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

**Authors:** Elad Ben-Meir, Lucy Perrem, Gyde Nissen, Michelle Shaw, Felix Ratjen, Hartmut Grasemann

PMC · DOI: 10.3390/ijms27031616 · International Journal of Molecular Sciences · 2026-02-06

## TL;DR

This study explores sputum biomarkers to detect acute respiratory events in children with cystic fibrosis, finding that certain inflammatory markers increase during these events.

## Contribution

The study identifies specific inflammatory cytokines that may serve as complementary biomarkers for tracking acute respiratory events in cystic fibrosis.

## Key findings

- Calprotectin, IL-8, and IL-1β were elevated during acute respiratory events compared to stable periods.
- Cytokines like GM-CSF and IL-17A predicted shorter time to subsequent acute respiratory events.
- No biomarker correlated with lung function measures like ppFEV1 or LCI.

## 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.

## Linked entities

- **Proteins:** IL8L1 (interleukin 8-like 1), CXCL8 (C-X-C motif chemokine ligand 8), IL1B (interleukin 1 beta), CSF2 (colony stimulating factor 2), IL17A (interleukin 17A), IL1A (interleukin 1 alpha), TNF (tumor necrosis factor), BPIFA1 (BPI fold containing family A member 1)
- **Diseases:** cystic fibrosis (MONDO:0009061)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, BPIFA1 (BPI fold containing family A member 1) [NCBI Gene 51297] {aka LUNX, NASG, PLUNC, SPLUNC1, SPURT, bA49G10.5}
- **Diseases:** CF (MESH:D003550), Inflammation (MESH:D007249), lung damage (MESH:D008171)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12898048/full.md

## References

57 references — full list in the complete paper: https://tomesphere.com/paper/PMC12898048/full.md

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Source: https://tomesphere.com/paper/PMC12898048