The usefulness of soluble receptor for advanced glycation end-products in the identification of COPD frequent exacerbator phenotype

Abstract

Joanna Miłkowska-Dymanowska,1,2,* Adam J Białas,1,2,* Karolina Szewczyk,1 Zofia Kurmanowska,1 Paweł Górski,1,2 Wojciech J Piotrowski1,2 1Department of Pneumology and Allergy, Medical University of Łódź, Łódź, Poland; 2Healthy Ageing Research Centre, Medical University of Łódź, Łódź, Poland *These authors contributed equally to this work Introduction: Exacerbations of COPD (ECOPDs) are important events in the course of COPD, accelerating the rate of decline in lung function and increasing the mortality risk. A growing body of evidence suggests the significance of the “frequent exacerbator” phenotype. This phenotype seems to be associated with a more severe airflow limitation, symptoms, health-related quality of life impairment, and higher mortality. However, there is no described biomarker that would help to identify this group of patients. Patients and methods: Patients with COPD in “D” GOLD category were monitored for 3 years according to events of ECOPD. Serum samples were collected from the patients. Circulating level of plasma soluble receptor for advanced glycation end-products (sRAGE) was measured using commercially available high sensitivity kits. The receiver operating characteristic (ROC) curve analysis was used to assess the usefulness of sRAGE to identify frequent exacerbator phenotype. Log-rank test was used in the analysis of time to the subsequent exacerbation. Pearson (R) or Spearman’s rank (RS) correlation coefficients were used for correlation analysis. Results: Nineteen patients were enrolled. The area under the ROC curve (AUROC) for sRAGE for the identification of frequent exacerbator phenotype was 0.81. Analysis identified the cutoff point as 850.407 pg/mL, characterized by a sensitivity of 0.80 (95% CI: 0.28–1.0) and specificity of 0.93 (95% CI: 0.66–1.0). Additionally, in the group with sRAGE ≤850.407 pg/mL, we observed significantly shorter time to the subsequent exacerbation: median of 32 vs 105.5 days (P=0.03). Correlation analysis revealed significant negative correlation between sRAGE and the number of exacerbations requiring hospitalization during the whole time of follow-up (RS=-0.53; P=0.02) and significant positive correlation with FEV1 expressed as the percentage of reference value (R=0.6; P=0.006). Conclusion: sRAGE seems to be useful in the identification of frequent exacerbator phenotype. This parameter may also be used in the prediction of time to ECOPD. Our findings should be confirmed in a sufficiently powered larger sample. Keywords: sRAGE, frequent exacerbator phenotype of COPD, exacerbations of COPD, COPD, prediction of AECOPD

Keywords

• sRAGE
• frequent exacerbator phenotype of COPD
• exacerbations of COPD
• COPD