Integrating high dose inhaled corticosteroids into oral corticosteroids stewardship Arnaud Bourdin 1,2 , Carey Suehs 1,3 and Jérémy Charriot 1 Affiliations: 1 Dept of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France. 2 Univ Montpellier, PhyMedExp, INSERM, CNRS CHU Montpellier, Montpellier, France. 3 Dept of Medical Information, Univ Montpellier, CHU Montpellier, Montpellier, France. Correspondence: Arnaud Bourdin, Dept of Respiratory Diseases, Montpellier University Hospital, Hôpital Arnaud de Villeneuve, 371, av. du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. E-mail: a-bourdin@chu-montpellier.fr @ERSpublications If high doses of ICS are equivalent to low dose OCS, they should be considered as such http://bit.ly/2CYssfB Cite this article as: Bourdin A, Suehs C, Charriot J. Integrating high dose inhaled corticosteroids into oral corticosteroids stewardship. Eur Respir J 2020; 55: 1902193 [https://doi.org/10.1183/13993003.02193-2019]. Uncertainties still surround high dose inhaled corticosteroids (ICS) use in asthma. In hindsight, certain aspects of the ICS development story can help elucidate why. In 1973, CAMERON et al. [1] signed a brilliant paper reporting the results of a double blind, randomised controlled trial demonstrating the oral corticosteroid (OCS)-sparing effect of ICS as the primary outcome. A few years later, the assessment of this benefit was mitigated when a complete weaning of OCS remained unachievable [2]. The benefit of ICS was therefore understood to be mostly based on an improved safety profile purportedly due to reduced systemic diffusion. Thus, the understanding of how ICS was of any benefit to asthma patients when compared to OCS was mostly based on a greater safety profile supposedly due to a reduced systemic diffusion. Similarly, topically administered corticosteroids were also developed in the same time period for diseases affecting the skin, the eyes, the nose or the joints. As for ICS, whether or not these formulations reduce corticosteroid-associated adverse events remains largely debated [3]. Outside rare conditions such as eosinophilic granulomatosis with polyangiitis, the systemic components of asthma are not obvious and the reasons driving requirements for systemic corticosteroids quite unknown [4]. Interestingly, multiple studies have raised safety concerns related to the use of ICS, especially at high doses [5]. Specific adverse-effect studies have focussed mainly on skin bruising or osteoporosis [6, 7]. However, hypothalamo-pituitary axis (HPA) suppression has been described for high-dose ICS since at least the 1990s [8, 9]. In a slightly provocative way, MAIJERS et al. [10] suggest in the present issue of the European Respiratory Journal that around two thirds of high-dose ICS effects are due to their systemic diffusion. To reach this point, they compiled studies where OCS-sparing effects attributed to ICS were studied, and then computed the meta-regression between the change in prednisone dose and the dose of ICS. Based on HPA suppression data, their findings suggest that at least 60% of the OCS dose reduction can be attributed to systemic absorption. Although the conclusion put forward by MAIJERS et al. [10] is limited by a paucity of studies and patients, it provides evidence that the systemic diffusion of ICS is far from minimised. Moreover, even though HPA suppression is not necessarily related to efficacy, the result is more consistent when considering the Received: 12 Nov 2019 | Accepted: 14 Nov 2019 Copyright ©ERS 2020 https://doi.org/10.1183/13993003.02193-2019 Eur Respir J 2020; 55: 1902193 | EDITORIAL ASTHMA