RESUMEN
Severe asthma represents a true challenge for clinicians from two basic perspectives, i.e.: a rational assessment of the underlying endo/phenotype and the subsequent selection of the best fitted (personalized) and effective treatment. Even though asthma is a heterogeneous disease, in the majority of therapy-compliant patients, it is possible to achieve (almost) complete disease control or even remission through conventional and quite uniform step-based pharmacotherapy, even without phenotyping. However, the absence of deeper assessment of individual patients revealed its handicap to its fullest extent during the first years of the new millennium upon the launch of biological therapeutics for patients with the most severe forms of asthma. The introduction of differentially targeted biologics into clinical practice became a challenge in terms of understanding and recognizing the etiopathogenetic heterogeneity of the asthmatic inflammation, pheno/endotyping, and, consequently, to choose the right biologic for the right patient. The answers to the following three questions should lead to correct identification of the dominant pheno/endotype: Is it really (severe) asthma? Is it eosinophilic asthma? If eosinophilic, is it (predominantly) allergen-driven? The identification of the best achievable and relevant alliance between endotypes and phenotypes ("euphenotypes") should be based not only on the assessment of the actual clinical characteristics and laboratory biomarkers, but more importantly, on the evaluation of their development and changes over time. In the current paper, we present a pragmatic three-step approach to severe asthma diagnosis and management.
RESUMEN
Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy-driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non-immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non-specific eosinophil-targeting therapies. Despite the overall favourable safety profile of the currently available anti-eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.
