Introduction: The efficacy of inhaled products is affected by the degree, and potentially the site, of drug particle deposition in the lungs. Lung deposition correlates with the fine particle fraction (FPF; the proportion of dose containing particles \5 lm in aerodynamic diameter). This in vitro study (defining fluticasone propionate/ formoterol particulate size [DIFFUSE]) examined the effects of inhalation flow rate on the FPF of the fluticasone propionate/ formoterol (FP/FORM) pMDI aerosol compared with three other inhaled corticosteroids/longacting b 2-agonist (ICS/LABA) combination therapies administered by either DPI or pMDI [fluticasone propionate/salmeterol (FP/SAL), budesonide/formoterol (BUD/FORM) and beclometasone dipropionate/formoterol (BDP/ FORM)]. Methods: Aerodynamic particle size distribution was determined for each product using an 8-stage Andersen Cascade Impactor at two inhalation flow rates: 28.3 and 60.0 L/min. Fine particle dose (mass of dose \5.0 lm) and FPF were calculated as a percentage of the labeled dose for the LABA and ICS of each product at both flow rates. Results: FP/FORM suspension aerosol provided a high and consistent FPF of approximately 40% for the ICS and LABA components at both flow rates. At 28.3 L/min, the FPF of each component of FP/FORM (41.2% and 39.2%) was greater than that of FP/SAL DPI (12.5% and 11.3%), BUD/FORM DPI (8.2% and 6.6%) and BDP/ FORM pMDI (28.5% and 26.0%). At 60.0 L/min, the FPFs of the FP/FORM components (43.7% and 42.1%) were greater than those of FP/SAL

Dosing performance of dry powder inhalers is dependent on patient's inspiratory effort. This study compares the inhalation profiles generated by patients with severe obstructive lung disease using Diskus and Turbuhaler inhalers. The patient profiles are subsequently used to determine the dosing performance of fluticasone propionate Diskus and budesonide Turbuhaler inhalers. Inhalation profiles were recorded in COPD patients (FEV1 < or = 30% predicted) as they inhaled with maximal effort through the inhalers. The profiles were used in an inhalation simulator to assess the dosing performance by measuring the total emitted dose and the fine particle mass for each inhaler type. Peak inspiratory flow was significantly higher through the Diskus (mean 82.31 min(-1)) compared with Turbuhaler (mean 53.51 min(-1), difference = 28.8 l min(-1); P < 0.0001). In addition, in direct comparison of the two devices. the Diskus was shown to deliver a more consistent dose irrespective of flow than the Turbuhaler in this patient population. These findings may be of importance in optimising selection of devices for patients with severe airway obstruction.

Mundipharma Research Limited, Cambridge, UK.

Background Methotrexate (MTX) immunosuppressive therapy is selectively used to assist with the reduction of the oral corticosteroid demand thereby decreasing the risk of potential side effects in individuals with steroid dependant asthma. Previous reported data has demonstrated similar significant reduction in corticosteroid load, asthma exacerbation and hospital admission rate. This study aims to compare similar variables collated from UK severe asthma specialist centres to further generate evidence for the continued use of MTX as an effective aid in the reduction of corticosteroid burden in a severe asthma cohort. Methods A retrospective data collection was performed across two UK severe asthma centres with data from a third pending. Patients included had a confirmed diagnosis of severe asthma and had been treated with MTX for at least 12 months to allow sufficient analysis. Variables assessed included mean average daily corticosteroid dose, overall percentage reduction of corticosteroid, exacerbation frequency and acute admission events both twelve months prior to and post commencement of MTX therapy. Data collection was examined for each individual centre then combined and examined for consistency of results. Conclusion When monitored and supervised in the correctly chosen severe asthma patient, MTX can significantly reduce the demand for corticosteroids and consequently reduce steroid related side effects, admission and exacerbation this has been demonstrated across two specialist centres with correlating data.

We would like to clarify some points about the DIFFUSE (Defining fluticasone propionate/ formoterol particulate size) study (December 2013, p 39) [1] in light of the recent review by De Maria and colleagues [2]. Our in vitro study assessed the effects of inhalation flow rate on the aerodynamic particle size distribution Hence, the flow rate dependency of inhalers is of interest to physicians as well as regulators. Including a faster flow rate of 60 L/min in our study was therefore appropriate, and is relevant to the real-life use of these inhalers.All inhalers were tested across pre-defined parameters, using the same apparatus and the same ambient conditions, to ensure a fair and appropriate comparison. The review questions the use of an Andersen Cascade Impactor (ACI):an ACI is arguably the most widely used tool for testing inhalers, and is routinely used at flow rates of 30, 60 L/min, and above [9][10][11][12][13][14]. Indeed, the authors of the review have themselves used