Unravelling the complexity of tissue inflammation in uncontrolled and severe asthma.

PURPOSE OF REVIEW: The clinical and inflammatory heterogeneity in asthma constitutes a major challenge for improved treatment. This review describes the nature of the inflammatory complexity and how it can be decoded to yield improved disease understanding and personalized treatment. The focus is on the difficult task of revealing the immunological complexity as it occurs inside diseased patient tissues. RECENT
FINDINGS: The inflammatory heterogeneity in asthma stretches beyond the classical division into allergic Th2 eosinophilic versus Th1 and/or Th17 neutrophilic (or paucigranulocytic) phenotypes. Rather than having one distinct type of inflammation, many patients display a patchwork of overlapping immune signatures. The patient diversity is further increased by differences in regard of distal lung involvement. Faced with this staggering complexity, calls have been made for a pragmatic biomarker-guided identification of treatable traits. In parallel, novel high-dimensional analyses and multiplex imaging aid the long-term goal of decoding the underlying molecular endotypes.
SUMMARY: Asthma is vastly heterogeneous with multiple and superimposed inflammatory and anatomical phenotypes. Despite the intensive research and introduction of highly immune-selective dugs, basic questions remain; especially as still too many of today's uncontrolled patients remain poorly understood. Here, pragmatic biomarker strategies, combined with novel methodological approaches that ultimately reveal the complete immunological complexity, will pave the way for improved differential diagnosis and personalized medication.