Sputum Exosomal microRNAs as Non-Invasive Biomarkers in COPD: A Cross-Sectional Study

Area of Science:

• Biochemistry
• Molecular Biology
• Pulmonology

Background:

• Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and airflow limitation.
• Exosomal microRNAs (exo-miRNAs) are emerging as stable biomarkers for molecular changes in the airways.
• Sputum-derived exo-miRNA profiles for COPD remain largely unexplored compared to serum or bronchoalveolar lavage fluid.

Purpose of the Study:

• To investigate the potential of sputum-derived exosomal microRNAs as non-invasive biomarkers for diagnosing and phenotyping COPD.
• To identify specific exo-miRNA signatures associated with COPD and their correlation with disease characteristics.

Main Methods:

• Induced sputum was collected from stable COPD patients and healthy controls.
• Exosomes were isolated and characterized using transmission electron microscopy and Western blotting.
• Quantitative real-time PCR (RT-qPCR) was employed to measure the levels of nine candidate miRNAs.
• Statistical analyses included Mann-Whitney U test, Pearson's correlation, and Receiver Operating Characteristic (ROC) curve analysis.

Main Results:

• Sputum exosomes exhibited characteristic morphology and protein markers.
• Significant dysregulation of several exo-miRNAs was observed in COPD patients, including upregulation of miR-21 and miR-223, and downregulation of miR-155, miR-126, and miR-146a.
• miR-21 correlated with symptom burden (CAT score).
• miR-155 showed the highest diagnostic performance for COPD detection (AUC = 0.730).
• A composite panel of miR-155, miR-126, and miR-146a improved diagnostic accuracy (AUC = 0.841).
• miR-126 effectively discriminated between mild and moderate-to-severe COPD (AUC = 0.728).

Conclusions:

• Sputum exosomal miRNAs present a distinct COPD-specific molecular signature.
• This signature reflects underlying airway inflammation, impaired repair mechanisms, and immune dysregulation in COPD.
• Composite panels of specific exo-miRNAs (miR-155, miR-126, miR-146a) offer promising potential for non-invasive COPD diagnosis and clinical staging.