Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients

PLoS One. 2014 Feb 12;9(2):e88567. doi: 10.1371/journal.pone.0088567. eCollection 2014.


Introduction: Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.

Methods: We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.

Results: Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.

Conclusion: Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Cystic Fibrosis / blood*
  • Disease Progression
  • Fatty Acids, Unsaturated / blood
  • Female
  • Humans
  • Inflammation
  • Interleukins / blood
  • Kaplan-Meier Estimate
  • Lipid Peroxidation
  • Longitudinal Studies
  • Lung Diseases / blood
  • Lung Diseases / complications*
  • Male
  • Middle Aged
  • Probability
  • Proportional Hazards Models
  • Prospective Studies
  • Quality of Life
  • Recurrence
  • Respiratory Function Tests
  • Risk Factors
  • Spirometry
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Endothelial Growth Factor A / blood
  • Young Adult


  • Biomarkers
  • Fatty Acids, Unsaturated
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A