Pilot Study Uses CRP, Calprotectin to Diagnose Pulmonary Exacerbations

Blood C-reactive protein (CRP) and calprotectin levels can reliably identify pulmonary exacerbations in cystic fibrosis (CF) patients, making them promising diagnostic biomarkers, a pilot study has found.

Although further investigations are necessary to determine their clinical applicability, the researchers note that “a step-wise algorithm that incorporates both absolute and fold-change cut-offs can increase the diagnostic performance of these biomarkers.”

The study, “Circulating CRP and calprotectin to diagnose CF pulmonary exacerbations,” was published in the Journal of Cystic Fibrosis.

CF patients are particularly susceptible to bouts of increased respiratory symptoms and diminished lung function called pulmonary exacerbations, which may result from infection or inflammation. For many CF patients, pulmonary exacerbations go undiagnosed and untreated, leaving them at risk for permanent lung damage and loss of function. Tools to better identify pulmonary exacerbations will help with the treatment and long-term outcomes of CF patients. 

CRP and calprotectin are widely-used biomarkers for systemic inflammation and they have been used to monitor chronic inflammation in disorders like CF. Both proteins show elevated levels during pulmonary exacerbations and a reduction after treatment.

Now, researchers at the University of British Columbia, Canada, sought to assess the variability of CRP and calprotectin levels in CF patients, as well as their potential as diagnostic biomarkers for pulmonary exacerbations.

The pilot study included 19 patients enrolled in a longitudinal CF blood biomarker study at St. Paul’s Hospital Adult CF Clinic in Vancouver, from July 2012 to August 2018. The group of patients analyzed was 63.2% male (12 of 19) with a mean age of 40.8 yeas and a total of 102 clinic visits, of which 56 were stable and 46 were during pulmonary exacerbations.

CRP and calprotectin levels varied widely within and between individuals with CF, particularly when compared to other disease signs and symptoms such as Chronic Respiratory Infection Symptom Score and lung function. The CRP and calprotectin thresholds to distinguish a stable clinical visit from a pulmonary exacerbation also were evaluated. 

The optimal absolute threshold for CRP was 9.5 mg/L, with 73% specificity (the ability of a test to correctly identify people without a certain condition), and 76% sensitivity (the ability of a test to correctly identify people with a certain condition ). The optimal CRP fold-change between stable and pulmonary exacerbation was 2.2, with 96% specificity and 50% sensitivity.

The optimal absolute threshold for calprotectin was 8.1 mg/L, with 79% specificity and 61% sensitivity. The optimal fold-change was 1.3-fold, with a specificity of 88% and a sensitivity of 57%.

An algorithm that combines both the absolute and fold-change thresholds for CRP and calprotectin was able to distinguish between a stable visit and pulmonary exacerbation with 80% sensitivity and 88% specificity. Similar sensitivity was demonstrated when using the algorithm to evaluate post-treatment visits.

“In conclusion, despite the substantial variability in CRP and calprotectin levels within and between individuals, these biomarkers appear capable of discriminating stable vs. PEx [pulmonary exacerbation] in CF patients using a combination of absolute and fold-change cut-offs,” the researchers wrote.

However, “further validation studies are required prior to implementing these diagnostic thresholds,” the team added.