Abstract
BackgroundAsthma 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.MethodsWe 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.ResultsThe 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).ConclusionsSevere 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.
Highlights
Asthma is a heterogeneous disease and understanding this heterogeneity will enable the realisation of precision medicine
Subjects that had an exacerbation visit had a higher body mass index (BMI) and a higher proportion of severe asthma (Step 5 according to the Global Initiative for Asthma (GINA) guidelines)
The strongest discriminators of an exacerbation in adults were sputum TNF-R2 and IL-6R, with Receiver-operator characteristic (ROC) area under the curve (AUC) of 0.69 and 0.68, respectively (Fig. 2a)
Summary
Asthma is a heterogeneous disease and understanding this heterogeneity will enable the realisation of precision medicine. Comparisons of cytokine profiles in eosinophilic versus non-eosinophilic and Type 2 (T2)high versus T2low asthma and between asthma, chronic obstructive pulmonary disease (COPD) and asthma/COPD overlap have provided insights into potential underlying mechanisms and responses to therapy [5,6,7,8]. Approaches to stratify cytokine profiles in stable disease have been applied widely, but to date there are only a few studies that have explored sputum inflammatory mediators at exacerbations in adults [9,10,11,12,13] and children [14, 15]. There is a paucity of data profiling a broad array of sputum inflammatory mediators in stable disease versus severe exacerbations
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