Table 1. Challenges in developing therapeutics for type-2 low neutrophilic asthma, compared with successes in eosinophilic asthma.
| Characteristic | Eosinophilic asthma | Neutrophilic asthma |
|---|---|---|
| Biology of granulocytes | Eosinophils: | Neutrophils: |
| - long-lived haematopoietic cells. | - short-lived haematopoietic cells. | |
| - reside predominantly in mucosal tissues | - predominantly circulating in blood. | |
| - absent in sputum and airways in health. (e.g. airways). | - present in sputum and airways in health. | |
|
| ||
| Role in pathogenesis | Inflammatory eosinophils in the airways of patients with asthma are pathogenic and associate with exacerbations. | Role of neutrophils in the airways of patients with asthma is unknown; neutrophils are beneficial in airway infection. |
|
| ||
| Non-invasive biomarkers | Elevated FeNO | None. Non-invasive biomarkers (e.g. VOC) are not available in clinical practice. |
| Blood eosinophils correlate with sputum eosinophils in asthma. | Blood neutrophil levels do not correlate with sputum neutrophil levels in asthma. | |
|
| ||
| Heterogeneity of phenotype | Moderate heterogeneity within eosinophilic asthma: allergic versus nonallergic; early-onset versus late-onset. | Huge heterogeneity within neutrophilic asthma; multiple associated factors e.g. smoking, air pollution, obesity, infection. |
|
| ||
| Differential diagnosis | Limited: eosinophilic COPD; eosinophilic pneumonia; ABPA; EGPA. | Very broad: e.g. COPD; bronchiectasis; cystic fibrosis; diffuse panbronchiolitis; bacterial and fungal infections; tuberculosis; NTM infection. |
|
| ||
| Therapeutic targets | Clearly delineated: | Less well defined: [see Table 3] |
| - corticosteroids. | - pro-inflammatory cytokines such as IL-1β, IL-6, TNF, IL-17, IL-17R, IL-23 | |
| - type-2 cytokines and their receptors: IL-5, IL-5R and IL-4R. | - CXC chemokines or their receptors | |
| - IgE in allergic eosinophilic severe asthma. | - β-tryptase, G-CSF, GM-CSF | |
| - epithelial alarmins (e.g. TSLP, IL-33). | - epithelial alarmins (e.g. TSLP; IL-33) | |
ABPA, allergic bronchopulmonary aspergillosis; COPD, chronic obstructive pulmonary disease; CXC, C-X-C motif chemokine ligand; EGPA, eosinophilic granulomatosis with polyangiitis; FeNO, fractional exhaled nitric oxide; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte/monocyte colony-stimulating factor; IgE, immunoglobulin E; IL, interleukin; NTM, non-tuberculous mycobacteria; TNF, tumour necrosis factor; TSLP, thymic stromal lymphopoietin; VOC, volatile organic compounds.