Lung hyaluronan levels are decreased in alpha-1 antiprotease deficiency COPD

Jerome Cantore， Gerard Armand， Gerard Turino

St John's University College of Pharmacy and Health Sciences and St Luke's – Roosevelt Hospital Center, New York City, NY, United States

Introduction

Hyaluronan (HA), a long-chain polysaccharide, is currently being evaluated as a potential therapeutic agent for pulmonary emphysema, based on previous studies from this laboratory indicating its protective effect against elastic fiber breakdown. To determine whether exogenously administered HA might replace a loss of this extracellular matrix component in this disease, we measured the content of HA in lung biopsies from both healthy individuals and alpha-1 antiprotease-deficient (AAPD) COPD patients with pulmonary emphysema.

Methods

Tissue samples (9 from COPD patients, 5 from controls) were digested with papain to isolate glycosaminoglycans, and lung HA was quantified with an enzyme-linked immunoabsorbent assay.

Results

HA was significantly decreased in the AAPDCOPD population compared to normal individuals (13.5 vs 21.7 ng/mg wet lung; p < 0.01). Furthermore, there was a positive correlation between HA levels and the following parameters: 1) percent predicted FEV1 (r = 0.78; p < 0.001), 2) percent predicted DLCO (r = 0.74; p < 0.05), and 3) serum levels of AAP (r = 0.61; p < 0.05).

Conclusions

These findings support the hypothesis that depletion of lung HA plays a role in the pathogenesis of pulmonary emphysema, and that replacement of this matrix component could slow the progression of the disease.

respiratory medicine

May 2015Volume 109, Issue 5, Pages 656–659

DOI: http://dx.doi.org/10.1016/j.rmed.2015.03.006 |