Serum Hyaluronic Acid Levels Predict Severity and Survival in COPD

ELISA plate
Enzyme-linked immunosorbent assay (ELISA) plate, Immunology testing in laboratory
Serum hyaluronic acid is associated with COPD severity and outcome, and predicts overall survival.

High levels of serum hyaluronic acid was associated with chronic obstructive pulmonary disease (COPD) exacerbations, and was predictive of overall survival, according to results of a new study published in the European Respiratory Journal.

Serum samples were obtained from patients with COPD at both stable state and exacerbation, and hyaluronic acid was measured using a hyaluronic acid-binding protein-based sandwich ELISA. Hyaluronidase activity was measured by hyaluronic acid substrate zymography. At baseline, patients underwent clinical evaluation, sputum analysis, and standard spirometry after the administration of an inhaled short-acting bronchodilator. Each patient underwent 6-minute walk testing and quality-of-life questionnaires, using the St. George’s Respiratory Questionnaire and the Short Form-36.

Among the 638 patients recruited, 506 patients attended a visit at 6 months and were included in the analysis. Hyaluronic acid was measured at stable state, at exacerbation, and at follow-up (4 weeks after exacerbation). Hyaluronic acid was significantly increased at moderate and severe exacerbations, as compared with the stable state of the disease (P <.001 for both comparisons). At follow-up, serum levels of hyaluronic acid remained significantly higher compared with serum levels at stable state (P <.001).

Hyaluronic acid levels in the serum at stable state were positively correlated with age (P <.001), with postbronchodilatation forced expiratory volume in 1 second (FEV1) percent predicted (P =.002), with FEV1/forced vital capacity (P =.025), and with the age-adjusted Charlson score (P =.001). Furthermore, hyaluronic acid was significantly associated with time to death (P <.001). In addition, hyaluronic acid serum levels did not differ between patients under treatment with inhaled corticosteroids.

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“[T]he results of our study indicate that [hyaluronic acid] is associated with COPD severity and outcome and predicts overall survival,” wrote the investigators. Because enzymatic degradation of hyaluronic acid is associated with airflow limitation and impairment of lung function during COPD exacerbations, “[hyaluronic acid] and its degrading enzyme [hyaluronidase-1] may be proved to serve as potential targets to control airway inflammation and remodeling in COPD,” they concluded.


Papakonstantinou E, Bonovolias I, Roth M, et al. Serum levels of hyaluronic acid are associated with COPD severity and predict survival [published February 14, 2019]. Eur Respir J. doi:10.1183/13993003.01183-2018