Revising old principles of inhaled treatment in new fixed combinations for asthmaPulmonary Pharmacology & Therapeutics


Nicola Scichilone, Andrea Rossi, Andrea Melani
Pharmacology (medical) / Pulmonary and Respiratory Medicine / Biochemistry, medical


Real-world effects of two inhaled corticosteroid/long-acting β 2 -agonist combinations in the treatment of asthma

Kazuhiro Yatera, Kei Yamasaki, Chinatsu Nishida, Shingo Noguchi, Keishi Oda, Kentarou Akata, Shuya Nagata, Yukiko Kawanami, Toshinori Kawanami, Hiroshi Ishimoto, Hiroshi Mukae

Inhaled β 2 -Agonists in the Treatment of Asthma

Paul M. O'Byrne, Huib A.M. Kerstjens

Atorvastatin in combination with inhaled beclometasone modulates inflammatory sputum mediators in smokers with asthma

Neil C. Thomson, Catherine E. Charron, Rekha Chaudhuri, Mark Spears, Kazuhiro Ito, Charles McSharry


ei c

Article history:

Accepted 11 June 2015

Available online 13 June 2015

The major influencing factors on persistent asthma control are the selected treatment(s), the drug dehabit), comorbid conditions and specific asthma phenotypes. Inhaled corticosteroids (ICS) in combinae a de asthma in accordance with guidelines [1,2], as it allows the release priate for delivery to the lungs, and iii) be user friendly. As the role of inhaled drugs and devices is well recognized as a key factor for optimal control of the disease, an increasing amount of drug/device systems have been designed andmarketed. Four different classes of devices are currently available for pulmonary drug delivery: nebulizers have both advantages and limitations [3]. Inhalers are and represent the cumbersome and andard of care for stered as maintea long-acting b2with uncontrolled acting b2-agonist (SABA) therapy represents a rescue treatment for symptom relief in intermittent and uncontrolled persistent asthma [1,2]. According to the different geographical habits and availability, pMDIs are mostly used for SABAs delivery. By contrast, LABA/ICS fixed combinations are mainly available in the market delivered by DPIs.

Recently, a new LABA/ICS fixed combination has been marketed for maintenance treatment in asthma, formulated with fluticasone propionate (FP) and formoterol fumarate (FF) in a single combination pMDIinhaler (Flutiform®, Mundipharma Res Ltd, Cambridge, * Corresponding author. Department of Medicine, University of Palermo, via

Trabucco 180, 90146 Palermo, Italy.

Contents lists available at ScienceDirect

Pulmonary Pharmaco .e l

Pulmonary Pharmacology & Therapeutics 33 (2015) 32e38E-mail address: (N. Scichilone).of drug directly to the site where action is needed, thus minimizing systemic side effects. Inhalation procedure is influenced by several patient-, drug- and device-related factors, which can impair efficient distribution and deposition of aerosolized particles at the target site. Advancement of technology has allowed the development of modern inhaler devices meeting needs of patients and aim of treatment. An inhaler device is expected to: i) deliver drug(s) at each specific selected dosage, ii) produce particles of size approusually preferred by patients and physicians most used devices in asthma, because are less time-consuming than nebulizers.

Inhaled corticosteroid (ICS) therapy is the st persistent asthma. ICSs are commonly admini nance therapy, alone or in combination with agonist (LABA) in a single inhaler, for patients asthma with ICS monotherapy. Inhaled short-Inhalation is currently the preferred route of drug delivery in currently marketed for drug delivery in asthma. DPIs, pMDIs andKeywords:


Inhaled treatment


Fluticasone propionate

Formoterol fumarate 1. Introduction: how would we lik 1094-5539/© 2015 Published by Elsevier Ltd.with maximal local targeting and minimal systemic side effects. Several innovative inhaler devices have been developed for effective local drug administration and good patient compliance to therapy. Recently, a new ICS/LABA fixed combination, formulated with fluticasone propionate (FP) and formoterol fumarate (FF), has been proposed for maintenance treatment of asthma in adults and adolescent patients. FP/FF combines the anti-inflammatory and bronchodilating properties of powerful compounds in a single inhaler. Its pharmacological characteristics allow rapid speed of onset and dosage flexibility required for step-up and step-down strategies, improving adherence to treatment of asthmatic patients. The efficacy of the FP/FF fixed combination at all dosages in controlling asthma symptoms and the reduced rate of discontinuation have been demonstrated by all randomized trials conducted so far. © 2015 Published by Elsevier Ltd. vice to perform? pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers (SMIs) and nebulizers. SMIs are notReceived in revised form 9 June 2015 tion with a long-acting b2-agonist (LABA) are the gold standard for management of persistent asthma,Received 15 April 2015 livery route and patient's adherence to therapy, together with the influence of lifestyle (i.e. sedentaryRevising old principles of inhaled treatm combinations for asthma

Nicola Scichilone a, *, Andrea Rossi b, Andrea Melan a Department of Medicine, University of Palermo, Palermo, Italy b Pulmonary Unit, A.O.U.I and University of Verona, Verona, Italy c Respiratory Pathophysiology, S.Maria Scotte Hospital, AOU of Siena, Siena, Italy a r t i c l e i n f o a b s t r a c t journal homepage: wwwnt in new fixed logy & Therapeutics sevier .com/locate/ypupt acolUK), hereinafter described as Flutiform®. Flutiform® implements drug/device options for asthma treatment in adults and adolescent patients [4]. FP has a well-established role in asthma, being one of the most potent ICS with low oral bioavailability [5]. Efficacy and safety profile of FF is also well characterized with a more rapid onset of action and greater intrinsic efficacy than the other commonly used LABA, salmeterol xinafoate (SX) [6]. Therefore,

Flutiform® combines the anti-inflammatory and bronchodilating properties of powerful compounds in a single inhaler [7,8].

The efficacy of an inhaled therapy relies not only on the drug, but on the performances of the drug/device system and the characteristics of the emitted aerosol. Drug delivery to the lungs and the consequent clinical outcome are largely linked to total emitted dose (TED) from the drug/device system and aerosol particle size distribution [9]. As a consequence studies carried out in laboratory are a preliminary and essential component of marketing authorization for inhaler formulations. Another key characteristic of a drug/device system is its usability. Despite the advancements in inhaler technology, device misuse is still common in real life and may undermine effectiveness of aerosol therapy [10]. Therefore the usability of a drug/device system is also fundamental to foster a proper inhalation procedure [11].