Multimodal Noninvasive Assessment of C-Reactive Protein for Systemic Inflammation in Adults: Cross-Sectional Study
Background: Accurate and accessible measurements of inflammatory biomarkers are crucial for the diagnosis and monitoring of inflammatory diseases. The gold-standard C-reactive protein (CRP) requires venipuncture, which, despite providing high-quality samples, can cause discomfort, anxiety, and pain, particularly in vulnerable populations such as elderly patients. It is also resource intensive, unsuitable for remote or at-home use, and lacks continuous monitoring capability. These limitations limit patient autonomy and self-management, potentially leading to poorer prognosis due to delays in assessment and medical treatments. As digital health technologies advance, there is increasing interest in leveraging digital biomarkers for remote and real-time monitoring of systemic inflammation (SI). Digital biomarkers derived from non-invasive biofluids could provide a scalable solution for tracking inflammatory status, offering a patient-centered alternative to traditional blood-based assessments. To date, however, there is no consensus on the most suitable modality for assessment or its digitization potential. Therefore, a comprehensive evaluation of the #feasibility, reliability, and patient acceptability towards non-invasive, digital inflammatory biomarkers is needed. Objective: Our aim is to evaluate the #feasibility of various non-invasive methods to assess inflammatory markers and identify the optimal modality for predicting serum CRP levels. Methods: Inflammatory biomarkers were assessed in 20 participants (10 patients with SI defined as a CRP level >5 mg/l and 10 controls) using six non-invasive samples (urine, sweat, saliva, exhaled breath, core body temperature, and stool samples) alongside serum samples. Patient preferences were retrieved via a questionnaire. Mann-Whitney U test, Spearman’s correlation, and all-subset regression were conducted to assess the relationships between serum and non-serum biomarkers and to identify optimal predictive models for serum CRP levels. Results: CRP levels were significantly elevated in the inflammation group compared to controls in urine (median: 4.5 vs. 0.69 μg/mmol, p=0.001) and saliva (median: 4910 vs. 473 pg/ml, p=0.001). Urine and saliva CRP levels strongly correlated with serum CRP (rsp=0.886, p