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C-Reactive Protein in Stable Cystic Fibrosis: An Additional Indicator of Clinical Disease Activity and Risk of Future Pulmonary Exacerbations

Abstract

Elias Matouk, Dao Nguyen, Andrea Benedetti, Joanie Bernier, James Gruber, Jennifer Landry, Simon Rousseau, Heather G Ahlgren, Larry C Lands, Gabriella Wojewodka and Danuta Radzioch

Introduction: In stable adult cystic fibrosis (CF) patients, we assessed the role of baseline high sensitivity C-reactive protein (hs-CRP) on CF clinical variables and frequency of intravenous (IV) treated pulmonary exacerbations (PExs) 1-year post- baseline. Methods: We recruited 51 clinically stable CF patients from our Adult CF Center. We incorporated collected parameters into Matouk CF clinical score and CF questionnaire-revised quality of life score (QOL). We used the clinical minus complications subscores as a clinical disease activity score (CDAS). We dichotomized our patients according to the cohort median baseline hs-CRP of 5.2 mg/L. Results: Patients in the high hs-CRP group (≥ 5.2 mg/L) demonstrated worse CDAS (r=0.67, p=0.0001) and QOL scores (r=0.57, p=0.0017) at a given FEV1 % predicted. In both hs-CRP groups, prior-year IV-treated PExs and baseline CDASs were significant predictors of future IV-treated PExs. Interestingly, the association between baseline CDAS and future PExs frequency was more robust in the high compared to the low hs-CRP group (r=–0.88, p<0.0001, r=–0.48, p=0.017, respectively) with a steeper regression slope (p=0.001). In addition, a significant interaction was demonstrated between elevated baseline hs-CRP levels and CDASs for the prediction of increased risk of future PExs (p=0.02). This interaction provided an additional indicator of clinical disease activity and added another dimension to the prior year PExs frequency phenotype to identify patients at increased risk for future PExs. Conclusion: Stable CF patients with elevated baseline hs-CRP (≥ 5.2 mg/L) demonstrated worse clinical disease activity and QOL scores at a given level of disease severity (FEV1 % predicted). Elevated baseline hs-CRP values combined with clinical disease activity scores are associated with increased risk for future IV-treated PExs even in those with mild clinical disease activity scores.

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