Sputum Biomarkers of Inflammation to Track Acute Respiratory Events in School-Age Children with Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is characterized by neutrophil-driven airway inflammation and acute respiratory events (AREs) that contribute to progressive lung damage. AREs are clinically heterogeneous and often occur without measurable changes in lung function. This study aimed to evaluate the utility of molecular airway inflammatory markers for detecting AREs in school-age children with CF. We performed a secondary analysis of a prospective observational study of children with CF (ages 6.7–16.8 years) followed for two years. Sputum samples were collected from 50 participants during stable visits and AREs. Concentrations of 14 inflammatory cytokines were measured using ELISA and multiplex assays. Associations with lung function (ppFEV1 and lung clearance index [LCI]) and time to next ARE were assessed. A total of 179 sputum samples were analyzed, including 64 collected during AREs. Calprotectin, interleukin-8 (IL-8), and IL-1β were increased during AREs compared with stable visits, although concentrations frequently remained within ranges observed at stable visits. Other cytokines, including GM-CSF, IL-17A, IL-1α, TNF-α, and SPLUNC-1, were predictive of shorter time to subsequent AREs. No biomarker correlated with lung function measures. These findings indicate that airway inflammatory cytokine changes are associated with clinically diagnosed AREs but not with pulmonary function, supporting their potential role as complementary biomarkers in CF care.