Abstract
Stratification of asthmatics based on relevant biomarkers enables it to predict the responsiveness against immune-targeted therapies in patients with asthma. Individualised therapy in patients with eosinophilic asthma has yielded improved clinical outcomes, and similar approaches in those with neutrophilic asthma have yet to be developed. We determined whether the colony stimulating factors (CSFs) in the airway reflect the inflammatory phenotypes of asthma and contribute to disease progression of neutrophilic asthma.
We analysed three different mouse models of asthma and assessed the cytokine profiles in sputum from human patients with asthma stratified according to inflammatory phenotype; in addition, we evaluated the therapeutic efficacy of various cytokine blockades in a mouse model of neutrophilic asthma.
Among the CSFs, airway granulocyte-CSF (G-CSF) contributes to airway neutrophilia by promoting neutrophil development in the bone marrow (BM), and thereby distinguishes neutrophilic inflammation from eosinophilic inflammation in mouse models of asthma. G-CSF is produced by concurrent stimulation of the lung epithelium with IL-17A and TNF-α; therefore, dual blockade of upstream stimuli using monoclonal antibodies or genetic deficiency of the cytokines in IL-17A × TNF-α double knockout (DKO) mice reduced the serum level of G-CSF, leading to alleviation of neutrophilic inflammation in the airway. In humans, the sputum level of G-CSF can be used to stratify patients with asthma with neutrophil-dominated inflammation.
Our results indicated that myelopoiesis-promoting G-CSF and cytokines as the upstream inducing factors are potential diagnostic and therapeutic targets in patients with neutrophilic asthma.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Kim reports In addition, Dr. Kim has a patent 10-2019-0057637 pending.
Conflict of interest: Dr. Kim has nothing to disclose.
Conflict of interest: Dr. Kim has nothing to disclose.
Conflict of interest: Dr. Kim reports In addition, Dr. Kim has a patent 10-2019-0057637 pending.
Conflict of interest: Dr. Lee has nothing to disclose.
Conflict of interest: Dr. Choi has nothing to disclose.
Conflict of interest: Dr. Park has nothing to disclose.
Conflict of interest: Dr. You has nothing to disclose.
Conflict of interest: Dr. Kang has nothing to disclose.
Conflict of interest: Dr. Lee has nothing to disclose.
Conflict of interest: Dr. Park has nothing to disclose.
Conflict of interest: Dr. Park has nothing to disclose.
Conflict of interest: Dr. Park has nothing to disclose.
Conflict of interest: Dr. Park reports In addition, Dr. Park has a patent 10-2019-0057637 pending.
Conflict of interest: Dr. Lee reports In addition, Dr. Lee has a patent 10-2019-0057637 pending.
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- Received April 26, 2019.
- Accepted November 5, 2019.
- Copyright ©ERS 2019