Abstract
Asthma can be broadly subdivided into eosinophilic or non-eosinophilic phenotypes based on the inflammatory cellular patterns seen in sputum, blood, and airway tissue. However, the most appropriate cutoff value of non-eosinophilic asthma that identifies individuals in whom neutrophils are activated and contributing to the pathogenic processes in asthma is not elucidated compared to eosinophilic asthma. Major clinical phenotypes of non-eosinophilic asthma include those patients with neutrophilic, paucigranulocytic, and late-onset obesity-related asthma. The mechanism of non-eosinophilic asthma is very complicated and has not been investigated in detail; nonetheless many potential molecular pathways may be implicated in the development of non-eosinophilic asthma.
The cause of airway neutrophilia in asthma is possibly due to augmented innate immunity, IL-23-Th17-IL-17-ILC3 pathway-mediated neutrophilic inflammation, delayed apoptosis of neutrophils caused by epithelial cell-derived cytokines and growth factors, corticosteroid treatment inducing impaired apoptosis of neutrophils, and ineffective macrophage efferocytosis of neutrophils, upregulated NLRP-3 inflammasome and p38/MAPK activity, and reduced lipoxin levels, as well as an altered airway microbiome. Non-eosinophilic inflammation is associated with an impaired therapeutic response to inhaled corticosteroids and usually results in severe uncontrolled asthma. Better understanding of the mechanisms of non-eosinophilic inflammation in asthma will identify new approaches for the treatment of severe non-eosinophilic asthma patients.
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Abbreviations
- CXCL1:
-
Chemokine ligand 1
- CXCR2:
-
Chemokine receptor 2
- Cys-LTs:
-
Cysteinyl leukotrienes
- ECP:
-
Eosinophil cationic protein
- EPO:
-
Eosinophil peroxidase
- IFN:
-
Interferon
- ILC:
-
Innate lymphoid cell
- LT:
-
Leukotriene
- MBP:
-
Major basic protein
- MMP-9:
-
Matrix metalloproteinase-9
- NK cell:
-
Natural killer cell
- NKT cell:
-
Natural killer T cell
- PGD2:
-
Prostaglandin D2
- ROS:
-
Reactive oxygen species
- TGF-β:
-
Transforming growth factor-β
- TNF-α:
-
Tumor necrosis factor-α
- TSLP:
-
Thymic stromal lymphopoietin
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Kanehiro, A. (2019). Mechanisms for Non-eosinophilic Asthma. In: Yokoyama, A. (eds) Advances in Asthma. Respiratory Disease Series: Diagnostic Tools and Disease Managements. Springer, Singapore. https://doi.org/10.1007/978-981-13-2790-2_4
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DOI: https://doi.org/10.1007/978-981-13-2790-2_4
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