Abstract and Introduction
Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E. Individually or in combination, they may help to identify, for example, if the dominant effector protein is interleukin (IL) 5, IL13, or IgE. There is no reliable marker of a "non-Th2 endotype" although sputum neutrophil may provide some indication. The unbiased systems biology approach to severe asthma endotyping which integrates omics signatures and clinical data using large cohort studies may provide more comprehensive information than simple cellular measurements. Novel imaging techniques, such as hyperpolarized noble gas magnetic resonance imaging and computed tomography parametric response maps and metabolomics profiling in breath and other body fluids are also being evaluated as potential biomarkers to guide therapy and to assess prognosis.
Severe asthma (SA) is increasingly recognized to be a complex disease with heterogeneous clinical and inflammatory characteristics that can be classified into different endotypes.[1,2] Biologics are important treatment adjuncts for this group of patients who have high disease burden and limited treatment options.[3,4] However, we do not have a good way of assessing treatment response to the various biologics. This is largely due to the complex interaction between the environmental stimuli and the different pathways such as the type 2 T helper cell 1 (TH1), TH2, TH9, TH17 immune pathways. They converge to form the characteristic asthma features of airway inflammation, variable airflow obstruction, and airway hyperresponsiveness.
These clinicophysiological features can be similar in different SA endotypes; hence it is more precise to characterize SA by their inflammatory profile. The TH2 is now more aptly termed the "type 2 (T2)-high" endotype, since non-TH2 cells, such as innate lymphoid cells 2, natural killer cells, invariant T-Cells (iT-cells), may also be able to produce "TH2" cytokines-like interleukin (IL) 4, IL5, and IL13. This endotype had been the focus of biomarker and biologic development targeting eosinophilic inflammation. The "T2-low" endotype, on the other hand, is still poorly characterized. Hence biomarkers are now being developed to distinguish between the T2 eosinophilic/steroid responsive (T2-high) patients from the neutrophilic/steroid insensitive group (T2-low) endotype. There is a current pressing need to develop more precise biomarkers to predict response to targeted therapy to optimize the cost-effectiveness of this treatment.
Semin Respir Crit Care Med. 2018;39(1):56-63. © 2018 Thieme Medical Publishers