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Pulmonary type2 innate lymphoid cells in paediatric severe asthma
Kamis, 13 Jun 2019 09:08:33

Prasad NagakumarFranz PutturLisa G. GregoryLaura DenneyLouise FlemingAndrew BushClare M. LloydSejal Saglani

European Respiratory Journal 2019; DOI: 10.1183/13993003.01809-2018

Pulmonary type2 innate lymphoid cells in paediatric severe asthma : phenotype and response to steroids

Abstract

Children with severe therapy resistant asthma (STRA) have poor control despite maximal treatment, while those with difficult asthma (DA) have poor control from failure to implement basic management including adherence to therapy. Although recognised as clinically distinct, the airway molecular phenotype, including the role of ILCs and their response to steroids in DA and STRA is unknown.

Immunophenotyping of sputum and blood ILCs and T cells from STRA, DA and non-asthmatic controls was undertaken. Leukocytes were analysed longitudinally pre and post intramuscular triamcinolone in children with STRA. Cultured ILCs were also evaluated to assess steroid responsiveness in vitro.

Airway eosinophils, Th2 cells and ILC2s were significantly higher in STRA patients compared to DA and disease controls, while IL-17+ lymphoid cells were similar. ILC2s and Th2 cells were significantly reduced in vivo following intramuscular triamcinolone and in vitro with steroids. Asthma attacks and symptoms also reduced after systemic steroids despite persistence of steroid resistant IL-17+ cells and eosinophils.

Paediatric STRA and DA have distinct airway molecular phenotypes with STRA characterised by elevated type2 cells. Systemic corticosteroids but not maintenance inhaled steroids resulted in improved symptom control and exacerbations concomitant with a reduction in functional ILC2s despite persistently elevated IL-17+ lymphoid cells.

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. Puttur has nothing to disclose.

Conflict of interest: Dr. Gregory has nothing to disclose.

Conflict of interest: Dr. Denney has nothing to disclose.

Conflict of interest: Dr. Fleming reports other from GSK, other from Sanofi, other from Novartis, other from Boerhringer Ingelheim, other from Astra Zeneca, outside the submitted work.

Conflict of interest: Dr. Bush has nothing to disclose.

Conflict of interest: Dr. Lloyd has nothing to disclose.

Conflict of interest: Dr. Saglani has nothing to disclose.

Conflict of interest: Dr. Nagakumar has nothing to disclose.