Abstract
BackgroundThere is a strong need for biomarkers to better characterize individuals with COPD and to take into account the heterogeneity of COPD. The blood protein sRAGE has been put forward as promising biomarker for COPD in general and emphysema in particular. Here, we measured plasma sRAGE levels using quantitative LC–MS and assessed whether the plasma sRAGE levels associate with (changes in) lung function, radiological emphysema parameters, and radiological subtypes of emphysema.MethodsThree hundred and twenty-four COPD patients (mean FEV1: 63%predicted) and 185 healthy controls from the COPDGene study were selected. Plasma sRAGE was measured by immunoprecipitation in 96-well plate methodology to enrich sRAGE, followed by targeted quantitative liquid chromatography-mass spectrometry. Spirometry and HRCT scans (inspiration and expiration) with a 5-year follow-up were used; both subjected to high quality control standards.ResultsLower sRAGE values significantly associated with the presence of COPD, the severity of airflow obstruction, the severity of emphysema on HRCT, the heterogeneous distribution of emphysema, centrilobular emphysema, and 5-year progression of emphysema. However, sRAGE values did not associate with airway wall thickness or paraseptal emphysema.ConclusionsRather than being a general COPD biomarker, sRAGE is especially a promising biomarker for centrilobular emphysema. Follow-up studies should elucidate whether sRAGE can be used as a biomarker for other COPD phenotypes as well.
Highlights
There is a strong need for biomarkers to better characterize individuals with Chronic obstructive pulmonary disease (COPD) and to take into account the heterogeneity of COPD
Klont et al Respiratory Research (2022) 23:15 been explored in large-scale longitudinal studies like ECLIPSE, SUMMIT, SPIROMICS and COPDgene [1,2,3,4,5]. All these studies identified the soluble receptor for advanced glycation end-products to be amongst the most promising blood biomarkers. sRAGE is the extracellular domain of the pro-inflammatory pattern recognition receptor Receptor for advanced glycation end-products (RAGE)
The COPDGene study was chosen because we aimed to determine the role of sRAGE as a biomarker in subtypes of emphysema and the progression of emphysema over time, which could be assessed in COPDGene because this study had a 5-year follow-up, and because COPD patients were radiologically phenotyped on High-resolution computed tomography (HRCT) using a standardized classification [26]
Summary
Klont et al Respiratory Research (2022) 23:15 been explored in large-scale longitudinal studies like ECLIPSE, SUMMIT, SPIROMICS and COPDgene [1,2,3,4,5]. All these studies identified the soluble receptor for advanced glycation end-products (sRAGE) to be amongst the most promising blood biomarkers. It became evident that RAGE signaling plays a key role in the development of COPD, contributing both to airway inflammation as well as emphysema [8,9,10,11]. The association with emphysema is strong, showing significant correlations with carbon monoxide (CO) diffusion capacity [13, 20], and a number of quantitative HRCT measurements that reflect emphysema [20,21,22], as well as progression of emphysema [23]
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