Urinary desmosine: A biomarker of structural lung injury during CF pulmonary exacerbation

Abstract

Summary Rationale 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. Methods 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. Results Desmosine was measured by radioimmunoassay in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0–235 pmol Des/mL). Specific gravity 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. Conclusions Urinary desmosine 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.

Diagnostic Value of Exhaled Carbon Monoxide as an Early Marker of Exacerbation in Children with Chronic Lung Diseases

“…Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents [10]. Inflammation is triggered by inflammatory events as infection or hypersensitivity.…”

Novel end points for clinical trials in young children with cystic fibrosis

“…For example, urinary concentrations of the breakdown products of elastin, desmosine and isodesmosine, correspond to neutrophil elastase activity and reflect neutrophilic airway inflammation (108). Although there is evidence that changes in these compounds may reflect therapeutic effects (109, 110), there is currently insufficient evidence to recommend using such markers as outcome measures in young children.…”

Treatment of pulmonary exacerbations in cystic fibrosis

“…During a pulmonary exacerbation, there is increased expression of some markers of inflammation and/or lung damage, for example C-reactive protein, white cell counts, interleukin-8, neutrophil elastase alpha 1-antiprotease complexes [15][16][17] and matrix metalloproteins [18], in blood or serum. Circulating markers may not truly reflect the local inflammatory response in the lung; however, this can be examined by measuring the sputum concentrations of bioactive lipid mediators, such as the cysteinyl leukotrienes and prostaglandin-E2 [19], or sputum cell counts [16] or analysing exhaled breath [20][21][22] or urine [23] during exacerbations. However, none of these are routinely used in clinical practice.…”