sRAGE: A novel potential biomarker to assess the risk of acute respiratory events

Frequent episodes of acute respiratory events (AREs) in chronic obstructive pulmonary disease (COPD) or chronic bronchitis (CB) are associated with poor prognosis, but often difficult to recognise. Serum sRAGE may help to differentiate patients experiencing AREs in mild COPD from those with chronic bronchitis (CB).

Frequent episodes of AREs in mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I) or CB accelerate the progression to more severe COPD [1,2]. Thus, assessing ARE risk is crucial for managing COPD and CB, to decide whether additional therapy is necessary. ARE risk depends on the history of earlier aggravations and related scores, which are relatively subjective and can often not be detected. Dr Jinying Chen (Sichuan University, China) and his team conducted an analytical study to identify blood-based biomarkers to objectively distinguish CB and mild COPD patients with a high risk of AREs [3]. The researchers extracted relevant data from a comprehensive, prospective, longitudinal cohort study (COMPASS; NCT04853225 [4]) in which they investigated disease progression and patient outcomes of COPD in China. The researchers enrolled 347 patients in a COMPASS sub-cohort (96 with CB and 251 with COPD [82 GOLD I, 121 GOLD II, and 48 GOLD III]) and assessed 4 blood-based biomarkers (CC16, HbA1c, IP-10, and soluble receptor for advanced glycation end products [sRAGE]) that are potentially related to a negative prognosis.

Analysis revealed that, out of the 4 investigated biomarkers, only the sRAGE levels showed significant changes. It was lower in COPD patients with frequent ARE compared with COPD patients with infrequent ARE (672.45 pg/mL vs 844.01 pg/mL; P=0.020) but was higher in CB patients with frequent ARE compared with CB patients with infrequent ARE (912.9 pg/mL vs 811.30 pg/mL; P=0.058). Receiver operating characteristic curve analysis also indicated that sRAGE levels could distinguish between COPD patients with frequent ARE and COPD patients with infrequent ARE  (area under the curve [AUC] 0.620; P=0.013) and between CB patients with frequent ARE and CB patients with infrequent ARE  (AUC 0.647; P=0.058).

Despite presenting with similar symptoms (except airflow limitation in CB), CB patients with frequent ARE and GOLD-I-COPD patients with frequent ARE had varied sRAGE levels (912.90 vs 699.60; P=0.018), suggesting its role in the deterioration of CB to frequent COPD.

The authors concluded that sRAGE is a promising blood biomarker for the differentiation of frequent CB and frequent COPD. The different sRAGE pattern between CB and COPD can imply a distinct pathogenic role. These findings emphasise the need for further research into sRAGE as a diagnostic tool and potential therapeutic target in respiratory diseases.

1. Global Strategy for the Diagnosis, Management, and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease 2023.
2. Dransfield MT, et al. Am J Respir Crit Care Med 2017;195:324-330.

3. Chen J, et al. Blood-biomarkers to assess acute respiratory events (ARE) risk in COPD and chronic bronchitis (CB). Abstract 617, ERS International Congress 2023, 9–13 September, Milan, Italy.
4. Liang Z, et al. ERJ Open Res. 2021 Sep 13;7(3):00201-2021.
5. Jones P, et al. Eur Respir J 2022;60:4552.

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Posted on 29 October 202329 October 2023