Chronic Obstructive Pulmonary Disease. A Biomarker and a Potential Therapy

Abstract

This article assesses developments in cardiorespiratory medicine since the Nobel Prize in Physiology or Medicine was awarded in 1956 for advancements in the study of cardiorespiratory disease. In chronic obstructive pulmonary disease, advances were accelerated by the discovery of a genetically determined cause for pulmonary emphysema in the genetic abnormality alpha-1 antitrypsin deficiency. This causes a deficiency of the inhibitor of neutrophil elastase, which results in increased degradation of lung elastin and the development of pulmonary emphysema. This discovery gave focus to two amino acids that reside only in body elastin, desmosine and isodesmosine, which can be measured as biomarkers of elastin degradation in body fluids with increased accuracy and sensitivity. Studies of this biomarker have shown that augmentation therapy in alpha-1 antitrypsin deficiency does decrease lung and body elastic tissue degradation and in the RAPID (Randomized, Placebo-controlled Trial of Augmentation Therapy in Alpha-1 Proteinase Inhibitor Deficiency) Study, over 4 years, showed a preservation of lung density by computer tomography correlating with decreases in plasma levels of desmosine and isodesmosine. This insight indicates the potential of agents that prevent lung elastin degradation. Such an agent is hyaluronan aerosol, which is deficient in post mortem lungs with chronic obstructive pulmonary disease and has been shown to block elastin degradation, possibly by a barrier function. Thus it would appear that hyaluronan could have therapeutic potential in chronic obstructive pulmonary disease.

Elastin degradation markers are elevated in never-smokers with past history of prolonged exposure to secondhand tobacco smoke and are inversely associated with their lung function

“…39, 40, 42 Later, human studies confirmed similar findings. 15, 41, 42 Stone et al extensively explored levels of D/I in relation to presence of COPD, or with smoking status. 43 They found higher excretion of D/I in urine of COPD patients, and in smokers without presence of COPD compared to healthy lifetime nonsmokers, suggesting smoking and the presence of COPD to be independently associated with elevated urinary D/I levels.…”

“…12 Lung elastin is a recognized target for injury in COPD, and systemic levels of D/I, which are specific for elastin degradation, are elevated in COPD as well as in those without COPD but with acute exposure to tobacco smoke, direct or secondhand. [13][14][15] However, it is unclear whether past remote exposure to SHS in those without a diagnosis of COPD is also associated with continued lung injury, elastin degradation, and elevated levels of D/I.…”