Letter in Response to the Review by De Maria et al. 2014

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 (APSD) of fluticasone propionate/formoterol pMDI (FP/FORM; flutiform , Jagotec AG, Muttenz, Switzerland) compared with three other ICS/LABA combinations: fluticasone propionate/salmeterol DPI (FP/SAL; Seretide Accuhaler , GlaxoOperations UK Ltd, Herts, UK), budesonide/formoterol DPI (BUD/FORM; Symbicort Turbohaler , AstraZeneca AB, Södertälje, Sweden) and beclometasone dipropionate/formoterol pMDI (BDP/FORM; Foster, Chiesi Farmaceutici S.p.A, Parma, Italy) [1]. Contrary to the suggestions in the review, the patient information leaflets for FP/FORM and BDP/FORM do not specify a flow rate or ‘a long breath’ [3, 4]. Inhalation flow rates of 30–60 L/min are recognised as ‘clinically effective’ for pMDIs and DPIs, according to the In-Check DIAL [5]. pMDIs are active aerosols with relatively low resistance, and patients often use them at flow rates [30 L/min [6–8]. 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 [9–14]. Indeed, the authors of the review have themselves used B. Johal (&) Mundipharma Research Limited, Cambridge Science Park, Milton Road, Cambridge CB4 0GW, UK e-mail: Baljinder.Johal@mundipharma-rd.eu