C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response

Background: C-reactive protein (CRP) has been proposed as a biomarker for pulmonary exacerbation (PEx) diagnosis and treatment response. CRP >75mg/L has been associated with increased risk of PEx treatment failure. We have analyzed CRP measures as biomarkers for clinical response during the STOP2 PEx study (NCT02781610). Methods: CRP measures were collected at antimicrobial treatment start (V1), seven to 10 days later (V2), and two weeks after treatment end (V3). V1 log₁₀CRP concentrations and log₁₀CRP change from V1 to V3 correlations with clinical responses (changes in lung function and symptom score) were assessed by least squares regression. Odds of intravenous (IV) antimicrobial retreatment within 30 days and future PEx hazard associated with V1 and V3 CRP concentrations and V1 CRP >75 mg/L were studied by adjusted logistic regression and proportional hazards modeling, respectively. Results: In all, 951 of 982 STOP2 subjects (92.7%) had CRP measures at V1. V1 log₁₀CRP varied significantly by V1 lung function subgroup, symptom score quartile, and sex, but not by age subgroup. V1 log₁₀CRP correlated moderately with log₁₀CRP change at V3 (r²=0.255) but less so with lung function (r²=0.016) or symptom (r²=0.031) changes at V3. Higher V1 CRP was associated with greater response. CRP changes from V1 to V3 only weakly correlated with lung function (r²=0.061) and symptom (r²=0.066) changes. However, V3 log₁₀CRP was associated with increased odds of retreatment (P = .0081) and future PEx hazard (P = .0114). Discussion: Despite consistent trends, log₁₀CRP change was highly variable with only limited utility as a biomarker of PEx treatment response.