Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum

BMC Pulmonary Medicine

Pee Hwee Pang¹  Chris Newby²  Dhananjay Desai²  Beverley Hargadon²  Michael A. Ghebre²  Chris E. Brightling²  Erol A. Gaillard²  Joanne Woods³  Richard D. May³  Suzanne E. Cohen³  Athula Herath³  Laura Rapley³ 

[1] Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital;Institute for Lung Health NIHR Leicester Biomedical Research Centre Department of Respiratory Sciences, University of Leicester and University Hospitals of Leicester NHS Trust;MedImmune Ltd;

关键词: Asthma;    Cytokines;    Sputum;    Biomarkers;   

DOI  :  10.1186/s12890-019-0906-7

来源: DOAJ

【 摘 要 】

Abstract Background Asthma is a heterogeneous disease and understanding this heterogeneity will enable the realisation of precision medicine. We sought to compare the sputum and serum inflammatory profiles in moderate-to-severe asthma during stable disease and exacerbation events. Methods We recruited 102 adults and 34 children with asthma. The adults were assessed at baseline, 3, 6, and 12-month follow-up visits. Thirty-seven subjects were assessed at onset of severe exacerbation. Forty sputum mediators and 43 serum mediators were measured. Receiver-operator characteristic (ROC) curves were constructed to identify mediators that distinguish between stable disease and exacerbation events. The strongest discriminating sputum mediators in the adults were validated in the children. Results The mediators that were significantly increased at exacerbations versus stable disease and by ≥1.5-fold were sputum IL-1β, IL-6, IL-6R, IL-18, CXCL9, CXCL10, CCL5, TNFα, TNF-R1, TNF-R2, and CHTR and serum CXCL11. No mediators decreased ≥1.5-fold at exacerbation. The strongest discriminators of an exacerbation in adults (ROC area under the curve [AUC]) were sputum TNF-R2 0.69 (95% CI: 0.60 to 0.78) and IL-6R 0.68 (95% CI: 0.58 to 0.78). Sputum TNF-R2 and IL-6R were also discriminatory in children (ROC AUC 0.85 [95% CI: 0.71 to 0.99] and 0.80 [0.64 to 0.96] respectively). Conclusions Severe asthma exacerbations are associated with increased pro-inflammatory and Type 1 (T1) immune mediators. In adults, sputum TNF-R2 and IL-6R were the strongest discriminators of an exacerbation, which were verified in children.

【 授权许可】

Unknown