Sputum TWEAK expression correlates with severity and degree of control in non-eosinophilic childhood asthma

BACKGROUND: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to play a role in the pathogenesis of various inflammatory diseases. However, no study has been performed on childhood asthma. METHODS: Ninety-five children with asthma and 78 controls aged 5-18 years were included. Sputum induction, pulmonary function test (PFT), and methacholine challenge test were performed. The subjects were divided into the eosinophilic airway (EA) and non-EA (NEA) groups based on sputum analysis and into the high and low TWEAK groups according to the TWEAK cutoff level (263.0 pg/mL). TWEAK in induced sputum supernatant was measured through enzyme-linked immunosorbent assay. RESULTS: Children with asthma had higher TWEAK levels than healthy controls (493.0 [157.1-904.3] vs 118.2 (67.5-345.5) pg/mL, P < .001). Sputum TWEAK levels were significantly correlated with PFT parameters reflecting airway obstruction. This association was particularly prominent in subjects with NEA inflammation. Significant differences in FEF25-75 (maximum mid-expiratory flow, % predicted; P = .017), AX (reactance area; P < .001), R5-R20 (difference between resistance at 5 and 20 Hz; P = .025), and X5 (reactance at 5 Hz, % predicted; P < .001) were noted between the high and low TWEAK groups within the NEA group. Sputum TWEAK level also showed significant positive correlations with asthma severity (r = .358, P = .001) and control status (r = .470, P < .001), distinctively in subjects with NEA inflammation. CONCLUSIONS: Airway TWEAK may play a role in small airway inflammation especially in children with non-eosinophilic asthma.restrictio