Physical activity mediates a healthier body weight in the presence of obesity

FF is an inhaled corticosteroid (ICS) with higher glucocorticoid receptor affinity, tissue permeability and lung retention than other ICS. We investigated whether these attributes improve the therapeutic index (TI), defined as systemic activity to topical efficacy ratio. In this escalating dose, randomised, incomplete-block, 2-period cross-over study (GSK study 203162, NCT02991859), 54 asthmatic subjects were randomised to one or two of four treatment periods. Each period comprised five dose escalations (µg/d) of 7-days duration: FF (25,100,200,400,800), FP (50, 200,500,1000,2000), BUD (100,400,800,1600,3200) or placebo, with a ≥25-day washout between periods. At the end of each escalation, 12h post-dose adenosine-5’-monophosphate (AMP) challenge PC20 and 24h plasma cortisol were assessed. Both endpoints showed a dose response (Figure 1). The ED50 µg/d (95% CI) values were: 49 (18,129), 1081 (448,2610), and 1467 (547,3940) for AMP PC20 and 900 (698,1102), 1986 (1575,2397) and 1927 (1699,2156) for 24h plasma cortisol and TI values (ED50 24h cortisol/ED50 AMP PC20) were 18.6, 1.84 and 1.31 for FF, FP and BUD respectively. No on treatment SAEs were reported. Within the approved dose ranges for asthma, FF gave more protection against airway hyperresponsiveness with less systemic activity compared to FP and BUD.