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


OBJECTIVE
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).


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.
Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, British Columbia, Canada.
Ashutosh
A
Sharma
Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Gordon
G
Kirkpatrick
Prevention Of Organ Failure (PROOF) Centre of Excellence, Vancouver, British Columbia, Canada.
Virginia
V
Chen
Department of Medicine, Division of Respiratory Medicine, University of Calgary, Calgary, Alberta, Canada.
Kate
K
Skolnik
Prevention Of Organ Failure (PROOF) Centre of Excellence, Vancouver, British Columbia, Canada.
Zsuzsanna
Z
Hollander
Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, British Columbia, Canada.|Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Pearce
P
Wilcox
Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, British Columbia, Canada.|Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Bradley S
BS
Quon
D000328:Adult; D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000097:blood* / Q000150:complications* / Q000235:genetics / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008171:Lung Diseases / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D012129:Respiratory Function Tests; D013183:Sputum / Q000382:microbiology; D055815:Young Adult
D015415:Biomarkers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002097:C-Reactive Protein