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This research investigates how extracellular matrix dysregulation in the lungs relates to COPD pathology and functional decline.

July 4, 2026Open Access

Direct visualisation and measurement of lung microstructure reveal insights into extracellular matrix dysregulation in COPD

Key Points

This research investigates how extracellular matrix dysregulation in the lungs relates to COPD pathology and functional decline.
16 patients with COPD and 20 controls were assessed using pulmonary function tests, CT imaging, bronchoscopy, and probe-based confocal laser endomicroscopy (pCLE).
Alveolar morphometrics and elastin linearity scores were quantified with an automated algorithm.
Serum biomarkers of elastin and collagen turnover were measured in a combined cohort of 54 COPD patients and 61 controls.
Current smokers without airflow obstruction had larger alveolar dimensions (AOA 46,282 ± 16,805 vs. 33,549 ± 2,595 μm², p = 0.003).
COPD patients demonstrated larger AOA compared to controls (56,468 ± 11,079 vs. 46,282 ± 16,805 μm², p < 0.001) and greater elastin fibre disorganisation (ELS 54.9 ± 6.0 vs. 47.5 ± 10.7, p = 0.032).
Higher circulating elastin and collagen degradation biomarkers were found in COPD, correlating with pCLE morphometrics (all p < 0.05).

Abstract

Abstract Background Extracellular matrix (ECM) dysregulation is a key process in the pathology of COPD. However, an inability to characterise ECM remodelling in vivo has limited our understanding of its relationship with functional decline and disease mechanisms. We aimed to quantify in vivo ECM remodelling using probe-based confocal laser endomicroscopy (pCLE) and determine associations with physiological, radiological, histological, and serological markers of COPD. Methods 16 patients with COPD and 20 controls underwent pulmonary function testing, CT imaging, bronchoscopy, and pCLE. Alveolar morphometrics and elastin linearity scores (ELS) were quantified using a novel automated algorithm. Bronchial biopsies were analysed for elastin and collagen content. Serum biomarkers of elastin and collagen turnover were measured in a combined cohort of 54 COPD patients and 61 controls. Results Compared with never-smoking controls, current smokers without airflow obstruction demonstrated larger alveolar dimensions including increased alveolar opening area (AOA) (46,282 ± 16,805 vs. 33,549 ± 2,595 μm², p = 0.003). Alveolar dimensions were further increased in COPD, with larger AOA (56,468 ± 11,079 vs. 46,282 ± 16,805 μm², p < 0.001) compared with all controls. COPD was also associated with greater elastin fibre disorganisation (ELS 54.9 ± 6.0 vs. 47.5 ± 10.7, p = 0.032). Across the cohort, ELS correlated with airflow obstruction and surrogate markers of small airway disease. Airway collagen content was increased in COPD and correlated with ELS ( r = 0.665, p = 0.005). COPD was associated with higher circulating elastin and collagen degradation biomarkers, including ELP-3, C1M, C6M, and EL-CG (all p < 0.05), which correlated with pCLE morphometrics. Conclusion Using an innovative lung imaging technique, we provide the first objective quantification of in vivo airway elastic fibre disorganisation and demonstrate quantifiable lung microstructural changes that may precede abnormalities detected by established techniques. These quantifiable signals relate to biomarkers of lung ECM turnover, offering a new platform for early disease detection and mechanistic understanding of COPD.

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