Lung function is associated with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in school-aged children

Abstract

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. A complex relationship exists between TRAIL and the lung where both elevated TRAIL and TRAIL deficiency are associated with lung impairment. In neonatal mice, TRAIL is thought to translate respiratory infections into chronic lung disease but the association between TRAIL and lung function in childhood has not been assessed.

Aim: To assess the cross-sectional relationship between TRAIL levels and lung function in school-aged children.

Methods: The study cohort consisted of 170 school-aged children attending four schools in Malmö, Sweden. Lung volumes, impulse oscillometry (IOS) and serum TRAIL were measured for all children. Linear regression was used to assess changes in lung function per 1-SD increase in TRAIL. General linear models were used to assess mean lung function by tertiles (T) of TRAIL.

Results: Mean age was 9.9 years (±0.6). A 1-SD increase in TRAIL was associated with lower values of FEV₁ and FEV₁/VC (change in FEV₁ (L) and FEV₁/VC ratio: -0.047, p-value 0.002, and -0.011, p-value 0.020, respectively) and higher values of lung resistance (change in R₅ and R₂₀ (kPa/(L/s)): 0.035, p-value <0.001 and 0.027, p-value 0.004, respectively). These associations remained significant after excluding children with pre-existing lung disease. Higher TRAIL levels were associated with more negative values for X₅ in general linear models (Mean X₅ (kPa/(L/s)) in T1 (low TRAIL): -0.193 vs T3 (high TRAIL): -0.216, p-value 0.026).

Conclusions: High TRAIL levels are significantly associated with markers of pulmonary airflow obstruction in school-aged children.

Keywords: Impulse oscillometry; Lung function; Tumour necrosis factor-related apoptosis-inducing ligand.