Desmosine: The Rationale for Its Use as a Biomarker of Therapeutic Efficacy in the Treatment of Pulmonary Emphysema.

Abstract

Desmosine and isodesmosine (DID) are elastin-specific crosslinking amino acids that play a critical role in maintaining the structural integrity of elastic fibers, and their levels in body fluids may serve as biomarkers for alveolar wall injury. To support this concept, we present studies demonstrating the use of DID to detect elastic fiber damage that reflects distention and the rupture of airspaces. The emergence of airspace enlargement may be modeled by a percolation network describing the effect of changing proportions of intact and weak elastic fibers on the transmission of mechanical forces in the lung. Following the unraveling and fragmentation of weakened elastic fibers, the release of DID may correlate with an increasing alveolar diameter and provide an endpoint for clinical trials of novel agents designed to treat pulmonary emphysema. The limitations of the DID measurements related to specificity and reproducibility are also addressed, particularly regarding sample source and analytical techniques. Standardizing protocols to isolate and quantify DID may increase the use of this biomarker for the early detection of alveolar wall injury, which permits timely therapeutic intervention.