Assessment of sputum inflammatory, neural, and remodelling mediators in eosinophilic and non-eosinophilic asthma

Abstract

Aims: To assess the role of neural and remodelling pathways, alongside inflammatory mechanisms, in eosinophilic (EA) and non-eosinophilic asthma (NEA).

Methods: 111 asthmatics and 62 non-asthmatics (14-21 years) underwent sputum induction testing. Twenty-four mediators were measured in supernatant. EA (n=52) and NEA (n=59) were defined using a sputum eosinophil cut-point of 2.5%.

Results: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, p=0.03), periostin (33.8 vs 9.4 pg/mL, p=0.01), and eosinophil cationic protein (ECP; 220.1 vs 83.7 ng/mL, p=0.03) were found in asthmatics compared to non-asthmatics. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, p=0.02) but not NEA (27.8 vs 22.4 ng/mL, p=0.22). EA had higher levels of inflammatory (ECP: 496 vs 100.3 ng/mL, p=<0.01; interleukin-1β: 286 vs 209.3 pg/mL, p=0.03; histamine: 5805 vs 3173 pg/mL, p=<0.01) and remodelling (vascular endothelial growth factor: VEGF; 3.3 vs 2.5 ng/mL, p=0.03; periostin: 47.7 vs 22.1 pg/mL, p=0.04) mediators compared to NEA. Whilst macrophage counts were correlated with neural mediators such as neurokinin A (r=0.27, p=0.01), nociceptin (r=0.30, p=0.02), and nerve growth factor-β: NGF-β; r=0.19, p=0.04), granulocytes correlated with inflammatory and remodelling mediators; e.g., ECP and VEGF correlated with neutrophils (r=0.53 & r=0.33 respectively, p≤0.01) and eosinophils (r=0.53& r=0.29 respectively, p≤0.01).

Conclusions: Inflammatory cells/mediators were often associated with neural and remodelling mediators, suggesting that these mechanisms coexist with inflammation. Neural and remodelling pathways may not play a role in NEA, but nociceptin may be important in EA.