Neonates with reduced neonatal lung function have systemic low-grade inflammation

Abstract

Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced lung function.

Objective: We sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation.

Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children of the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort who had completed neonatal lung function testing at age 4 weeks. Associations between neonatal lung function indices and inflammatory biomarkers were investigated by conventional statistics and unsupervised principal component analysis.

Results: The neonatal forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP (β-coefficient, -0.12; 95% CI, -0.21 to -0.04; P < .01) and IL-6 (β-coefficient, -0.10; 95% CI, -0.18 to -0.01; P = .03) levels. The multivariate principal component analysis approach, including hs-CRP, IL-6, TNF-α, and CXCL8, confirmed a uniform upregulated inflammatory profile in children with reduced forced expiratory volume at 0.5 seconds (P = .02). Adjusting for body mass index at birth, maternal smoking, older children in the home, neonatal bacterial airway colonization, infections 14 days before, and asthmatic symptoms, as well as virus-induced wheezing, at any time before biomarker assessment at age 6 months did not affect the associations.

Conclusion: Diminished neonatal lung function is associated with upregulated systemic inflammatory markers, such as hs-CRP.

Keywords: Asthma; children; high-sensitivity C-reactive protein; proinflammatory cytokines; spirometry.