Large efficacy RCTs, which are essential to show that novel treatments are effective and safe during research and development programmes, have clear limitations in relation to the transferability of their conclusions to usual care mainly because the enrolled patients are selected and not representative of the population encountered in daily practice; moreover, the research environment is substantially different from that of the real world

Alternatively, the possibility of using meta-analyses can be taken into account. Meta-analysis can be considered as a systematic evaluation of all studies that have been conducted to answer a specific question or hypothesis

Recently, several meta-analyses have attempted to clarify the role of triple therapy delivered in a single inhaler in COPD

The results of meta-analyses described in this article suggest that triple combination therapy offers only a further modest clinical benefit in the general COPD population, but it is clinically relevant when a patient is on LABA/LAMA therapy and still suffers from AECOPD and has blood eosinophil counts ≥ 300 cells·μl−1, but adding a LAMA to an ICS/LABA combination induces a relevant clinical benefit in the general COPD population without increasing the risk of cardiovascular SAEs

Unfortunately, the step-up approach from dual bronchodilation to triple therapy proposed by the GOLD strategy does not reflect the important differences in AECOPDs (they differ in aetiology, severity and biological substrate), and thus it is not tailored to the patient’s specific needs to be treated