This is the first real-life study comparing the clinical effects of BDP/F extrafine to other combinations. Previously published RCTs found that there were no differences between BDP/F extrafine pMDI and BUD/F or FP/S in terms of lung function, use of rescue medications, exacerbations and safety [22, 23]. However, these studies do not reflect routine use, during which compliance or each patient's ability to use the device may influence the result. In addition to the improved lung deposition and distribution, there is less reliance on using an optimal inhalation technique for pMDIs formulated with extrafine particles . Although these were not assessed in this study, the result would include these elements. Previous studies have shown that, when inhalers emitting large particles are used, the magnitude of inhalation technique errors for a pMDI and DPI are similar .
The results show that asthma control was significantly better in patients receiving BDP/F extrafine pMDI formulation compared to the DPI group. Daytime symptoms and use of rescue medications were significantly lower in the BDP/F extrafine pMDI group, further supporting a greater control of asthma in a real-life setting. Asthma is an inflammatory disorder affecting both central and peripheral airways [24, 25], which justifies the clinical need for anti-asthmatic medication which is also able to reach peripheral airways. The inverse correlation on particle size and pulmonary deposition is well known . Of the fixed combinations of ICS currently available on the market, BDP/F extrafine pMDI drug particles are approximately half the size in diameter compared to FP/S and BUD/F DPIs . BDP/F extrafine pMDI is the only fixed combination which has been demonstrated to reach not only large, but also small airways when administered in asthmatic patients . Accordingly, the improved drug delivery, which enables a more uniform treatment of inflammation and bronchoconstriction throughout the entire bronchial tree, contributes to the higher level of asthma control achieved with BDP/F extrafine combination in this study. In other words, extrafine BDP/F can reach and treat distal areas of the lung left untargeted by larger particle sized medications, and this translates into a greater clinical benefit for patients. A significantly superior asthma control with the BDP/F extrafine combination vs. the combination of the same drugs (BDP plus F) given as larger particles, non extrafine agents, has been found in a large 6-month RCT carried-out in asthmatic patients . However, in this study, the definition of asthma control was established according to Zetterström  and was therefore different from the GINA guidelines, which is a limitation of our analysis. No differences in lung function parameters were observed among treatments. This finding is not surprising considering that the spirometric tests performed in this study do not provide comprehensive evaluation of the entire bronchial tree as they are unable to properly reflect small airway abnormalities.
In our real-life study, current or former smokers were not excluded since they represent a large proportion of asthmatic patients. Generally, the level of asthma control in smokers was similar to that in non smokers; however, the proportion of uncontrolled patients was significantly increased in these patients as compared to never smokers. Smoking asthmatics are mostly excluded from clinical trials, therefore only sparse data are available on asthma control in current or former smoker asthmatic patients.
Notably, these results were obtained with a lower mean daily ICS dose indicating that BDP/F extrafine delivers a greater efficacy per μg of steroid when compared to BUD/F and FP/S. This is of interest considering that reduced compliance in asthmatic patients is often due to steroid phobia, an issue that can be decreased by offering a medication with a low corticosteroid dose .
In the studied population, 45.9% of patients had controlled asthma, 38.7% were partially controlled, and 15.3% were uncontrolled. These findings are in agreement with recent observational trials focusing on asthma control. A study performed across 10 different European countries showed that asthma is suitably controlled in 45% of non-inhaled corticosteroid users and only in 15% of patients using ICS . Similarly, a web-based survey to assess the prevalence of uncontrolled asthma in the United States reported that symptoms were successfully controlled in 45% of patients .
This real-life observational study shows that GINA-based asthma control is achieved in a good proportion of asthmatic patients treated with fixed combinations of ICS and LABA. Patients treated with BDP/F extrafine pMDI achieved a greater level of asthma control as compared to patients treated with FP/S or BUD/F larger particle combinations, suggesting that differences in inhaler devices and formulations can have an impact on important clinical outcomes and should be therefore taken into consideration when managing patients with asthma.