Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations

PLoS One. 2017 Feb 8;12(2):e0171229. doi: 10.1371/journal.pone.0171229. eCollection 2017.

Abstract

Rationale: C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain.

Objectives: To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response.

Methods: We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE).

Measurements and main results: 53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61-0.83; p<0.001). 23% of PEx events were characterized by an admission CRP of > 75 mg/L with a specificity of 90% for treatment non-response.

Conclusions: Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • C-Reactive Protein / metabolism*
  • Cystic Fibrosis / blood*
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Disease Progression
  • Female
  • Genotype
  • Humans
  • Lung Diseases / diagnosis*
  • Lung Diseases / etiology*
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Respiratory Function Tests
  • Sputum / microbiology
  • Young Adult

Substances

  • Biomarkers
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • C-Reactive Protein

Grants and funding

This study was supported by Cystic Fibrosis Canada (http://www.cysticfibrosis.ca/research/what-we-are-funding), the British Columbia Lung Association (https://bc.lung.ca/recent-grant-recipients-0), the University of British Columbia Summer Student Research Program (http://www.med.ubc.ca/current-learners/summer-student-research-program/), and the Providence Health Care Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.