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Mechanisms for Non-eosinophilic Asthma

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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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Authors and Affiliations

  1. Department of Internal Medicine, Allergy and Respiratory Center, Okayama Rosai Hospital, Okayama, Japan

    Arihiko Kanehiro

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  1. Arihiko Kanehiro
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Correspondence to Arihiko Kanehiro .

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Editors and Affiliations

  1. Department of Hematology and Respiratory Medicine, Kochi Medical School, Nankoku-shi, Kochi, Japan

    Akihito Yokoyama

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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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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-2789-6

  • Online ISBN: 978-981-13-2790-2

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