Mechanisms for Non-eosinophilic Asthma

  • Arihiko KanehiroEmail author
Part of the Respiratory Disease Series: Diagnostic Tools and Disease Managements book series (RDSDTDM)


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.


Eosinophilic asthma Non-eosinophilic asthma Non-eosinophilic airway inflammation Neutrophilic inflammation Paucigranulocytic inflammation 



Chemokine ligand 1


Chemokine receptor 2


Cysteinyl leukotrienes


Eosinophil cationic protein


Eosinophil peroxidase




Innate lymphoid cell




Major basic protein


Matrix metalloproteinase-9

NK cell

Natural killer cell

NKT cell

Natural killer T cell


Prostaglandin D2


Reactive oxygen species


Transforming growth factor-β


Tumor necrosis factor-α


Thymic stromal lymphopoietin


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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineAllergy and Respiratory Center, Okayama Rosai HospitalOkayamaJapan

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