Abstract
Guidelines for the management of severe asthma do not emphasize the measurement of the inflammatory component of airway disease to indicate appropriate treatments or to monitor response to treatment. Inflammation is a central component of asthma and contributes to symptoms, physiological, and structural abnormalities. It can be assessed by a number of endotyping strategies based on “omics” technology such as proteomics, transcriptomics, and metabolomics. It can also be assessed using simple cellular responses by quantitative cytometry in sputum. Bronchitis may be eosinophilic, neutrophilic, mixed-granulocytic, or paucigranulocytic (eosinophils and neutrophils not elevated). Eosinophilic bronchitis is usually a Type 2 (T2)-driven process and therefore a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against T2 cytokines such as IL-4, IL-5, and IL-13. Neutrophilic bronchitis represents a non-T2-driven disease, which is generally a predictor of response to antibiotics and may be a predictor to therapies targeted at pathways that lead to neutrophil recruitment such as TNF, IL-1, IL-6, IL-8, IL-23, and IL-17. Paucigranulocytic disease may not warrant anti-inflammatory therapy. These patients, whose symptoms may be driven largely by airway hyper-responsiveness may benefit from smooth muscle-directed therapies such as bronchial thermoplasty or mast-cell directed therapies. This review will briefly summarize the current knowledge regarding “omics-based signatures” and cellular endotyping of severe asthma and give an overview of segmentation of asthma therapeutics guided by the endotype.
Highlights
The definition of asthma has not changed in over 50 years [1]
Eosinophilic bronchitis is usually a Type 2 (T2)-driven process and a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against T2 cytokines such as IL-4, IL-5, and IL-13
We suggest that asthma endotype characterization can be reliably done on the nature of underlying airway inflammation assessed by sputum cytometry [1]
Summary
The definition of asthma has not changed in over 50 years [1]. The variability in airflow that characterizes the disease may be driven by airway hyper-responsiveness or by airway inflammation that is one of the determinants of airway hyper-responsiveness [2]. While several non-invasive biomarkers exist for the detection of the Th2-high endotype [blood eosinophils, serum IgE, serum periostin, and exhaled nitric oxide (eNO)], sputum cytometry is currently the most clinically validated quantitative and responsive method to assess airway inflammation. Based on our clinical experience of over 20 years in over 5,000 patients, a patient can be determined to have eosinophilic asthma if there is evidence of elevated sputum (>3% with or without degranulation) and/or blood eosinophils (≥400 cells/μL) on at least two occasions, and if treatment strategies aimed at suppressing eosinophils are effective in controlling symptoms and exacerbations [26]. Somewhat contradictory to the findings of Baines et al, when unbiased hierarchical clustering was performed on 508 genes that were differentially expressed between severe asthmatics with and without eosinophilic airway inflammation confirmed by sputum cytometry, one Th2-high and two non-Th2 transcriptome-associated clusters (TACs) were defined [33]. Yan et al [31] did not detect significant between cluster differences
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
