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

Abstract

RationaleC-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.ObjectivesTo 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.MethodsWe 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 results53% 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.ConclusionsAdmission 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.

Cystic fibrosis year in review 2017

“…Tools to predict response to exacerbation therapy could optimize care and allow more precise anticipatory guidance to patients. Change in C‐reactive protein (CRP) from days 0 to 5 of IV antibiotic therapy did not predict response in an analysis of 83 exacerbations from 2013 to 2015 in a single hospital . However, very high CRP (>75 mg/L) at admission predicted non‐response and CRP level at admission predicted time to next exacerbation, demonstrating the potential utility of CRP as a clinical predictor for exacerbations.…”

C‐reactive protein levels in acute respiratory exacerbations of cystic fibrosis

“…7 A study of 27 patients reported that the CRP level was not associated with the severity of pulmonary exacerbations but was associated with specific clinical characteristics, which included Pseudomonas and Aspergillus infection and treatment with corticosteroids. 9 Loh et al assessed the role on CRP and procalcitonin and erythrocyte sedimentation rate in acute exacerbations of CF. 9 Loh et al assessed the role on CRP and procalcitonin and erythrocyte sedimentation rate in acute exacerbations of CF.…”

“…8 Sharma et al found that the admission CRP predicted treatment non-response and time until next exacerbation. 9 Loh et al assessed the role on CRP and procalcitonin and erythrocyte sedimentation rate in acute exacerbations of CF. They found CRP levels rise with exacerbations.…”

Serum and Sputum Iron Trends Distinguigh Responders and Non-Responders to Treatment of Cystic Fibrosis Pulmonary Exacerbation

“…In ammation is a pathophysiologic hallmark of CF (21), but limited information exists about correlations between in ammatory mediator levels and lung function (22)(23)(24) or HRQoL (22) during PEXs because few studies have monitored PwCF throughout a complete PEX cycle (i.e., from baseline health to PEX onset and serially during PEX treatment to recovery). Accordingly, there remains a need to identify biochemical tests that are easily performed in clinical laboratories and are able to identify groups of PwCF with different physiologic and symptomatic responses to PEX treatment.…”

“…Accordingly, there remains a need to identify biochemical tests that are easily performed in clinical laboratories and are able to identify groups of PwCF with different physiologic and symptomatic responses to PEX treatment. Concentrations of certain cytokines and protein effectors of in ammation in blood and sputum from PwCF measured before, during, and after PEXs could have diagnostic and prognostic utility (12,(24)(25)(26)(27). With the exceptions of calprotectin and C-reactive protein, clinical laboratories do not routinely quantify these substances in biological samples, which is a barrier to their widespread application as tools to monitor PEX treatment responses (28,29).…”