Arun Nair

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Conventional spacers help overcome problems with co‐ordination and may improve lung deposition and decrease oropharyngeal impaction.• Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery.• The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. WHAT THIS STUDY ADDS • This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat‐V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma.• All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers.AIMS: The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti‐static plastic (Zerostat‐V and Aerochamber Max), metal (Nebuchamber) anti‐static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)].METHODS: A randomized, double‐blind, double‐dummy, four‐way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA‐FP 2 mg via the 280‐ml Zerostat‐V (ZS); 250‐ml Nebuchamber (NC); 197‐ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose.RESULTS: Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001).CONCLUSION: All three antistatic spacers significantly increased the relative systemic bioavailability of HFA‐FP compared with the standard pMDI.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Respirable dose delivery of inhaled steroids may be improved by the use of conventional valved holding chambers (such as the Aerochamber Plus spacer), but these are bulky and cumbersome to use.• A novel compact breath actuated device with integrated vortex chamber (Synchro‐Breathe) has been developed to overcome these problems,• The lung bioavailability of inhaled fluticasone propionate is dependant on respirable dose delivery, and hence the performance of inhaler devices can be quantified by measuring the degree of adrenal suppression as a surrogate for relative lung dose. WHAT THIS STUDY ADDS • This study compares the respirable dose delivery (as relative adrenal suppression) of inhaled fluticasone delivered via Synchro‐Breathe, conventional pMDI (Evohaler), and an optimally prepared Aerochamber Plus spacer in patients with asthma.• The Aerochamber Plus and the Synchro‐Breathe devices produced significantly higher respirable dose delivery of inhaled fluticasone than the pMDI, in terms of the relative degree of adrenal suppression.AIMS: To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA‐FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro‐Breathe (SB) device, and pMDI Evohaler (EH).METHODS: Seventeen mild to moderate asthmatics completed the study using a randomized, double‐blind, double‐dummy, three way crossover design. Single doses of placebo or HFA‐FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose.RESULTS: Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively).CONCLUSIONS: The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA‐FP.