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

Pediatr Allergy Immunol. 2018 Feb;29(1):42-49. doi: 10.1111/pai.12827. Epub 2017 Nov 29.

Abstract

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.

Keywords: airway inflammation; asthma; children; tumor necrosis factor-like weak inducer of apoptosis (TWEAK).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / metabolism*
  • Asthma / physiopathology
  • Bronchial Provocation Tests / methods
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Cytokine TWEAK / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Methacholine Chloride / administration & dosage
  • Oscillometry / methods
  • Severity of Illness Index
  • Spirometry / methods
  • Sputum / metabolism*

Substances

  • Cytokine TWEAK
  • TNFSF12 protein, human
  • Methacholine Chloride