desmosine and Airway-Remodeling

Chronic obstructive pulmonary disease (COPD) can no longer be considered as a disease affecting only the lungs. Increasing evidence supports the presence of a systemic inflammatory component which is thought to provide the link between COPD and the co-morbidities commonly associated with this disease. These include cardiovascular disorders, skeletal muscle dysfunction, diabetes, and osteoporosis. The majority of current therapies for COPD have been developed to improve airway obstruction or to target airway inflammation, leaving an unmet medical need with respect to the systemic inflammatory component of COPD and its extra-pulmonary manifestations. This review describes systemic biomarkers in COPD and their relationship with both the local lung and systemic manifestations of the disease. A summary is provided of the most promising biomarkers that have been investigated in COPD and its co-morbidities. Such biomarkers may be used to assess and manage the systemic effects of COPD, and may guide future development of novel therapeutic interventions to provide a more holistic approach to treating this multi-faceted disease.

Topics: Adiponectin; Aging; Airway Remodeling; Biomarkers; C-Reactive Protein; Cachexia; Cardiovascular Diseases; CD40 Ligand; Chemokines, CC; Cytokines; Desmosine; Fibrinogen; Humans; Inflammation; Intercellular Adhesion Molecule-1; Isodesmosine; Lung Neoplasms; Matrix Metalloproteinases; Natriuretic Peptide, Brain; Osteoprotegerin; Pulmonary Disease, Chronic Obstructive; Pulmonary Surfactant-Associated Protein D; Serum Amyloid A Protein; Severity of Illness Index; Telomere; Uteroglobin

Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators.. Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration.. Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0-235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P < 0.01 (average length of stay = 11 days). No correlation was observed between UDes concentration and lung function or inflammatory markers.. UDes decreased significantly following treatment for an acute pulmonary exacerbation and may be a useful biomarker of short-term injury to the CF lung. Further investigation is needed to evaluate the utility of UDes concentration in the long-term progression of CF lung disease.

Topics: Airway Remodeling; Biomarkers; C-Reactive Protein; Cohort Studies; Cystic Fibrosis; Desmosine; Disease Progression; Elastin; Female; Humans; Interleukin-8; Lung Injury; Male; Pneumonia; Prospective Studies; Respiratory Function Tests