as they may be more breathless and unable to perform inhalation manoeuvres correctly or poor inhaler technique may have affected the benefits of therapy and led to poor health status and lung function.
Differences in the relative importance of specific errors may also confound the interpretation of the data. Critical errors have largely been defined empirically, on the assumption that they will affect the efficacy of the inhaled therapy. For some, such as failing to remove a protective cap from the inhaler, the assumption seems valid, but the clinical significance of others, such as not sitting or standing straight with head tilted, are more open to question. In some instances, there is evidence which shows that incorrect use impacts the effectiveness of the inhaled therapy. For example, the bioavailability of salbutamol in the lungs is greater after slow inhalation (10 l/min) from a pMDI compared with fast inhalation (50 l/min).35 In other cases, there is evidence that casts doubt on their importance. For example, studies using the clinical bronchodilator response to inhaled salbutamol as an endpoint found that there was no significant difference in the bronchodilatation induced by a 10 s as compared with a 4 s or no breath hold.36 37
Most studies identified in our systematic review considered errors collectively and only the PIFotal COPD study reported the relationship between specific mistakes using a DPI and outcomes.23 27 28 The study found that only some errors were related to outcomes but there were inconsistencies. Mistakes in the technique used to breathe in were associated with significantly worse health status, higher secondary healthcare costs and higher total COPD-related healthcare costs.23 27 28 They were also associated with an increased rate of severe, but not moderate, exacerbations, suggesting that the finding may be confounded and more likely to be due to patients with more severe diseases having problems using inhalers correctly. There was no statistically significant relationship between other errors and worse outcomes.23 27 28 Of note, failure to ‘remove protective cap’, was not associated with significantly worse health status or increased exacerbation rates,28 calling into question the relevance of the overall findings of the study and the definition of critical errors.
One of the main strengths of our review is that it examined the relationship between inhaler technique and outcomes in patients with COPD and did not include patients with asthma. It also included recent studies not considered in previous reviews. There are limitations to the review. The main ones relate to the quality of the studies included. There was heterogeneity in the study designs and short follow-up in most of the prospective cohort studies. Exacerbation rates were mostly based on patient recall and it was not clear how patients were selected for inclusion. Most studies failed to take adherence into account and lacked sufficient detail to enable quantitative synthesis. A narrative review was the only form of synthesis possible, but an individual participant data meta-analysis would have offered the best synthesis had the data been available.