What percolation theory can tell us about COPD

Abstract

Damage to the lung elastic fiber network is largely responsible for the distention and rupture of alveolar walls in chronic obstructive pulmonary disease (COPD). It has therefore been suggested that blood or urine levels of the unique elastic fiber crosslinks, desmosine and isodesmosine (DID), may serve as a biomarker for the progression of the disease. The prognostic value of DID may be limited, however, by the large degree of variance associated with their measurement in patients with COPD. To overcome this problem, we propose that specific patterns of DID release from damaged elastic fibers, rather than their absolute quantity, may provide a better indication of morphological changes in the lungs of patients with COPD. Using percolation theory to model the elastic fiber network in the lung, it will be shown that the relative amounts of damaged and intact elastic fibers may be reflected at the molecular level by urinary levels of free and peptide-bound DID, respectively. The self-similar nature of percolation networks further suggests that detachment of crosslinks from elastic fibers may be analogous to the rupture of alveolar walls in COPD. Consequently, the ratio of free to bound DID may be a measure of emphysematous changes in this disease.