What question did this study set out to answer?

To investigate age-related proteins involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).

June 12, 2026Open Access

Plasma proteomic profiling uncovers the age-related molecular changes in chronic obstructive pulmonary disease

Key Points

To investigate age-related proteins involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Analyzed 70 plasma samples (35 healthy controls, 35 COPD patients) using data-independent acquisition mass spectrometry (DIA-MS).
Stratified groups into young (≤ 50 years) and aged (≥ 70 years) subgroups for differential expression analysis.
Utilized multivariable linear regression and Spearman’s correlation to assess associations between protein levels and lung function.
Identified 534 proteins via DIA-MS, with 413 proteins retained after filtering.
Found 20 differentially expressed proteins between young and aged COPD patients, significantly enriched in metabolic pathways.
Developed an exploratory model with four proteins (PIGR, TSP1, SPRC, ADIPO) achieving an AUC of 0.818 for COPD discrimination.

Abstract

Abstract Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, with aging as a major risk factor. This study aimed to investigate age-related proteins potentially involved in COPD pathogenesis. Methods A total of 70 plasma samples (35 healthy controls, 35 COPD patients) were analyzed by data-independent acquisition mass spectrometry (DIA-MS), with each group stratified into young (≤ 50 years) and aged (≥ 70 years) subgroups. Differentially expressed proteins were identified using the limma package in R, followed by functional enrichment and protein–protein interaction analyses. Spearman’s correlation and multivariable linear regression were used to assess associations between protein levels and lung function. Receiver operating characteristic curves (ROC) were generated to evaluate the diagnostic value of aging-related proteins in COPD. Results A total of 534 proteins were detected by DIA-MS. Following missing value imputation and quality filtering, 413 proteins were retained for analysis. Comparative analysis revealed 20 proteins differentially expressed between young and aged COPD patients (11 upregulated, 9 downregulated), which were significantly enriched in pathways including glutathione metabolism, nitrogen metabolism, endoplasmic reticulum protein processing, and PI3K-Akt signaling. Notably, expression levels of polymeric immunoglobulin receptor (PIGR), thrombospondin-1 (TSP1), secreted protein acidic and rich in cysteine (SPRC), and adiponectin (ADIPO) were correlated with FEV₁/FVC ratio in COPD patients; PIGR and ADIPO remained independently associated after adjusting for covariates. An exploratory model integrating these four proteins with age demonstrated reasonable discriminatory ability for COPD (AUC 0.818; 95% CI: 0.718–0.917). Conclusion Our findings identify four plasma proteins—PIGR, SPRC, TSP1, and ADIPO—as age-related biomarkers in COPD that may offer value for patient stratification and endotyping. These results provide new insights into the role of aging in COPD pathogenesis and warrant further validation.

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