The burden of corticosteroid overload in severe and difficult to treat asthma: how to reduce this? Purpose of review Severe asthma is a serious condition that requires an individualized approach combining several treatment agents administered simultaneously in order to reach adequate control. Glucocorticosteroid treatment, as the cornerstone of asthma pharmacotherapy, has great disease-controlling capability, although it may induce a vast amount of severe adverse effects. This review describes our current knowledge of the monitoring and managing options of these adverse effects and possibilities to prevent them, including new therapeutic options. Recent findings A large amount of new drugs is emerging, which may offer a better control of glucocorticosteroid-induced adverse effects. At the same time, major achievements in our understanding of the underlying mechanisms in severe asthma and in the field of biologic agents may help to substantially reduce the need of glucocorticosteroids in the first-line treatment. Summary We discuss new insights and approaches to treatment strategy of severe asthma allowing less oral glucocorticosteroid use and hence, substantial less severe adverse effects of the treatment. Correspondence to Tomas Slisz, MD, Department of respiratory Medicine, 1st Faculty of Medicine of Charles University and Thomayer Hospital, Videnska 800, 140 59, Prague 4, Czech Republic. Tel: +42 0261082373; e-mail: tomas.slisz@ftn.cz Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Precision medicine in severe pediatric asthma: opportunities and challenges Purpose of review Severe pediatric asthma exerts a substantial burden on patients, their families and society. This review provides an update on the latest insights and needs regarding the implementation of precision medicine in severe pediatric asthma. Recent findings Biologicals targeting underlying inflammatory pathways are increasingly available to treat children with severe asthma, holding the promise to enable precision medicine in this heterogeneous patient population with high unmet clinical needs. However, the current understanding of which child would benefit from which type or combination of biologicals is still limited, as most evidence comes from adult studies and might not be generalizable to the pediatric population. Studies in pediatric severe asthma are scarce due to the time-consuming effort to diagnose severe asthma and the challenge to recruit sufficient study participants. The application of innovative systems medicine approaches in international consortia might provide novel leads for – preferably noninvasive – new biomarkers to guide precision medicine in severe pediatric asthma. Summary Despite the increased availability of targeted treatments for severe pediatric asthma, clinical decision-making tools to guide these therapies are still lacking for the individual pediatric patient. Correspondence to Dr Susanne J.H. Vijverberg, Amsterdam UMC, University of Amsterdam, Department of Respiratory Medicine, PO Box 22700, 1105 AZ Amsterdam, the Netherlands. Tel: +31 20 566 27 63; e-mail: s.j.vijverberg@amsterdamumc.nl Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ecological interactions in asthma: from environment to microbiota and immune responses Purpose of review Asthma is a heterogeneous condition shaped not only by genetics but also host conditioning by environmental factors. Recognizing the ecological context of microbe-immune interactions across environments and body sites is a necessary step toward better understanding how human microbiota influence or drive the pathogenesis and pathophysiology of asthma in its various presentations. Recent findings There is increasing evidence of a critical role for microbiota in asthma pathogenesis and outcomes across various body compartments, including the upper and lower airways, and gut. We discuss recent studies from this area including: development of a method to quantify microbial farm-effect in nonfarm environments, relationships between environmental microbial exposures and asthma prevalence across different geographies, microbiome-mediated responses to ozone, and microbiome-immune interactions within and across body compartments. Beyond bacteria, recent reports of asthma-associated differences in archaea and fungal organisms also are highlighted. Summary Collective evidence warrants application of an ecological framework to advance mechanistic insights into microbiota-immune interactions in asthma. This is necessary to achieve goals of developing successful therapeutic interventions targeting modification of microbiomes. Correspondence to Yvonne J. Huang, MD, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109-5642, USA. Tel: +1 734 936 5047; e-mail: yvjhuang@umich.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Anti-alarmin approaches entering clinical trials Purpose of review The alarmins, thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, are upstream regulators of T2 (type 2) inflammation and found to be expressed at high levels in airway epithelium of patients with T2 asthma. This review will summarize how alarmins regulate the inflamed asthmatic airways through previously described and newly identified mechanisms. Recent findings Alarmins drive allergic and nonallergic asthma through activation of innate lymphoid cell 2 (ILC2), which are a rich source of cytokines such as IL-5 and IL-13, with resulting effects on eosinophilopoeisis and remodelling, respectively. Findings from bronchial allergen challenges have illustrated widespread expression of alarmins and their receptors across many effector cells in airways, and recent studies have emphasized alarmin regulation of CD4+ T lymphocytes, eosinophils and basophils, and their progenitors. Furthermore, a link between alarmins and lipid mediators is being uncovered. Summary Alarmins can drive well defined inflammatory pathways through activation of dendritic cells and polarizing T cells to produce type 2 cytokines, as well as they can directly activate many other effector cells that play a central role in allergic and nonallergic asthma. Clinical trials support a central role for TSLP in driving airway inflammation and asthma exacerbations, while ongoing trials blocking IL-33 and IL-25 will help to define their respective role in asthma. Correspondence to Gail M. Gauvreau, McMaster University, 1200 Main St W., HSC 3U26, Hamilton, ON L8N 3Z5, Canada. Tel: +1 905 525 9140 x22791; e-mail: gauvreau@mcmaster.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.