Sputum desmosine during hospital admission for pulmonary exacerbation in cystic fibrosis.
BACKGROUND
Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active structural destruction during pulmonary exacerbation in patients with CF. The noninvasive measurement of desmosine, a breakdown product of elastin, may reflect ongoing lung injury and serve as a biomarker of short-term damage. Our objectives were to measure desmosine in the sputum of patients with CF hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine levels and other markers of clinical improvement, including lung function and inflammatory mediators, following hospitalization.


METHODS
Sputum and blood samples collected and lung function measurements were made at multiple time points during hospitalization. We used a repeated measures model, adjusted for age and time between measurements, to compare log-transformed sputum desmosine levels across multiple time points and to correlate those levels with related variables.


RESULTS
Desmosine levels were measured by radioimmunoassay in 71 expectorated sputum samples from 19 patients with CF hospitalized for 26 pulmonary exacerbations (range of results, 0 to 200 pmol/L desmosine/mL). Sputum desmosine levels decreased significantly during the first week of hospitalization (p = 0.04). Desmosine levels were positively associated with plasma C-reactive protein (rho = 0.59; p = 0.03), sputum interleukin-8 (rho = 0.86; p < 0.01), and sputum neutrophil elastase (rho = 0.78; p < 0.01).


CONCLUSIONS
Sputum desmosine, a novel measure of acute structural lung injury, may serve as a marker of structural lung damage occurring during exacerbations of lung disease in CF.
Laguna
Theresa A
TA
Department of Pediatrics, University of Minnesota Medical School and the University of Minnesota Amplatz Children's Hospital, Minneapolis, MN. Electronic address: lagun005@umn.edu.
Wagner
Brandie D
BD
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
Luckey
Heidi K
HK
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Mike McMorris Cystic Fibrosis Research and Treatment Center, the Children's Hospital, Aurora, CO.
Mann
Shelley A
SA
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Mike McMorris Cystic Fibrosis Research and Treatment Center, the Children's Hospital, Aurora, CO.
Sagel
Scott D
SD
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Mike McMorris Cystic Fibrosis Research and Treatment Center, the Children's Hospital, Aurora, CO.
Regelmann
Warren
W
Department of Pediatrics, University of Minnesota Medical School and the University of Minnesota Amplatz Children's Hospital, Minneapolis, MN.
Accurso
Frank J
FJ
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Mike McMorris Cystic Fibrosis Research and Treatment Center, the Children's Hospital, Aurora, CO.
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003895:Desmosine / Q000378:metabolism*; D005260:Female; D006760:Hospitalization; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011446:Prospective Studies; D012720:Severity of Illness Index; D013183:Sputum / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers; D016209:Interleukin-8; D003895:Desmosine; D002097:C-Reactive Protein; D019272:Leukocyte Elastase